Senna petersiana inhibits key digestive enzymes and modulates dysfunctional enzyme activities in oxidative pancreatic injury

Objective:To evaluate the effect of Senna petersiana leaf extracts on key digestive enzymes and FeSO_(4)-induced oxidative injury.Methods:Dried Senna petersiana leaf powder(60 g)was defatted in n-hexane and then extracted sequentially at room temperature with dichloromethane,methanol,and distilled water.The total phytochemical content of the extracts was estimated using established methods.The in vitro antioxidant,anti-lipase,and antidiabetic activities and the effect of the extracts on intestinal glucose absorption and FeSO_(4)-induced pancreatic oxidative injury were determined using different protocols.Moreover,GC-MS analysis was performed to identify the main compounds of the plant extract.Molecular docking analysis was also carried out to evaluate the binding energy of compounds with digestive enzymes.Results:Senna petersiana leaf extracts showed significant antioxidant activities in FRAP,DPPH,and hydroxyl radical scavenging assays.They also inhibited pancreatic lipase and lowered intestinal glucose absorption by suppressing activities ofα-amylase andα-glucosidase.Treatment with the extracts also lowered lipid peroxidation(malondialdehyde),nitric oxide level,acetylcholinesterase,and ATPase activities with simultaneous improvement of antioxidant(catalase,superoxide dismutase,glutathione)capacity in the type 2 diabetes model of oxidative pancreatic injury.GC-MS characterization of the extracts revealed the presence of stilbenoids,alkaloids,and other compounds.Molecular docking screening assay indicated the extract phytochemicals showed strong interaction with the active site amino acids of the targeted digestive enzymes.Among the Senna petersiana compounds,veratramine had the highest affinity forα-amylase and lipase,whereas dihydrostilbestrol was most attracted toα-glucosidase.Conclusions:Senna petersiana inhibits carbohydrate digestive enzymes,reduces intestinal glucose absorption,and exerts ameliorative effects on FeSO_(4)-induced oxidative pancreatic injury with significant antioxidant capabilities.Detailed in vivo studies are underway to understand the plant's therapeutic potential in diabetes management.

Diagnosis and Treatment of 42 Cases of Multiple Injuries with Pancreatic Injury

In order to summarize the clinical diagnosis and treatment methods for 42 cases of multiple injuries with pancreatic injury, a retrospective analysis on 42 cases of multiple injuries with pancreatic injury from January 1990 to January 2006 was carried out in our hospital. Most cases were associated with hemopneumothorax and rib fractures （52.3%）, shock （50%）, multiple fractures （47.6%）, and severe brain injury （26.1%）. In 42 cases, one case died of severe hemorrhagic shock, and the remaining 41 cases （97.6%） were cured （including 40 cases receiving surgical operation and one case receiving the conservative treatment）. Postoperative complications occurred in 16 cases （21 cases/times）： pancreatic fistula （5 cases/times） and incisional wound infection （5 cases/times）, intra-abdominal infection （3 cases/times）, stress ulcer （3 cases/times）, pleural effusion （3 cases/times）, pulmonary infection （one case） and wound dehiscence （1 case）. The principle therapy of multiple injuries with pancreatic injury is to rescue life, followed by active treatment to prevent injuries which giving rise to the abnormal respiratory and circulatory functions, management of cerebral hernia and other injuries which endangers life at last, and the pancreatic injury to increase the survival rate and survival quality.

Blunt Abdominal Trauma Leading to Pancreatic Injury in Childhood. Delay in Diagnosis Leads to Poor Outcomes—A Case Presentation

This case report illustrates the difficulty in diagnosing paediatric patients with life threatening pancreatic injuries. A high index of suspicion is essential as late diagnosis significantly affects outcomes. A 9-year-old child presented with epigastric pain following an accident on his pushbike. The patient was examined in paediatric accident and emergency (A/E) and was discharged. He returned twice more to A/E and on the third visit, 5 days after the initial incident, a CT scan was performed. This showed a classical injury to the body of the pancreas with a collection in the lesser sac. The patient was transferred to the regional hepato-pancreato-biliary unit (HPB unit) and underwent surgery. Pancreatic injuries can be difficult to detect clinically and patients may be well on initial presentation with normal observations and routine bloods. Early CT scanning confirms the diagnosis and results in early specialist referral and better outcomes.

Traumatic pancreatic ductal injury treated by endoscopic stenting in a 9-year-old boy:A case report

BACKGROUND Traumatic pancreatic injury is relatively rare in children,accounting for approximately 3%-12%of blunt abdominal trauma cases.Most traumatic pancreatic injuries in boys are related to bicycle handlebars.Traumatic pancreatic injuries often result in delayed presentation and treatment,leading to high morbidity and mortality.The management of children with traumatic main pancreatic duct injuries is still under debate.CASE SUMMARY We report the case of a 9-year-old boy who was presented at our institution with epigastric pain after being stuck with his bicycle handlebar at the upper abdomen and then treated with endoscopic stenting because of a pancreatic ductal injury.CONCLUSION We believe that endoscopic stenting of pancreatic ductal injuries may be a feasible technique in certain cases of children with traumatic pancreatic duct injuries to avoid unnecessary operations.

Relationship between Carbachol Hyperstimulation-Induced Pancreatic Acinar Cellular Injury and Trypsinogen or NF-κB Activation in Rats in vitro

The relationship between M3 cholinergic receptor agonist （carbachol） hyperstimulationinduced pancreatic acinar cellular injury and trypsinogen activation or NF-κB activation in rats was studied in vitro. Rat pancreatic acinar ceils were isolated, cultured and treated with carbachol, the active protease inhibitor （pefabloc）, and NF-κB inhibitor （PDTC） in vitro. Intracellular trypsin activity was measured by using a fluorogenic substrate. The cellular injury was evaluated by measuring the leakage of LDH from pancreatic acinar ceils. The results showed that as compared with control group, 10-3 mol/L carbachol induced a significant increase of the intracellular trypsin activity and the leakage of LDH from pancreatic acinar cells. Pretreatment with 2 mmol/L pefabloc could significantly decrease the activity of trypsin and the leakage of LDH from pancreatic acinar cells （P〈0. 01） following the treatment with a high concentration of carbachol （10^-3 mol/L） in vitro. The addition of 10^-2mol/L PDTC didn＇t result in a significant decrease in the activity of trypsin and the leakage of LDH from pancreatic acinar cells treated with a high concentration of carbachol （10^-3 mol/L） in vitro （P〉0. 05）. It was concluded that intracellular trypsinogen activation is likely involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro. NF-κB activation may not be involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro.

Lipase and pancreatic amylase activities in diagnosis of acute pancreatitis in patients with hyperamylasemia

BACKGROUND: Measurement of total serum amylase (AMY) is the most widely used biochemical test for the diagnosis of acute pancreatitis, but it is commonly considered a nonspecific marker. To improve the biochemical diagnosis of acute pancreatitis, lipase ( LIP ) and pancreatic amylase (PAMY) have been tested in recent years. The present study was designed to evaluate whether serum LIP and pancreatic PAMY tests could replace total amylase test to improve diagnostic efficiency in the evaluation of acute pancreatitis in patients with hyperamylasemia. METHODS: LIP and PAMY values were determined in serum samples from 92 patients with hyperamylasemia. Reference values for each enzyme were derived from serum samples of 147 healthy subjects. The activities of LIP and PAMY in patients with various diseases were shown directly by the boxplot graph. The diagnostic accuracy of LIP and PAMY was defined as the area under the receiver operating characteristic (ROC) curve. Their sensitivity and specificity in detecting acute pancreatitis at varying cutoff points were shown by the curve, and the best cutoff value for each enzyme was shown by the modified ROC curve. The diagnostic values of LIP, PAMY and LIP + AMY with each upper limit of reference range (ULR) were compared with the corresponding best cutoff values. RESULTS: The references values of LIP and PAMY were 12.2-47.6 U/L and 28-95 U/L, respectively. These values in patients with acute pancreatitis were higher than those patients with other diseases. The areas under the ROC curve ( AUC) of LIP and PAMY were 0. 799 and 0. 792, respectively, With the best diagnostic cutoff point of maximum (sensitivity + specificity) -100%, we obtained values of 97.9 U/L(LIP97.9 =2. 06 × ULR) for LIP and 209 U/L (PAMY209 =2.20 ×ULR) for PAMY. The best cutoff values for LIP, PAMY and LIP +AMY demonstrated the specificity, positive predictive value, and diagnostic efficiency higher than the corresponding ULRs. CONCLUSIONS: Serum LIP and PAMY are specific for the pancreas and might replace total amylase for the diagnosis of acute pancreatitis in hyperamylasemia patients. LIP97.9 is more efficient than PAMY209 in the diagnosis of acute pancreatitis. A combined test of both enzymes is not superior to single test of either enzyme in diagnostic accuracy.

Feasibility and safety of “bridging” pancreaticogastrostomy for pancreatic trauma in Landrace pigs

BACKGROUND In recent years,we created and employed a new anastomosis method,“bridging”pancreaticogastrostomy,to treat patients with extremely severe pancreatic injury.This surgery has advantages such as short length of surgery,low secondary trauma,rapid construction of shunts for pancreatic fluid,preventing second surgeries,and achieving good treatment outcomes in clinical practice.However,due to the limited number of clinical cases,there is a lack of strong evidence to support the feasibility and safety of this surgical procedure.Therefore,we carried out animal experiments to examine this procedure,which is reported here.AIM To examine the feasibility and safety of a new rapid method of pancreaticogastrostomy,“bridging”pancreaticogastrostomy.METHODS Ten Landrace pigs were randomized into the experimental and control groups,with five pigs in each group.“Bridging”pancreaticogastrostomy was performed in the experimental group,while routine mucosa-to-mucosa pancreaticogastrostomy was performed in the control group.After surgery,the general condition,amylase levels in drainage fluid on Days 1,3,5,and 7,fasting and 2-h postprandial blood glucose 6 mo after surgery,fasting,2-h postprandial peripheral blood insulin,and portal vein blood insulin 6 mo after surgery were assessed.Resurgery was carried out at 1 and 6 mo after the former one to examine the condition of the abdominal cavity and firmness and tightness of the pancreaticogastric anastomosis and pancreas.RESULTS After surgery,the general condition of the animals was good.One in the control group did not gain weight 6 mo after surgery,whereas significant weight gain was present in the others.There were significant differences on Days 1 and 3 after surgery between the two groups but no differences on Days 5 and 7.There were no differences in fasting and 2-h postprandial blood glucose and fasting and 2-h insulin values of postprandial peripheral blood and portal vein blood 6 mo after surgery between the two groups.One month after surgery,the sinus tract orifice/anastomosis was patent in the two groups.Six months after surgery,the sinus tract orifice/anastomosis was sealed,and pancreases in both groups presented with chronic pancreatitis.CONCLUSION“Bridging”pancreaticogastrostomy is a feasible and safe a means of damage control surgery during the early stage of pancreatic injury.

Indications for the surgical management of pancreatic trauma: An update

Pancreatic trauma is rare compared to other abdominal solid organ injuries,accounting for 0.2%-0.3% of all trauma patients. Moreover, this type of injury may frequently be overlooked or not readily appreciated on initial clinical examinations and investigations. The organ injury scale determines the severity of the trauma. Nonetheless, there are conflicting recommendations for the best strategy in severe cases. Overall, conservative management of induced severe traumatic pancreatitis is adequate. Modern imaging modalities such as ultrasound scanning and computed tomography scanning can detect injuries in fewer than 60% of patients. However, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography(ERCP) have diagnostic accuracies approaching 90%-100%. Thus, management options include ERCP and stent placement or distal pancreatectomy in cases of complete gland transection and wide drainage only for damage control surgery, which can prevent mortality but increases the risk of morbidity. In the majority of cases, surgical intervention is not required and should be reserved for only severe grade Ⅲ to grade Ⅴ injuries.

Intraoperative endoscopic retrograde cholangiopancreatography for traumatic pancreatic ductal injuries:Two case reports

BACKGROUND In order to successfully manage traumatic pancreatic duct(PD)leaks,early diagnosis and operative management is paramount in reducing morbidity and mortality.In the acute setting,endoscopic retrograde cholangiopancreatography(ERCP)can be a useful,adjunctive modality during exploratory laparotomy.ERCP with sphincterotomy and stent placement improves preferential drainage in the setting of injury,allowing the pancreatic leak to properly heal.However,data in this acute setting is limited.CASE SUMMARY In this case series,a 27-year-old male and 16-year-old female presented with PD leaks secondary to a gunshot wound and blunt abdominal trauma,respectively.Both underwent intraoperative ERCP within an average of 5.9 h from time of presentation.A sphincterotomy and plastic pancreatic stent placement was performed with a 100%technical and clinical success.There were no associated immediate or long-term complications.Following discharge,both patients underwent repeat ERCP for stent removal with resolution of ductal injury.CONCLUSION These experiences further demonstrated that widespread adaption and optimal timing of ERCP may improve outcomes in trauma centers.

Clinical diagnosis and surgical treatment of pancreatic and/or duodenal injuries

Objective: To investigate the points of the clinical diagnosis and surgical treatment for pancreatic and/or duodenal injuries. Methods: Clinical data of 30 patients who suffered from pancreatic and/or duodenal injuries were reviewed. Results: There were 29 cases who received surgical management. Of the 30 cases, 22 cases were cured, seven cases died, and postoperative complications occurred in 16 cases. The cure rate was 73.3%. Conclusion: Pancreatic and/or duodenal injuries are severe abdominal injuries and difficult to treat. The mortality and complication rate are high. The keys to successful treatments for pancreatic and/or duodenal injuries are early diagnosis, careful exploration and proper operational management.

A novel machine learning-assisted clinical diagnosis support model for early identification of pancreatic injuries in patients with blunt abdominal trauma:a cross-national study

Background:The recognition of pancreatic injury in blunt abdominal trauma is often severely delayed in clinical practice.The aim of this study was to develop a machine learning model to support clinical diagnosis for early detection of abdominal trauma.Methods:We retrospectively analyzed of a large intensive care unit database(Medical Information Mart for Intensive Care[MIMIC]-IV)for model development and internal validation of the model,and performed outer validation based on a cross-national data set.Logistic regres-sion was used to develop three models(PI-12,PI-12-2,and PI-24).Univariate and multivariate analyses were used to determine variables in each model.The primary outcome was early detection of a pancreatic injury of any grade in patients with blunt abdominal trauma in the first 24 hours after hospitalization.Results:The incidence of pancreatic injuries was 5.56%(n=18)and 6.06%(n=6)in the development(n=324)and internal validation(n=99)cohorts,respectively.Internal validation cohort showed good discrimination with an area under the receiver operator characteristic curve(AUC)value of 0.84(95%confidence interval[CI]:0.71–0.96)for PI-24.PI-24 had the best AUC,specificity,and positive predictive value(PPV)of all models,and thus it was chosen as the final model to support clinical diagnosis.PI-24 performed well in the outer validation cohort with an AUC value of 0.82(95%CI:0.65–0.98),specificity of 0.97(95%CI:0.91–1.00),and PPV of 0.67(95%CI:0.00–1.00).Conclusion:A novel machine learning-based model was developed to support clinical diagnosis to detect pancreatic injuries in patients with blunt abdominal trauma at an early stage.

A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses

Acute pancreatitis(AP)is a devastating disease characterized by an inflammatory disorder of the pancreas.P-selectin glycoprotein ligand-1(PSGL-1)plays a crucial role in the initial steps of the adhesive at process to inflammatory sites,blockade of PSGL-1 might confer potent anti-inflammatory effects.In this study,we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1,RH001-6 and RH001-22,which were screened from immunized rhesus macaques.We found that RH001-6,can effectively block the binding of P-selectin to PSGL-1,and abolish the adhesion of leukocytes to endothelial cells in vitro.In vivo,we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and L-arginine induced AP models.We also evaluated the safety profile after RH001-6 treatment in mice,and verified that RH001-6 did not cause any significant pathological damages in vivo.Taken together,we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity,named RH001-6,which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP.Therefore,RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases,such as AP.