Pathophysiology and diagnostic value of urinary trypsin inhibitors

Inflammation is an important indicator of tissue injury. In the acute form, there is usually accumulation of fluids and plasma components in the affected tissues. Platelet activation and the appearance in blood of abnormally increased numbers of polymorphonucleocytes, lymphocytes, plasma cells and macrophages usually occur. Infectious disorders such as sepsis, meningitis, respiratory infection, urinary tract infection, viral infection, and bacterial infection usually induce an inflammatory response. Chronic inflammation is often associated with diabetes mellitus, acute myocardial infarction, coronary artery disease, kidney diseases, and certain auto-immune disorders, such as rheumatoid arthritis, organ failures and other disorders with an inflammatory component or etiology. The disorder may occur before inflammation is apparent. Markers of inflammation such as C-reactive protein (CRP) and urinary trypsin inhibitors have changed our appraisal of acute events such as myocardial infarction; the infarct may be a response to acute infection and (or) inflammation.We describe here the pathophysiology of an anti-inflammatory agent termed urinary trypsin inhibitor (uTi). It is an important anti-inflammatory substance that is present in urine, blood and all organs. We also describe the anti-inflammatory agent bikunin, a selective inhibitor of serine proteases. The latter are important in modulating inflammatory events and even shutting them down.

Characterization of Purified Urinary Trypsin Inhibitors

Human urine was passed through Celite 545 column, and the non adsorbed eluate was adsorbed to Bentnite, then eluted with 2 % pyridine. The eluate was precipitated with ammonia sulfate, and the precipitate was dissolved, then passed through DEAE-Sephadex A-50, trypsin-Sepharose and Sephadex G-200. There were three types of urinary trypsin inhibitors (UTI) of m.w. of 69,000, 45,000, and 25,000 respectively. No difference in inhibitory spectra was observed among these three UTI’s. Purified UTI inhibited trypsin, chymotrypsin, and kallikrein. The inhibition of chymotrypsin did not exceed 50even at the high concentration of UTI. UTI inhibited plasmin to a lesser extent but no inhibition of thrombin, Cls, Clr or urokinase was observed.UTI had 7% carbohydrate and no HIS, PRO, or TRP was found in aminoacid analysis. UTI was not identical to α1A but related to inter α- trypsin inhibitor immunologically. Some persons excreted both UTI and α1A in the urine although most people did only UTI. Since α1A is not found in the urine of most people, UTI may not be the same as inter α-trypsin inhibitor which is filtered into the urine.

Effect of Growth of Walker 256 Carcinosarcoma on the Fibrinolytic System of the Rat Plasma and Urine

Growth of a transplanted Walker 256 carcinosarcoma in rats was accompanied by: 1) An increase in plasma fibrinogen and urinary trypsin inhibitors; 2) A significant decrease in plasma plasminogen and hematocrit; 3) A decrease in urokinase activity in urine; 4) A decrease in fibrinolytic activity of the euglobulin fraction of plasma and serum. There was no significant change in the plasma inhibitors for trypsin or bovine fibrinolysin.