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)

Proteolytic enzymes play an important role during remodeling and digestion of extracellular matrix proteins. An overproduction of extracellular matrix or insufficient extracellular matrix digestion may result in fibrosis. Enhanced proteolytic activity or an insufficient inhibitory potential could be followed by emphysema development. Since the first reports showed an emphysema induction in rats after intratracheal application of the cysteine protease papain, a number of proteolytic enzymes involved in the remodeling of the extracellular matrix of the lung were discovered. Most of them are cysteine-, metallo-, serine- or aspartic proteases. In this paper some new findings concerning the expression, function and regulation of the activity of papain-like cysteine proteases in the process of tissue destruction and remodeling in the lung are reviewed. The functional relationship between cathepsins and other proteolytic enzymes are discussed.
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PMID:[Cathepsin cysteine proteinases in the lung]. 1048 79

Aerosol measures of effective airspace diameter (EAD) were correlated with morphometric parameters in a series of 8 canine lungs, 5 of which had been exposed to papain in order to cause experimental emphysema. In an effort to preserve alveolar dimensions without shrinkage, the lungs were fixed by air drying at total lung capacity. EAD was measured with 400-cm2 boluses, with mean penetration index (Pen), defined as volumetric bolus penetration/total lung capacity, equal to 0.34 (EAD400), and with 800-cm2 aerosol boluses, with mean Pen equal to 0.59 (EADdeep). Morphometric analysis, following measurement of EADs, determined the mean linear intercept and other parameters of the chordlength distribution, including the 90th, 95th, and 99th percentiles (p90, p95, p99), the standard deviation, and the geometric standard deviation (GSD). EAD400 was significantly correlated with Lm (r2 = .68, P < .05), p95, (r2 = .85, P < .01), p99 (r2 = .94, P < .001), and GSD (r2 = .94, P < .001). Similar results were found with EADdeep. In general, correlations were stronger between EAD and p95, p99, or GSD than between EAD and Lm. A comparison with a previous similar study relating EAD to morphometry in a series of lungs fixed by formalin fixation found closer agreement between EAD and morphometry when lungs were fixed by air drying. Overall, the data support the validity of EAD as an in vivo method of determining airspace size at total lung capacity.
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PMID:Aerosol measurement of airspace diameter correlates with morphometry in normal and papain-exposed air dried lungs. 1048 25

When the deposition of aerosol boluses is used to estimate mean pulmonary airspace size, an implicit assumption is made that the inhaled particles are distributed uniformly among normal and diseased lung regions. This assumption was examined in a series of dogs in which emphysema was experimentally induced by exposure to papain. After the experimental disease had developed for several weeks, boluses of fluorescent particles were inhaled, using a breathing pattern similar to that used for aerosol measurements of airspace size. The lungs were then excised and 18-20 tissue blocks were obtained from each lung. A section from each tissue block was analyzed to determine the mean liner intercept (Lm), which was considered as an index of lung injury. In the same sections, the density of particles was determined by counting particles in a number of microscopic fields and dividing the particle count by the number of fields sampled. Correlation analysis generally revealed a negative correlation of particle density with Lm, indicating fewer particles being delivered to diseased regions. One lung, however, showed a positive correlation between particle density and Lm. Correction for the fractional deposition of aerosol in the lung regions weakened but did not reverse the relationship between particle density and Lm. A model calculation of the effect of the observed nonuniform distribution of aerosol on the determination of airspace size found a negligible effect of uneven ventilation on mean airspace size determination in this experimental preparation.
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PMID:The distribution of inhaled particles in aerosol measurements of pulmonary airspace size. 1126 38

Lung volume reduction surgery (LVRS), the removal of damaged, hyperexpanded lung, has been shown to improve respiratory function in many patients with end-stage emphysema. We report the results of an animal study using a new transbronchoscopic alternative to LVRS in which a washout solution and fibrin-based glue are used to collapse, seal, and scar target regions of abnormal lung. Twelve sheep had static and dynamic lung functions measured at baseline. Emphysema was produced by inhaled papain (7,000 U/wk x 4 wk), resulting in a significant increase of lung volumes, compliance, and airway resistance. The animals were then divided into three treatment groups of four animals, and underwent surgical volume reduction (SVR), bronchoscopic volume reduction (BVR), or bronchoscopy alone (Sham-BVR). Response to each intervention was assessed 8 to 12 wk after treatment by measuring lung function and examining lung tissue. BVR and SVR groups responded with significant and similar decreases in TLC and residual volume (RV). Tissue examination demonstrated that BVR caused collapse of the lung with focal scarring in 11 of 20 target territories (55% success rate). Three of the 11 target zones developed sterile abscesses. Postprocedure complications were less frequent with BVR than with SVR. This pilot study suggests that lung volume reduction can be achieved in animals without surgery using a bronchoscopic approach and a novel fibrin-based glue system. BVR has the potential for simplifying volume reduction, extending indications, and reducing morbidity, mortality, and costs in humans.
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PMID:Bronchoscopic volume reduction: a safe and effective alternative to surgical therapy for emphysema. 1146 4

The effect of pulmonary resection on the maximal emptying of the remaining lobes was examined in an open-chest preparation in normal canine lungs and in a unilobar papain emphysema model. The objectives were to determine whether, compared with when both lungs were deflated (BL), maximal emptying of the normal lower lobes or the emphysematous right lower lobe would be altered 1) when acute pneumonectomy of the contralateral lung was performed (OL) and 2) when the lower lobe deflated alone (LA). The alveolar capsule technique was used to measure alveolar pressures (Palv) at 75, 50, and 30% lobar vital capacity (VC). During forced deflation, the maximal rates of deflation (dPalv/dt) and flows (lobarV(max)) of the lower lobes were determined under the three different conditions. The Pitot-static tube technique was used to measure intrabronchial pressures and to estimate bronchial area and compliance in which values were obtained at the same central airway during the conditions studied. The results showed that, compared with BL and OL, dPalv/dt and lobar V(max) decreased during LA (P < 0.05). These findings were due to a reduction in bronchial area during LA that limited flow at a lower maximal value compared with BL. This decrease in area appeared to be due to a change in bronchial pressure area behavior that resulted in a smaller bronchial area during LA for similar transmural pressures between conditions. There were no differences in findings between normal and emphysematous lobes. This study suggested that removal of lobes may alter the pressure area behavior of central airways. Possible mechanisms considered were differences in axial tension between conditions, negative effort dependence, or parenchymal-bronchial interdependence that may be relevant to understanding the dynamic collapsibility of central as well as intraparenchymal airways.
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PMID:Interdependence of flow between lobes reduces maximal emptying postresection in dogs. 1174 48

Bronchoscopic lung volume reduction (BLVR), a minimally invasive procedure based on tissue engineering principles, was performed in six sheep with papain-induced experimental emphysema (EMPH). Physiologic measurements, at baseline, after generation of EMPH, and at 3 and 9 weeks after BLVR, included lung volumes, diffusing capacity (DL(CO)), pressure-volume relationships for the lung and chest wall, pleural pressures generated during active respiratory muscle contraction, lung resistance and dynamic elastance. The animal model displayed hyperinflation (change in total lung capacity +8%; change in residual volume +66%), reduced DL(CO) (-21%), and elevated airway resistance (+76%) that resembled advanced human EMPH. BLVR was well tolerated without complications, and it reduced lung volumes (change in total lung capacity -16%; change in residual volume -55%) in a pattern that resulted in significant improvements in vital capacity (10%). At autopsy, well-organized, peripheral scars associated with tissue contraction were observed at 33 of the 36 (91%) treated sites. There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyperinflated lung, reduced overall lung volume, and improved respiratory function safely and consistently. The BLVR technology employed in this study addresses the limitations identified in our prior attempt at BLVR therapy and appears safe and effective enough to justify a trial in humans.
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PMID:Bronchoscopic lung volume reduction using tissue engineering principles. 1240 35

The relations between mRNA expression of basic fibroblast growth factor (bFGF) and the changes in collagen I and collagen III in pulmonary tissues from a single intratracheal instillation of papain-induced emphysema in rats were investigated. Wistar rats (n = 42) were randomly divided into normal group and emphysema model 1, 3, 5, 7, 15, 30-day groups (n = 6 in each group). The rat model of emphysema was induced by a single intratracheal instillation of papain. The results of immunohistochemistry SABC and in situ hybridization with bFGF probe were quantitatively analyzed to examine the changes of collagen I and collagen III and bFGF mRNA expression in lung tissues and the percent of positive expression of bFGFmRNA in alveolar macrophages. The results were as follows: (1) In the emphysema model groups the optical densities of collagen I and collagen III began to increase after 3 days, reached the highest at the 7th day, and began to reduce at the 15th day; (2) No expression of bFGFmRNA in pulmonary tissues was detectable in the normal group. The positive expression of bFGFmRNA was detectable in lung tissues one day after the intratracheal instillation of papain. The average optical densities reached the peak (41.895 +/- 7.017) at the 7th day, significantly higher than in the normal group (0.581 +/- 0.139, P < 0.01). The positive expression of bFGFmRNA in lung tissues began to reduce at the 15th day; (3) Positive expression of bFGFmRNA in alveolar macrophages of instillation papain rats was detectable 3 days after the intratracheal instillation of papain, and reached the highest at the 7th day with the percent of positive expression of bFGF mRNA in alveolar macrophages being 70.13 +/- 11.21, higher than in the normal group (5.12 +/- 0.18, P < 0.01); (4) The expression of bFGF mRNA in the lung tissues and macrophages was positively related with the changes in collagen I and collagen III (P < 0.01 or P < 0.05) respectively. It was suggested that the up-regulation of bFGF mRNA expression during the development of emphysema can lead pulmonary interstitial fibrosis, which may take part in the injury and repair and the lung tissue reconstruction.
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PMID:mRNA expression of basic fibroblast growth factor from a single intratracheal instillation of papain-induced emphysema in rats. 1253 52

The Shengenaqi oral liquid has a function of improving the inspiration and can be used in the treatment of chronic bronchitis, pulmonary emphysema and pulmonary heart disease etc. In the research, animal models for TCM dyspnea of deficiency were made by inhaling papain and injection hydrocotison into the abdominal eavity and afterwards, treated with Shengenaqi oral liquid. The effects showed: The medicine can improve the susfainability of swimming mice, increase the ability of cold tolerance and prevent the thymus from atrophy. The SOD activity in the lung tissue of mice can be improved and MDA be decreased.
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PMID:[Pharmacological studies on shengenaqi oral liquid on animal model for TCM dyspnea of deficiency]. 1257 69

The effects of Shenmai injection (SMI) and aminophylline on apoptosis of small airway smooth muscle cells (SASMC) and the Fas/FasL expression in rats with papain-induced emphysema were investigated. Rat emphysema model was established by a single intratracheal instillation of papain. Apoptosis and Fas/FasL expression of SASMC were detected by immunohistochemistry SABC and TUNEL assay at day 1, 3, 5, 7, 15, 30 after modeling, and the effect of SMI and aminophylline on them were observed. The results indicated that the Fas/FasL expression positive rate in SASMC was 2.31 +/- 0.55/1.28 +/- 0.47 respectively. After a single intratracheal instillation of papain, the expression of Fas/FasL positive rate in the placebo group was increased in a time-dependent manner. SMI could inhibit the expression of Fas/FasL, but aminophylline couldn't. The positive rate of apoptosis in the control group was 0.87 +/- 0.32. After a single intratracheal instillation of papain, the SASMC apoptosis positive rate in the placebo group was increased in a time-dependent manner. The SASMC apoptosis rate in all groups was declined after treatment with SMI, but the effect of aminophylline was not obvious. It was demonstrated that in the pathogenesis of emphysema Fas/FasL played an important role in the regulation of SASMC apoptosis. SMI influenced the expression of Fas/FasL and declined SASMC apoptosis by inhibiting the releasing of inflammatory media and played an important role in the therapy of emphysema.
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PMID:Effects of shenmai and aminophylline on apoptosis of small airway smooth muscle cells and the expression of relevant genes in rats with emphysema. 1267 66

Human emphysema is a progressive, destructive lung disease that produces morphologic and functional heterogeneity throughout its course. Consequently, the mature form of the disease is described by a broad range of anatomic, radiological, and physiologic patterns. This report describes the development and characterization of a sheep model of emphysema that represents many of the essential features of both homogeneous and heterogeneous emphysema. Emphysema was produced by two different techniques of papain exposure: (1) aerosol (75 IU/kg) given weekly for 4 treatments (HM) or (2) aerosol (75 IU/kg) weekly for 3 treatments following subsegmental intrabronchial instillations, 75 IU (in 10 saline) per lobe in 6 lobes (HT). Dexamethasone (0.06 mg/kg iv) was administered prior intrabronchial instillations only. On computed tomography, the HM group had homogeneous emphysema, the HT group gross nonuniformity of disease and bullae formation. Both groups demonstrated a significant (p < 0.05) increase in residual volume (HM, +38%; HT, +30%). There was a significant increase (p = 0.002) in total lung capacity per kilogram for the HM group. Emphysema had no effect on active or passive chest wall compliances. Diffusion capacity was significantly (p < 0.05) reduced in both groups. Both elastic (p = 0.066) and resistive (p = 0.025) components of impedance were increased in the HT, and airway resistance increased significantly in the HM groups. The HM model demonstrated gas trapping, a characteristic feature of emphysema, but failed to replicate the alterations in lung dynamics observed in the human form of this disease. The HT model demonstrated less static hyperinflation but significant frequency dependence and hence appeared to better represent the dynamic characteristics of human emphysema.
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PMID:Physiologic responses of sheep to two different methods of papain exposure. 1282 52


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