Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study determined whether inhibitors of angiotensin converting enzyme (ACE) can ameliorate radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a range of single doses of 60Co gamma rays to the right hemithorax. Four indices of pulmonary endothelial function were monitored: right lung ACE and plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Hydroxyproline (HP) content served as an index of pulmonary fibrosis. Rats consumed either control powdered chow or feed containing one of five modifying agents continuously after irradiation. The modifiers included three ACE inhibitors: Captopril, CL242817, and CGS13945, respectively, a thiol, a thioacetate, and a nonthiol compound. All of the ACE inhibitors are analogues of proline. Two additional modifiers were tested: penicillamine, a thiol with no ACE inhibitory activity; and pentoxifylline, a vasodilator that is neither a thiol nor an ACE inhibitor. Radiation produced a dose-dependent decrease in lung ACE and PLA activity, and an increase in PGI2 and TXA2 production and in HP content. All ACE inhibitors attenuated the radiation-induced suppression in lung ACE and PLA activity. All thiol or thioacetate compounds ameliorated the radiation-induced increase in PGI2, TXA2, and HP. The two agents that were both thiols and ACE inhibitors (Captopril and CL242817) spared all of the radiation reactions, while the compound that was neither a thiol nor an ACE inhibitor (pentoxifylline) spared none of the reactions. These data suggest a novel application for ACE inhibitors in general, and for Captopril in particular, as modifiers of radiation pneumotoxicity.
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PMID:Radiation pneumotoxicity in rats: modification by inhibitors of angiotensin converting enzyme. 173 1

Pulmonary injury induced by the plant alkaloid monocrotaline is partially prevented by the angiotensin-converting enzyme (ACE) inhibitor captopril. CL242817 [(S-[R*,S*])-1-([3-acetylthio]-3-benzoyl-2-methyl-propionyl)- L-proline] is a new orally active ACE inhibitor under evaluation as an antihypertensive agent. To determine whether CL242817 also can modify monocrotaline-induced pulmonary injury, male rats were divided into four groups: control; CL242817 (60 mg/kg/day, po); monocrotaline (2.4 mg/kg/day, po); or monocrotaline plus CL242817, and were sacrificed after 6 weeks of continuous treatment. Rats receiving monocrotaline alone exhibited occlusive medial thickening of the pulmonary arteries, cardiomegaly, and right ventricular hypertrophy. Electron micrographs of monocrotaline-treated lung revealed degeneration of both endothelial and Type I epithelial cells, as well as marked interstitial hypercellularity and fibrosis. Hydroxyproline (collagen) content of monocrotaline-treated lung also increased significantly, confirming the fibrosis observed in the electron micrographs. These structural changes were accompanied by decreased lung ACE and plasminogen activator (PLA) activities, indicative of pulmonary endothelial dysfunction. Concomitant CL242817 treatment ameliorated all anatomic manifestations of monocrotaline injury, particularly the right ventricular hypertrophy, pulmonary arterial occlusion, epithelial degeneration, and interstitial fibrosis. CL242817 also significantly prevented the monocrotaline-induced increase in lung hydroxyproline content. In contrast, concomitant CL242817 did not significantly influence the suppressed lung ACE and PLA activities in monocrotaline-treated rats. CL242817 alone produced retarded weight gain, decreased heart weight relative to body weight, decreased lung hydroxyproline content and ACE activity, and increased serum ACE activity and plasma AII concentration. Thus CL242817 resembles captopril, both in its ability to ameliorate monocrotaline-induced pulmonary injury in rats, and in many of its side effects.
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PMID:Monocrotaline-induced cardiopulmonary damage in rats: amelioration by the angiotensin-converting enzyme inhibitor CL242817. 301 47

Several surgical disciplines apply cartilage grafts for reconstructive purposes and have to overcome the scarcity of donor sites for this unique tissue. Employing the techniques of tissue engineering, cartilage might be generated in reasonable amounts for clinical purposes. Application of growth factors together with biochemical and biomechanical scaffold properties influence the process of ex vivo transplant production. The aims of this study are: 1) to investigate the influence of IGF-1 and TGFbeta-2 on tissue engineered human septal cartilage in vitro and in vivo after transplantation in nude mice; 2) to analyse the effect of the polydioxanone (PDS) content of the biodegradable Ethisorb E210 scaffold on the properties of the implanted constructs. Cells were three-dimensionally cultured on biodegradable Ethisorb E210 (PGA-PLA-copolymer fleeces with polydioxanone (PDS) adhesions), or on E210 scaffolds with a reduced polydioxanone content. Wet weight (ww), GAG-, and hydroxyprolin-content, as well as the cellularity of the neocartilage constructs were quantitatively evaluated. Additionally, the in vivo resorption of the two types of cell carriers was monitored. Addition of growth factors clearly increased the wet weight of the in vitro cultured constructs before transplantation. After transplantation, high PDS content improved the in vivo stability and macroscopic morphometric appearance of the tissue engineered specimens and led to enhanced deposition of glycosaminoglycans in transplanted constructs. Hydroxyproline content of the implants was not affected by either growth factors or PDS content. These data suggest a role for IGF-1 and TGFbeta-2 in preparative in vitro culture of chondrocytes before implantation, while PDS content of the scaffold is important for in vivo properties of the implanted material.
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PMID:Growth factors and scaffold composition influence properties of tissue engineered human septal cartilage implants in a murine model. 1914 66