Objective To systematically review the effectiveness and safety of alanyl-glutamine dipeptide for severe acute pancreatitis (SAP). Methods Such databases as MEDLINE, EMbase, CENTRAL, VIP, WanFang Data, CBM and CNKI were electronically searched from inception to October, 2012 for randomized controlled trials on alanyl-glutamine dipeptide for SAP. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then, meta-analysis was performed using RevMan 5.2. Results Five trials were included involving a total of 227 patients. The results of meta-analysis showed that: compared with the control group, the alanyl-glutamine dipeptide group had the lower incidence of SAP complications (RR=0.41, 95%CI 0.20 to 0.82), the lower incidence of infected pancreatic necrosis (RR=0.12, 95%CI 0.02 to 0.89), less time for alleviating bellyache (MD= –0.90, 95%CI –1.72 to –0.08). There was a tendency in decreasing SAP mortality (RR=0.15, 95%CI 0.02 to 1.19) and lessening the recovery time of blood amylase (SMD=0.37, 95%CI –0.04 to 0.79). Conclusion Current evidence shows that, alanyl-glutamine dipeptide can lower the incidence of complications and the incidence of infected pancreatic necrosis, and shorten the time for alleviating bellyache in SAP patients. Due to the limited quality of the included studies, the above conclusion needs to be verified by more high quality studies.
Objective To establish a stable and reliable lung injury model caused by severe acute pancreatitis（SAP）in rats， which is helpful to study the acute lung injury （ALI）and acute respiratory distress syndrome （ARDS） induced by SAP.Methods Sixty Sprague-Dawley rats were randomized into ligature group （n=20）， traditional group （n=20），and sham operation group （n=20）. SAP model was established through retrograde injection of 5% taurocholic acid. After injection， the pancreatic duct of rats was ligated in ligature group， but not in traditional group. The lung damage and edema at 24 h after operaton and natural course of rats were observed.Results The ALI model of rats induced by SAP was established successfully in ligature group. The rats died of acute respiratory failure within 48 h in ligature group， the mortality was significantly higher than that in traditional group （100% vs.20%），P＜0.05. Pleural effusion occurred in four rats in ligature group， while no pleural effusion was found in rats in other two groups. The volume of ascites of rats in ligature group was （21.15±5.33） ml， which was more than that in traditional group 〔（7.75±2.66） ml〕，P＜0.05， while no ascites was found in rats in sham operation group. The level of serum amylase of rats in ligature group was （2 470.70±399.73） U/L，which was significantly higher than that in traditional group 〔（1 528.40±289.54） U/L〕 and sham operation group 〔（831.10±93.26） U/L〕，P＜0.001. The level of serum albumin of rats in ligature group was （6.90±1.66）g/L， which was significantly lower than that in traditional group 〔（13.10±0.99） g/L〕 and sham operation group 〔（16.20±0.92） g/L〕，P＜0.001.The lung wet-to-dry weight ratio （W/D） of rats in ligature group was 6.50±0.23， which was greater than that in traditional group （4.92±0.18） and sham operation group （4.61±0.16）， P＜0.001. The score of lung histopathologic of rats in ligature group was 29.25±1.07， which was significantly higher than that in traditional group （12.65±1.98） and sham operation group （0），P＜0.001. The score of pancreas histopathologic of rats in ligature group was 15.95±0.15，which was significantly higher than that in traditional group （13.75±0.66） and sham operation group （0.13±0.29），P＜0.001. Under transmission electron microscope， basement membrane of pulmonary capillary of rats in ligation group was destructive， the nuclei was dissolved， endothelial pinocytotic vesicles was functional active， and tight junctions between capillary endothelial cells were blurred and even ruptured. Moreover， tight junctions between alveolar epithelial cells were destructive. Pathological changes of lung ultrastructure of rats in ligation group were more severe than that in traditional group， while no pathological change of lung ultrastructure was observed in rats in sham operation group. Conclusions Injury process and pathogenesis of ALI or ARDS clinically caused by acute gallstone pancreatitis can be reproduced in this animal model， which is suitable to explore the related mechanisms of ALI caused by SAP and provides good animal model for the study of ALI caused by SAP.
ObjectiveTo study the effects of continuous regional arterial infusion (CRAI) of dexamethasone on plasma inflammatory factors of severe acute pancreatitis (SAP) rabbits. MethodsTwentyfour rabbits were randomly divided into sham operation group, SAP group, intravenous infusion of dexamethasone group and CRAI of dexamethasone group (each group 6 rabbits) by random number table. The serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and amylase (AMY) levels in rabbits were tested at hour 0.5, 3, 6, 9, and 12 after modeling succeed. The pathological changes of pancreas and the survival were observed on day 3 after modeling succeed. ResultsCompared with the sham operation group, the serum levels of IL-6 significantly increased at 3 h and reached the peak at 6 h, decreased at 9 h (all Plt;0.05); levels of IL-10 significantly increased at 6 h, continuously elevated at 9 h and 12 h (all Plt;0.001); levels of TNF-α significantly increased at 0.5 h (Plt;0.001), reached the peak at 6 h (Plt;0.001) and decreased at 9 h (Plt;0.05); levels of AMY significantly increased at 9 h, continuously elevated at 12 h (all Plt;0.05) in the SAP group. Compared with the SAP group, the serum levels of IL-6 and IL-10 in the CRAI of dexamethasone group all significantly decreased at 6 h, 9 h, and 12 h (Plt;0.001); levels of IL6 significantly decreased only at 6 h in the intravenous infusion of dexamethasone group; levels of TNF-α in the CRAI of dexamethasone group significantly decreased at 3 h, 6 h, 9 h, and 12 h (all Plt;0.001), which in the intravenous infusion of dexamethasone group significantly decreased only at 6 h (Plt;0.05); levels of AMY in the CRAI of dexamethasone group and intravenous infusion of dexamethasone group all significantly decreased at 12 h (Plt;0.05). Compared with the intravenous infusion of dexamethasone group, the serum levels of IL-6 and IL-10 in the CRAI of dexamethasone group all significantly decreased at 6 h (Plt;0.05) and 12 h (Plt;0.001); levels of TNF-α all significantly decreased at 3 h, 6 h, 9 h, and 12 h (all Plt;0.001); levels of AMY were not significantly different (Pgt;0.05). The pathological changes of pancreas in the CRAI of dexamethasone group were obvious, the death of rabbits reduced on day 3 after modeling succeed. ConclusionCRAI dexamethasone can effectively reduce the systemic inflammatory response and pancreatic inflammation, and reduce mortality.
Objective To explore the effects of ulinastatin (UTI) on renal apoptosis and expression of bcl-2 in rats with severe acute pancreatitis (SAP). Methods Sixty rats weighing 250-300 g were randomized divided into 3 groups: pseudo-operation group (SO group, n=20), SAP group (n=20) and UTI treated group (UTI group, n=20). The model of SAP was established by retrograde injection of 5% sodium taurocholate solution into the biliopancreatic duct in the rats. Serum Cr and BUN were determined. The left kidneys were resected for light and electronic microscopic study. Renal cell apoptosis was determined by TUNEL. Expression of bcl-2 was detected by immunohistochemical staining of SABC. Results Serum Cr, BUN, renal cell apoptotic index and bcl-2 expression were markedly increased in SAP group compared with SO group （P＜0.05， P＜0.01）, Renal tissue injuries were aggravated in SAP group under light and electronic microscopic study as well. In UTI group, serum Cr, BUN and renal cell apoptotic index were decreased significantly while the expression of bcl-2 increased remarkably and renal tissue injuries relieved compared with SAP group （P＜0.05）. Positive correlations were found between the renal cell apoptotic index and BUN as well as Cr (r=0.807, P＜0.05; r=0.812, P＜0.05). Conclusion The protective effect of UTI on SAP renal injury is probably through increasing bcl-2 expression and decreasing apoptosis.
【Abstract】Objective To study the influence of early hemofiltration on plasma concentrations of proinflammatory cytokines TNF-α and IL-1β and their transcription levels in severe acute pancreatitis (SAP) pigs. Methods The model of SAP was induced by retrograde injection of artificial bile into pancreatic duct in pigs. Animals were divided randomly into two groups: SAP hemofiltration treatment group (HF group, n=8) and SAP no hemofiltration treatment group (NHF group, n=8). TNF-α and IL-1β plasma concentrations were measured by ELISA. Their transcription levels in the tissues of pancreas, liver and lung were assayed by semi-quantitative reverse transcription polymerase chain reaction. Results After hemofiltration treatment, the plasma concentrations of TNF-α and IL-1β increased gradually but were lower than those of NHF group at the same time spot 〔at 6 h after hemofiltration treatment, (618±276) pg/ml vs (1 375±334) pg/ml and (445±141) pg/ml vs (965±265) pg/ml, P＜0.01〕. At 6 h after hemofiltration treatment, the transcription levels of TNF-α and IL-1β in tissues of pancreas, liver and lung were lower than in NHF group (57.8±8.9 vs 85.7±17.4, 48.0±8.1 vs 78.1±10.2, 46.2±9.6 vs 82.4±10.5; 55.9±9.0 vs 82.2±15.7, 40.6±9.2 vs 60.0±10.6, 35.7±9.8 vs 58.1±9.3, P＜0.01). Conclusion Early hemofiltration can reduce TNF-α and IL-1β plasma concentrations and transcription levels in SAP pigs.
ObjectiveTo evaluate the effect of the early enteral nutrition（EEN） on the natural course in dogs with severe acute pancreatitis（SAP）.MethodsSAP model was induced by injecting 1 ml/kg of combined solution of 5% sodium taurocholate and 8 000-10 000 BAEE units trypsin/ml into pancrease via pancreatic duct.Fifteen dogs were divided into parenteral nutrition(PN) group and EEN group.Two groups were isonitrogenous and isocaloric.EEN was used at postoperative 24 h.Systemic plasma endotoxin level was quantified by the chromogenic limulus amebocyte lysate technique.Both portal and systemic blood sample were obtained before and 1，4，7 d following SAP, and cultured for aerobic as well as anaerobic bacterial.Serum glucose, calcium,amylase and lysosomal enzymes were determined.All dogs were injected with 1.85×106 Bq 125IBSA 4 h before sacrificed.The 125IBSA index of the pancreas/muscle and pancreas/blood was measured,and pancreas pathology was observed.Specimens of tissue from mesenteriolum and mesocolon lymph nodes,lung,pulmonary portal lymph nodes and pancreas were removed,weighed and homogenized in grinding tubes.Aliquots of the homogenata were cultured as blood mentioned above.The thickness of mucosa,the whole gut layer,the height of intestinal villi and their protein and DNA contents in the intestinal and transverse colon were determined.ResultsThe study showed that EEN significantly reduced the levels of systemic plasma endotoxin and the magnitude of bacterial translocation to the portal and systemic blood and distant organ,serum glucose in PN group was higher than that in EEN after SAP 4 d.There were no difference between two groups in the data of serum calcium,amylase and lysosomal enzymes,pathologic index and 125IBSA index of pancreas/muscle and pancreas/blood.EEN improved the gut barrier function by increasing the thickness of mucosa,the whole gut layer and the height of intestinal villi,increasing its protein and DNA contents in the bowel.ConclusionOur results suggest that EEN is safe and effective,and can decrease the rate of intestinal bacterial translocation.
【Abstract】Objective To investigate a more rational modality which is in the treatment of severe acute pancreatitis (SAP) and effective in preventing liver from damages due to SAP. Methods SAP model was established by retrograde injection of 5% sodium taurocholate (1.0 ml) in the subserosa of pancreas in rats (n=80) weighting 200-250 g.The rats were catheterized using PE-50 angiocatheter from femoral artery to celiac trunk. Then they were randomly divided into four groups. Twenty animals served as controls (A group) and received only fluid infusion. The 40 animals, B and C group (20 animals in each one group) received continuous regional arterial infusion (CRAI) of somatostatin （4 μɡ/kg） and the medicines improving microcirculatory (dextran-40 1.5 ml, dopamine hydrochloride 5 μg/kg, anisodaminum 1.5 ml/kg) respectively. The other 20 animals (D group) were treated by somatostatin combined with the medicine improving microcirculatory through CRAI simultaneously with the induction of pancreatitis. The AST, ALT, ALP and serum amylase were recorded, the liver and pancreas tissue were observed pathologicaly after 6 hours. Results There were a ignificant decrease in the serum amylase in B group (Plt;0.05) and D group (Plt;0.05). The AST, ALT, ALP was decreased in B and D group (Plt;0.05). The damage to liver and pancreas were reduced in D group. Conclusion CRAI is effective in preventing liver damages due to SAP and is an effective way in the treatment of SAP.
To evaluate the role of octreotide in the treatment of severe acute pancreatitis (SAP). Seventy-six patients were divided into two groups (octreotide group, n＝38, control group, n＝38). All patients were treated by the same conservative regime. The octreotide group received octreotide. Results: The abdominal symptoms and signs, WBC count, serum amylase level, and volume of ascites were more effective controlled, with fewer complications occurred in octreotide group. Conclusion: Octreotide has a beneficial effect on the treatment of SAP, but the mechanism will be further investigated.
Objective To systematically assess the efficacy and clinical significance of antibiotic prophylaxis in severe acute pancreatitis (SAP), so as to provide references for its rational clinical application. Methods For collecting the randomized controlled trials (RCTs) about antibiotic prophylaxis in SAP, a search was conducted in MEDLINE, EMbase, Cochrane Central Register of Controlled Trials, CBM and CNKI from the date of their establishment to August, 2010. After the clinical studies meeting the inclusive criteria were extracted and their quality was assessed. Meta-analysis was conduced by using RevMan 5.0 software. Results Twelve RCTs were included with a total of 777 patients. The results of Meta-analysis showed compared with the control group, the antibiotic prophylaxis group was not associated with a statistically significant reduction in mortality (RR=0.75, 95%CI 0.50 to 1.12), in the incidence of infected pancreatic necrosis (RR 0.82, 95%CI 0.63 to 1.09), in surgical interventions (RR=0.97, 95%CI 0.74 to 1.26), and in the incidence of nonpancreatic infections (RR=0.73, 95%CI 0.48 to 1.10). Conclusion Antibiotic prophylaxis for SAP does not reduce mortality, infected necrosis, or surgical intervention.
Objective To evaluate the effectiveness and safety of total enteral nutrition (TEN) versus total parenteral nutrition (TPN) in patients with severe acute pancreatitis (SAP). Methods The databases such as Pubmed (1996 to June 2011), EMbase (1984 to June 2011), Cochrane Central Register of Controlled Trials of The Cochrane Library (Issue 6, 2011) and CBM (1978 to June 2011) were electronically searched, and the relevant references of the included papers were also manually searched. Two reviewers independently screened the trials according to inclusion and exclusion criteria, extracted the data, and assessed the methodology quality. Meta-analyses were performed using the Cochrane Collaboration’s RevMan 5.1 software. Results Seven randomized controlled trials (RCTs) involving 379 patients with SAP were included. The results of meta-analyses showed that compared with TPN, TEN could significantly reduce the risk of mortality (RR=0.33, 95%CI 0.20 to 0.55, Plt;0.000 1), pancreatitis-related infections (RR=0.35, 95%CI 0.25 to 0.50, Plt;0.000 01), required rate of surgical intervention (RR=0.43, 95%CI 0.23 to 0.82, P=0.01), and incidence of multiple organ failure (MOF) (RR=0.28, 95%CI 0.17 to 0.46, Plt;0.000 01). There was no significant difference in the nutrition strategies associated complications between TPN and TEN (RR=1.16, 95%CI 0.42 to 3.22, P=0.78). Conclusion Meta-analyses show that compared with TPN, TEN can reduce the risk of mortality, pancreatitis-related infections, required rate of surgical intervention, and incidence of MOF; and it will not increase the nutrition strategies associated complications. Consequently, TEN should be considered a better choice for SAP patients as early as possible.