【Abstract】Objective To investigate the protective effect of improving the pancreatic ischemia and calcium channel blockers on preventing the progression of acute pancreatitis. Methods Twenty-four patients with mild acute pancreatitis were randomly divided into two groups： control group and treated group. Within the first 72 hours from the onset of AP, routine conservative managements were performed in control group, improving the pancreatic ischemia and preventing Ca2+ overload were performed in treated group for two weeks. The hemorrheological parameters were measured at 1,4,7,14 days after adimission, simultanously, serum TNFα, IL-1β, C-reactive protein and plasma TXB2, 6-keto-PGF1α levels were determined with ELISA methods. Results The hemorrheological changes were improved in treated group, serum TNFα, IL-1β, C-reactive protein and plasma TXB2, 6-keto-PGF1α levels were significantly decreased each time point in treated group as compared with control group. Conclusion Improving the pancreatic ischemia and calcium channel blockers have protective effect through reducing the generation of cytokines and inflammatory mediators on preventing the progression of acute pancreatitis.
Objective To assess the effectiveness and safety of ulinastatin in the treatment of patients with acute pancreatitis. Methods A systematic review of randomized controlled trials (RCT) of ulinastatin for acute pancreatitis was performed. Trials were identified by searching The Cochrane Library (issue 3, 2004), MEDLINE, EMBASE (1984-2004) and Chinese Biological Medicine Database (1978-2004), handsearching, and personal contact with pharmaceutical companies. All RCTs comparing ulinastatin with other interventions were included. Two reviewers assessed the quality of each studiy, and extracted data independently. Statisticsal analysis was performed by using RevMan 4.2. Results Seventeen trials involving 1 199 patients were included. Most included trials were of poor quality. Only two trials reported death at the end of follow-up. Meta-analysis of 6 RCTs showed that the clinical effective rate of Ulinastatin plus basic treatment group was 93.12% (176/189), and was 73.33% in basic treatment group. A statistic significant difference was found between the two groups (Peto OR 4.29, 95%CI 2.49 to 7.37, P＜0.000 01). Compared with basic treatment group, Ulinastatin plus basic treatment group significantly reduced the mean hospitalization (WMD -4.93, 95%CI -7.76 to -2.09, P＜0.000 7). Meta-analysis of 2 RCTs showed that the clinical effective rate of Ulinastatin plus basic treatment group was 86.75% (131/151), and was 80.49% (99/123) in other drugs plus basic treatment group. No statistic significant difference was found between the two groups (Peto OR 1.46, 95%CI 1.76 to 2.80, P＜0.26). One trial found that comparing with control group (23.5±7.5 days), Ulinastatin group (34.0±6.4 days) significantly reduced the mean hospitalization (P＜0.05).The reported severe adverse events of ulinastatin appeared to be rare (7/488, 1.43%). Conclusion Ulinastatin appears to be a modality of safe and effective treatment with a favorable trend, but there is no enough evidence to support this conclusion at present as the published trials with poor quality. More trials with enough sample size and scientifically sound methodology are required.
Objective To investigate therapeutic effects of continous regional arterial infusion with verapamil on preventing the progression of acute pancreatitis. Methods Forty-five patients with mild acute pancreatitis were randomly divided into three groups: conventional treatment group, intravenous treatment group and arterial infusion group. After admission, conventional treatments were performed in conventional treatment group. Reasonable fluid and verapamil were intravenously injected to the patients in intravenous treatment group, and fluid treatments and continous regional arterial infusion with verapamil were performed in arterial infusion group for 1－2 weeks. The levels of serum TNF-α, IL-1β, ICAM-1 and P-selectin were determined on the 1st, 4th and 7th day after treatment, respectively. Results On the 4th and 7th day after treatment, the levels of serum TNF-α and P-selectin significantly decreased in arterial infusion group compared with the other two groups （P＜0.05）, while the level of serum IL-1β significantly decreased in arterial infusion group and intravenous treatment group compared with the conventional treatment group （P＜0.05）. The level of serum ICAM-1 significantly decreased in arterial infusion group compared with the conventional treatment group （P＜0.05）.Conclusion Continous regional arterial infusion with verapamil could reduce the production of inflammatory cytokines and inhibit the up-regulation of adhesion molecules ICAM-1 and P-selectin, and prevent the progression of acute pancreatitis ultimately.
To evaluate the effects of different pressure and duration of autologous bile perfusion into dog’s pancreatic duct on the severity of induced acute pancreatitis. Thirty mongrel dogs were divided into five groups, with each group consisting of six dogs. Histological changes of pancreas were observed. Results: Histological changes of pancreas were correlated with the pressure and duration of autologous bile perfusion into pancreatic duct. It was easier to produce acute hemorrhagic necrotizing pancreatitis in the groups with a higher pressure and a longer duration of perfusion than in the groups with a lower pressure and a shorter duration. The results indicated that there was a significant effect of higher pressure and longer duration bile perfusion into pancreatic duct on the severity of induced acute pancreatitis.
Objective To summarize the change in the cytokine network, the classification of various cytokines, interaction, and systemic impact on patients with acute pancreatitis (AP). Methods The recently published literatures in domestic and abroad about advancement of cytokines in AP were reviewed. Results Cytokines had a complex network and interactions. There were a variety of regulatory mechanisms. The tumor necrosis factor-α (TNF-α) and interleukin cytokines played important roles in the progress of AP. Conclusions Change of cytokines during AP is a complex process. Any separate regulation for the release of sigle factor has no significant effect on the disease. The treatment according to immune balance should be a better direction.
Objective To evaluate the role of interleukin-10 (IL-10) in acute pancreatitis. Methods Thirty mongrel dogs were divided into three groups based on the severity: acute edematous pancreatitis (AEP) group (n＝11), acute hemorrhagic necrotizing pancreatitis (AHNP) group (n＝12), and control group (n＝7). Serum level of IL-10 was determined with enzyme-linked immuno-sorbent assay (ELISA). Results Within 24 hours, AEP group had serum level of IL-10 significantly higher than that of AHNP group. Control group had no detectable serum IL-10. No significant difference was observed between AEP group and AHNP group at 48 hours. Conclusion The finding of low values of serum IL-10 suggests that there may be more consumption in AHNP group than in AEP group and it may be beneficial to decrease the severity of experimental acute pancreatitis.
Objective To evaluate the activity of the pancreatic tissue phospholipase A2 (PLA2) in acute pancreatitis (AP) and the therapeutic effects of verapamil in rats. MethodsThe model of rat AP induced by a closed duodenal loop technique was established to observe the changes of PLA2 activity in AP group and treated group. The pancreatic histology was examined by light and electron microscopy. Results At 16 and 24 hours after induction of AP in rats, significant inhibition of the pancreatic tissue PLA2 activity was shown in the treated group as compared with AP group, with 32.34±3.87u, 35.26±4.52u and 44.83±5.31u, 47.77±5.86u respectively. The treated animals also showed a decrease in the severity of pancreatic hemorrhage, necrosis and damage to the cellular ultrastructures. Conclusion There exists high activity of PLA2 in rats AP. Calcium channel blocker, verapamil might take therapeutic effects on AP by inhibiting activity of PLA2.
The serum activities of 3 cytokines (TNF,IL-1 and IL-6) were observed in 23 patients admitted within 4 days of onset of acute pancreatitis (AP). The results showed that the serum level of 3 cytokines raised in all of the AP patients, significant difference between TNF and IL-1 was abserved at admission and IL-6 did after one week of admission, suggesting that proper cytokine criteria are useful in predicting severity of the disease but the relationship between cytokines and MOF had not established.
This study based on two serial animal experiments: ①caerulein-induced edematous pancreatitis with gut motility inhibited by administration of lopemin (an opium antidiarrheal agent) and ②deoxycholate intraductal-injection induced pancreatitis with gut motility improved by administration of rhubarb solution. The results of these experiments indicated that inhibition of gut motility will increase the incidence of bacterial translocation and endotoxemia during acute pancreatitis; and acceleration of gut motility will significantly decrease the incidence of bacterial translocation and endotoxemia during severe type of acute pancreatitis. The authors conclude that promotion of gut motility may protect the inflammatory pancreas from infection and prevent the multiple organ failure during acute pancreatitis, and eventualy improve the prognosis of pancreatitis.
【Abstract】Objective To investigate the production and possible significance of plasma trypsinogen activation peptides (TAP) in rat experimental acute pancreatitis. Methods Ninety SD rats were randomly allocated to five groups: group EP with retrograde ductal infusion of 3%sodium taurocholate; group NP with retrograde ductal infusion of 5%sodium taurocholate; group TP with retrograde ductal infusion of 3%sodium taurocholate and ulinastatin(UTI) intravenous infusion half an hour later; group CP with 0.9% NS retrograde ductal infusion; group OP with sham operation. Animals in each group were killed 3h,6h and 24h after infusion. Plasma TAP was determined by EIA.The histological severity of the pancreas were assessed by Schmidt method. Results The pancreatic pathological changes in group NP was significantly severe than in group EP. At 3h and 6h after infusion, plasma TAP concentration of group NP (4.798±0.169)nmol/L and (3.999±0.299)nmol/L were significant higher than that of group EP(2.416±0.148)nmol/L and (3.356±0.211)nmol/L. At 6h after infusion plasma TAP concentration of group TP 〔(1.611±0.113)nmol/L〕 was significant lower than that of group EP(3.356±0.211)nmol/L. The difference of plasma TAP concentration between group EP and group NP appeared prior to the difference of the histopathological changes of pancreas between two groups. Conclusion Plasma TAP concentration is connected with the severity of sodium taurocholate-induced rat pancreatitis. Plasma TAP concentration may be used as a marker for early assessment of the severity of this experimental acute pancreatitis.