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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3 Pt 2
pubmed:dateCreated
1995-4-27
pubmed:abstractText
Cardiopulmonary bypass causes hemorrhagic complications and initiates a biochemical and cellular "whole body inflammatory response." This study investigates whether a variety of selective inhibitors of the contact pathway of intrinsic coagulation modulate complement and neutrophil activation during simulated extracorporeal circulation. After 60 min of recirculation in the presence of the slow tight-binding boronic acid inhibitor, Bz-Pro-Phe-boroArg-OH (10.7 microM), complete inhibition of kallikrein-C1-inhibitor complex formation and marked inhibition of C1-C1-inhibitor complex formation and the release of human neutrophil elastase were observed. Arg15-aprotinin (3.1 microM), Ala357,Arg358 alpha 1-antitrypsin (2.6 microM), and soybean trypsin inhibitor (48.0 microM) either completely or partially inhibited the generation of kallikrein-C1-inhibitor complexes but were less effective inhibitors of human neutrophil elastase release. The second-order rate constants for the inhibition of kallikrein in purified systems are consistent with the order of effectiveness of the inhibitors in blocking human neutrophil elastase release in heparinized blood. Our results suggest that low-molecular-weight selective inhibitors of kallikrein may be effective agents in the attenuation of the contact-mediated inflammatory response in cardiopulmonary bypass.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
H1352-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7535008-Amino Acid Sequence, pubmed-meshheading:7535008-Aprotinin, pubmed-meshheading:7535008-Blood Coagulation, pubmed-meshheading:7535008-Boron Compounds, pubmed-meshheading:7535008-Cardiopulmonary Bypass, pubmed-meshheading:7535008-Complement Pathway, Classical, pubmed-meshheading:7535008-Heparin, pubmed-meshheading:7535008-Humans, pubmed-meshheading:7535008-Kallikreins, pubmed-meshheading:7535008-Kinetics, pubmed-meshheading:7535008-Leukocyte Elastase, pubmed-meshheading:7535008-Molecular Sequence Data, pubmed-meshheading:7535008-Neutrophils, pubmed-meshheading:7535008-Oligopeptides, pubmed-meshheading:7535008-Pancreatic Elastase, pubmed-meshheading:7535008-Platelet Aggregation, pubmed-meshheading:7535008-Trypsin Inhibitors, pubmed-meshheading:7535008-alpha 1-Antitrypsin
pubmed:year
1995
pubmed:articleTitle
Selective kallikrein inhibitors alter human neutrophil elastase release during extracorporeal circulation.
pubmed:affiliation
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia 19140.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't