Document Detail

The effect of the specific elastase inhibitor, alanyl alanyl prolyl alanine chloromethylketone, on elastase-induced emphysema.
MedLine Citation:
PMID:  6899738     Owner:  NLM     Status:  MEDLINE    
The chloromethylketone derivative of the tetrapeptide, alanyl alanyl prolyl alanine significantly diminishes the extent of experimental elastase-induced emphysema in hamsters. A total of 19 mg of alanyl alanyl prolyl alanine chloromethylketone was administered intraperitoneally in divided doses before and immediately after intratracheal instillation of a standard dose (4 units) of porcine pancreatic elastase. Morphologic evaluation and measurement of mean linear intercept, internal surface area, and lung volume performed 7, 45, and 120 days after exposure to elastase indicated a marked decrease in the extent of emphysema in the group treated with alanyl alanyl prolyl alanine chloromethylketone compared with the control group. Lung elastin content determined biochemically confirmed the preservation of elastin in the hamsters treated with alanyl alanyl prolyl alanine chloromethylketone. At postmortem examination by light microscopy, no pathologic abnormalities were observed in the organs of hamsters treated with alanyl alanyl prolyl alanine chloromethylketone. These data indicate that alanyl alanyl prolyl alanine chloromethylketone in the doses administered (1) had significant anti-elastase activity in vivo; (2) markedly decreased the extent of elastase-induced emphysema; and (3) produced no adverse toxic effect during the period covered by this study protocol.
J Kleinerman; V Ranga; D Rynbrandt; J Sorensen; J C Powers
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American review of respiratory disease     Volume:  121     ISSN:  0003-0805     ISO Abbreviation:  Am. Rev. Respir. Dis.     Publication Date:  1980 Feb 
Date Detail:
Created Date:  1980-05-30     Completed Date:  1980-05-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370523     Medline TA:  Am Rev Respir Dis     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  381-7     Citation Subset:  AIM; IM    
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MeSH Terms
Amino Acid Chloromethyl Ketones / pharmacology*,  therapeutic use,  toxicity
Collagen / analysis
Dose-Response Relationship, Drug
Elastin / analysis
Hydroxyproline / analysis
Lung / analysis,  drug effects*,  pathology
Pancreatic Elastase / antagonists & inhibitors*
Pulmonary Emphysema / chemically induced*,  pathology,  prevention & control
Reg. No./Substance:
0/Amino Acid Chloromethyl Ketones; 51-35-4/Hydroxyproline; 9007-34-5/Collagen; 9007-58-3/Elastin; EC Elastase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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