Morphological changes of the pancreas in course of acute pancreatitis during treatment with Ulinastatin

Wallner, Grzegorz; Solecki, Michał; Ziemiakowicz, R; Ćwik, Grzegorz; Dyndor, Przemysław; Maciejewski, Ryszard

doi:10.2478/pjs-2013-0020

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…Four-micrometer sections were stained with hematoxylin and eosin (H&E) to observe the morphological changes under the light microscope. The degree of development of pancreatic lesions was evaluated according to point Spormann scale, as previously described [ 20 ]. Histological analysis was conducted in control group, SAP group, and SAP treated with ulinastatin group (30000U/kg).…”

Section: Methodsmentioning

confidence: 99%

Ulinastatin ameliorates tissue damage of severe acute pancreatitis through modulating regulatory T cells

et al. 2017

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BackgroundUlinastatin or urinary trypsin inhibitor (UTI) has been shown to ameliorate the inflammatory response induced by experimental severe acute pancreatitis (SAP) and hence reduce the mortality, however the mechanism of its action remains incompletely understood. We have investigated the effect of ulinastatin on regulatory T-cells (Tregs) in an established rat model of SAP.MethodsWe established a rat SAP model by injecting 5% Na-taurocholate into the pancreatic duct and treated the SAP rats with ulinastatin with different dose level (5000, 10000, 30000 U/kg) through intraperitoneal injection at 0, 6 and 12 h.ResultsWe showed that the tissue damage of pancreas and the mortality of the SAP rats were significantly reduced by ulinastatin. We also showed that in the SAP rats the frequencies of CD4+ T cells and Tregs, as well as the expressions of TGF-β1, CTLA-4, and Foxp3 were decreased in the SAP animals while IL-1β, IL-10 and TNF-α were significantly increased. Treatment with ulinastatin up-regulated the proportion of Tregs in CD4+ T cells and the expression of IL-10, Foxp3 and CTLA-4 in the SAP rats in a dose dependence fashion, while down-regulating the levels of L-1β and TNF-α, myeloperoxidase (MPO) activity.ConclusionsOur findings suggest that ulinastatin alleviates inflammatory response and tissue damage in SAP rats by increasing the proportion of Tregs. Our study provides a new mechanism for the beneficial effect of ulinastatin in SAP rat model.

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Section: Methodsmentioning

confidence: 99%

Ulinastatin ameliorates tissue damage of severe acute pancreatitis through modulating regulatory T cells

et al. 2017

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“…Therefore, peritoneal lavage and antiprotease therapy may bring an improved therapeutic effect through being applied locally to the peritoneal cavity ( 10 ). The glycoprotein ulinastatin is widely used to treat patients with SAP via the intravenous route ( 11 , 12 ); one of its therapeutic functions is regulation of the inflammatory response. Ulinastatin may provide a greater therapeutic effect for SAP if administered by peritoneal lavage as only a small amount of intravenously administered ulinastatin is able to reach the pancreas and other organs because of microcirculatory dysfunction ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of peritoneal lavage with ulinastatin on the expression of NF-κB and TNF-α in multiple organs of rats with severe acute pancreatitis

Feng

Wang

et al. 2015

Experimental and Therapeutic Medicine

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The aim of the present study was to investigate the effect of peritoneal lavage with ulinastatin on the expression levels of nuclear factor κB (NF-κB) and tumor necrosis factor (TNF)-α in multiple organs of rats with severe acute pancreatitis (SAP). Male Wistar rats were randomly divided into the following groups: Sham-operated (C), SAP model (SAP), saline lavage (SL), intravenous ulinastatin (IU) and peritoneal lavage with ulinastatin (UL). The SAP model was induced by the retrograde infusion of 5% sodium taurocholate into the biliopancreatic ducts of the rats. Intraperitoneal lavage or injection was performed immediately following the establishment of the SAP model in groups SL, IU and UL. Intraperitoneal lavage with or without ulinastatin was performed for 3 h. The survival time of half of the rats in each group was recorded over a 12-h period. At 3 h after the induction of SAP, inflammatory mediators and the expression levels of NF-κB and TNF-α in multiple organs of the rats in each group were also detected. The survival rates of the rats in group UL at 6 h and 9 h were increased compared with those in group SAP, and were also higher than that in groups SL and IU. The levels of serum inflammatory mediators were effectively reduced in groups SL, IU and UL, the greatest effects were observed in group UL. The expression levels of NF-κB and TNF-α in multiple organs were significantly lower in group UL compared with other groups. Intraperitoneal lavage with ulinastatin significantly ameliorated the inflammatory reaction and inhibited NF-κB and TNF-α expression in multiple organs of SAP model rats.

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“…Although some studies in humans have not shown a significant improvement in survival with peritoneal antiprotease lavage therapy, it was reported that this treatment could counteract the development of pancreatic necrosis for patients with SAP and reduce the need for surgical intervention (12,15,16). Ulinastatin is a purified glycoprotein from healthy adult male urine, and numerous studies suggest that it has a significant therapeutic effect on SAP (17)(18)(19). In previous years, ulinastatin has been widely used for the treatment of patients with SAP in Asia.…”

Section: Discussionmentioning

confidence: 99%

Ulinastatin enhances the therapeutic effect of intraperitoneal lavage on severe acute pancreatitis in rats

Feng

Chen

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The present study investigated the therapeutic effect of peritoneal lavage with ulinastatin on the outcome of rats with severe acute pancreatitis (SAP). A total of 110 male Wistar rats were randomly divided into the following groups: Control (C), SAP model (SAP), saline lavage (SL), intravenous ulinastatin (IU) and low-dose (LUL), medium-dose (MUL), high-dose (HUL) and ultrahigh-dose (UHUL) ulinastatin lavage. The treatments were performed immediately subsequent to the establishment of the SAP model. Intraperitoneal lavage with or without ulinastatin was performed for 3 h. Survival time was recorded for 12 h and the median survival time was calculated. Histopathological analyses, and measurements of plasma amylase and lipase levels were performed. Blood pH, lactic acid and base excess were also detected. The LUL, MUL, HUL, UHUL and IU groups showed an increase in the median survival time compared with the SAP group, with the maximal effect observed in the MUL group (P<0.01). The SL, MUL and IU groups showed a reduced activity of amylase and lipase compared with the SAP group. The SL (P<0.01) and the MUL groups (P<0.01) additionally showed a reduction in the lactic acid in arterial blood relative to the SAP group but the IU group did not. The MUL group showed greater improvements in pH (P<0.01) and base excess (P<0.01) versus the SAP group than the SL and IU groups. Furthermore the MUL group demonstrated a more marked reduction in the histological changes in necrosis, edema and inflammation compared with the SL and IU groups. Intraperitoneal lavage with ulinastatin significantly improves the prognosis of SAP in rats.

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Morphological changes of the pancreas in course of acute pancreatitis during treatment with Ulinastatin

Abstract: Application for the treatment of UTI leads to inhibition of the inflammatory process at the stage of pancreatic edema and in cases of severe necrotizing course limits the progression of the disease which gives grounds for its clinical use in humans.

Cited by 7 publications

References 9 publications

Ulinastatin ameliorates tissue damage of severe acute pancreatitis through modulating regulatory T cells

Ulinastatin ameliorates tissue damage of severe acute pancreatitis through modulating regulatory T cells

Effect of peritoneal lavage with ulinastatin on the expression of NF-κB and TNF-α in multiple organs of rats with severe acute pancreatitis

Ulinastatin enhances the therapeutic effect of intraperitoneal lavage on severe acute pancreatitis in rats

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