Antiproteases: Effective Treatment with Gabexate Mesilate

  • M. V. Singer
  • H. Goebell


Since the introduction of Chiari’s concept of “tryptic autodigestion” of the pancreatic gland in 1869 [7], several pancreatic enzymes have been implicated as triggers of acute pancreatitis. However, the initiating factor(s) has still not been clarified. Many of the pancreatic enzymes have been suggested. Activated proteases, such as trypsin [5, 10] and elastase [33, 36], have been found in complex with protease inhibitors in both blood and peritoneal fluid [24, 25]. The probable role of granulocyte proteases has also been emphasized [6, 20]. All these findings indicate liberation of active proteases during the disease. In addition, some studies have shown activation of the different cascade systems of the body, such as the complement, kinin, coagulation and fibrinolytic systems. A similar activation has also been shown in other conditions in which active proteases are set free, for example, sepsis [26, 31], abscesses [17], burns [17] and multiple trauma [17, 19]. The clinical importance of these biochemical events and of their interrelation is, as yet, not fully understood.


Acute Pancreatitis Fibrinolytic System Cascade System Alcoholic Pancreatitis Pancreatic Gland 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Balldin G (1980) On protease-antiprotease imbalance with special reference to the protective role of protease inhibitors in acute pancreatitis. Thesis, MalmöGoogle Scholar
  2. 2.
    Balldin G, Eddeland A, Ohlsson K (1981) Studies on the role of the plasma protease inhibitors on C3-activation in vitro and in acute pancreatitis. Scand J Gastroenterol 16:603–609PubMedCrossRefGoogle Scholar
  3. 3.
    Balldin G, Ohlsson K (1979) Demonstration of pancreatic protease-antiprotease complexes in the peritoneal fluid of patients with acute pancreatitis. Surgery 85:451–456PubMedGoogle Scholar
  4. 4.
    Barrett AJ, Starkey PM (1973) The interaction of alpha-2-macroglobulin with proteinases. Biochem J 133:709–724PubMedGoogle Scholar
  5. 5.
    Borgström A, Ohlsson K (1978) Immunoreactive trypsin in serum and peritoneal fluid in acute pancreatitis. Hoppe Seylers Z Physiol Chem 359:677 — 681PubMedGoogle Scholar
  6. 6.
    Brower MS, Harpel PC (1982) Proteolytic cleavage and inactivation of alpha-2-plasmin inhibitor and Cl-inactivator by human polymorphonuclear leucocyte elastase. J Biol Chem 257:9849–9854PubMedGoogle Scholar
  7. 7.
    Chiari H (1896) Über die Selbstverdauung des menschlichen Pankreas. Z Heilkd 17:69–96Google Scholar
  8. 8.
    Creutzfeldt W, Schmidt H (1970) Aetiology and pathogenesis of pancreatitis (current concepts). Scand J Gastroenterol [Suppl] 6:47 — 62Google Scholar
  9. 9.
    Dürr HK (1979) Acute pancreatitis. In: Howat HT, Sarles H (eds) The exocrine pancreas. Saunders, LondonGoogle Scholar
  10. 10.
    Elias E, Redshaw M, Wood T (1977) The diagnostic importance of changes in circulating concentrations of immunoreactive trypsin. Lancet 2:66–68PubMedCrossRefGoogle Scholar
  11. 11.
    Freise J (1983) Inhibition of phospholipase A2 by gabexate mesilate, camostate and aprotinine. Enzyme 30:209PubMedGoogle Scholar
  12. 12.
    Freise J, Melzer P, Schmidt FW, Horbach L (1986) Gabexat Mesilat in der Behandlung der akuten Pankreatitis. Ergebnisse der Hannoverschen multizentrischen Doppelblindstudie mit 50 Patienten. Z Gastroenterol 24:200–211PubMedGoogle Scholar
  13. 13.
    Freise J, Schmidt FW (1984) Gabexat Mesilat (FOY) in der Behandlung der akuten Pankreatitis. Z Gastroenterol 22:531 (Abstract)Google Scholar
  14. 14.
    Fritz H, Krück J (1979) Immunofluorescence studies indicate that the basic trypsin-kal-likrein-inhibitor of bovine organs (Trasylol) originates from mast cells. Hoppe Seylers Z Physiol Chem 360:437–444PubMedCrossRefGoogle Scholar
  15. 15.
    Fritz H, Oppitz KH, Meckl D, Kemkes B, Haendle H, Schult H, Werle E (1969) Verteilung und Ausscheidung von natürlich vorkommenden und chemisch modifizierten Proteaseinhibitoren nach intravenöser Injektion bei Ratte, Hund (und Mensch). Hoppe Seylers Z Physiol Chem 350:1541–1550PubMedCrossRefGoogle Scholar
  16. 16.
    Geokas MC, Largman C, Durie PR, Brodrick JW, Ray SB, O’Rourke M, Vollmer J (1981) Immunoreactive forms of cationic trypsin in plasma and ascites fluid of dogs in experimental pancreatitis. Am J Pathol 105:31–39PubMedGoogle Scholar
  17. 17.
    Heideman M, Saravis C, Clowes GHA (1982) Effect of nonviable tissue and abscesses on complement depletion and the development of bacteremia. J Trauma 22:527–532PubMedCrossRefGoogle Scholar
  18. 18.
    Kazal LA, Spicer DS, Brahinsky RA (1948) Isolation of a crystalline trypsin inhibitor. J Am Chem Soc 70:3034–3040PubMedCrossRefGoogle Scholar
  19. 19.
    Kierulf P, Aasen AO, Aune S, Godai MC, Ruud TE, Vaage J (1982) Chromogenic peptide substrate assays in patients with multiple trauma. Acta Chir Scand [Suppl] 509:69–72Google Scholar
  20. 20.
    Klingemann HG, Egbring R, Holst F, Gramse M, Havemann K (1981) Digestion of alpha-2-plasmin inhibitor by neutral proteases from human leucocytes. Thromb Res 24:479–483PubMedCrossRefGoogle Scholar
  21. 21.
    Kraut H, Frey EK, Werle E (1930) Über die Inaktivierung des Kallikreins. Hoppe Seylers Z Physiol Chem 192:1–21CrossRefGoogle Scholar
  22. 22.
    Kunitz M, Northrop JH (1936) Isolation from beef pancreas of crystalline trypsinogen, trypsin, a trypsin inhibitor, and an inhibitor-trypsin compound. J Gen Physiol 19:991–1007PubMedCrossRefGoogle Scholar
  23. 23.
    Lake-Bakaar G, McKavanagh S, Gatus B, Summerfleld JA (1980) The relative values of serum immuno-reactive trypsin concentration and total amylase activity in the diagnosis of mumps, chronic renal failure, and pancreatic disease. Scand J Gastroenterol 15:97–101PubMedCrossRefGoogle Scholar
  24. 24.
    Lasson A, Ohlsson K (1984) Protease inhibitors in acute human pancreatitis. Correlation between biochemical changes and clinical course. Scand J Gastroenterol 19:779–786PubMedGoogle Scholar
  25. 25.
    Lasson A, Ohlsson K (1984) Acute pancreatitis. The correlation between clinical course, protease inhibitors, and complement and kinin activation. Scand J Gastroenterol 19:707–710PubMedGoogle Scholar
  26. 26.
    McConn R, Wasserman F, Haberland G (1982) The role of chemical mediators in the pathophysiology of acute illness and injury. Raven, New YorkGoogle Scholar
  27. 27.
    McMahon MJ, Bowen M, Mayer AD, Cooper EH (1984) Relation of alpha-2-macro-globulin and other antiproteases to the clinical features of acute pancreatitis. Am J Surg 147:164–170PubMedCrossRefGoogle Scholar
  28. 28.
    Nevalainen TJ (1980) The role of phospholipase A in acute pancreatitis. Scand J Gastroenterol 15:641–650PubMedCrossRefGoogle Scholar
  29. 29.
    O’Connor CM, O’Donnell MD, McGeeney KF (1981) Problems associated with the radioimmunoassay of serum trypsin. Clin Chim Acta 114:29–35PubMedCrossRefGoogle Scholar
  30. 30.
    Opie EL (1901) The etiology of acute hemorrhagic pancreatitis. Bull Johns Hopk Hosp 12:182–188Google Scholar
  31. 31.
    Smith-Erichsen N, Aasen AO, Amundsen E (1982) Treatment of sepsis in the surgical patient evaluated by means of chromogenic peptide substrate assays. Acta Chir Scand [Suppl] 509:33–38Google Scholar
  32. 32.
    Tanaka N, Tsuchiya R, Ishii K (1979) Comparative clinical study of FOY and Trasylol in acute pancreatitis. In: Fuji S, Meriva H, Suzuki T (eds) Kinins II: systemic proteases and cellular function. Plenum, New YorkGoogle Scholar
  33. 33.
    Toki N, Takasugi S, Sumi H (1982) Isolation and characterization of a pancreatic elastase from plasma of patients with acute pancreatitis. Clin Sei 62:321–328PubMedGoogle Scholar
  34. 34.
    Vincent JP, Lazdunski M (1976) Pre-existence of the active site in zymogens, the interaction of trypsinogen with the basic pancreatic trypsin inhibitor (Kunitz). FEBS Lett 63:240–244PubMedCrossRefGoogle Scholar
  35. 35.
    Vogel R, Trautschold I, Werle E (1966) Natural protease inhibitors — biochemistry and clinical aspects. Thieme, StuttgartGoogle Scholar
  36. 36.
    Wellborn JC, Alston JD, Cannon DJ, Read RC (1983) Serum proteolytic and antiproteolytic activity in acute pancreatitis. Am J Surg 146:834–837PubMedCrossRefGoogle Scholar
  37. 37.
    Wendt P, Fritsch A, Schulz F, Wunderlich G, Blümel G (1984) Proteinases and inhibitors in plasma and peritoneal exudate in acute pancreatitis. Hepatogastroenterology 31:277–281PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • M. V. Singer
    • 1
  • H. Goebell
    • 1
  1. 1.Department of Medicine, Division of GastroenterologyUniversity of EssenEssenGermany

Personalised recommendations