Muscle Proteolysis Induced by a Circulating Peptide in Patients with Sepsis or Trauma

Accelerated proteolysis of muscle is characteristic in patients with trauma or sepsis, but its cause is not well understood. Using rat muscle in vitro, we developed a bioassay to compare the proteolytic activity of plasma from 50 patients with trauma or sepsis with that of plasma from 14 normal volu...

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Veröffentlicht in:The New England journal of medicine 1983-03, Vol.308 (10), p.545-552
Hauptverfasser: Clowes, George H. A, George, Barbara C, Villee, Claude A, Saravis, Calvin A
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container_title The New England journal of medicine
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creator Clowes, George H. A
George, Barbara C
Villee, Claude A
Saravis, Calvin A
description Accelerated proteolysis of muscle is characteristic in patients with trauma or sepsis, but its cause is not well understood. Using rat muscle in vitro, we developed a bioassay to compare the proteolytic activity of plasma from 50 patients with trauma or sepsis with that of plasma from 14 normal volunteers and from 15 patients who had undergone "clean" elective surgical procedures. The mean proteolytic activity in the plasma of patients with trauma or sepsis was found to be 190±8.0 per cent of the control value (rat muscle incubated in medium alone), whereas the activity in normal plasma was 124±4.5 per cent (P
doi_str_mv 10.1056/NEJM198303103081001
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In 25 of the patients with trauma or sepsis the rate of amino acid release from one leg was measured by subtracting the concentration of tyrosine plus phenylalanine in the femoral artery plasma from that in the femoral vein; this rate correlated well with the bioactivity of the plasma in the bioassay system (r = 0.67, P&lt;0.001). By means of ultrafiltration and chromatography, the plasma factor inducing proteolysis was isolated and found to be a peptide, probably containing sialic acid, with a chain of 33 amino acids and a molecular weight of approximately 4274 daltons. (N Engl J Med. 1983; 308: 545–52.) The rapid onset of muscle wasting, protein depletion, and elevated urea excretion in patients with trauma 1 or sepsis 2 contrasts with the economic conservation of protein observed during starvation in the normal person. 3 After a brief fast, infected and injured patients were found to release amino acids from the leg at rates three to five times those observed in normal people in the postabsorptive state. 4 , 5 Thus, an increased supply of amino acids is made available in sepsis or trauma not only for energy production by gluconeogenesis and oxidation 2 , 6 but, more important, to satisfy the requirements of the liver and other visceral . . .</description><identifier>ISSN: 0028-4793</identifier><identifier>EISSN: 1533-4406</identifier><identifier>DOI: 10.1056/NEJM198303103081001</identifier><identifier>PMID: 6828080</identifier><language>eng</language><publisher>United States: Massachusetts Medical Society</publisher><subject>Amino acids ; Amino Acids - blood ; Animals ; Bioassays ; Biological activity ; Biological Assay ; Biopsy ; Breakdowns ; Chromatography ; Fasting ; Femoral artery ; Femur ; Glycopeptides - blood ; Hospitals ; Humans ; Hydrolysis ; In Vitro Techniques ; Infection - blood ; Infection - metabolism ; Insulin ; Metabolism ; Metabolites ; Molecular Weight ; Muscle Proteins - metabolism ; Musculoskeletal system ; Peptides - blood ; Phenylalanine ; Plasma ; Protein synthesis ; Proteins ; Proteolysis ; Rats ; Rats, Inbred Strains ; Rodents ; Sepsis ; Sialic Acids - blood ; Surgery ; Trauma ; Tyrosine ; Ultrafiltration ; Wounds and Injuries - blood ; Wounds and Injuries - metabolism</subject><ispartof>The New England journal of medicine, 1983-03, Vol.308 (10), p.545-552</ispartof><rights>Copyright Massachusetts Medical Society Mar 10, 1983</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-e53eb6f04475bfb5d37a28a13868db715fea44983c2e485a340b590dbabe846e2</citedby><cites>FETCH-LOGICAL-c402t-e53eb6f04475bfb5d37a28a13868db715fea44983c2e485a340b590dbabe846e2</cites></display><links><openurl>$$Topenurl_article</openurl><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6828080$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Clowes, George H. 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The activity in the plasma of patients who had undergone elective surgery was slightly elevated at 142±2.5 per cent (P&lt;0.005). In 25 of the patients with trauma or sepsis the rate of amino acid release from one leg was measured by subtracting the concentration of tyrosine plus phenylalanine in the femoral artery plasma from that in the femoral vein; this rate correlated well with the bioactivity of the plasma in the bioassay system (r = 0.67, P&lt;0.001). By means of ultrafiltration and chromatography, the plasma factor inducing proteolysis was isolated and found to be a peptide, probably containing sialic acid, with a chain of 33 amino acids and a molecular weight of approximately 4274 daltons. (N Engl J Med. 1983; 308: 545–52.) The rapid onset of muscle wasting, protein depletion, and elevated urea excretion in patients with trauma 1 or sepsis 2 contrasts with the economic conservation of protein observed during starvation in the normal person. 3 After a brief fast, infected and injured patients were found to release amino acids from the leg at rates three to five times those observed in normal people in the postabsorptive state. 4 , 5 Thus, an increased supply of amino acids is made available in sepsis or trauma not only for energy production by gluconeogenesis and oxidation 2 , 6 but, more important, to satisfy the requirements of the liver and other visceral . . .</description><subject>Amino acids</subject><subject>Amino Acids - blood</subject><subject>Animals</subject><subject>Bioassays</subject><subject>Biological activity</subject><subject>Biological Assay</subject><subject>Biopsy</subject><subject>Breakdowns</subject><subject>Chromatography</subject><subject>Fasting</subject><subject>Femoral artery</subject><subject>Femur</subject><subject>Glycopeptides - blood</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>In Vitro Techniques</subject><subject>Infection - blood</subject><subject>Infection - metabolism</subject><subject>Insulin</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Molecular Weight</subject><subject>Muscle Proteins - metabolism</subject><subject>Musculoskeletal system</subject><subject>Peptides - blood</subject><subject>Phenylalanine</subject><subject>Plasma</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Proteolysis</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Rodents</subject><subject>Sepsis</subject><subject>Sialic Acids - blood</subject><subject>Surgery</subject><subject>Trauma</subject><subject>Tyrosine</subject><subject>Ultrafiltration</subject><subject>Wounds and Injuries - blood</subject><subject>Wounds and Injuries - metabolism</subject><issn>0028-4793</issn><issn>1533-4406</issn><fulltext>false</fulltext><rsrctype>article</rsrctype><creationdate>1983</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kFtLw0AQhRdRaq3-AhEWBF8kOpu9ZPMopWrFasH2OewmE03Jpe4mSP-9KS0-iDgvAzPfOcwcQs4Z3DCQ6vZl8jRjsebAGXDQDIAdkCGTnAdCgDokQ4BQByKK-TE58X4FfTERD8hA6VCDhiFZzjqflkjnrmmxKTe-8HRaZ12KGbUbaui4cGlXmrao3-kc122RIS1qOu8nWLeefhXtB33D9VbYOLpwpqvMKTnKTenxbN9HZHk_WYwfg-fXh-n47jlIBYRtgJKjVTkIEUmbW5nxyITaMK6VzmzEZI5GiP7DNEShpeECrIwhs8aiFgrDEbna-a5d89mhb5Oq8CmWpamx6XyigUexVmEPXv4CV03n6v62hOlIaCVDxXqK76jUNd47zJO1KyrjNgmDZBt58kfkvepi793ZCrMfzT7jfn-921eVT2pcVf-6fQOEX4cC</recordid><startdate>19830310</startdate><enddate>19830310</enddate><creator>Clowes, George H. 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The mean proteolytic activity in the plasma of patients with trauma or sepsis was found to be 190±8.0 per cent of the control value (rat muscle incubated in medium alone), whereas the activity in normal plasma was 124±4.5 per cent (P&lt;0.001). The activity in the plasma of patients who had undergone elective surgery was slightly elevated at 142±2.5 per cent (P&lt;0.005). In 25 of the patients with trauma or sepsis the rate of amino acid release from one leg was measured by subtracting the concentration of tyrosine plus phenylalanine in the femoral artery plasma from that in the femoral vein; this rate correlated well with the bioactivity of the plasma in the bioassay system (r = 0.67, P&lt;0.001). By means of ultrafiltration and chromatography, the plasma factor inducing proteolysis was isolated and found to be a peptide, probably containing sialic acid, with a chain of 33 amino acids and a molecular weight of approximately 4274 daltons. (N Engl J Med. 1983; 308: 545–52.) The rapid onset of muscle wasting, protein depletion, and elevated urea excretion in patients with trauma 1 or sepsis 2 contrasts with the economic conservation of protein observed during starvation in the normal person. 3 After a brief fast, infected and injured patients were found to release amino acids from the leg at rates three to five times those observed in normal people in the postabsorptive state. 4 , 5 Thus, an increased supply of amino acids is made available in sepsis or trauma not only for energy production by gluconeogenesis and oxidation 2 , 6 but, more important, to satisfy the requirements of the liver and other visceral . . .</abstract><cop>United States</cop><pub>Massachusetts Medical Society</pub><pmid>6828080</pmid><doi>10.1056/NEJM198303103081001</doi><tpages>8</tpages></addata></record>
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subjects Amino acids
Amino Acids - blood
Animals
Bioassays
Biological activity
Biological Assay
Biopsy
Breakdowns
Chromatography
Fasting
Femoral artery
Femur
Glycopeptides - blood
Hospitals
Humans
Hydrolysis
In Vitro Techniques
Infection - blood
Infection - metabolism
Insulin
Metabolism
Metabolites
Molecular Weight
Muscle Proteins - metabolism
Musculoskeletal system
Peptides - blood
Phenylalanine
Plasma
Protein synthesis
Proteins
Proteolysis
Rats
Rats, Inbred Strains
Rodents
Sepsis
Sialic Acids - blood
Surgery
Trauma
Tyrosine
Ultrafiltration
Wounds and Injuries - blood
Wounds and Injuries - metabolism
title Muscle Proteolysis Induced by a Circulating Peptide in Patients with Sepsis or Trauma
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