Disease relevance of Acid-stable protease inhibitor

• Inhibition of the soluble and the tumor cell receptor-bound plasmin by urinary trypsin inhibitor and subsequent effects on tumor cell invasion and metastasis [1].
• Isolation of urinary trypsin inhibitor-like inhibitor from human lung cancer tissue [2].
• Characterization of binding properties of urinary trypsin inhibitor to cell-associated binding sites on human chondrosarcoma cell line HCS-2/8 [3].
• Urinary trypsin inhibitor (ulinastatin) is a characteristic protein pharmaceutical which contains both glycosaminoglycans and N-linked glycans in its molecule and has been used for treatment of acute pancreatitis [4].
• The purposes of this study were to clarify the role of neutrophilic proteases in the pathogenesis of hepatic ischemia/reperfusion injury and to determine whether urinary trypsin inhibitor (UTI) pretreatment attenuated liver ischemia/reperfusion injury in rats [5].

Psychiatry related information on Acid-stable protease inhibitor

• Change in the equilibrium of the levels of free and bound forms of alpha1-microglobulin and ulinastatin in patients with mood disorders [6].
• Significant decreases of ulinastatin-like immunoreactive substance in the cerebrospinal fluid of patients with dementia [7].
• Changes in the ratio of urinary alpha 1-microglobulin to ulinastatin levels in patients with Alzheimer-type dementia and vascular dementia [8].

High impact information on Acid-stable protease inhibitor

• Urinary trypsin inhibitor (UTI) has a multipotent inhibitory effect on proteases such as trypsin, chymotrypsin, plasmin, human leukocyte elastase, or hyaluronidase [9].
• The present study was undertaken to determine whether highly purified human urinary trypsin inhibitor (UTI) efficiently inhibits the soluble and the tumor cell receptor-bound plasmin [1].
• Suppression of urokinase expression and invasiveness by urinary trypsin inhibitor is mediated through inhibition of protein kinase C- and MEK/ERK/c-Jun-dependent signaling pathways [10].
• Urinary trypsin inhibitor (UTI) forms membrane complexes with UTI-binding proteins (UTI-BPs) and initiates modulation of urokinase-type plasminogen activator (uPA) expression, which results in UTI-mediated suppression of cell invasiveness [3].
• The cell surface receptor-bound UTI derived from ITI may be the result of the limited proteolysis on the cell surface [11].

Chemical compound and disease context of Acid-stable protease inhibitor

• Monocytes from heparinized blood of three healthy volunteers were incubated with 0.125 or 1.25 U/ml of ulinastatin, and then endotoxin (Escherichia coli lipopolysaccharide) was added at concentrations of 0.1, 1.0, and 10.0 micrograms/ml [12].
• Post-ERCP pancreatitis was observed in two (4.3%), three (6.5%) and four (8.5%) cases in the gabexate mesilate, high-dose ulinastatin and low-dose ulinastatin groups, respectively [13].
• CONCLUSION: The administration of low- and high-dose ulinastatin has similar effects to high-dose gabexate in the prevention of post-ERCP pancreatitis [13].
• We investigated the protective effect of human ulinastatin against gentamicin-induced acute renal failure in rats [14].
• New endoscopic treatment for chronic pancreatitis, using contrast media containing ulinastatin and prednisolone [15].

Biological context of Acid-stable protease inhibitor

• This up-regulation of PHS-2 was suppressed by ulinastatin (a neutrophil-elastase inhibitor) treatment [16].
• The mechanisms by which urinary trypsin inhibitor (UTI) prevents preterm premature rupture of fetal membrane and premature cervical ripening were investigated [17].
• Pretreatment with human urinary trypsin inhibitor and with chicken-egg-white trypsin inhibitor caused dose-dependent inhibition against trypsin-induced vasorelaxation [18].
• On the repeated trials of the response to trypsin, the responses gradually developed tachyphylaxis in control aortic rings, whereas no tachyphylaxis developed in rings pretreated with human urinary trypsin inhibitor (10 U/mL) [18].
• STUDY DESIGN: An isometric uterine contraction test was used to study this inhibitory effect of urinary trypsin inhibitor on the myometrium [19].

Anatomical context of Acid-stable protease inhibitor

• Protease inhibitors (gebexate mesylate and ulinastatin) stimulate intracellular chemiluminescence in human neutrophils [20].
• Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo [21].
• In the UTI group, there was slight congestion and hepatocyte necrosis [5].
• Effects of urinary trypsin inhibitor on the invasion of reconstituted basement membranes by ovarian cancer cells [22].
• CONCLUSIONS: The data indicate that relaxation induced by trypsin is attributable to nitric oxide released from the endothelium, and that human urinary trypsin inhibitor protects vessels against trypsin-induced endothelial injury [18].

Associations of Acid-stable protease inhibitor with other chemical compounds

• A model for cell surface UTI formation is proposed in which ITI binding to cells from serum used for the culture is followed by the limited proteolysis by trace amounts of active serine proteases, to form cell-surface receptor-bound UTI and the H-chains intercalated into cell surface HA [11].
• The purpose of this study is to determine whether ITI binding to tumor cell surface is mediated by urinary trypsin inhibitor (UTI)-receptor or cell-associated hyaluronic acid (HA) [11].
• Thus, ulinastatin inhibits arachidonate PHS metabolism by inhibiting new induction of PHS-2 at the mRNA level, which is a novel pharmacologic action of this substance [16].
• The experimental group was divided into a control group, a UTI (urinary trypsin inhibitor) group and a GM (gabexate mecilate) group [23].
• Protease inhibitors such as gabexate mesilate (GM) and ulinastatin (UTI) have been shown to have various beneficial effects by inhibiting the activation of leukocytes, but the mechanism for this has yet to be fully elucidated [24].

Gene context of Acid-stable protease inhibitor

• CONCLUSION: These results suggest that ulinastatin may suppress the increase in IL-8 production and the expression of ICAM-1 during cardiac surgery [25].
• Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H2 synthase-type 2 in Kawasaki disease [16].
• Inhibition of neutrophil elastase-induced interleukin-8 gene expression by urinary trypsin inhibitor in human bronchial epithelial cells [26].
• We have previously demonstrated the protective role of urinary trypsin inhibitor (UTI) against acute inflammatory lung injury induced by lipopolysaccharide (LPS) using UTI-deficient (-/-) mice and corresponding wild-type (WT) mice [27].
• CONCLUSION: Urinary trypsin inhibitor attenuates I/R injury in mouse intestinal transplantation by reducing monocytes infiltration and down-regulation of TNFalpha and i-NOS mRNA expression [28].

Analytical, diagnostic and therapeutic context of Acid-stable protease inhibitor

• Its antigenicity was confirmed to be quite the same as that of human urinary trypsin inhibitor by double immunodiffusion, immunoelectrophoresis, and neutralization with anti-urinary trypsin inhibitor rabbit immunoglobulin [2].
• Rats were divided into a UTI group and a control group [5].
• The results of this study suggest that pretreatment with UTI significantly attenuates liver reperfusion injury, perhaps by inhibiting neutrophil proteases [5].
• The comparability of ulinastatin preparations of different lots or from different companies was studied by using conventional analytical approaches such as SDS-PAGE, cellulose acetate membrane electrophoresis, and HP size-exclusion chromatography (SEC) and also by using newly developed techniques such as CE and MALDI-TOF MS [4].
• The aim of this study is to examine the expression pattern of UTI in the human ovarian carcinoma ascites fluid by Western blotting, zymography, immunoprecipitation, immunohistochemistry, biochemical and gene analyses and animal experiments [29].

References