Project description:Purpose: The purpose of this study was to compare the hepatic transcriptome in the control group, acute pancreatitis, and severe acute pancreatitis, in order to identify metabolic gene changes during pancreatitis. Methods: 6-week Balb/c mice were subjected to AP (caerulein), SAP (caerulein and LPS) and control (saline), and mice liver tissues were harvested at 24 hours for RNA preparation (n=8 each group). Results: Among 11952 mapped genes, 8977 differentially expressed genes were identified by RNA-seq, including 351 genes induced in AP compare to Control and 5249 genes down regulated in SAP compare to AP. The genes up regulated were mainly related to fatty acid oxidation and ketone body synthesis especially Cpt2 and Acadvl, while genes that down regulated were associated with energy metabolism and inflammation. The overlap of two gene sets were 96 genes that involved in fatty acid metabolism. Conclusions: Our study revealed that in AP, genes associated with ketone body synthesis are upregulated in liver, in SAP, fatty acid oxidation related genes are downregulated in liver. Our data revealed the crosstalk between pancreas and liver, illustrated the difference of metabolism in AP and SAP.
Project description:Purpose of reviewThere have been significant advancements in different aspects of management of severe acute pancreatitis (SAP). Our review of the most recent literature focuses on severity prediction, fluid resuscitation, analgesic administration, nutrition, and endoscopic intervention for SAP and its extra-pancreatic complications.Recent findingsRecent studies on serum cytokines for the prediction of SAP have shown superior prognostic performance when compared with conventional laboratory tests and clinical scoring systems. In patients with established SAP and vascular leak syndrome, intravenous fluids should be administered with caution to prevent intra-abdominal hypertension and volume overload. Endoscopic retrograde cholangiopancreatography improves outcomes only in AP patients with suspected cholangitis. Early enteral tube-feeding does not appear to be superior to on-demand oral feeding. Abdominal compartment syndrome is a highly lethal complication of SAP that requires percutaneous drainage or decompressive laparotomy. Endoscopic transmural drainage followed by necrosectomy (i.e., "step-up approach") is the treatment strategy of choice in patients with symptomatic or infected walled-off pancreatic necrosis.SummarySAP is a complex clinical syndrome associated with a high mortality rate. Early prediction of SAP remains challenging due to the limited accuracy of the available prediction tools. Early fluid resuscitation, organ support, enteral nutrition, and prevention of/or prompt recognition of abdominal compartment syndrome remain cornerstones of its management. A step-up, minimally invasive drainage/debridement is the preferred approach for patients with infected pancreatic necrosis.
Project description:BACKGROUND: Proteinuria is a characteristic feature of severe acute pancreatitis (SAP) that may allow unique insights into AP pathophysiology. This study used a proteomic approach to differentiate the abundant urinary proteins in AP patients. MATERIALS AND METHODS: Urine samples were prospectively collected from 4 groups (5 SAP, 10 mild gallstone AP, 7 mild alcohol AP, 7 controls). Reverse-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (LC MALDI) were used to identify urinary proteins and determine any differences between the groups. RESULTS: There were 17 RP-HPLC major peaks in SAP groups of significantly greater absorbance magnitude than the corresponding ones in mild and control groups. Various mass spectrometry methods were used to identify 21 different parent proteins from these SAP peaks. They included fibrinogen, serum amyloid A, insulin and calcitonin gene-related peptides. There were no identifiable protein peaks at the corresponding elution times in the mild pancreatitis and controls samples. DISCUSSION: Proteomic techniques offer a unique unexplored window into AP pathophysiology. The utility of these proteins as markers of pancreatitis severity now need to be further investigated and the identification extended to the full urinary proteome as technology permits.
Project description:AimTo assess the rate of spontaneous tube migration and to compare the effects of naso-gastric and naso-intestinal (NI) (beyond the ligament of Treitz) feeding in severe acute pancreatitis (SAP).MethodsAfter bedside intragastric insertion, tube position was assessed, and enteral nutrition (EN) started at day 4, irrespective of tube localization. Patients were monitored daily and clinical and laboratory parameters evaluated to compare the outcome of patients with nasogastric (NG) or NI tube.ResultsSpontaneous tube migration to a NI site occurred in 10/25 (40%) prospectively enrolled SAP patients, while in 15 (60%) nutrition was started with a NG tube. Groups were similar for demographics and pancreatitis aetiology but computed tomography (CT) severity index was higher in NG tube patients than in NI (mean 6.2 vs 4.7, P = 0.04). The CT index seemed a risk factor for failed obtainment of spontaneous distal migration. EN trough NG or NI tube were similar in terms of tolerability, safety, clinical goals, complications and hospital stay.ConclusionSpontaneous distal tube migration is successful in 40% of SAP patients, with higher CT severity index predicting intragastric retention; in such cases EN by NG tubes seems to provide a pragmatic alternative opportunity with similar outcomes.
Project description:Purpose: The purpose of this study was to compare the hepatic transcriptome in the control group and severe acute pancreatitis, in order to identify metabolic gene changes during pancreatitis. Methods: 6-week Balb/c mice were subjected to control (Saline*12) and SAP (caerulein *12), and mice liver tissues were harvested at 24 hours for RNA preparation (n=6 each group). Results: Among 18257 mapped genes, 3639 differentially expressed genes were identified by RNA-seq, including 1714 genes induced in SAP compare to Control and 1892 genes down regulated in SAP compare to Control. The genes up regulated were mainly related to immune response and ER stress, while genes that down regulated were associated with fatty acids oxidation and oxidative phosphorylation. Conclusions: Our study revealed that in SAP, genes associated with immune response are upregulated in liver, fatty acid oxidation related genes are downregulated in liver. Our data revealed the crosstalk between pancreas and liver, illustrated the change of liver metabolism in SAP.
Project description:IntroductionSevere acute pancreatitis (AP) is associated with high morbidity and mortality. Early prediction of severe AP is needed to improve patient outcomes. The aim of the present study was to find novel cytokines or combinations of cytokines that can be used for the early identification of patients with AP at risk for severe disease.MethodsWe performed a prospective study of 163 nonconsecutive patients with AP, of whom 25 had severe AP according to the revised Atlanta criteria. Admission serum levels of 48 cytokines and growth factors were determined using Bio-Plex Pro Human Cytokine Assay 21-plex and 27-plex magnetic bead suspension panels. Admission plasma levels of C-reactive protein (CRP), creatinine and calcium were measured for comparison. In subgroup analyses, we assessed the cytokine profiles of patients with severe AP (n = 14) who did not have organ dysfunction (OD) upon admission (modified Marshall score <2).ResultsOf 14 cytokines elevated in the severe AP group, interleukin 6 (IL-6) and hepatocyte growth factor (HGF) levels were independent prognostic markers of severe AP. IL-6, HGF and a combination of them predicted severe AP with sensitivities of 56.0%, 60.0% and 72.0%, respectively, and specificities of 90.6%, 92.8% and 89.9%, respectively. The corresponding positive likelihood ratio (LR+) values were 5.9, 8.3 and 7.1, respectively. The predictive values of CRP, creatinine and calcium were comparable to those of the cytokines. In subgroup analyses of patients with severe AP and without OD upon admission, we found that IL-8, HGF and granulocyte colony-stimulating factor (G-CSF) levels predicted the development of severe AP, with G-CSF being the most accurate cytokine at a sensitivity of 35.7%, a specificity of 96.1% and a LR+ of 9.1.ConclusionsIL-6 and HGF levels upon admission have prognostic value for severe AP which is similar to levels of CRP, creatinine and calcium. Although IL-6 and HGF, as either single or combined markers, were not perfect in identifying patients at risk for severe AP, the possibility that combining them with novel prognostic markers other than cytokines might improve prognostic accuracy needs to be studied. The accuracy of IL-8, HGF and G-CSF levels in predicting severe AP in patients without clinical signs of OD upon admission warrants larger studies.
Project description:Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM's active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy.
Project description:Study the serum miRNA expression profiles in hypertriglyceridemia induced acute pancreatitis and report a possible role of circulating miRNAs as biomarker in the progression of HTAP.