scholarly journals A Severe Acute Pancreatitis Mouse Model Transited from Mild Symptoms Induced by a “Two-Hit” Strategy with L-Arginine

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 126
Jing Yang ◽  
Xujiao Tang ◽  
Qingqing Wu ◽  
Panpan Ren ◽  
Yishu Yan

To develop a severe acute pancreatitis (SAP) model transited from mild symptoms, we investigated a “two-hit” strategy with L-arginine in mice. The mice were intraperitoneally injected with ice-cold L-arginine (4 g/kg) twice at an interval of 1 h on the first day and subjected to the repeated operation 72 h afterwards. The results showed the “two-hit” strategy resulted in the destructive damage and extensive necrosis of acinar cells in the pancreas compared with the “one-hit” model. Meanwhile, excessive levels of pro-inflammatory mediators, namely IL-6 and TNF-α, were released in the serum. Remarkably, additional deleterious effects on multiple organs were observed, including high intestinal permeability, kidney injury, and severe acute lung injury. Therefore, we confirmed that the SAP animal model triggered by a “two-hit” strategy with L-arginine was successfully established, providing a solid foundation for a deeper understanding of SAP initiation and therapy research to prevent worsening of the disease.

Inflammation ◽  
2009 ◽  
Vol 32 (3) ◽  
pp. 191-201 ◽  
Tian Hua ◽  
Zhang Xiping ◽  
Wu Chengjun ◽  
Chen Li ◽  
Ying Rongchao ◽  

2020 ◽  
Vol 16 (3) ◽  
Subash Bhattarai ◽  
Merina Gyawali

Background: Acute pancreatitis (AP) is inflammatory process of pancreas presenting with acute abdominal pain.The majority of patients have mild disease. Some patients develop local and systemic complications with increased morbidity and mortality. This study was undertaken to describe the clinical profile and outcomes in patients with acute pancreatitis.   Methods:  A cross-sectional hospital based study comprising of 62 consecutive patients with acute pancreatitis were enrolled between Jan 2019 to August 2020. Clinical profile at admission, complications and clinical outcomes including mortality were studied. Patients were classified into mild, moderately severe and severe acute pancreatitis based on revised Atlanta classification and modified CT severity index.  Data entry was done in Statistical Packages for the Social Sciences version 20. Results: The mean age of study subjects was 44±10.87 years with 43 (56%) males and 19 (44%) females (M:F=2.1:1). The commonest etiology of pancreatitis was alcohol (53.2%) followed by biliary pancreatitis (37.1%)  The most common presentation was abdominal pain (100%). The most common complication was pancreatic necrosis (21%) followed by acute kidney injury (19.4%) and pleural effusion (17.3%). Majority( 72.6%) was mild and 17.7% had severe acute pancreatitis. Mortality was seen in 6.5% patients. Mortality was observed in patients with persistent complications, organ failure, low serum calcium and high modified CT severity index.   Conclusions: Alcohol and gallstones were the two main etiologies of acute pancreatitis and were common in males, and in middle age groups. Majority presented with mild severity. Mortality was observed in some patients with severe acute pancreatitis.   Keywords: alcohol; biliary; CT severity index; mortality; outcome; pancreatitis          

2018 ◽  
Vol 32 ◽  
pp. 205873841881863
Ming-wei Liu ◽  
Yun-qiao Huang ◽  
Ya-ping Qu ◽  
Dong-mei Wang ◽  
Deng-yun Tang ◽  

Panax notoginseng saponins are extracted from Chinese ginseng— Panax notoginseng Ledeb—and are known to have therapeutic anti-inflammatory effects. However, the precise mechanism behind their anti-inflammatory effects remains relatively unknown. To better understand how Panax notoginseng saponins exert their therapeutic benefit, we tested them in a rat model of severe acute pancreatitis (SAP). Rats received a tail vein injection of Panax notoginseng saponins and were administered 5% sodium taurocholate 2 h later. Pancreatic tissue was then harvested and levels of miR-181b, FSTL1, TREM1, TLR4, TRAF6, IRAK1, p-Akt, p-p38MAPK, NF-κBp65, and p-IκB-α were determined using Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assays were used to determine serum levels of tumor necrosis factor-α (TNF-α), TREM1, interleukin (IL)-6, ACAM-1, IL-8, and IL-12 and DNA-bound levels of NF-KB65 and TLR4 in pancreatic and ileum tissue. Serum levels of lipase and amylase, pancreatic myeloperoxidase (MPO) activity, and pancreatic water content were also measured. Hematoxylin and eosin staining was used for all histological analyses. Results indicated upregulation of miR-181b, but negligible levels of FSTL1, p-p38MAPK, TLR4, TRAF6, p-Akt, IRAK1, TREM1, p-NF-κBp65, and p-IκB-α, as well as negligible DNA-bound levels of NF-KB65 and TLR4. We also observed lower levels of IL-8, IL-6, ACAM-1, TNF-α, MPO, and IL-12 in the Panax notoginseng saponin–treated group when compared with controls. In addition, Panax notoginseng saponin–treated rats had significantly reduced serum levels of lipase and amylase. Histological analyses confirmed that Panax notoginseng saponin treatment significantly reduced taurocholate-induced pancreatic inflammation. Collectively, our results suggest that Panax notoginseng saponin treatment attenuated acute pancreatitis and pancreatic inflammation by increasing miR-181b signaling. These findings suggest that Panax notoginseng saponins have therapeutic potential in the treatment of taurocholate-induced SAP.

Shock ◽  
2003 ◽  
Vol 19 (Supplement) ◽  
pp. 20
L. Vona-Davis ◽  
K. Magabo ◽  
B. Jackson ◽  
T. Evans ◽  
D. Riggs ◽  

Gut ◽  
1998 ◽  
Vol 43 (2) ◽  
pp. 232-239 ◽  
M O Osman ◽  
J U Kristensen ◽  
N O Jacobsen ◽  
S B Lausten ◽  
B Deleuran ◽  

Background—Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis.Aims—To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis.Methods—Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis.Results—Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor α (TNF-α) from three to six hours after induction of acute pancreatitis (p=0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-α, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose.Conclusion—WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-α, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.

2016 ◽  
Vol 64 (4) ◽  
pp. 942.1-942 ◽  
N Vyas ◽  
H Alkhawam ◽  
R Sogomonian ◽  
RA Ching Companioni ◽  
M Tiba ◽  

IntroductionPegaspargase (Oncaspar) is a modified version of L-asparaginase conjugated with polyethylene glycol. In leukemic cells, asparaginase hydrolyzes L- asparagine to ammonia and L-aspartic acid leading to depletion of asparagine. Despite its potential benefits there are a wide range of side effects. One rare but potentially deadly complication is severe pancreatitis.CaseThe patient was a 24 year old Mexican male with a history of Acute T-Cell Lymphoblastic Leukemia (ALL) on recent chemotherapy including pegaspargase, admitted for abdominal pain, found to have acute pancreatitis secondary to hypertriglyceridemia. Heart rate was 127 bpm, chest revealed decreased air entry in right lung bases, and a distended severely tender abdomen. Laboratory tests were remarkable for elevated liver enzymes ALP 360 U/L, AST 310 U/L, GGT 216 U/L, ALT 44 U/L, LDH 829 U/L, elevated lipase 228 U/L, and hypertriglyceridemia >3,000 mg/dL. Abdominal CT showed pancreatitis with necrosis; peripancreatic, intraperitoneal and extensive retroperitoneal fluid. Subsequently his severe pancreatitis was associated with acute kidney injury and respiratory failure which is illustrated by his (BUN 22 Creatinine 2.16, and persistent hypoxia.) According to the Atlanta Classification, patient is classified under severe acute pancreatitis.DiscussionPegaspargase is used for treatment of ALL and is gaining in popularity over Asparaginase therapy due to it having fewer incidences of hypersensitivity reactions and because of its long half life (367 hrs) allowing dosing every 14 days as opposed to Asparaginase which is dosed daily. Pegaspargase definitely has its benefits but we can't lose sight of one of its rare, but potentially deadly complications, pancreatitis. In one study nine of the 50 patients (18%) with ALL treated with pegaspargase were diagnosed to have pancreatitis. In contrast, only one out of 52 (1.9%) ALL patients who received native E. coli L-asparaginase during the same time period developed pancreatitis. One proposed mechanism of this drug-induced pancreatitis is hypertriglyceridemia, which is seen in our case. It is suggested that apolipoprotein E polymorphism may influence the development of hyperlipidemia in ALL patients receiving pegaspargase therapy.We report a case to increase the awareness of higher incidence of pegaspargase-induced pancreatitis, which is a rare but potentially deadly complication. Clinicians should monitor triglycerides while on treatment and suspect pancreatitis if patient develops abdominal pain. If pancreatitis occurs, therapy should be stopped and not reinstituted. For patients with hypertriglyceridemia without pancreatitis discontinuation of therapy should be considered.Abstract ID: 36 Figure 1Impression: Severe acute pancreatitis. Significant interval worsening.

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