Some clinicians associate small doses of heparin or low-molecular weight-heparin with the administration of fibrinogen. In case of thromboembolic

complications, direct anti-Xa or thrombin inhibitors can bind thrombus-bound thrombin, which is not the case with heparin. Thromboembolic complications are always difficult to deal with, since at the same time it is necessary to give anticoagulants but also fibrinogen preparations in severe fibrinogen disorders. The second class of hereditary fibrinogen abnormalities are the type II disorders, i.e. dysfibrinogenaemia and hypodysfibrinogenaemia [46,47,52,53]. As in afibrinogenaemia and hypofibrinogenaemia, both are heterogeneous disorders caused by many different mutations in the three fibrinogen-encoding genes. Dysfibrinogenaemias and hypodysfibrinogenaemias are generally associated with autosomal dominant inheritance, caused click here by heterozygosity for missense mutations in the coding region of one of the three fibrinogen genes and so they are more frequent than type I disorders. Indeed, over 400 cases of dysfibrinogenaemia have been reported to date, with more than 40 distinct mutations identified

(more than 60 distinct mutations in dysfibrinogenaemia and hypodysfibrinogenaemia combined). Missense mutations at residue FGA R35, which is part of the thrombin cleavage site in the fibrinogen α-chain, are the most common causative mutations accounting for dysfibrinogenaemia, found in Lapatinib approximately 40% of cases [47]. Most dysfibrinogenaemia mutant molecules are found in plasma at normal antigenic levels; thus they can be diagnosed by the combination of a prolonged thrombin time, normal levels of fibrinogen antigen, and low functional levels of fibrinogen. Most cases are asymptomatic and are only identified as a result of routine coagulation screening. Approximately 25% of patients with dysfibrinogenaemia have a history of bleeding, and in approximately 20%

a tendency towards thrombosis is observed [52]. Women with dysfibrinogenaemia can also suffer from spontaneous abortion. Some mutations in the Aα chain of fibrinogen are associated with a particular form of hereditary amyloidosis [54]. The gold standard for the Adenosine diagnosis of dysfibrinogenaemia is the characterization of the molecular defect. Some mutations are predictive of the clinical phenotype: e.g. the R573C substitution in the Aα chain predisposes patients to thrombosis whereas mutations in the amino-terminal region of the Aα chain are associated with bleeding. These examples illustrate how determining the causative mutation can allow to take precautionary measures and guide treatment, which, however, should be based mainly on the personal and family history. Knowledge regarding RBDs is expanding, and recent studies have established important milestones in understanding these rare disorders.

The use of FFP can be complicated by an increasing risk of transfusion-transmitted diseases, allergic reactions and even anaphylactic shock, especially in those with immunoglobulin A (IgA) deficiency when IgA-depleted FFP is not used. FXI concentrate (plasma derived, heat treated) is another option offered in some countries, in the absence of recombinant FXI. It is efficient in predicting the expected incremental increase

in FXI levels when a given dosage is administered, and since it has a long half-life, this treatment can be given on alternate days. The target level should be 30–40 IU dL−1. The caveat of the use of FXI concentrates is that both currently available products [Bio Products Laboratory Tigecycline (BPL), selleck chemicals llc UK and LFB Biomedicaments, France] have been associated with thrombosis even after adding heparin to the antithrombin in the BPL product, and antithrombin and heparin to the C1 esterase in the LFB product [17, 24, 25]. Furthermore, patients with undetectable plasma levels of FXI are at risk of developing inhibitors following exposure to the concentrates [26], and they cannot be used in IgA deficient patients. Thus, before these concentrates can be prescribed for use, screening for antibodies is mandatory in patients with undetectable FXI levels who were previously exposed to FFP, FXI concentrates, or immunoglobulin. Low-dose (15–30 μg kg−1)

recombinant factor VIIa (rFVIIa), a bypassing agent, has been successfully used in patients with severe FXI deficiency, both with and without inhibitors [27, 28]. Caution is required when used at higher doses, such as those regularly used to treat haemophilia A and B, because of the increased risk of thrombosis [29, Interleukin-3 receptor 30]. It is the only treatment available for patients with inhibitors, and has recently been suggested for primary treatment to avoid exposure to blood

products. Antifibrinolytic agents, e.g. tranexamic acid or 6-aminocaproic acid, are currently used as monotherapy for minor procedures such as before tooth extraction, or in combination with very low-dose rFVIIa or FFP in major procedures. Altogether, before planning prophylactic treatment for patients with severe FXI deficiency, the following issues must be addressed: Site and type of surgery [31] Presence of an inhibitor Combined haemostatic defects Thrombotic risk Volume overload Presence of IgA deficiency Previous exposure/lack of exposure to blood products Environmental interactions . In conclusion, therapy tailored to an individual’s risk and type of procedure constitutes the ideal management of FXI deficient patients. It remains to be established whether one of the global coagulation tests, including assays of fibrinolysis and/or clot structure, will eventually efficiently predict the bleeding risk of a given individual before innovative prophylactic treatment can be recommended.

Methods: The present study retrospectively studied 106 patients diagnosed as NTM lung disease at Bundang buy Opaganib Seoul National University Hospital, between 2009 and 2013. 31 patients had NTM lung disease with GERD and 75 age-sex matched patients had NTM lung disease without GERD. The diagnosis of reflux esophagitis was based on the endosopic findings, such as mucosal break around the distal esophageal sphincter. Results: No statistically significant differences were found between the two groups with regard to age, sex, body mass index.

There were no differences in the positivity of acid-fast bacilli smear, the number of involved lobe. In the patients with GERD, 19 patients (62%) did not report any reflux or heartburn symptoms. 7 Patients (25%) had atypical GERD symptoms such as dyspepsia, epigastric discomfort. The patients without GERD were more likely to have M.abscessus infection (2 of 31 patients, 6.5%) than those without GERD (17 of 75 patients, 22.7%) (p = 0.048) Conclusion: Patients with NTM lung disease have a high prevalence of asymptomatic gastroesophageal reflux. The presence of GERD in NTM lung disease is associated with the

ethiology of NTM infection. The results of this study are not consistent with the previous study. Key Word(s): 1. Gastroesophageal reflux; 2. nontuberculous mycobacteria; 3. endoscopy Presenting Author: JU SEOK KIM Additional Authors: HEE SEOK MOON, SEOK buy BMS-777607 HYUN KIM Corresponding eltoprazine Author: JU SEOK KIM Affiliations: Chungnam National University College of Medicine, Chungnam National University College of Medicine Objective: Primary gastric lymphoma is less than 5% of primary gastric neoplasm but the incidence of this malignancy is increasing. The most common histology is representing diffuse large B cell lymphoma. Complication of gastric lymphoma such as perforation and peritonitis, nearly always required a surgical management. Although

unusual, the occurrence of perforation is potentially life threatening and leads to morbidity from sepsis, multi-organ failure, prolonged hospitalization, delay the initiation of chemotherapy and mortality. We report a case with gastric lymphoma initially presenting as peritonitis because of spontaneous gastric perforation. Case Report; A 64-year-old man was hospitalized via our emergency room with sudden onset of abdominal pain. A physical examination revealed abdominal tenderness and muscular defense. The laboratory tests on admission showed WBC 9,270/mm3, Hb 10.3 g/dl, platelet count 406,000/mm3. Others value were within the normal range. Chest X-ray finding was free air below the right diaphragm (Figure 1A). We checked abdominal CT scan. It showed massive free air in the peritoneal cavity and large wall defect in lesser curvature of gastric lower body (Figure 1B). We performed emergency surgery and primary closure was done.

Additional Supporting Information may be found in the online version of this article. “
“Secondary stomach cancer in lesions of the remnant stomach occurs relatively soon after distal gastrectomy using the Billroth I reconstruction procedure. Prophylactic eradication of Helicobacter pylori after endoscopic resection of early gastric cancer should be

used to prevent the development of metachronous gastric carcinoma. However, the effect of H. pylori eradication on the gastric remnant has not been clearly determined. Eight patients who were H. pylori-positive after distal gastrectomy for primary gastric cancer underwent eradication therapy and were followed by endoscopy for 9 years. Upper gastroenteroscopy series were done before and at 1, 3, 5, 7 and 9 years after eradication, and biopsy specimens were taken from the lesser and greater curvatures, respectively. Histological changes, including chronic AUY-922 in vivo inflammation, activity, atrophy, and intestinal metaplasia, were evaluated using the updated Sydney system. Successful eradication was confirmed using the urea breath test in all eight patients. Chronic inflammation scores were improved after eradication at both the lesser

(mean scores ± SD: before eradication, 2.9 ± 0.5; 1 year after, 2.3 ± 0.4; 3 years, 1.8 ± 0.3; 5 years, 1.5 ± 0.3; 7 years, 1.3 ± 0.3; and 9 years, 1.0 ± 0.3) and greater curvatures (before, 2.9 ± 0.4; 1 year after, 1.9 ± 0.3; 3 years, 1.4 ± 0.4; 5 years, www.selleckchem.com/products/dabrafenib-gsk2118436.html 1.3 ± 0.3; 7 years, 1.1 ± 0.2; and 9 years, 0.6 ± 0.3). Atrophy scores improved more quickly after eradication than Beta adrenergic receptor kinase chronic

inflammation scores at both the lesser (before, 2.4 ± 0.5; 1 year after, 1.8 ± 0.4; 3 years, 0.8 ± 0.3; 5 years, 0.3 ± 0.1; 7 years, 0.0; and 9 years, 0.0) and greater curvatures (before, 2.2 ± 0.4; 1 year after, 1.3 ± 0.3; 3 years, 0.5 ± 0.3; 5 years, 0.0; 7 years, 0.0; and 9 years, 0.0). No secondary stomach cancers were found on endoscopy. Undergoing H. pylori eradication improved possible precancerous lesions of the gastric remnant among patients who had undergone distal gastrectomy. Prophylactic H. pylori eradication in the gastric remnant may be useful in preventing the development of metachronous gastric carcinoma. Since the first report by Marshall and Warren in 1984 identifying curved bacilli adjacent to the gastric epithelium of patients with chronic gastritis,[1] the link between Helicobacter pylori and chronic gastritis has grown stronger.[2] The bacteria colonize the stomach for years or decades, and causes continuous inflammation. Chronic gastritis caused by H. pylori infection does not produce symptoms in the majority of infected persons, but is a significant risk factor for the subsequent development of atrophic gastritis and gastric adenocarcinoma. Uemura et al.[3] prospectively studied 1526 Japanese patients, 1246 with H.

Dig Dis Sci. 2008; 53(8): 2258–2267. 2. Lenhart M, Paetzel C, Sackmann M, et al. Superselective arterial embolisation with a liquid polyvinyl alcohol copolymer in patients with acute gastrointestinal haemorrhage. Eur Radiol. 2010; 20:1994–1999. 3. Tian X, Shi Y, Hu Y, et al. Percutaneous transhepatic variceal embolization with cyanoacrylate vs. transjugular intrahepatic portal systemic shunt for esophageal variceal bleeding. Hepatol Int. 2013; 7(2): 636–644. 4. Sun A, Shi YJ, Xu XG, et al. MDCT angiography to evaluate the therapeutic

effect of PTVE for esophageal varices. World J Gastroenterol. https://www.selleckchem.com/products/r428.html 2013; 19(10): 1563–1571. EH TSOI,1 CY GOH,1 N PARTHASARATHY,1 KE MARION,3 C MCNAB,1 S GLANCE,1 C LEUNG2 1Department of Gastroenterology, The Northern Hospital, Northern Health, Victoria, Australia,

2University of Melbourne, PFT�� clinical trial Melbourne, Victoria, Australia, 3School of Mathematical and Geospatial Sciences College of Science, Engineering and Health, RMIT University, Victoria, Australia Introduction: Current American Association for the Study of Liver Diseases guidelines recommend hepatitis B virus (HBV) screening with hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (antiHBs) and hepatitis B core antibody (antiHBc) in all persons born in high and intermediate endemic areas. Our aim is to audit the screening practices for HBV infection in at-risk patients who attended a metropolitan hospital inflammatory bowel disease clinic. Methods: All patients born in high and intermediate endemic areas with inflammatory bowel disease (IBD) who attended an IBD clinic between January 2012 and January 2014 were identified from clinic records

based on country of birth. Medical records and hospital laboratory results were reviewed; and general practitioners were contacted to determine hepatitis screening practices. Multivariate analysis was used to determine if there were any factors that predicted screening for HBV in these patients. BCKDHA Results: 70 patients who attended IBD clinic between 2012 and 2014 were identified to be from high and intermediate endemic areas. 44% were male with a median age of 55 years. 50% of patients had Crohn’s disease and 50% had ulcerative colitis. The majority of patients were born in Turkey (16%), Italy (13%) and Greece (7%). Only thirty-eight patients (54%) had hepatitis B serology performed and of these, 36 (95%) had HBsAg, 19 (50%) had antiHBs and 20 (53%) had antiHBc tested. Patients with Crohn’s disease were more likely to be tested compared to those with ulcerative colitis (60% vs 45% respectively, p = 0.048). Gender and country of birth did not affect screening practices for HBV infection (p = 0.141 & p = 0.168 respectively).

‘Declined’ is at least one endoscopist decided NBI is inferior. ‘Unchanged’ is other than above evaluations. Results: Concordance rate of diagnosis by BLI and NBI with microvascular classification was 91.7 %. The preoperative diagnostic rate of depth of invasion was in eight of ten lesions (accuracy rate 80.0%). 50% was improved and 40% was unchanged

in visibility. Only one case was declined by BLI. Conclusion: This study suggested that BLI is equivalent with NBI in the diagnosis of early esophageal cancer. In addition, BLI may have superior visibility compared with NBI. Key Word(s): 1. IEE; 2. BLI; 3. esophageal cancer; Presenting Author: LIANG ZHAO Additional Authors: YI-JUAN DING, HONG-GANG YU, TAO DENG, JUN LIU, HE-SHENG LUO Corresponding Author: LIANG ZHAO Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University Objective: To investigate the safety, diagnostic value and clinical impact of double balloon HSP inhibitor PXD101 ic50 enteroscope (DBE) on advanced aged patients and analysis etiological characteristics. Methods: The

clinical data of advanced aged patients underwent DBE in the Department of Gastroenterology in Remin Hospital of Wuhan University from January 2008 to June 2012 were retrospectively analyzed. Results: DBE presents a diagnostic yield of 83.7 %(72/86) and a complication rate of 1.2% (1/86) in 42 advanced aged patients, with clinical impact on 76.2%(32/42) of all patients. The leading causes of OGIB were tumor (53.3%, 11/30) and ulcer (16.7%, 5/30) while angioectasis (6.7%, 2/30) was uncommon. Conclusion: DBE is an G protein-coupled receptor kinase effective and safe method for diagnosis of small bowel disease on advanced aged patients. Tumor and ulcer were common causes of OGIB while angioectasis was uncommon. Diagnosis and therapeutic strategy based on those characteristics is worthy of further investigation. Key Word(s): 1. DBE; 2. Aged patient; 3. Small bowel disease; Presenting Author: SHANYU QIN Additional Authors: HAIXING JIANG Corresponding Author: HAIXING JIANG Affiliations: The First Affiliated Hospital of Guangxi Medical University Objective: Cytological smear is widely employed to analyse specimens

obtained from endosonography-guided fine-needle aspiration (EUS-FNA), but false-negative or inconclusive results may occur. A better diagnostic yield can be obtained from processing cell blocks. We compared the effectiveness of the conventional smear cytology, liquid-based cytology (LBC) and the cell block in the diagnosis of pancreatic neoplasms. Methods: From December 2010 to March 2013, 53 patients with pancreatic tumors were evaluated by EUS-FNA. Surgery was performed in 43 cases, and the other 8 patients were followed clinically for an average of 9 months. In total, all patients were evaluated with cytological smears and cell blocks. The EUS-FNA samples of all patients were processed by conventional smear cytology, liquid-based cytology (LBC) and the cell block. Results: Malignant disease was detected in 39 (73.

38 ± 0.07 MPa.m1/2, 122.83 ± 6.13 MPa, and 70.69 ± 3.67 VHN, respectively, all of which were significantly higher than 1.07 ± 0.06 MPa.m1/2,

104.61 ± 8.73 MPa, and 52.14 ± 4.02 VHN of the control, respectively (Tukey’s multiple comparison test; family confidence coefficient = 0.95). Measured values for composites at 20% mass fraction BIBW2992 of silica nanoparticles were 0.94 ± 0.06 MPa.m1/2, 103.41 ± 7.62 MPa, and 42.87 ± 2.61 VHN, respectively; relevant values for composites at 30% mass fraction of silica nanoparticles were 1.16 ± 0.07 MPa.m1/2, 127.91 ± 7.05 MPa, and 51.78 ± 3.41 VHN, respectively. Conclusions: Reinforcement of dental composite resins with silica nanoparticles resulted in a significant increase in the evaluated mechanical properties in comparison with the conventional composite.

The filler mass fraction played a critical role in determining the composite’s mechanical properties. “
“Purpose: Edentulism and conventional complete denture treatment have been shown to have a negative impact on oral health quality of life (OHQoL). The use of an adhesive agent can provide an alternative to implant-supported prostheses. The objective of this study was to show that new complete dentures using a denture adhesive (DA) improve oral health-related quality of life. Materials and Methods: The oral health QoL of 143 patients was assessed after 3 months of wearing new complete dentures. Fourteen participants selleck presented a low geriatric oral health assessment index (GOHAI) score and were included in this study and asked to use a DA. Oral

health QoL and masticatory parameters were assessed at the beginning of the study, then at 3 and 6 months. Results: Significant improvements were observed in the scores obtained for each field of GOHAI (function, pain, discomfort, psychosocial); however, even after use of the DA, no statistically significant change in masticatory Methane monooxygenase parameters was found. Conclusions: These results show that using a DA may improve subjects’ ability to manage conventional dentures and enhance their oral quality of life. A larger, prospective, multicenter study is subsequently needed to confirm these results. “
“Purpose: The purpose of this in vitro investigation was to measure the forces generated during the continuous seating and unseating of prefabricated attachment systems used to retain implant overdentures. Materials and Methods: An experimental design consisting of interchangeable fixture mounts, a radially indexable fixture holder, and a materials testing systems (MTS) machine was used to measure forces generated during the insertion and removal of spherical stud attachments (Straumann, Inc, Waltham, WA).

PPARα suppresses tumor cell growth through reducing cell proliferation and inducing cell apoptosis by direct targeting IκBα. PPARα acts as a tumor suppressor in the liver, partly through inhibition of NF-κB signaling pathways. Key Word(s): 1. PPARα; 2. HCC; 3. tumor suppressor; Presenting Author: XIN XU Additional Authors: KUNLUN CHEN, ZHONGWEI LIU, YING LIU, ZHIKAI ZHANG, JIANGYI CAI, JIE LI, JINKAI XU, JIE WU, YI YANG Corresponding Author: XIN XU Affiliations: Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong Selleck EPZ 6438 University; Medical school of Xi’an Jiaotong University; Medical School of Xi’an Jiaotong University; Xi’an Aerospace General Hospital; Department of

Digestive, The Second Affiliated Hospital, Xi’an Jiaotong University Objective: Musashi1(Msi1) belongs to the RNA-binding protein (RBP) family, with functions as transcriptional activator or suppressor of specifically bound mRNA. MSi1 has been shown to play important roles in the maintenance of stemness of neural progenitor or stem cells and in the progression of several types of cancers. However, its function in hepatocellular carcinoma (HCC) has not been deeply unexplored. Methods: The expression of Msil in HCC cells was detected by western blotting. MSI1 expressing vector was constructed and stably transfected into HepG2 cell. We AG 14699 knocked down the expression of Msi1 in Huh7

cell lines by stable gene transfection. Cell growth was measured using MTT assay, and cell cycle progression and apoptosis was analyzed using FACS. Dual luciferase assays were employed to test the change of Wnt signal pathway. Results: In this study, we initially reported that overexpression of Msi1 in HepG2 cell lines resulted in significantly promoted cell growth and PRKACG cell cycle progression.

Consistently, knockdown of Msi1 in Huh7 cell lines remarkably inhibited cell growth, induced augmented cell apoptosis, and caused cell cycle arrest at the G1/S transition. Several important signaling pathways, including Wnt are frequently found to be activated in cancer. In the study, dual luciferase assays indicated that Msi1 activated Wnt signal pathway. Conclusion: Taken together, these findings indicate that an oncogenic role of Msi1 in HCC may be through modulation of cell growth and cell cycle by activating Wnt pathway. Key Word(s): 1. Msi1; 2. HCC; 3. Wnt; Presenting Author: BIGUANG TUO Additional Authors: BEI JI, JINGYU XU, GUORONG WEN, HAI JING, YUAN YANG, XUEMEI LIU, RUI XIE Corresponding Author: BIGUANG TUO Affiliations: Department of Gastroenterology, Affiliated Hospital of Zunyi Medical College Objective: It is well known that chronic hepatitis is major cause of hepatocellular carcinoma (HCC) and inflammatory cytokines, TNFα and IL6, play important role in the development and progression of HCC. Maintenance of intracellular pH (pHi) is crucial to cell function. Na+/H+ exchanger 1 (NHE1) plays important role in the regulation of tumor cellular pH.

This correlated with improved viral response rates at Weeks 4 and 12 of treatment. To gain insight into the potential mechanisms of these early robust virologic responses with Lambda, we investigated the effects of HCV replication in vitro on the IFN signaling pathway Trametinib order in primary human hepatocytes

(PHH). Methods: PHH obtained from healthy individuals were inoculated with cell culture adapted HCV (HCVcc) or with GT1 viruses derived from patient serum (HCVser). RNA was isolated from cells at multiple time-points and gene expression analysis performed using Affymetrix array profiling. Immunblotting analysis of HCV infected PHH was used to determine protein levels of IFN receptor subunits and to assess functionality of JAK-STAT signaling upon stimulation with alfa or Lambda. Results: Acute HCV infection induced a rapid down-regulation of the IFN alpha receptor subunit 1 (IFNAR1) transcript in PHH while transcriptional level of the unique IFN lambda receptor subunit IL28RA was increased. Immunoblotting analysis confirmed the repression of the IFNAR1 protein during infection with HCVcc or HCVser, which expression could be restored upon treatment with an NS3 protease inhibitor. Furthermore, induction of the IFN-responsive JAK-STAT signaling pathway was altered upon treatment with alfa selleck whereas response to Lambda was not affected. Conclusions: Differential effects

of HCV infection on expression of the IFN alpha and IFN lambda receptors in PHH may provide an explanation for the more robust early virologic response observed upon Lambda dosing in patients. The implications of this in vitro hepatic receptor modulation may be further explored during IFN-based combination therapy with direct-acting antivirals. Disclosures: Petra Ross-MacDonald – Employment: learn more Bristol-Myers Squibb Fiona McPhee – Employment: Bristol-Myers Squibb The following people have nothing to disclose: Jacques Friborg, Jian Cao, Betsy J. Eggers, Baiqing Lin Purpose: This study

characterized the activity, safety and early pharmacokinetic (PK) profile of IDX20963, a novel uridine liver-targeted nucleotide prodrug for the treatment of HCV. Methods: Anti-HCV activity was determined using recombinant HCV NS5B and in standard cell-based assays. Cytotoxicity was evaluated in a large panel of hepatic and non-hepatic mammalian cells and included galactose-cultured cells and TEM analysis of mitochondria. In vitro experiments were conducted using animal and human hepatocytes and subcellular fractions as well as human drug metabolizing enzymes and transporters. In vivo experiments were performed in mice, rats and monkeys following doses of 0.5 to 100 mg/kg. Results: The triphosphate (TP) of IDX20963 was active against HCV NS5B from genotypes 1 through 6 (97 to 250 nM), but not against cellular polymerases. IDX20963 was also active against HCV genotypes in cell-based assays, but inactive against 15 non-HCV viruses.

RUVBL1 bound

F-actin in cell protrusions, and increased concentration of G-actin and additional formation of actin filaments in cell protrusions. Conclusion: RUVBL1 contributes to the formation of membrane protrusions by promoting peripheral actin polymerization. These RUVBL1-actin interactions enhance the invasive properties of PDAC cells. Inhibition of binding between RUVBL1 and actin filaments may be a rational approach learn more to a targeted molecular therapy for PDAC because any such therapy would inhibit the formation of cell protrusions and consequently limit the motility and invasiveness of PDAC cells. Key Word(s): 1. pancreatic ductal adenocarcinoma; 2. AAA + ATPase; 3. invasiveness; 4. cell protrusion; 5. actin polymerization Presenting Author: MASAHIKO UCHIDA

Additional Authors: TAICHI NAKAMURA, TETSUHIDE ITO, MASAYUKI NAKAYAMA, HIROYUKI SAKATA, RYUICHI IWAKIRI, KAZUMA FUJIMOTO Corresponding Author: MASAHIKO UCHIDA Affiliations: Kyushu University, Kyushu Lumacaftor datasheet University, Saga University, Saga University, Saga University, Saga University Objective: Chronic pancreatitis (CP) worsens with drinking, and pancreatic stellate cells (PSCs) play an important role in the pathogenesis of alcoholic CP. Fractalkine is chemokines, and membrane type and soluble type is present. A membrane-bound extracellular region is cut by sheddase, and soluble type fractalkine shows migration activity for the inflammatory cell with CX3CR1 (fractalkine receptor). Serum levels of fractalkine (CX3CL1) are elevated in patients with alcoholic CP, however the mechanism remains unclear. This study aims to determine the effects of cytokines, pathogen-associated molecular patterns (PAMPs), and ethanol and its metabolites on CX3CL1 secretion by PSCs. Methods: Male Wistar/Bonn Kobori (WBN/Kob) rats were used as models PIK3C2G of CP in vivo. PSCs were isolated from 6-week-old male Wistar rats.

The effects of cytokines, PAMPs, and ethanol on chemokine production and activation of signaling pathways in PSCs in vitro were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and enzyme-linked immunosorbent assay. Results: Expression of CX3CL1 and matrix metalloprotease (MMP)-2 was increased in the pancreas of WBN/Kob rats. The rat PSCs expressed CX3CL1, MMP-2, and a disintegrin and metalloprotease domain (ADAM) 17. Cytokines and PAMPs induced CX3CL1 release. Ethanol synergistically increased CX3CL1 release via ERK and ADAM17 activation in PSCs. Several cellular signaling cascades are activated by CX3CL1 in PSCs and associated with cell proliferation. Conclusion: We demonstrated for the first time that ethanol synergistically increased CX3CL1 release from PSCs in part through activation of ERK and ADAM17. This might be one of the mechanisms of serum CX3CL1 elevation and disease progression in patients with alcoholic CP. Key Word(s): 1. chronic pancreatitis; 2. PSCs; 3. chemokine; 4.