New endoscopic treatment for chronic pancreatitis, using contrast media containing ulinastatin and prednisolone

Ohwada, M; Watanabe, Naoki; Gotoh, Mikio; Teramoto, Junko; Moriya, Hideshige; Nakajima, Tomohiro; Okamoto, Takahiro; Tsuji, Naoki; Kobayashi, Daisuke; Niitsu, Yoshiro

doi:10.1007/bf02936371

Cited by 9 publications

(6 citation statements)

References 15 publications

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“…UTI is recognized to be degenerated from pre-␣-/inter-␣-trypsin inhibitors during inflammation (Pratt et al, 1989). UTI reportedly inhibits neutrophil elastase activity in vitro (Ogawa et al, 1987;Gando and Tedo, 1995) and trypsin activity in patients with pancreatitis (Ohwada et al, 1997). Although therapeutic effects of UTI on circulatory shock have been recognized, especially in Japan, detailed explanations about the target mechanisms remains unsatisfactory.…”

Section: Discussionmentioning

confidence: 99%

Urinary Trypsin Inhibitor Protects against Systemic Inflammation Induced by Lipopolysaccharide

Inoue¹,

Takano²,

Shimada³

et al. 2005

Molecular Pharmacology

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Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation, shock, and pancreatitis in Japan. Recent studies have demonstrated that serine protease inhibitors may play an anti-inflammatory role beyond merely an inhibitory action on neutrophil elastase at the site of inflammation at least in vitro. To clarify the direct contributions of UTI to inflammatory condition in vivo, we analyzed its roles in experimental systemic inflammatory response induced by intraperitoneal administration of lipopolysaccharide (LPS) using UTI deficient (Ϫ/Ϫ) mice and corresponding wild-type (WT) mice. After LPS (1 mg/kg) challenge, UTI (Ϫ/Ϫ) mice revealed a significant elevation of plasma fibrinogen and fibrinogen/fibrin degradation products and a decrease in white blood cell counts compared with WT mice. LPS treatment induced more severe neutrophilic inflammation in the lung and the kidney obtained from UTI (Ϫ/Ϫ) mice than in those from WT mice, which was confirmed by histological examination. The protein levels of proinflammatory mediators, such as macrophage chemoattractant protein (MCP)-1 in the lungs, MCP-1 and keratinocyte chemoattractant (KC) in the kidneys, and interleukin-1␤, macrophage inflammatory protein-2, MCP-1, and KC in the liver, were significantly greater in UTI (Ϫ/Ϫ) mice than in WT mice after LPS challenge. Our results suggest that UTI protects against systemic inflammatory response and subsequent organ injury induced by bacterial endotoxin, at least partly through the inhibition of the enhanced expression of proinflammatory cytokines and chemokines.

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Section: Discussionmentioning

confidence: 99%

Urinary Trypsin Inhibitor Protects against Systemic Inflammation Induced by Lipopolysaccharide

Inoue¹,

Takano²,

Shimada³

et al. 2005

Molecular Pharmacology

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show abstract

“…UTI is degenerated from pre-α-/inter-α-trypsin inhibitors during inflammation [ 14 ]. UTI reportedly inhibits neutrophil elastase activity in vitro [ 15 , 16 ] and trypsin activity in patients with pancreatitis [ 17 ]. Although the therapeutic effects of UTI on circulatory shock have been recognized, especially in Japan, the current understanding of the target mechanisms/pathways remains unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Urinary Trypsin Inhibitor on Systemic Inflammatory Response Induced by Lipopolysaccharide

Inoue

Takano

Yanagisawa

et al. 2008

J. Clin. Biochem. Nutr.

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Summary Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used in Japan as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation (DIC), shock, and pancreatitis. Recent in vitro studies have demonstrated that serine protease inhibitors may have anti-inflammatory properties beyond their inhibition of neutrophil elastase at the site of inflammation. However, the therapeutic effects of UTI in vivo remain unclear. In this review, we introduce the roles of UTI in the experimental systemic inflammatory response induced by both intraperitoneal and intratracheal administration of lipopolysaccharide using UTI deficient and wild-type mice. Our experiments suggest that UTI can protect against systemic inflammatory response and subsequent organ injury induced by bacterial endotoxin, at least partly, through the inhibition of proinflammatory cytokine and chemokine expression. UTI may therefore present an attractive "rescue" therapeutic option for systemic inflammatory response syndromes such as DIC, acute lung injury, and multiple organ dysfunction.

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“…As a commonly used clinical drug, ulinastatin is mainly used for acute pancreatitis and chronic recurrent pancreatitis ( Ohwada et al, 1997 ; Wang et al, 2016 ). Recent studies show that ulinastatin is also beneficial in treatment of cerebral ischemia/reperfusion injury ( Cao et al, 2011 ; Liu M. et al, 2017 ), early cardiopulmonary resuscitation, lung injury induced by hip fracture and pulmonary fibrosis as well as others ( Liu Q. et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Ulinastatin Inhibits Osteoclastogenesis and Suppresses Ovariectomy-Induced Bone Loss by Downregulating uPAR

et al. 2018

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Recent studies indicate that uPAR acts a crucial part in cell migration and the modulation of bone homeostasis. As a natural serine protease inhibitor, ulinastatin owns the capacity to reduce proinflammatory factors, downregulate the activation of NF-κB and mitogen-activated protein kinases (MAPKs) signaling pathways. Osteoclastogenesis has been demonstrated to be related with low-grade inflammation which involves cell migration, thus we speculate that ulinastatin may have a certain kind of impact on uPAR so as to be a potential inhibiting agent of osteoclastogenesis. In this research, we investigated the role which ulinastatin plays in RANKL-induced osteoclastogenesis both in vivo and in vitro. Ulinastatin inhibited osteoclast formation and bone resorption in a dose-dependent manner in primary bone marrow-derived macrophages (BMMs), and knockdown of uPAR could completely repress the formation of osteoclasts. At the molecular level, ulinastatin suppressed RANKL-induced activation of cathepsin K, TRAP, nuclear factor-κB (NF-κB) and MAPKs, and decreased the expression of uPAR. At the meantime, ulinastatin also decreased the expression of osteoclast marker genes, including cathepsin K, TRAP, RANK, and NFATc1. Besides, ulinastatin prevented bone loss in ovariectomized C57 mice by inhibiting the formation of osteoclasts. To sum up, this research confirmed that ulinastatin has the ability to inhibit osteoclastogenesis and prevent bone loss, and uPAR plays a crucial role in that process. Therefore, ulinastatin could be chosen as an effective alternative therapeutics for osteoclast-related diseases.

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New endoscopic treatment for chronic pancreatitis, using contrast media containing ulinastatin and prednisolone

Cited by 9 publications

References 15 publications

Urinary Trypsin Inhibitor Protects against Systemic Inflammation Induced by Lipopolysaccharide

Urinary Trypsin Inhibitor Protects against Systemic Inflammation Induced by Lipopolysaccharide

Protective Effects of Urinary Trypsin Inhibitor on Systemic Inflammatory Response Induced by Lipopolysaccharide

Ulinastatin Inhibits Osteoclastogenesis and Suppresses Ovariectomy-Induced Bone Loss by Downregulating uPAR

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