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. 1972 Aug;53(4):359–373.

An Investigation of the Role of Intraluminal Proteolytic Enzymes and Intracellular Enzyme Inhibitors in Ulcerative Colitis

D M Goldberg, R Campbell, A D Roy
PMCID: PMC2072409  PMID: 4538442

Abstract

The output of trypsin and chymotrypsin was determined in 26 patients with ulcerative colitis and 8 with polyposis coli, each of whom had undergone total colectomy and ileostomy. Measurements were made in each subject over periods ranging from 3 to 8 days on a standard diet. The output of each enzyme was lower in the group with ulcerative colitis, but serial post-operative measurements suggested that this was due to the relatively poorer nutritional status of patients in this group, and no consistent difference was apparent between individuals in both groups whose ileostomy had been established more than one year before the measurements were made.

The activity of proteolytic enzyme inhibitors was determined in 20 samples of colonic mucosa obtained from patients with ulcerative colitis and 18 samples of histologically normal colonic mucosa from patients with carcinoma of the colon. Higher levels of trypsin inhibitor were found in mucosa affected by ulcerative colitis, there being an apparent correlation between inhibitor level and the severity of the lesion as assessed by the extent of ulceration, necrosis and haemorrhage.

The data do not support the view that a high intraluminal concentration of pancreatic proteases, or a reduced cellular protection against their action, are primary or secondary causes of mucosal damage in ulcerative colitis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ammann R. W., Tagwecher E., Kashiwagi H., Rosenmund H. Diagnostic value of fecal chymotrypsin and trypsin assessment for detection of pancreatic disease. A comparative study. Am J Dig Dis. 1968 Feb;13(2):123–146. doi: 10.1007/BF02232955. [DOI] [PubMed] [Google Scholar]
  2. BALL W. P., BAGGENSTOSS A. H., BARGEN J. A. Pancreatic lesions associated with chronic ulcerative colitis. Arch Pathol (Chic) 1950 Sep;50(3):347–358. [PubMed] [Google Scholar]
  3. BOUNOUS G., BROWN R. A., MULDER D. S., HAMPSON L. G., GURD F. N. ABOLITION OF 'TRYPTIC ENTERITIS' IN THE SHOCKED DOG. CREATION OF AN EXPERIMENTAL MODEL FOR STUDY OF HUMAN SHOCK AND ITS SEQUELAE. Arch Surg. 1965 Sep;91:371–375. doi: 10.1001/archsurg.1965.01320150001001. [DOI] [PubMed] [Google Scholar]
  4. BOUNOUS G., HAMPSON L. G., GURD F. N. CELLULAR NUCLEOTIDES IN HEMORRHAGIC SHOCK: RELATIONSHIP OF INTESTINAL METABOLIC CHANGES TO HEMORRHAGIC ENTERITIS AND THE BARRIER FUNCTION OF INTESTINAL MUCOSA. Ann Surg. 1964 Oct;160:650–668. doi: 10.1097/00000658-196410000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BUNDY H. F., MEHL J. W. Trypsin inhibitors of human serum. I. Standardization, mechanism of reaction, and normal values. J Clin Invest. 1958 Jul;37(7):947–955. doi: 10.1172/JCI103689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barbezat G. O., Hansen J. D. The exocrine pancreas and protein-calorie malnutrition. Pediatrics. 1968 Jul;42(1):77–92. [PubMed] [Google Scholar]
  7. Bieth J., Metais P., Warter J. Activation, inhibition and protection of tryptic and alpha-chymotryptic activity by normal human serum. Clin Chim Acta. 1968 Apr;20(1):69–80. doi: 10.1016/0009-8981(68)90386-0. [DOI] [PubMed] [Google Scholar]
  8. Bounous G. "Tryptic enteritis": its role in the pathogenesis of stress ulcer and shock. Can J Surg. 1969 Oct;12(4):397–409. [PubMed] [Google Scholar]
  9. Bounous G., McArdle A. H., Hodges D. M., Hampson L. G., Gurd F. N. Biosynthesis of intestinal mucin in shock: relationship to tryptic hemorrhagic enteritis and permeability to curare. Ann Surg. 1966 Jul;164(1):13–22. doi: 10.1097/00000658-196607000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bounous G. Metabolic changes in the intestinal mucosa during hemorrhagic shock. Can J Surg. 1965 Oct;8(4):332–339. [PubMed] [Google Scholar]
  11. Bounous G. Role of pancreatic secretions in uremic gastroenterocolitis. Am J Surg. 1970 Mar;119(3):264–268. doi: 10.1016/0002-9610(70)90049-8. [DOI] [PubMed] [Google Scholar]
  12. Bounous G. Role of the intestinal contents in the pathophysiology of acute intestinal ischemia. Am J Surg. 1967 Sep;114(3):368–375. doi: 10.1016/0002-9610(67)90158-4. [DOI] [PubMed] [Google Scholar]
  13. DREILING D. A. The pancreatic secretion in the malabsorption syndrome and related malnutrition states. J Mt Sinai Hosp N Y. 1957 May-Jun;24(3):243–250. [PubMed] [Google Scholar]
  14. De Koos E. B., Gibson W. J., Bounous G., Hampson L. G. The influence of pancreatic duct ligation on the course of E. coli endotoxin shock in the dog. Can J Surg. 1966 Jul;9(3):227–230. [PubMed] [Google Scholar]
  15. Goldberg D. M., Campbell R., Roy A. D. Binding of trypsin and chymotrypsin by human intestinal mucosa. Biochim Biophys Acta. 1968 Nov 19;167(3):613–615. doi: 10.1016/0005-2744(68)90053-3. [DOI] [PubMed] [Google Scholar]
  16. Goldberg D. M., Campbell R., Roy A. D. Fate of trypsin and chymotrypsin in the human small intestine. Gut. 1969 Jun;10(6):477–483. doi: 10.1136/gut.10.6.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goldberg D. M., Campbell R., Roy A. D. On the absorption of pancreatic enzymes from the intestine in man. Digestion. 1970;3(5):285–293. doi: 10.1159/000197046. [DOI] [PubMed] [Google Scholar]
  18. Goldberg D. M., Campbell R., Roy A. D. Studies on the binding of trypsin and chymotrypsin by human intestinal mucosa. Scand J Gastroenterol. 1969;4(3):217–226. [PubMed] [Google Scholar]
  19. Goldberg D. M., Campbell R., Roy A. D. The interaction of trypsin and chymotrypsin with intestinal cells in man and several animal species. Comp Biochem Physiol B. 1971 Apr 15;38(4):697–706. doi: 10.1016/0305-0491(71)90272-0. [DOI] [PubMed] [Google Scholar]
  20. Goldberg D. M., McAllister R. A., Roy A. D. Proteolytic enzymes of human intestinal mucosa in non-malignant diseases of the ileum and colon. Br J Exp Pathol. 1969 Jun;50(3):241–249. [PMC free article] [PubMed] [Google Scholar]
  21. Goldberg D. M., McAllister R. A., Roy A. D. Studies on human intestinal proteolysis. Scand J Gastroenterol. 1968;3(2):193–201. doi: 10.3109/00365526809180122. [DOI] [PubMed] [Google Scholar]
  22. HOWARD F., YUDKIN J. EFFECT OF DIETARY CHANGE UPON THE AMYLASE AND TRYPSIN ACTIVITIES OF THE RAT PANCREAS. Br J Nutr. 1963;17:281–294. doi: 10.1079/bjn19630031. [DOI] [PubMed] [Google Scholar]
  23. Hiatt N., Warner N. E., Furman G., Merchey M. Nitrogen mustard hyperamylasemia and intestinal lesions. Surgery. 1967 Apr;61(4):596–601. [PubMed] [Google Scholar]
  24. Kirsner J. B. Ulcerative colitis 1970--recent developments. Scand J Gastroenterol Suppl. 1970;6:63–91. [PubMed] [Google Scholar]
  25. LAKE M., NICKEL W. F., Jr, ANDRUS W. D. Possible role of pancreatic enzymes in the etiology of ulcerative colitis. Gastroenterology. 1951 Mar;17(3):409–413. [PubMed] [Google Scholar]
  26. MAGEE D. F., WHITE T. T. Effect of alternation in dietary protein levels on pancreatic enzymes in rats. Am J Physiol. 1958 Apr;193(1):21–24. doi: 10.1152/ajplegacy.1958.193.1.21. [DOI] [PubMed] [Google Scholar]
  27. Maneche H. C., Paul T. M., Kahn D. S. Pancreatic enzyme inhibitors in health and disease. Am J Clin Pathol. 1971 Apr;55(4):458–464. doi: 10.1093/ajcp/55.4.458. [DOI] [PubMed] [Google Scholar]
  28. Morgenstern L., Hiatt N. Injurious effect of pancreatic secretions on postradiation enteropathy. Gastroenterology. 1967 Dec;53(6):923–929. [PubMed] [Google Scholar]
  29. Morgenstern L., Patin C. S., Krohn H. L., Hiatt N. Prolongation of survival in lethally irradiated dogs by pancreatic duct ligation. Arch Surg. 1970 Nov;101(5):586–589. doi: 10.1001/archsurg.1970.01340290042009. [DOI] [PubMed] [Google Scholar]
  30. Reboud J. P., Marchis-Mouren G., Paséro L., Cozzone A., Desnuelle P. Adaptation de la vitesse de biosynthèse DE L'amylase pancréatique et du chymotrypsinogène A des régimes riches en amidon ou en protéines. Biochim Biophys Acta. 1966 Apr 25;117(2):351–367. [PubMed] [Google Scholar]
  31. Roy A. D., Campbell R., Goldberg D. M. Effect of diet on the trypsin and chymotrypsin output in the stools of patients with an ileostomy. Gastroenterology. 1967 Oct;53(4):584–589. [PubMed] [Google Scholar]
  32. SAMMONS H. G., ROSS C. A., WOOD W. A. Proteolytic activity in the faeces of children and adults and its relationship to pancreatic fibrosis, coeliac disease and ulcerative colitis. Clin Sci. 1955 Feb;14(1):157–162. [PubMed] [Google Scholar]
  33. SCRIMSHAW N. S., BEHAR M. Protein malnutrition in young children. Science. 1961 Jun 30;133(3470):2039–2047. doi: 10.1126/science.133.3470.2039. [DOI] [PubMed] [Google Scholar]
  34. SHAPER A. G. Chronic pancreatic disease and protein malnutrition. Lancet. 1960 Jun 4;1(7136):1223–1224. doi: 10.1016/s0140-6736(60)91103-x. [DOI] [PubMed] [Google Scholar]
  35. SNOOK J. T., MEYER J. H. EFFECT OF DIET AND DIGESTIVE PROCESSES ON PROTEOLYTIC ENZYMES. J Nutr. 1964 Jun;83:94–102. doi: 10.1093/jn/83.2.94. [DOI] [PubMed] [Google Scholar]
  36. SNOOK J. T., MEYER J. H. RESPONSE OF DIGESTIVE ENZYMES TO DIETARY PROTEIN. J Nutr. 1964 Apr;82:409–414. doi: 10.1093/jn/82.4.409. [DOI] [PubMed] [Google Scholar]
  37. Snook J. T. Dietary regulation of pancreatic enzyme synthesis, secretion and inactivation in the rat. J Nutr. 1965 Nov;87(3):297–305. doi: 10.1093/jn/87.3.297. [DOI] [PubMed] [Google Scholar]
  38. Stearner S. P., Azuma S. A. Early radiation lethality: enzyme release and the protective action of soybean trypsin inhibitor. Proc Soc Exp Biol Med. 1968 Jul;128(3):913–917. doi: 10.3181/00379727-128-33156. [DOI] [PubMed] [Google Scholar]
  39. THOMPSON M. D., TROWELL H. C. Pancreatic enzyme activity in duodenal contents of children with a type of kwashiorkor. Lancet. 1952 May 24;1(6717):1031–1035. doi: 10.1016/s0140-6736(52)90692-2. [DOI] [PubMed] [Google Scholar]
  40. Wilding P., Banwell J. G., Cooke W. T. Fecal enzyme assay as an aid to the diagnosis of pancreatic exocrine insufficiency. Am J Dig Dis. 1966 Sep;11(9):722–727. doi: 10.1007/BF02239425. [DOI] [PubMed] [Google Scholar]
  41. Wormsley K. G. Tests of pancreatic function. Br J Clin Pract. 1970 Jul;24(7):271–275. [PubMed] [Google Scholar]
  42. Wright R. Ulcerative colitis. Gastroenterology. 1970 Jun;58(6):875–897. [PubMed] [Google Scholar]
  43. de Dombal F. T., Burch P. R., Watkinson G. Aetiology of ulcerative colitis. Gut. 1969 Apr;10(4):270–277. doi: 10.1136/gut.10.4.270. [DOI] [PMC free article] [PubMed] [Google Scholar]

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