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)

We studied the effect of low-protein diet (8% casein) on lung growth in rats from 3 to 7 weeks of age. Their diet was isocaloric with that of control animals fed a diet of 20% casein. The calorie intake of experimental animals was increased during the first 3 weeks of the experiment, but they increased less (about 10%) in body weight, had less protein and less water when the whole body was examined, and had lower serum proteins and decreased urinary hydroxyproline. The experimental animals remained in positive nitrogen balance by maintaining low urinary nitrogen excretion. The lungs of the experimental animals were abnormal, with decreased absolute amounts of hydroxyproline and desmosine and of these relative to unit lung weight. The lungs contained more air per gram of lung tissue, and the volume of air in the lung was increased at all transpulmonary pressures above zero. When corrected for increased total lung capacity, there was a loss of recoil at mid-lung volumes. Saline-filled volume-pressure curves, corrected for lung volume, showed similar loss of recoil. Alveolar multiplication was quantitatively normal, but the experimental animals had larger alveoli. We conclude that the protein deprivation in isocalorically fed animals has a specific effect on lung scleroprotein content, which may be due to diminished synthesis, and this results in both structural and functional abnormalities in the lung. Our results indicate the importance of dietary protein in lung development and possibly as one of the causes of emphysema. Further studies are needed to know whether this would be a problem in infants of Kwashiokor.
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PMID:Connective tissue, mechanical, and morphometric changes in the lungs of weanling rats fed a low protein diet. 279 30

A study was made of the evolution of emphysema and airway injury induced in the lungs of male golden Syrian hamsters by a single intratracheal injection of 350 micrograms human neutrophil elastase (HNE). Saline control and HNE-treated groups of 8 animals were studied 1, 3, 6, 12, and 18 months posttreatment. HNE treatment caused a significant increase in all lung volumes and a significant decrease in maximum expiratory flows at all study times. The mean linear intercept (MLI) values of the left lung were significantly increased over control values. There was no progression with time in MLI values, lung volumes, or lung compliance. Secretory-cell metaplasia was present at 1 month and persisted throughout the study. The HNE-treated lungs showed clusters of ferric iron-containing macrophages in the terminal airspaces. The amount of iron in the lungs, determined morphometrically, was greatest at 1 month, was decreased by 6 months, and then did not change further to 18 months. At 18 months the amount of iron was still significantly above control amounts. We conclude that the airway and parenchymal lesions induced by HNE persist without progression for 18 months. Clearance of ferric iron, which was probably a result of the hemorrhage induced by HNE treatment, continued for 6 months with no evident subsequent clearance.
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PMID:An 18-month study of the effects on hamster lungs of intratracheally administered human neutrophil elastase. 322 98

This study was undertaken to determine whether elastase injury, which results in extensive remodelling of the hamster lung to produce a panacinar type of emphysema, also induces significant lung cell damage. Anaesthetised hamsters were given a single intratracheal injection of 0.3 mg (18 units) purified elastase (Sigma Type IV) in physiologic saline and were killed 4, 6, 8, 16, 24 h, 2, 4, 8, and 16 days after exposure. DNA synthesis was assessed by autoradiography of sectioned tissue and scintillation counting of tissue blocks using injected tritiated thymidine (3HTdR). DNA, RNA and protein levels were also measured. Saline injected and unexposed animals were used as controls. Widespread mitotic activity was induced in three separate cell compartments, the peak of activity in each compartment occurring at different times. The first peak in labelling index was seen in non-ciliated, non-secretory bronchial cells at 24 h when a value of 8 per cent was reached. This was followed by mitosis in Type II alveolar cells with a labelling index of 15 per cent at 2 days and, lastly, in endothelial cells which showed an index of 9.8 per cent at 4 days. The differences between the peaks was significant (P less than 0.001). RNA content on elastase-exposed animals showed prolonged depression and had not regained control values by the end of the experiment. Protein and DNA content, and 3HTdR incorporation showed significant elevations, particularly about the fourth day after injury. Protein and DNA content and 3HTdR incorporation were not significantly changed in either group of controls.
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PMID:Elastase-induced emphysema: asynchronous bronchial, alveolar and endothelial cell proliferation during the acute response to injury. 617 40

This report describes the unusual case of a four-year-old girl who developed subconjunctival emphysema as a complication of mechanical ventilatory support with high positive expiratory pressure (PEEP)--which was applied after she sustained multiple injuries in a motor vehicle accident. The patient's left lower palpebral conjunctiva ballooned outward with air collection subconjunctivally, but it was crepitant and deflatable with light pressure. Saline, garamycin ointment, and Lacrilube were used to prevent drying. The condition persisted during the period when the patient required high PEEP (more than 18 cm H2O) but resolved after PEEP was decreased to below 5 cm H2O. The patient eventually died on the 66th ventilatory day due to complications of intractable tracheobronchial fistula and Pseudomonas pneumonia.
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PMID:Subconjunctival emphysema as a complication of PEEP. 676 96

Chronically, hyperinflated human subjects with chronic obstructive pulmonary disease and animals with experimentally induced emphysema generate greater than expected levels of transdiaphragmatic pressure at high lung volume because of adaptive changes in the length-tension relationship of the costal diaphragm. The ability to lower intrathoracic pressure during inspiration depends on the mechanical action of all the inspiratory muscles acting in concert. However, the effect of chronic hyperinflation on the mechanical action of inspiratory muscles other than the costal diaphragm remains unknown. This study compares the effect of chronic hyperinflation in the form of elastase-induced emphysema on the contractile properties of the three major inspiratory muscles of the hamster (i.e., the costal and crural diaphragm and parasternal intercostals). Muscles were studied in vitro 6 months after emphysema was induced by intratracheal injection of elastase. Saline-injected animals served as controls. TLC in the elastase-injected hamsters was significantly greater than in controls (12.5 +/- 0.8 ml versus 9.0 +/- 0.3 ml, p < 0.002). Maximal tetanic tension, time to peak tension, maximal velocity of shortening, and the force-velocity relationship differed among the three muscles but for any given muscle were similar in control and emphysematous animals. In contrast, the fiber length optimal for tension generation (Lo) not only differed across muscles but was significantly shorter in the costal diaphragm of emphysematous animals compared with control animals. However, Lo of the parasternal intercostal and crural diaphragm was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The comparative effects of elastase-induced emphysema on costal and crural diaphragm and parasternal intercostal muscle contractility. 811 77

We investigated the effects of a novel oral neutrophil elastase inhibitor (ONO-6818) on acute lung injury and pulmonary emphysema induced by human neutrophil elastase (HNE). Young male Wistar rats were divided into four treatment groups: (1) control group (saline); (2) HNE group (HNE 200 U + 0.5% carboxymethyl-cellulose [solution for ONO-6818]); (3) low-dose ONO-6818 group (HNE 200 U + ONO-6818 10 mg/kg); and (4) high-dose ONO-6818 group (HNE 200 U + ONO-6818 100 mg/kg). Saline and HNE were applied via the trachea using a microsprayer. ONO-6818 was administered orally 1 hour before HNE application. Six hours after HNE application, neutrophil counts and hemoglobin concentration in bronchoalveolar lavage fluid and lung tissue myeloperoxidase activity were determined. Eight weeks after the application, FRC, TLC, lung compliance, and mean linear intercept were estimated. ONO-6818 attenuated dose-dependently HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count in bronchoalveolar lavage fluid. Furthermore, it significantly attenuated HNE-induced increases in FRC, TLC, lung compliance, and mean linear intercept. ONO-6818 inhibited acute lung injury induced by HNE by minimizing lung hemorrhage and accumulation of neutrophils in the lung. ONO-6818 also inhibited the development of HNE-induced emphysematous changes including lung hyperinflation, degradation of elastic recoil, and airspace enlargement.
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PMID:A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats. 1218 27

We investigated whether systemically administered EP2 receptor agonists would stimulate angiogenesis in the emphysematous lungs of mice. Saline or porcine pancreatic elastase was intratracheally administered to C57BL/6J mice to induce the formation of emphysematous lesions, and 4 weeks later the mice were intraperitoneally injected with an EP2 receptor agonist, ONO-AE1-259 or PGE2, or saline on days 1-5 each week for 3 weeks. Intraperitoneal ONO-AE1-259 in the mice in the intratracheal saline group increased pulmonary capillary volume to 114.9% of the control value (P<0.05), and when administered to the intratracheal elastase group, ONO-AE1-259 partially restored pulmonary capillary volume, from 70.9% of the control value to 88.3% of the control value (P<0.05). Intraperitoneal PGE2 tended to increase pulmonary capillary volume in the mice in the intratracheal saline group (P=0.07) but not in the intratracheal elastase group. Intraperitoneal ONO-AE1-259 and PGE2 each increased the concentration of vascular endothelial growth factor (VEGF) and the number of endothelial progenitor cells (EPCs) in circulating blood. These results suggest that systemically administered ONO-AE1-259 stimulates pulmonary angiogenesis in an elastase-induced murine model of emphysema.
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PMID:A systemically administered EP2 receptor agonist stimulates pulmonary angiogenesis in a murine model of emphysema. 1976 69

A single instillation of porcine pancreatic elastase (PPE) results in significant airspace enlargement on the 28th day after instillation, whereas cigarette smoke (CS) exposure requires 6 months to produce mild emphysema in rodents. Considering that there are differences in the pathogenesis of parenchymal destruction in these different experimental models, it is likely that there may be different patterns of extracellular matrix (ECM) remodeling. To evaluate ECM remodeling, C57BL/6 mice were submitted to either a nasal drop of PPE (PPE 28 Days) or exposed for 6 months to cigarette smoke (CS 6 months). Control groups received either an intranasal instillation of saline solution (Saline 28 Days) or remained without any smoke inhalation for six months (Control 6 months). We measured the mean linear intercept and the volume proportion of collagen type I, collagen type III, elastin and fibrillin. We used emission-scanning confocal microscopy to verify the fiber distribution. Both models induced increased mean linear intercept in relation to the respective controls, being larger in the elastase model in relation to the CS model. In the CS model, emphysema was associated with an increase in the volume proportion of fibrillin, whereas in the PPE model there was an increase in the parenchymal elastin content. In both models, there was an increase in collagen type III, which was higher in the CS-exposed mice. We concluded that ECM remodeling is different in the two most used experimental models of emphysema.
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PMID:A comparative study of extracellular matrix remodeling in two murine models of emphysema. 2327 9

An excessive pulmonary inflammatory response could explain the poor prognosis of chronic obstructive pulmonary disease (COPD) patients submitted to invasive mechanical ventilation. The aim of this study was to evaluate the response to normal tidal volume mechanical ventilation in an elastase-induced murine model of pulmonary emphysema. In this model, two time points, associated with different levels of lung inflammation but similar lung destruction, were analyzed. C57BL/6 mice received a tracheal instillation of 5 IU of porcine pancreatic elastase (Elastase mice) or the same volume of saline (Saline mice). Fourteen (D14) and 21 (D21) days after instillation, mice were anesthetized, intubated, and either mechanically ventilated (MV) or maintained on spontaneous ventilation (SV) during two hours. As compared with Saline mice, Elastase mice showed a similarly increased mean chord length and pulmonary compliance at D14 and D21, while bronchoalveolar lavage cellularity was comparable between groups. Lung mechanics was similarly altered during mechanical ventilation in Elastase and Saline mice. Activated alveolar macrophages CD11bmid were present in lung parenchyma in both Elastase SV mice and Elastase MV mice at D14 but were absent at D21 and in Saline mice, indicating an inflammatory state with elastase at D14 only. At D14, Elastase MV mice showed a significant increase in percentage of neutrophils in total lung, as compared with Elastase SV mice. Furthermore, alveolar macrophages of Elastase MV mice at D14 overexpressed Gr1, and monocytes showed a trend to overexpression of CD62L, compared with Elastase SV mice. In an elastase-induced model of pulmonary emphysema, normal tidal volume mechanical ventilation may produce an increase in the proportion of pulmonary neutrophils, and an activation of alveolar macrophages and pulmonary monocytes. This response seems to be observed only when the emphysema model shows an underlying inflammation (D14), reflected by the presence of activated alveolar macrophages CD11bmid.
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PMID:Inflammatory Cellular Response to Mechanical Ventilation in Elastase-Induced Experimental Emphysema: Role of Preexisting Alveolar Macrophages Infiltration. 3066 10