Treatment Of Acute Pancreatitis Research Articles

COVID-19 and comorbidities: A role for dipeptidyl peptidase 4 (DPP4) in disease severity?

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome (MERS-CoV), which cause acute respiratory distress syndrome and case fatalities. COVID-19 disease severity is worse in older obese patients with comorbidities such as diabetes, hypertension, cardiovascular disease, and chronic lung disease. Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS-CoV binds to the metalloprotease angiotensin-converting enzyme 2 (ACE2), MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. DPP4 is a ubiquitous membrane-bound aminopeptidase that circulates in plasma; it is multifunctional with roles in nutrition, metabolism, and immune and endocrine systems. DPP4 activity differentially regulates glucose homeostasis and inflammation via its enzymatic activity and nonenzymatic immunomodulatory effects. The importance of DPP4 for the medical community has been highlighted by the approval of DPP4 inhibitors, or gliptins, for the treatment of type 2 diabetes mellitus. This review discusses the dysregulation of DPP4 in COVID-19 comorbid conditions; DPP4 activity is higher in older individuals and increased plasma DPP4 is a predictor of the onset of metabolic syndrome. DPP4 upregulation may be a determinant of COVID-19 disease severity, which creates interest regarding the use of gliptins in management of COVID-19. Also, knowledge of the chemistry and biology of DPP4 could be utilized to develop novel therapies to block viral entry of some betacoronaviruses, potentially including SARS-CoV-2.

Treatment of Severe Hypertriglyceridemia-Induced Acute Pancreatitis with Subcutaneous Insulin: Case Report

Treatment of Severe Hypertriglyceridemia-Induced Acute Pancreatitis with Subcutaneous Insulin: Case Report

Clinical Efficacy and Influence of Anticoagulation in the Treatment of Severe Acute Pancreatitis Complicated with Sepsis

Clinical Efficacy and Influence of Anticoagulation in the Treatment of Severe Acute Pancreatitis Complicated with Sepsis

SAT-568 Hypertriglyceridemia-Induced Pancreatitis in a Pregnant Female Treated with Plasmapheresis

Hypertriglyceridemia-Induced Pancreatitis in a Pregnant Female Treated with PlasmapheresisBackground: Gestational hypertriglyceridemia can lead to critical and even life-threatening consequences to both mother and fetus. A well-known consequence is hypertriglyceridemia-induced acute pancreatitis. Few case reports described the successful management of triglyceride (TG) induced pancreatitis in pregnant women using plasmapheresis.Clinical Case:A 28-year-old primigravida patient, in the 29th week of gestation, was admitted with acute onset of epigastric pain and nausea for 24 hours. Laboratory findings were remarkable for an elevated serum lipase of 505 U/L (ref 23–300) and an abnormal lipid profile. Her total cholesterol was 1651 mg/dl and triglycerides (TG) from an undiluted sample was 1361 mg/dl. When a 1:5 dilution was performed the result was higher at >4000 mg/dl. She was transferred to the ICU for treatment of acute pancreatitis. She has no family history of hypertriglyceridemia. No MRI was obtained. Gemfibrozil, Lovaza™ (omega-3-acid ethyl esters), and an insulin infusion were started but serum TG levels did not improve. On hospital day 2 she developed worsening tachycardia, tachypnea with laboratory findings of metabolic acidosis and hypocalcemia. As there was no reduction in triglyceride levels with medical therapy and her clinical status was deteriorating, the treating multidisciplinary team decided to initiate plasmapheresis. After one session, TG levels decreased from >4000 mg/dl to 1829 mg/dl and continued to decline to 721 mg/dl. Hospital day 6 her TG level rose to 1245 mg/dl prompting a second plasmapheresis. TG levels decreased to 770 mg/dl shortly after but rose the next day to 1365 mg/dl. She underwent a 3rd plasmapheresis after which her TG ranged from 400–700 mg/dl for the remainder of her hospitalization. On the day of discharge, her TG level was 733 mg/dl. She was advised to restrict fat intake and continue both gemfibrozil and Lovaza™ but despite this her TGs again increased to 1693 mg/dl. From that point she started weekly sessions of plasmapheresis for a total of 8 sessions prior to an uneventful vaginal delivery at 36 weeks of gestation. One month later her lipid profile dramatically improved. Total cholesterol was 233 mg/dl and triglycerides were 304 mg/dl while on lipid lowering therapy.Conclusion: Pancreatitis during pregnancy is associated with a high maternal and fetal death rate. Early treatment is important for the survival of the mother and fetus. Plasmapheresis is an alternative and safe treatment for cases that are not responsive to medical therapy. It can be administered safely to reduce triglyceride levels and diminish the systemic inflammatory response leading to a shortened hospital stay and better outcomes.

Nitric Oxide Stimulates Acute Pancreatitis Pain via Activating the NF-κB Signaling Pathway and Inhibiting the Kappa Opioid Receptor.

Pain is the most important clinical feature of acute pancreatitis (AP); however, its specific mechanism is currently unclear. In this study, we showed that AP caused an increase in nitric oxide (NO) secretion, activated the NF-κB pathway in the dorsal root ganglia (DRGs), and caused pain. We established an AP model in vivo and tested the expression of NO, the kappa opioid receptor (KOR), and pain factors. We showed that NO in AP was significantly elevated and increased the expression of pain factors. Next, by treating DRGs in vitro, it was found that NO activated the NF-κB pathway; conversely, NF-κB had no effect on NO. Moreover, inhibition of NF-κB promoted the KOR, whereas NF-κB did not change after KOR activation. Finally, behavioral experiments showed that a NO donor increased the pain behavior of mice, while a NO scavenger, NF-κB inhibitor, or KOR agonist attenuated the pain response in mice. These results suggest that iNOS/NO/NF-κB/KOR may be a key mechanism of pain in AP, providing a theoretical basis for the use of peripheral-restricted KOR agonists for pain treatment in AP.

The efficacy of different doses of ulinastatin in the treatment of severe acute pancreatitis.

Severe acute pancreatitis (SAP) is a severe form of inflammatory disease with a high mortality rate. Ulinastatin, a urinary trypsin inhibitor, has anti-inflammatory properties and may be beneficial to critically ill patients with SAP. Nevertheless, there is currently insufficient evidence to conclude whether there is a dose-effect relationship between ulinastatin and SAP treatment outcomes. The present study examined the efficacy of ulinastatin at different doses in the treatment of SAP. A retrospective study was conducted examining the clinical outcomes of 130 SAP patients. Patients were categorized into a control group and three groups receiving different daily doses of ulinastatin (200,000; 400,000; and 600,000 IU). The study compared the 1-week mortality rate; the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score; abdominal pain relief time; time to recover a normal heart and respiratory rate; blood amylase, glucose, C-reactive protein, and procalcitonin levels; and white blood cell (WBC) count among the different groups. The 400,000 and 600,000 IU groups had significantly lower mortality rates and WBC count compared to the 200,000 IU group (P<0.05). Furthermore, the 400,000 IU group had a significantly shorter abdominal pain relief time compared to the 200,000 IU group (P<0.05). Compared to the 200,000 IU group, the 600,000 IU group had significantly shorter time to recover a normal respiratory rate and a lower APACHE-II score (P<0.05). Ulinastatin can improve the clinical outcomes of patients with SAP but efficacy varies with the dosage.

Comparación entre uso y no uso de antibióticos profilácticos en pancreatitis aguda grave. Ensayo Clínico Aleatorizado. Reporte preliminar.

Introducción: La pancreatitis aguda es una enfermedad frecuente en el país, con una tasa de mortalidad de 10-30%. La administración profiláctica de antibióticos ha sido parte del tratamiento de pancreatitis aguda grave (PAG), por la teórica prevención de complicaciones infecciosas y reducción de mortalidad. Sin embargo, la evidencia científica disponible es controversial.Objetivo: Demostrar que los antibióticos profilácticos no disminuyen las complicaciones locales y/o sistémicas, requerimiento de UPC, ni mortalidad en PAG. Definimos PAG como APACHE II ≥ 8 o PCR ≥150 o falla multiorgánica.Material y método: Ensayo clínico aleatorizado, con aleatorización simple mediante tabla electrónica (uso o no uso de antibióticos profilácticos) de pacientes con PAG. En el grupo que usó antibióticos profilácticos se utilizó ciprofloxacino y metronidazol por 7 días. El resto del manejo no tuvo variación.Resultados: n= 71, dos grupos aleatorizados; Grupo 1 (n=35), sin uso de antibióticos profilácticos, y grupo 2 (n=36) con uso de profilaxis antibiótica. 12 pacientes (16%) requirieron UPC; 6 pacientes del grupo 1, y 6 del grupo 2 (p=0,957). Siete pacientes (9,8%) tuvieron algún tipo de complicación, 3 en el grupo 1 y 4 en el grupo 2 (p=0,516). El promedio de estancia hospitalaria fue 18,2 ± 9,5 días en el grupo 1, y 22,6 ± 29.2 días en el grupo 2 (p=0,495). Mortalidad: 1 paciente (1,41%) en el grupo 2 (p= 0,493).Conclusión: En este reporte preliminar, el uso de antibióticos profilácticos en PAG no mostró reducir las complicaciones, necesidad de cama en UPC, ni la mortalidad.

Captopril induced acute pancreatitis: a case report

45 yaşında kadın hasta sırta vuran şiddetli karın ağrısı ile başvurdu ve akut pankreatit tanısıyla interne edildi. Hikayesinde yeni başlayan hipertansiyon nedeniyle iki gün önce bir defa 50 mg kaptopril aldığı ve alkol kullanmadığı öğrenildi. Abdominal ultrasonografide safra kesesi ve safra yollarında patoloji izlenmedi. Serum trigliserid ve IG G4 düzeyleri de normal olan hastada kaptoprile bağlı akut pankreatit düşünüldü. Kaptopril kesilip başka bir grup anti-hipertansif başlanan hasta akut pankreatit tedavisi sonrası taburcu edildi. Kaptoprilin öksürük, anjiyoödem ve böbrek yetmezliği gibi bilinen yan etkilerinin dışında akut pankreatit de yapabileceği akılda tutulmalıdır.

Aqueous extraction from dachengqi formula granules reduces the severity of mouse acute pancreatitis via inhibition of pancreatic pro-inflammatory signalling pathways

Ethnopharmacological relevanceDachengqi decoction (DCQD) belongs to a family of purgative herbal formulas widely used in China for the treatment of acute pancreatitis (AP). AP is a prevalent digestive disease currently without an effective pharmacological intervention. Formula granules have become the preferred method for delivery of herbal formulation in China given its benefit of potency retention, dosing precision and ease of use. The efficacy of DCQD formula granules (DFGs) in experimental AP models has not been investigated. Aim of the studyTo analyse and compare the differences in chemical composition of DFGs, with their aqueous extraction (AE) and chloroform extraction (CE) derivatives. To assess their efficacy on severity and targeted pancreatic pro-inflammatory signalling pathways in freshly isolated acinar cells and two models of experimental AP. Material and methodsUPLC-Q-TOF-MS was used to analyse chemical components of DFGs and their extractions. Freshly isolated mouse pancreatic acinar cells were treated with taurolithocholic acid 3-sulphate disodium salt (TLCS, 500 μM) with or without DFGs, AE and CE. Apoptotic and necrotic cell death pathway activation was measured by caspase 3/7 (10 μl/mL) and propidium iodide (PI, 1 μM), respectively, using a fluorescent plate reader. Necrotic acinar cells were also counted by epifluorescence microscopy. Mice received either 7 intraperitoneal injections of caerulein (50 μg/kg) at hourly intervals or retrograde infusion of TLCS (3 mM, 50 μl) to induce AP (CER-AP and TLCS-AP, respectively). In CER-AP, mice received oral gavage of DFGs (2.1, 4.2 and 5.2 g/kg), AE (0.6, 1.2, and 2.4 g/kg) and CE (4, 9 and 17 mg/kg), or matched DFGs (1.8 g/kg) and AE (1 g/kg) for 3 times at 2-hourly intervals, or a single intraperitoneal injection of DCQD-related monomers rhein (20 mg/kg), narigeinine (25 mg/kg), and honokiol (5 mg/kg) begun at the 3rd injection of caerulein. In TLCS-AP, DFGs (4.2 g/kg) were given orally at 1, 3 and 5 h post-surgery. Disease severity and pancreatic pro-inflammatory markers were determined. ResultsThe main effective anthraquinones and their glycosides, flavonoids and their glycosides, polyphenols and lignans were found in the DFGs. A higher proportion of polar components including glycosides attached to anthraquinones, phenols and flavonoids was found in AE. Conversely, lower polar components containing methoxy substituted flavonoids and anthraquinones were more abundant in CE. DFGs were given at 4.2 g/kg, a consistent reduction in the pancreatic histopathology score and severity indices was observed in both CER-AP and TLCS-AP. In vitro, AE significantly reduced both apoptotic and necrotic cell death pathway activation, while CE increased TLCS-induced acinar cell necrosis. In vivo, AE at dose of 1.2 g/kg consistently reduced pancreatic histopathological scores and myeloperoxidase in the CER-AP that were associated with suppressed expression of pro-inflammatory meditator mRNAs and proteins. CE increased lung myeloperoxidase and failed to protect against CER-AP in all dosages. AE was demonstrated to be more effective than DFGs in reducing pancreatic histopathological scores and myeloperoxidase. ConclusionsAE from DFGs alleviated the severity of mouse AP models via an inhibition of pancreatic pro-inflammatory signalling pathways. Efficacy of AE on experimental AP was more potent than its original DFGs and DCQD monomers.

Protective effects and mechanisms of bilirubin nanomedicine against acute pancreatitis

Acute pancreatitis (AP) is a sudden inflammatory reaction, caused by the activation of pancreatic enzymes in the pancreas, and in severe cases can lead to systemic inflammation and multiple organ failure. Oxidative stress contributed to the further deterioration of inflammation and played an important role in AP development. Bilirubin has been found to exert antioxidative, anti-inflammatory, and anti-apoptotic effects in a series of diseases accompanied by a high level of oxidative stress. However, the therapeutic effects of bilirubin for AP management have not yet been demonstrated. Additionally, the poor solubility and potential toxicity of bilirubin also limit its application. Thus, we developed bilirubin encapsulated silk fibrin nanoparticles (BRSNPs) to study the protective effects and mechanisms of bilirubin nanomedicine for the treatment of AP. BRSNPs could selectively delivery to the inflammatory lesion of the pancreas and release bilirubin in an enzyme-responsive manner. In the model of AP caused by L-Arginine hyperstimulation, BRSNPs exerted strong therapeutic effects against AP by the reduction of oxidative stress, decreased expression of pro-inflammatory cytokines, and impaired recruitment of macrophages and neutrophils. The mechanism study indicated that BRSNPs protected acinar cells against extensive oxidative damage and inflammation through inhibiting NF-κB pathway and activating the Nrf2/HO-1 pathway. Collectively, for the first time, this study demonstrated that bilirubin nanomedicine, BRSNPs, are effective in alleviating experimental acute pancreatitis, and the mechanisms are associated with its inhibition of NF-κB regulated pro-inflammatory signaling and activation of Nrf2-regulated cytoprotective protein expression.

Minimally invasive surgery in the treatment of acute pancreatitis

Background. In recent years, the lethality from acute pancreatitis in Russia has not undergone significant changes and according to various data is from 15% to 25%.&#x0D; Purpose. The evaluation of the performing minimally invasive interventions in the treatment of patients with moderate to severe acute pancreatitis.&#x0D; Materials and methods. The authors retrospectively analyzed the medical records of 169 patients, the structure of mortality and complications depending on the choice of surgical intervention for the patients with acute pancreatitis of moderate and severe degree.&#x0D; Results. Lethal outcomes in the group of patients using minimally invasive interventions amounted to 11.5%, in the group of patients using traditional operations 37.5%, p 0.05. Laparoscopic interventions were effective in 88.8% of the cases, and drug therapy had a positive effect in 81.2% of the cases, p 0.05.&#x0D; Conclusion. It is shown that the use of minimally invasive techniques in the treatment of pancreatic necrosis significantly reduces the levels of mortality, postoperative complications, which improves the overall results of acute pancreatitis treatment.

Anti-lipid therapy and risk factor management for triglyceridaemia-induced acute pancreatitis.

Pancreatitis secondary to hypertriglyceridaemia is rare, accounting for less than 5% of pancreatitis presentations. We reviewed our institutional experience with triglyceridaemia induced acute pancreatitis to report the clinical presentation, patient demographics and clinical management. The Acute Surgical Unit database at a high-volume general surgical referral centre was queried to identify cases of acute pancreatitis secondary to hypertriglyceridaemia between 2016 and 2019. Patient demographics, clinical manifestations, biochemical derangements and treatment regimens were analysed. Current related literature was reviewed. There were 496 presentations for acute pancreatitis of which 14 presentations (2.8%), amongst 12 patients were due to hypertriglyceridaemia. The mean triglyceride level at presentation was 92.46 (standard deviation 46.9) mmol/L. Ten patients (83%) had poorly controlled type 2 diabetes. All patients were managed using conservative therapy combined with a restricted fat diet and commenced on long-term anti-lipid therapy to manage associated risk factors. In addition, 10 patients received an insulin infusion and one patient received insulin infusion, plasmapheresis and heparin infusion in combination. The median length of hospital stay was 5.5 (range 3-13) days. Two patients (16%) developed a recurrent episode related to non-compliance to medical therapy. Hypertriglyceridaemia is a rare cause of acute pancreatitis. Successful management involves the treatment of acute pancreatitis in conjunction with long-term anti-lipid therapy and optimisation of associated risk factors.

Meta-Analysis of Efficacy of Rhubarb Combined With Early Enteral Nutrition for the Treatment of Severe Acute Pancreatitis.

Whether to provide rhubarb combined with early enteral nutrition (rhubarb/EEN) to patients with severe acute pancreatitis (SAP) remains controversial. This study aimed to systematically explore the efficacy and safety of rhubarb/EEN in SAP patients. We performed searches in EMBASE, PubMed, Medline, Cochrane Library, Chinese Biomedicine Literature Database (SinoMed), Chinese Scientific Journal Database (VIP), Chinese National Knowledge Infrastructure (CNKI), and Wanfang database to identify relevant literature comparing rhubarb/EEN with EEN for SAP. Eleven randomized controlled trials (724 patients) were included. Meta-analysis showed significantly shorter length of hospital stay (days) (mean difference [MD], -4.49; 95% CI, -6.09 to -2.90; P < .00001), shorter length of intensive care unit stay (days) (MD, -2.82; 95% CI, -4.00 to -1.64; P < .00001), shorter length of severe abdominal pain (days) (MD, -2.20; 95% CI, -2.50 to -1.90; P < .00001), shorter length of abdominal distention (days) (MD, -2.31; 95% CI, -2.84 to -1.78; P < .00001), shorter length of abnormal bowel sounds (days) (MD, -0.98; 95% CI, -1.12 to -0.88; P < .00001), less hospitalization expenditure ($1422.75/¥ 10,000) (MD, -1.40; 95% CI, -1.23 to -0.73; P < .00001), and smaller Acute Physiology and Chronic Health Evaluation II scores (points) (MD, -2.18; 95% CI, -2.81 to -1.56; P < .00001) in the rhubarb/EEN group than in the EEN group. Compared with EEN, rhubarb/EEN group had lower levels of white blood cells (109 /L) (MD, -2.77; 95% CI, -3.80 to -1.74; P < .00001), C-reactive protein (mg/L) (MD, -10.71; 95% CI, -13.40 to -8.02; P < .00001), and interleukin-6 (ng/L) (MD, -8.02; 95% CI, -11.38 to -4.65; P < .00001). However, there were no significant differences (P > .05) between the 2groups in terms of mortality rate (%) (P = .40), infection rate (%) (P = .28), and incidence of multiple organ dysfunction syndrome (%) (P = .09), but the overall effective rate was higher in the rhubarb/EEN group (MD, 2.57; 95% CI, 1.22 to ≈5.42; P = .01). Combination of EEN and rhubarb may improve the gastrointestinal function, inhibit systemic inflammation and disease severity, and enhance the efficacy of enteral nutrition, leading to better therapeutic effectiveness in SAP patients.

Advanced technologies for treatment of infected pancreatic necrosis: differentiated approach

This work is based on analysis of publications devoted to the problem of surgical approach to treatment of acute pancreatitis over the last 30 years. The main aim of this review is to identify the key steps of evolution of surgical approach to treatment of infected pancreatic necrosis and also to determine the most promising approach among existing methods. The analysis of the most modern clinical recommendations adopted in different countries of the world, as well as the search for such problems, the solution of which will be the main task of world medical science in the near future, is carried out. It has been established that medical communities of different countries give preference to minimally invasive methods of debridement: percutaneous and transluminal endoscopic drainage. According to the most advanced recommendations, the method of choice for surgical treatment of infected pancreatic necrosis is transluminal endoscopic drainage, with inefficiency – percutaneous puncture drainage. The main idea that defines the search vector for treatment methods for the disease is the recognition of the fact that all surgical approaches are aimed at achieving one goal – removing the maximum possible volume of necrotic masses with minimal damage to surrounding tissues. Only a method that satisfies both requirements can be recognized as leading.

Identification of impurities in nafamostat mesylate using HPLC-IT-TOF/MS: A series of double-charged ions

Nafamostat mesylate is a serine protease inhibitor used in the treatment of acute pancreatitis. The impurities in nafamostat mesylate, the active pharmaceutical ingredient (API), were profiled via high performance liquid chromatography tandem ion trap coupled with time-of-flight mass spectrometer (HPLC-IT-TOF/MS). The chromatography was performed on an ACE-3 C18 column (200 mm × 4.6 mm, 3 μm) using methanol and 0.1% formic acid in purified water as mobile phase at a flow rate of 1.0 mL/min. The ions were detected by IT-TOF/MS with a full-scan mass analysis from m/z 100 to 800. In total, eleven impurities were detected in nafamostat mesylate API. The impurity profile was estimated based on the HPLC-IT-TOF/MS data, including accurate masses, MSn fingerprints of fragmentation pathways and a series of double-charged ions. Finally, seven impurities were identified and reported for the first time. The results will provide technical support for the quality control and clinical safety of nafamostat mesylate.

Low molecular weight heparin treatment of acute moderate and severe pancreatitis: A randomized, controlled,open-label study.

Acute pancreatitis (AP) runs a moderately severe and severe course in 20%-30% of cases. The purpose of the present study was to determine the effect of low molecular weight heparin (LMWH) for the prevention of pancreatic necrosis (PN) in moderately severe and severe AP (MSAP). A total of 100 patients with MSAP were randomized to receive either standard care (SC) or SC plus LMWH. LMWH was administered at 1 mg/kg via subcutaneous injection twice a day between days 1 and 7. The revised Atlanta criteria were used in the diagnosis of MSAP. Patients with a Harmless AP Score of >1 and a Balthazar computed tomography (CT) score of D and E were included in the study. The mean age±SD of the patients (46 male and 54 female) was 52±19 years (range, 17-100). There were 50 patients in each group. On admission, clinical and laboratory parameters and Balthazar CT scores were similar between the groups. Initially, PN was present in one patient in the LMWH group and two in the SC group. Over the course, PN developed in 3 (6.1%) patients in the LMWH group and 11 (22.9%) in the SC group (p<0.05). Local and systemic complications were significantly lower in the LMWH group (p<0.05). No hemorrhagic complication occurred. Mortality was not significantly different between the groups (p=0.056). Low molecular weight heparin treatment is safe and provides better prognosis in MSAP.

Material basis and molecular mechanism of Dachengqi Decoction in treatment of acute pancreatitis based on network pharmacology

The network pharmacology was used to investigate the material basis and molecular mechanism of Dachengqi Decoction(DCQD) in the treatment of acute pancreatitis(AP). Potential targets of components from DCQD and relevant pathogenic genes of AP were identified through database retrieval. Then, crucial targets were verified with relevant active chemical components via molecular docking. DAVID database was used to explore the functions and pathways involved in the treatment of AP. A total of 108 components were correlated with 28 targets. Molecular docking showed a strong binding ability of key targets and their corresponding compounds. DAVID enrichment analysis showed 438 biological process, 31 molecular functions, 17 cellular components and 96 KEGG pathways. DCQD may achieve its pharmacological effects through anti-inflammatory and anti-oxidative effects, negative regulation of apoptosis and regulation of pancreatic secretion, involving multiple signals, such as IL-17, TNF and NF-κB signaling pathway. In this study, it is the first time to use the method of network pharmacology to reveal the molecular mechanism of DCQD in the treatment of AP by multiple components and multi-signaling pathways, which provides a basis for further biological experiments of AP.

Overexpression of Nrf2 Protects Against Lipopolysaccharide and Cerulein-Induced Pancreatitis In Vitro and In Vivo.

In this study, we focused on the function of nuclear factor E2-related factor 2 (Nrf2) in acute pancreatitis (AP), which has been shown to have protective effects in gliomas, hepatocytes, and astrocytes. Acute pancreatitis cell line and animal model were induced by administration of lipopolysaccharide and cerulein into the cell supernatant or intraperitoneal injection. Oxidative stress status was evaluated by measuring the level of amylase, C-reactive protein, malondialdehyde, superoxide dismutase, and myeloperoxidase. Morphological alterations in the pancreas were evaluated by hematoxylin-eosin staining, the wet-to-dry weight ratio, and the pathology injury scores. Western blot, reverse transcription-polymerase chain reaction, and immunofluorescence staining were performed to analyze the expression of Nrf2, Heme oxygenase 1, and NAD(P)H: quinone oxidoreductase 1. Overexpression of Nrf2 inhibits oxidative stress and inflammatory responses by inducting the expression of superoxide dismutase as well as reducing the level of amylase, malondialdehyde, and myeloperoxidase in the AR42J rat pancreatic acinar cells in AP. Importantly, overexpression of Nrf2 displayed the same protective effect in vivo. Data from an AP rat model showed that Nrf2 could relieve pancreatic damage. These results indicated that Nrf2 has a protective role in lipopolysaccharide and cerulein-induced cytotoxicity, providing potential therapeutic strategies for the treatment of AP.

The role of Th17 cells and cytokines in the diagnosis and treatment of acute pancreatitis

Objective To study the role of Th17 cells proportions and the cytokines levels in the diagnosis and treatment of acute pancreatitis (AP). Methods Patients with AP (n=82) treated in our hospital between August 2017 and August 2018 were divided into the mild AP group (MAP, n=36), the moderately severe AP group (MSAP, n=26) and the severe AP group (SAP, n=20). Twenty-five healthy subjects were chosen as the control group. The proportions of Th17 cells and the levels of cytokines including IL-17, IL-21, IL-22 and IL-23 in peripheral blood from the four groups were analyzed. The APACHE II and Ranson scores were used to evaluate the illness severity. Spearman correlation analysis was conducted to detect the correlation between the Th17 cells, cytokines, and inflammatory factor, APACHE II and Ranson scores. Results Compared with the control group, the proportion of Th17 cells and the levels of IL-17, IL-21, IL-22 and IL-23 in the peripheral blood of MAP, MSAP and SAP groups were significantly increased (SAP>MSAP>MAP, P<0.05). The levels of inflammatory cytokines IL-6, IL-8 and TNF-α, and the scores of APACHE II and Ranson in the SAP group were significantly higher than those in the MSAP group and MAP group (P<0.05). The proportion of Th17 cells and their cytokine levels were positively correlated with IL-6, IL-8, TNF-α, APACHE II and Ranson scores. The levels of Th17 cytokines returned to normal in AP patients after treatment. Conclusion Th17 cells and the cytokines have certain clinical significance in evaluating early inflammatory response, severity of illness, and therapeutic effect in AP patients. Key words: Pancreatitis, acute; Th17 cells; Cytokines; Inflammatory response; Disease assessment

Current trends in pharmacological approaches for treatment and management of acute pancreatitis - a review.

Acute pancreatitis (AP) is an inimical disorder associated with overall mortality rates between 10-15%. It is a disorder of the exocrine pancreas which is characterized by local and systemic inflammatory responses primarily driven by oxidative stress and death of pancreatic acinar cells. The severity of AP ranges from mild pancreatic edema with complete recuperative possibilities to serious systemic inflammatory response resulting in peripancreatic/pancreatic necrosis, multiple organ failure, and death. We have retrieved the potential alternative approaches that are developed lately for efficacious treatment of AP from the currently available literature and recently reported experimental studies. This review summarizes the need for alternative approaches and combinatorial treatment strategies to deal with AP based on literature search using specific key words in PubMed and ScienceDirect databases. Since AP results from perturbations of multiple signaling pathways, the so called "monotargeted smart drugs" of the past decade is highly unlikely to be effective. Also, the conventional treatment approaches were mainly involved in providing palliative care instead of curing the disease. Hence, many researchers are beginning to focus on developing alternate therapies to treat AP effectively. This review also summarizes the recent trends in the combinatorial approaches available for AP treatment.