To further evaluate the role of hepatocyte-derived damage-associated molecules in inflammasome activation and potential cross-talk between hepatocytes and mononuclear cells, we tested whether PA-treated hepatocytes could induce inflammasome activation in inflammatory cells. Hepatocytes Doxorubicin supplier were treated with PA for 6 hours and then were cultured in fresh media without PA. We found that these PA-free supernatants from PA-pretreated hepatocytes induced up-regulation of NALP3 (Fig. 7D) and IL-1β mRNA (Fig. 7E) in LMNCs; this suggests that FA-exposed hepatocytes can transfer activation to surrounding immune cells. The transmission of hepatocyte-derived

danger signals to mononuclear cells was dependent on caspase activation in hepatocytes;

this was suggested by the lack of LMNC activation with hepatocyte supernatants when ZVAD was added together with PA to hepatocytes (Fig. 7D,E). These results suggest that hepatocytes are the first target of FAs and produce inflammasome-mediated danger signals, which in turn activate macrophages in a caspase-dependent manner. The pathogenesis of steatosis and inflammation in NASH has been linked to multiple mechanisms,3 such as oxidative stress, mitochondrial damage in hepatocytes, and gut-derived LPS.7-9 Inflammation is a response to cellular injury and pathogens, and it is triggered by endogenous and exogenous danger signals, respectively. NALPs, the receptor components of the inflammasome, sense endogenous danger signals, which up-regulate the inflammasome, a multiprotein complex involved in caspase-1–mediated this website IL-1 cleavage. Inflammasome activation is typically a result of two signals via TLR activation 上海皓元医药股份有限公司 by exogenous or endogenous danger signals.10 Here we report several findings related to the novel role of inflammasome activation

in NASH. First, we describe up-regulation of the components of the NALP3 inflammasome (including NALP3, ASC, and pro–caspase-1) in mouse models of NASH and in human livers, and we demonstrate functional activation via caspase-1 activation and IL-1β production. Our data also suggest that inflammasome activation occurs in steatohepatitis and not in early steatosis in mice. Second, we report that although increased levels of circulating endotoxin likely contribute to inflammasome activation, exogenous LPS can amplify inflammasome activation and IL-1β secretion in steatohepatitis. Third, we demonstrate for the first time that inflammasome activation and IL-1β secretion occur in isolated hepatocytes in NASH. We reveal mechanistic insights into inflammasome activation and show that saturated FAs (but not unsaturated FAs) increase inflammasome expression and sensitize hepatocytes to IL-1β release by a second stimulus via TLR4 activation. Our novel data show that FAs not only up-regulate the inflammasome but also induce apoptosis and the release of danger signals in hepatocytes.

To further evaluate the role of hepatocyte-derived damage-associated molecules in inflammasome activation and potential cross-talk between hepatocytes and mononuclear cells, we tested whether PA-treated hepatocytes could induce inflammasome activation in inflammatory cells. Hepatocytes CP-673451 mouse were treated with PA for 6 hours and then were cultured in fresh media without PA. We found that these PA-free supernatants from PA-pretreated hepatocytes induced up-regulation of NALP3 (Fig. 7D) and IL-1β mRNA (Fig. 7E) in LMNCs; this suggests that FA-exposed hepatocytes can transfer activation to surrounding immune cells. The transmission of hepatocyte-derived

danger signals to mononuclear cells was dependent on caspase activation in hepatocytes;

this was suggested by the lack of LMNC activation with hepatocyte supernatants when ZVAD was added together with PA to hepatocytes (Fig. 7D,E). These results suggest that hepatocytes are the first target of FAs and produce inflammasome-mediated danger signals, which in turn activate macrophages in a caspase-dependent manner. The pathogenesis of steatosis and inflammation in NASH has been linked to multiple mechanisms,3 such as oxidative stress, mitochondrial damage in hepatocytes, and gut-derived LPS.7-9 Inflammation is a response to cellular injury and pathogens, and it is triggered by endogenous and exogenous danger signals, respectively. NALPs, the receptor components of the inflammasome, sense endogenous danger signals, which up-regulate the inflammasome, a multiprotein complex involved in caspase-1–mediated Roxadustat ic50 IL-1 cleavage. Inflammasome activation is typically a result of two signals via TLR activation MCE by exogenous or endogenous danger signals.10 Here we report several findings related to the novel role of inflammasome activation

in NASH. First, we describe up-regulation of the components of the NALP3 inflammasome (including NALP3, ASC, and pro–caspase-1) in mouse models of NASH and in human livers, and we demonstrate functional activation via caspase-1 activation and IL-1β production. Our data also suggest that inflammasome activation occurs in steatohepatitis and not in early steatosis in mice. Second, we report that although increased levels of circulating endotoxin likely contribute to inflammasome activation, exogenous LPS can amplify inflammasome activation and IL-1β secretion in steatohepatitis. Third, we demonstrate for the first time that inflammasome activation and IL-1β secretion occur in isolated hepatocytes in NASH. We reveal mechanistic insights into inflammasome activation and show that saturated FAs (but not unsaturated FAs) increase inflammasome expression and sensitize hepatocytes to IL-1β release by a second stimulus via TLR4 activation. Our novel data show that FAs not only up-regulate the inflammasome but also induce apoptosis and the release of danger signals in hepatocytes.

PHH treatment by the grapefruit flavonoid naringenin, known to inhibit MTP activity indirectly through a PPARα-mediated mechanism,

also led to a significant reduction of infectious HCV production without any detectable cytotoxic effect. Interestingly, no parallel GW-572016 molecular weight decrease of either ApoB or ApoE secretion was observed in this case. Conclusion. These data in differentiated human hepatocytes confirm that MTP function is indeed required for production of infectious HCV, yet this requirement may not necessarily involve the role of this enzyme in ApoB lipidation. MTP inhibitors developed primarily for the treatment of lipid metabolism disorders also appear as promising host-targeting buy Erlotinib drugs to combat HCV infection in complement with directly acting

antivirals. Disclosures: The following people have nothing to disclose: Veronique M. Pene, Arielle R. Rosenberg Background and aims: Hepatitis E virus (HEV) is a major cause of epidemic and acute sporadic hepatitis in many developing countries. HEV is believed to undergo zoonotic transmission, with a reservoir in pigs, in industrialized countries. We have recently demonstrated in vitro infection and replication of swine HEV in primary-cultured human hepatocytes, using a genotype 3 HEV. Previous reports demonstrated that genetic changes were found in HEV progenies in the course of its habituation in human cancer line cells, which may bring change of HEV infection spectrum. Therefore, we investigated mutational events and mode of swine HEV infection and replication in the primary-cultured human hepatocytes. Methods: Hepatocytes were primary cultured from the resected normal liver of patients with metastic malignant 上海皓元医药股份有限公司 tumor using collagenase treatment, and the cultured hepatocytes were infected with HEVs (genotype 3) derived from swine. Viral replication was monitored by a strand-specific reverse transcription-polymerase chain reaction assay. Viral replication sites in cells were investigated with in situ hybridization (ISH). Immunofluorescence assay was performed using antibody against HEV 〇RF2 antigen.

In addition, the sequences of propagated and inoculated HEV were determined in order to examine whether propagation of swine HEV in the primary-cultured human hepatocytes generate base change in HEV sequence. Results: The HEV RNA increased in cultured medium as well as in cells after infection of HEV to primary-cultured human hepatocytes. ISH using cRNA of HEV as a probe demonstrated existence of genotype 3 HEV RNA in cytoplasm of hepatocytes. The immunofluorescent study revealed the following. The infected cells were found to form “infected cell clusters” and the number of the clusters do not change. However, the number of infected cells in each cluster was found to increase with the passage of culture time.

So should we abandon cyclosporine in favor of infliximab? The jury is out while we

wait the results of two prospective randomized, controlled trials, which VX-770 price are currently underway, that compare cyclosporine and infliximab for the treatment of steroid-refractory, severe UC. The Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis is now complete, but is yet to be published in full.12 Preliminary reports suggest that cyclosporine and infliximab are equivalent at preventing colectomy at 90 days. Meanwhile, a British study comparison of infliximab and ciclosporin in steroid resistant ulcerative colitis: a trial continues to recruit patients.13 While rescue therapy remains important, and the results of the above studies are eagerly awaited, one should not forget the importance of performing the basics well when dealing with these very sick patients with UC. First of all, patients should be educated so as to know what to do when they are unwell in order that they seek medical attention early so that infections (e.g. cytomegalovirus and Clostridium

difficile) can be excluded, and a treatment plan established. Patient education, treatment plans, general practitioners, and IBD nurses can play an important role in expediting selleck inhibitor appropriate treatment. Second, patients requiring admission must be appropriately examined and investigated to diagnose severe disease (tachycardia, hypotension, peritonitis, raised C-reactive protein, low serum albumin), and imaged by plain abdominal radiology to exclude complications, such as toxic megacolon and perforation. Fluid resuscitation should be timely, and attention should be paid to the prevention of venous thromboembolism by using low molecular-weight heparin.14 Non-steroidalanti-inflammatory and opioid drugs should be avoided.

Finally, and most importantly, decisions regarding rescue therapy and surgery should be made in a timely fashion, and preferably within the first 3 days of intravenous steroid treatment by the patient, with guidance from both a gastroenterologist and colorectal surgeon, preferably conferring together. Patients with severe colitis who fail to respond to intravenous steroids in hospital continue to be a major clinical challenge. Attention must be paid to doing the basics well, but it is now pleasing to see that there are MCE公司 two rescue therapies available that might avert the need for colectomy. At this stage, it is not clear whether infliximab has usurped cyclosporine, but having a choice is likely to lead to improved outcomes for patients. “
“Although the incidence of bleeding from gastric varices is relatively low (10%–36%), the bleeding is massive once it has occurred and it increases the patient’s mortality. The management of esophageal variceal bleeding is highly differentiated with several effective treatments available. In contrast, bleeding from gastric varices continues to be a therapeutic challenge.

Fifty-seven patients (48%) underwent echocardiography with Doppler flow studies a minimum of 9 months after the onset of daily triptan use. The echocardiogram was abnormal in 10 patients (18%), but none of the abnormalities were considered related to the use of triptans. Of these PF2341066 patients, 6 (10%) had mitral valve prolapse; the other abnormalities were mitral regurgitation, enlarged aorta, mild right ventricular enlargement, and aortic regurgitation, each occurring in 1 patient. Twenty patients (17%) had cardiac stress tests performed for various reasons, unrelated to the triptan usage, and all were normal.

One patient had a cardiac catheterization, which was also normal. By comparison, there are a number of serious safety concerns with daily or almost daily use of opioids, opioid combinations,[8] or butalbital combinations.[9] In addition, the combinations may contain acetaminophen, which is the leading cause of death from over-the-counter medications, and over a period of a decade resulted in 1567 deaths from liver failure due to accidental selleck chemical overdoses.[10] With regard to the indications for daily or near-daily triptan use, it is not an established treatment and, therefore, there are no specific indications.

In addition, as Robbins and Maides[6] observed and what confirms my own experience, patients are not deliberately placed on daily triptan but rather discover, on their own, that the triptan is highly effective for the treatment of their daily headaches. Under those circumstances, it is hard to argue against the daily or almost-daily use of triptans, particularly if there are no indications of medication-overuse headache or safety concerns. The safety issue is addressed above, and that of medication-overuse headache still needs to be addressed. Specifically related to MCE triptans, medication-overuse headache

is defined by the International Headache Society as triptan use on 10 or more days per month for more than 3 months.[11] Of course, this definition is too simplistic to be true, is entirely arbitrary, and lacks appreciation of the complexity of what medication-overuse headache is all about. As I recently wrote in an opinion article in Headache,[12] the consideration of the clinical picture seems to have disappeared from the scene, not only for the diagnosis of medication-overuse headache but also, for example, for that of hemicrania continua, a condition I described with Ottar Sjaastad in 1984.[13] In medication-overuse headache, the clinical picture is that of the patient suffering from daily or almost-daily headaches, often tremendously, despite excessive use of abortive medications, a paradox that patients and physicians alike often still have a hard time comprehending.

[50] Especially, M2 macrophages might negatively regulate liver fibrosis via the production of anti-inflammatory cytokine IL-10.[51] However, under certain conditions, M2 macrophages may also promote liver fibrosis via TGF-β- and MCP-1/CCR2-dependent manners.[50] Although, Selleckchem Opaganib macrophages

can be classified into M1 and M2, there are no significant differences in their morphologic characteristics. Other macrophages such as scar-associated macrophages and BM-derived macrophages have shown to suppress liver fibrosis via matrix metalloproteinase (MMP) productions.[42, 52] Generally, DCs play important roles in both innate and adaptive immune responses as professional antigen-presenting cells.[9] However, the roles of DCs in liver fibrosis are not clearly demonstrated yet. Recent studies show dual roles of liver DCs in liver fibrosis. In thioacetamide-induced liver fibrosis, the characteristics of liver DCs are transformed from tolerogenic to immunogenic, which subsequently enhance inflammatory changes (enhanced activities of NK cells and CD8+ T cells but reduced population of Tregs) in liver fibrosis via the production of check details TNF-α.[53] In contrast, after cessation of liver injury, liver DCs are implicated in the regression

of CCl4-induced liver fibrosis via the production of MMP-9.[54] Therefore, further detailed studies are required to clarify the roles of DC during liver fibrogenesis and regression. HSCs are involved in the pathogenesis of all stages of alcoholic liver disease such as alcoholic steatosis (fatty liver), steatohepatitis, fibrosis, cirrhosis, medchemexpress and hepatocellular carcinoma by producing endocannabinoids, proinflammatory cytokines and chemokines, collagen fibers, and retinol metabolites.[55-57] Besides alcohol-mediated activation of HSCs, diverse liver immune cells such as

NK cells, Kupffer cells/macrophages, and IL-17-producing cells are under the influence of alcohol, leading to various interactions with HSCs compared with those in normal circumstances. Chronic alcohol consumption suppresses the cytotoxicity of NK cells against activated HSCs,[37] while alcohol-mediated TLR4 activation in Kupffer cells/macrophages induces enhanced activation of HSCs by producing proinflammatory cytokines such as TNF-α,[55] subsequently accelerating liver fibrosis. In addition, alcohol consumption accumulates IL-17-producing cells including neutrophils in the liver, which subsequently enhance activation of HSCs.[17, 18] However, the interactions between HSCs and other types of liver immune cells, especially adaptive immune cells, in alcoholic liver disease are still unclear. Thus, further studies are strongly required to address those matters. During liver injury, activated HSCs participate in various liver diseases via abnormal ECM accumulation and cytokine productions.

A 50-year-old woman presented with headaches. Evaluation revealed an unruptured 7-mm broad-based basilar artery fenestration aneurysm that incorporated both limbs of the basilar fenestration and both distal vertebral arteries. A 4.5 mm × 22 mm Enterprise stent (Codman Neurovascular, Raynham, MA, USA) was deployed from the right limb of the basilar fenestration into the right distal vertebral artery. Similarly, a 2.5 mm × 20 mm Neuroform EZ stent (Boston Scientific, Natick, MA, USA) was placed from the left limb of the MK-8669 concentration basilar fenestration into the

left distal vertebral artery. Following stent deployment, the aneurysm was treated with coil-embolization through a jailed microcatheter. In the case presented, a double-barrel stent

configuration enabled dense coil embolization of the aneurysm as well as preservation of both basilar fenestration limbs and both distal vertebral arteries. “
“A trigeminal artery as the most common persisting embryonic carotid-basilar anastomosis is found in up to .2% of adults. In rare instances, trigeminal-cavernous fistulas develop either spontaneously or after a trauma. We present a 16-year-old patient with a traumatic trigeminal-cavernous fistula (Saltzmann type 2), which was successfully treated by interventional occlusion of the persistent trigeminal artery. After intervention, clinical symptoms (chemosis, right-temporal bruits, and sixth nerve palsy) selleck inhibitor resolved. In this case, fistula occlusion was achieved by coil embolization with only 4 coils placed directly at the rupture point of the trigeminal artery but not into

the cavernous sinus. Thus, the cavernous sinus was preserved in function and structure. Special anatomy and interventional peculiarities of this unique case are described in detail. “
“Vertebrobasilar dolichoectasia (VBD) is a dilatative arteriopathy associated with a decreased blood flow velocity. Fluid attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is a phenomenon most likely representing slow arterial blood flow. We sought to examine the frequency and extent of FVH in VBD. We analyzed magnetic resonance imaging (MRI) findings in 77 VBD patients with special emphasis on FVH in relation to the diagnostic MRI criteria of VBD and the etiology in symptomatic patients. In 49 (63.6%) VBD patients, FVH could be detected: 上海皓元 in 22 (44.9%) a small hyperintense rim near the vessel wall (grade 1), in 20 (40.8%) a strong hyperintense rim near the vessel wall (grade 2), and in 7 (14.3%) the hyperintense signal filled the complete vessel lumen (grade 3). The diameter of the basilar artery moderately correlated with the extent of FVH. A higher FVH grade (2 and 3) was more common in patients with TIA/stroke related to VBD (9/16 [56.3%]) in comparison to patients with other etiology and asymptomatic patients (18/61 [29.5%]; P = .046). FVH may be useful to demonstrate the decreased blood flow velocity in VBD.

Using the NHANES III database, Liangpunsakul and Chalasani[34] reviewed over 6,800 patients and found 308 with unexplained elevation in alanine aminotransferase (ALT) and compared their serum vitamin D concentrations with

those of 979 matched controls. NHANES III Galunisertib research buy patients with elevated ALT were found to have lower vitamin D levels than the control group, even when controlling for metabolic syndrome, IR, and serum triglyceride level. This was confirmed in a study of 262 patients referred to an endocrinology clinic where the relationship between NAFLD and reduced vitamin D levels persisted regardless of age, sex, triglycerides, and IR.[35] Targher et al.[36] confirmed the association between NAFLD and VDD and importantly evaluated the relationship of liver histology to vitamin D levels. Vitamin D concentrations were lower in NASH patients when compared to those with isolated fatty liver and inversely correlated with liver histology. The understanding of NASH pathogenesis has evolved from the relatively simplistic “two-hit” hypothesis and includes a number of metabolic Temozolomide pathways resulting in hepatic steatosis, steatohepatitis, and hepatic fibrosis. A number of these pathways can be affected by vitamin D and relate to the hormonal, immunologic, and cellular differentiation “nonclassical” effects

of vitamin D. Hepatic steatosis is generally thought to arise from lipolysis derived flux of free fatty acids (FFA) from adipocytes, as well as dietary lipids, de novo lipogenesis, and impaired lipid disposal.[37] The buildup of FFA results in insulin signaling defects and impairment of cellular glucose metabolism, with the resulting hyperglycemia leading to increased lipogenesis through increased activation of sterol regulatory element binding proteins (SREBP)[38] as well as activation of carbohydrate response element binding proteins (CHREBP).[39] Visceral adipose tissue also plays an important role in a variety of inflammatory and immune reactions pertinent to NASH by way of secretion of adipocytokines such as adiponectin, resistin, and omentin.[40] Adiponectin has been described as the prototypic adipocytokine

medchemexpress by way of its function as an antiinflammatory agent.[41] Low adiponectin levels are independently associated with obesity and NASH[42] and adiponectin levels increase after weight loss.[43] In murine models, high levels of adiponectin have been experimentally shown to decrease necroinflammation and steatosis in alcoholic and nonalcoholic fatty liver disease,[44] as well as improved insulin resistance,[45] suggesting that, in humans, adiponectin may improve hepatic inflammation and hepatic insulin sensitivity.[46] Indeed, data suggest that when pioglitazone is given to NASH patients, adiponectin levels increase 2-fold to 3-fold with an associated improvement in IR as well as improved steatosis, necroinflammation, and fibrosis.

This information revealed how reliable the results were, if there was enough data to be representative and aided in determining which data set (annual or pooled) was more representative. Standard Errors (SE) were calculated from 1,000 bootstrap replications. Data sets with intermediate (S ~0.5) to high

(S close to or above 1.0) social differentiation need far fewer associations than data sets with low differentiation to detect preferred companionship (Whitehead 2008a). This community is made up of three social clusters: Northern, Central, and Southern (Elliser and Herzing 2012). In order to correctly interpret the pattern of social associations, it was important to determine whether www.selleckchem.com/products/NVP-AUY922.html these social clusters were still

present before and after the hurricanes. Cluster definition was Dabrafenib in vitro confirmed using nonmetric multidimensional scaling (MD) and hierarchical agglomerative cluster analysis conducted with SOCPROG 2.3. In a MD plot, strongly associated individuals were plotted together and weakly associated were farther apart (Whitehead 2009). A plot with stress <0.1 is considered a good ordination (Whitehead 2008a). Hierarchical agglomerative cluster analysis produced a dendrogram where the individuals were arranged on one axis and their degree of association on another (Whitehead 2009). The Average-linkage method was used. The cophenetic correlation coefficient (CCC) determined how well the dendrogram matched the association matrix. A CCC of >0.8 indicates a good match, (Whitehead 2008a). These clusters overlapped in range and associations and have been confirmed to be part of one community (Elliser and Herzing

2012); therefore all individuals were analyzed together for CoA analysis. In 393 d at sea there were 173 d with encounters, with a total of 251 encounters (Table 1). A total of MCE公司 89 individuals were identified and sex was determined for 96% of the community. There were 43 females, 42 males, and 4 of unknown sex. Fifty-six individuals (63%) were sighted in every year of this study that was possible for that individual (i.e., they had been born and they were not considered lost—indicated by no sightings for more than 3 yr in a row). Before the hurricanes an average of 103 individuals were identified per year. After the hurricanes, this number dropped dramatically to 67.7 individuals (Fig. 2). Thirty-six regularly seen individuals (16 females and 20 males) disappeared and have not been resighted to date (through the 2012 field season). Losses were fairly consistent over age classes: 9 two-tones, 11 speckled, 6 mottled, and 10 fused individuals.

Conclusion: It is critical for the rehabilitation of patients with mild acute pancreatitis to observe and analyze

the causes of serum amylase unfalling and Protein Tyrosine Kinase inhibitor take effective measures to deal with. Key Word(s): 1. acute pancreatitis; 2. serum amylase; 3. analysis; 4. treatment; Presenting Author: CHENWEN JING Additional Authors: TANGGUO DU Corresponding Author: TANGGUO DU Affiliations: guangxi medical university Objective: To investigate the relationship between AOPP and severity of AP by detecting serum levels of AOPP in patients with AP, combination the results of serum interleukin -6(IL-6), indicators which associated with disease severity and clinical datas. Methods: Fifty-eight patients who were diagnosed acute pancreatitis in our hospital from November 2010 to September 2012 were collected[18 cases with severe acute pancreatitis (SAP) and

40 cases with mild acute pancreatitis (MAP)]. Serum levels of AOPP and IL-6 were dectected by enzymelinked immunosorbent assay (ELISA) within 24 hours. Blood samples were sent to the laboratory to dectect blood routine, liver function, renal function, blood calcium, blood glucose and actate dehydrogenase. APACHE II scores, Ranson scores, CTSI scores, BISAP scores and Glasgow scores were also determined. Results: ① Serum levels of WBC, GLU, LDH in SAP group were higher than MAP group (P < 0.05). ALB and MCE公司 blood calcium in SAP group was lower than MAP group (P < 0.05). ② Serum levels of BUN, Cr, blood amylase were no significant difference between SAP Vismodegib molecular weight group and MAP group (P > 0.05). ③ In SAP group and MAP group, APACHE II scores were (5.00 ± 3.67) and (3.39 ± 2.91), Ranson scores were (2.04 ± 1.46) and (1.33 ± 1.21), CTSI scores were (5.87 ± 1.46) and (1.20 ± 1.26), BISAP scores were (1.52 ± 0.80) and (0.86 ± 0.76), Glasgow scores were (2.61 ± 1.20) and (1.24 ± 1.12), respectively, and SAP group was higher than MAP group (P < 0.05). ④ Serum levels of AOPP in

SAP group and MAP group were (38.1156 ± 11.67)ng/ml and (29.40 ± 14.19)ng/ml, respectively, and SAP group was higher than MAP group (P < 0.05). Serum levels of IL-6 in SAP group and MAP group were (211.01 ± 107.98)pg/ml and (129.72 ± 56.53)pg/ml, respectively, and SAP group was higher than MAP group (P < 0.05). ⑤ There are relations between AOPP and WBC, GLU (P < 0.05), but no relations with LDH, blood calcium, ALB, BUN, Cr and blood amylase (P > 0.05). Conclusion: Serum levels of AOPP may be associated with the severity of AP; AOPP may be associated with the process of inflammatory response in the occurrence and development of AP; AOPP and indicators which associated with disease severity may be used as markers to estimate the severity in AP. Key Word(s): 1. acute pancreatitis; 2. AOPP; 3.