PRIMARY BILIARY CIRRHOSIS (PBC) is an autoimmune liver disease ch

PRIMARY BILIARY CIRRHOSIS (PBC) is an autoimmune liver disease characterized by chronic progressive destruction of small intrahepatic Saracatinib manufacturer bile ducts. Antimitochondrial antibodies (AMA), which mainly target the different subunits of the pyruvate dehydrogenase complex (PDC), are detected in 90% of PBC patients. However,

the pathogenic role of AMA in PBC has not been elucidated.[1] Data from recent studies have suggested that some patients with PBC carry autoantibodies directed against muscarinic acetylcholine receptors, especially M3 muscarinic acetylcholine receptor (M3R).[1, 2] To date, five subtypes of muscarinic acetylcholine receptors (M1R–M5R) have been identified, and M3R is expressed in biliary tracts as well as exocrine glands and smooth muscles.[1] Therefore, anti-M3R antibodies may play an important role in the pathogenesis of PBC and explain the organ-specificity of PBC. In this regard, anti-M3R

antibodies are also detected in patients with Sjögren’s syndrome, which is an autoimmune disease often associated with PBC.[3-6] The purpose of this study was to clarify the presence, the potential use as a diagnostic marker and the clinical roles of anti-M3R antibodies in patients with PBC. SERUM SAMPLES WERE collected from 90 Japanese patients with PBC, 40 Japanese patients with chronic hepatitis C (CHC), 21 Japanese patients with non-alcoholic steatohepatitis (NASH), 10 Japanese patients with primary sclerosing cholangitis (PSC), 14 Japanese patients with obstructive jaundice, and 10 Japanese patients see more with drug-induced liver injury as disease controls, who had been followed up at the Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan. All patients with PBC satisfied the Japanese Ministry

of Health, Labor and Welfare criteria for the diagnosis of PBC described in the PBC Guideline 2011. In the criteria, patients who satisfy one of the following items are diagnosed with PBC: (i) pathological BCKDHA examination shows chronic non-suppurative destructive cholangitis (CNSDC) and laboratory data are compatible with PBC; (ii) positive AMA and pathological examination does not show CNSDC but are compatible with PBC; and (iii) although pathological examination is not performed, AMA is positive, and clinical course is compatible with PBC. We collected clinical data of these patients with PBC, including pathological stage, antinuclear antibody, anti-La antibody and anti-Ro antibody. Pathological staging was determined according to Sheuer’s classification[7] for 77 patients with PBC for whom histological examination was performed. All patients with NASH were diagnosed based on liver biopsy in non-alcoholic drinkers. Clinical and serological features of these disease controls are summarized in Table 1. Serum samples were also collected from 42 healthy volunteers at University of Tsukuba as healthy controls (HC). Ages and sexes of these HC are also presented in Table 1.

Analyses of a concatenated data set (5,220 nt) established 12 wel

Analyses of a concatenated data set (5,220 nt) established 12 well-supported clades in the order; seven of these constituted a superclade, termed “Zygnemataceae.” Together with genera (Zygnema, Mougeotia) traditionally

placed in the family Zygnemataceae, the “Zygnemataceae” also included representatives of the genera Cylindrocystis and Mesotaenium, traditionally placed in the family Mesotaeniaceae. A synapomorphic amino acid replacement (codon 192, cysteine replaced by valine) in the LSU of RUBISCO characterized this superclade. The traditional genera Netrium, Cylindrocystis, and Mesotaenium were shown to be para- or polyphyletic, highlighting the inadequacy of phenotypic traits used to define these genera. Species Luminespib solubility dmso of the traditional genus Netrium were resolved as three well-supported clades each distinct in the number of chloroplasts

per cell, their surface morphology (structure and arrangement of lamellae) and the position of the nucleus or nuclear behavior during cell division. Based on molecular phylogenetic analyses and synapomorphic phenotypic traits, the genus Netrium has been revised, and a new genus, Nucleotaenium gen. nov., was established. The genus Planotaenium, also formerly Apoptosis Compound Library research buy a part of Netrium, was identified as the sister group of the derived Roya/Desmidiales clade and thus occupies a key position in the evolutionary radiation leading to the most species-rich group of streptophyte green algae. “
“This study describes the relationships between dinitrogen (N2) fixation, dihydrogen (H2) production, and electron transport associated with photosynthesis and respiration in the marine cyanobacterium Trichodesmium erythraeum Ehrenb. strain IMS101. The ratio of H2 produced:N2 fixed (H2:N2) was controlled by the light intensity and by the light

spectral composition and was affected by the growth irradiance level. For Trichodesmium cells grown at 50 μmol photons · m−2 · s−1, the rate of N2 fixation, as measured by acetylene reduction, saturated at light intensities of 200 μmol photons · m−2 · s−1. In contrast, net H2 production continued to increase with light levels up to 1,000 μmol photons · m−2 · s−1. The H2:N2 ratios increased monotonically with irradiance, and the variable fluorescence measured using a fast repetition rate fluorometer (FRRF) MycoClean Mycoplasma Removal Kit revealed that this increase was accompanied by a progressive reduction of the plastoquinone (PQ) pool. Additions of 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), an inhibitor of electron transport from PQ pool to PSI, diminished both N2 fixation and net H2 production, while the H2:N2 ratio increased with increasing level of PQ pool reduction. In the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), nitrogenase activity declined but could be prolonged by increasing the light intensity and by removing the oxygen supply.

Esoptrodinium/Bernardinium dinoflagellates

Esoptrodinium/Bernardinium dinoflagellates Selleckchem EGFR inhibitor were described in early field observations as containing relatively large brown or dark red spherical masses in the episome that were not interpreted to be food bodies at the time (Thompson 1951, Javornický 1962, 1997). In fact, the type species E. gemma was so named because of its possession in the episome of large (gem-like) red bodies described as “the most spectacular objects in an otherwise colorless, clearly transparent plasma” (Javornický 1997). These large pigmented bodies were most likely food vacuoles containing ingested red-pigmented cryptophytes

or other microalgae. Observations reported here demonstrate that Esoptrodinium can feed upon a variety of freshwater protists similar in size to itself, indicating a prey generalist strategy. Yeast and ciliate cells were only ingested (or partially ingested) after they were freeze-injured, suggesting prey detection can occur through a generalized chemosensory mechanism directed toward injured or dying prey (Spero and Morée 1981). This is more typically a behavior exhibited by dinoflagellate species that feed by myzocytosis, the suctioning of cell contents through an extensible feeding tube (Elbrächter 1991b, Hansen and Calado 1999), and may have represented an artifact of unnatural culture conditions. Among tested prey taxa, Esoptrodinium seemed to prefer as food

photosynthetic flagellates similar to somewhat smaller in size to itself ioxilan (e.g., Chlamydomonas MK-2206 and Cryptomonas). Although the tested diatom and heterotrophic flagellates (Chilomonas and Polytomella) were ingested, they did not sustain reliable growth of Esoptrodinium. The photosynthetic microalga C. ovata in particular was most suitable for promoting vigorous feeding and sustained growth of the dinoflagellates. It is unknown why Esoptrodinium died after incubation with the chrysophyte Ochromonas danica; reports of other dinoflagellates feeding on chrysophytes are rare, but it has been documented at least once previously (Ucko et al. 1989). In field samples or enrichments, Esoptrodinium-like cells have been observed to feed on chlamydomonad

and chlorelloid microalgae (Calado et al. 2006), cryptophytes, and euglenoid microalgae (our observations). Most Esoptrodinium cells in feeding populations contain several food bodies representing independent phagocytic events, the undigested remnants of which are often egested upon cell division (Fawcett and Parrow 2012). Although Esoptrodinium is rarely reported, feeding by these dinoflagellates in abundance could play a significant quantitative role in community structure and energy flow in freshwater microbial ecosystems (Elbrächter 1991a, Jeong 1999). The feeding process observed in Esoptrodinium appears congruent with the ultrastructure reported by Calado et al. (2006), who also observed that the peduncle of feeding cells exhibited a distinctly thickened outer edge (referred to here as the ABP).

pylori seropositivity, the

optimum cut-off sPGII value wa

pylori seropositivity, the

optimum cut-off sPGII value was 10.25 microg/L (sensitivity 71.6%, specificity 70.1%). Conclusions:  We demonstrated that the mean values of sPGII in a healthy Chinese population are 7 microg/L and 6 microg/L for males and females, respectively. sPGII significantly selleck chemical increases in diseased and H. pylori-infected stomach, and the best sPGII cut-off value is 8.25 microg/L in the differentiation between patients with healthy and diseased stomach mucosae. Furthermore, Chinese patients with sPGII greater than 10.25 microg/L are at greater risk of various H. pylori-related gastropathies, and are therefore prior candidates for gastro-protection therapy. “
“Background and Aim:  Contemporary medications used in the treatment of gastric ulcers involve

the use of novel mucosal protective drugs. The present study aimed to investigate the gastroprotective effect of ginger extract and polaprezinc in a rat model of acetic selleck inhibitor acid-induced gastric ulcer. Methods:  ‘Kissing’ ulcers were induced in male Sprague-Dawley rats by using 60% acetic acid. Rhizoma Zingiber officinale (ginger) extract (1.5–5 g/kg) or polaprezinc (30 and 60 mg/kg) was orally given to the animals once daily for three consecutive days after ulcer induction. All animals were killed on day 5 by an overdose of ketamine. Results:  Both ginger extract and polaprezinc significantly reduce the gastric ulcer area in a dose-dependent manner, with concomitant attenuation of the elevated activities of xanthine oxidase and myeloperoxidase, as well as malondialdehyde level in the ulcerated mucosa. Nevertheless, only polaprezinc could restore the mucosal glutathione level. Polaprezinc also causes the overexpression of basic fibroblast growth factor, vascular endothelial growth factor

and ornithine decarboxylase, whereas ginger extract only increases the expression of the two growth factors in the gastric mucosa. Furthermore, polaprezinc could consistently downregulate the protein expression of tumor necrosis factor (TNF)-α, interleukin-1β, macrophage Low-density-lipoprotein receptor kinase inflammatory protein-2 and cytokine-induced neutrophil chemoattractant-2α that have been activated in the ulcerated tissues, whereas ginger extract mainly inhibits the expression of the chemokines and to some extent TNF-α. Conclusion:  Ginger extract and polaprezinc both show anti-oxidation that consequently alleviates gastric mucosal damage and promotes ulcer healing, which together serve as effective mucosal protective agents. “
“The liver contains macrophages and myeloid dendritic cells (mDCs) that are critical for the regulation of hepatic inflammation. Most hepatic macrophages and mDCs are derived from monocytes recruited from the blood through poorly understood interactions with hepatic sinusoidal endothelial cells (HSECs). Human CD16+ monocytes are thought to contain the precursor populations for tissue macrophages and mDCs.

In this model, the parietal lobe is thought to play a pivotal rol

In this model, the parietal lobe is thought to play a pivotal role in binding together the synaesthetic perceptions (hyperbinding). In addition, we hypothesized that the auditory cortex and the fusiform gyrus would qualify as strong hubs in synaesthetes. Although synaesthetes and non-synaesthetes demonstrated a similar small-world network topology, the parietal lobe turned out to be a stronger hub in synaesthetes

than in non-synaesthetes supporting the two-stage model. The auditory cortex was also identified as a strong hub in these coloured-hearing synaesthetes (for the alpha2 band). Thus, our a priori hypotheses receive strong support. Several additional hubs (for which no a priori hypothesis has been formulated) were found to be different in terms of the learn more degree measure Crizotinib manufacturer in synaesthetes, with synaesthetes demonstrating stronger degree measures indicating stronger interconnectedness. These hubs were found in brain areas known to be involved in controlling memory processes (alpha1: hippocampus and retrosplenial area), executive functions (alpha1 and alpha2: ventrolateral prefrontal cortex; theta: inferior frontal cortex), and the generation of perceptions (theta: extrastriate cortex; beta: subcentral area). Taken together this graph-theoretical analysis of the resting state EEG supports

the two-stage model in demonstrating that G protein-coupled receptor kinase the left-sided parietal

lobe is a strong hub region, which is stronger functionally interconnected in synaesthetes than in non-synaesthetes. The right-sided auditory cortex is also a strong hub supporting the idea that coloured-hearing synaesthetes demonstrate a specific auditory cortex. A further important point is that these hub regions are even differently operating at rest supporting the idea that these hub characteristics are predetermining factors of coloured-hearing synaesthesia. “
“Impaired social cognition has been claimed to be a mechanism underlying the development and maintenance of borderline personality disorder (BPD). One important aspect of social cognition is the theory of mind (ToM), a complex skill that seems to be influenced by more basic processes, such as executive functions (EF) and emotion recognition. Previous ToM studies in BPD have yielded inconsistent results. This study assessed the performance of BPD adults on ToM, emotion recognition, and EF tasks. We also examined whether EF and emotion recognition could predict the performance on ToM tasks. We evaluated 15 adults with BPD and 15 matched healthy controls using different tasks of EF, emotion recognition, and ToM. The results showed that BPD adults exhibited deficits in the three domains, which seem to be task-dependent. Furthermore, we found that EF and emotion recognition predicted the performance on ToM.

Additionally, patients who received TACE despite poor liver funct

Additionally, patients who received TACE despite poor liver function (Child-Pugh C) and patients at BCLC stage C were excluded. The results of the training cohort were then confirmed in an independent external validation database. This database includes all HCC patients >18 years diagnosed by dynamic imaging (CT/MRI) or histology according to EASL diagnostic criteria4 who received TACE between January 2001 and January 2008 at the Medical University of Innsbruck (n = 252). The selection criteria for the validation cohort were the same as for the training cohort (Fig. 1). In both institutions the presence of Child-Pugh C cirrhosis, portal vein thrombosis,

or Eastern Cooperative Oncology Group (ECOG) >1 were considered contraindications for retreatment with TACE. This study was FK866 price approved by the Ethics Committees of the Medical Universities of Vienna and Innsbruck. Baseline imaging find more (triphasic CT/MRI

scan) was performed 5-7 days before the first TACE session. HCC was staged according to the BCLC classification2, 3 and by the International Union Against Cancer (UICC) tumor node metastasis (TNM) classification, 6th edition.13 In both institutions, radiologic tumor response was assessed by CT/MRI scan prior to the second TACE session (maximal 90 days after the first TACE) according to EASL criteria.4 Objective tumor response was defined as partial response to the first TACE session, while stable disease (SD) and progressive disease (PD) were judged as the absence of objective tumor response. Patients with complete response (CR) after the first TACE did not receive a further TACE session and were therefore not included into this study analysis. All laboratory values including AFP levels as well as liver function parameters including the Child-Pugh score14 were determined 1 day GPX6 before the first TACE session and 1 day before the second TACE session. Additionally, we determined the dynamic of the Child-Pugh score (hereafter designated Child-Pugh score increase) between the timepoints pre-TACE-1 and pre-TACE-2. All other changes of liver function

related laboratory parameters (AST, alanine aminotransferase [ALT], etc.) between the first and second TACE were performed as outlined in the Statistics section. AFP response was defined as an AFP decrease by 50% from pre-TACE-1 values of ≥200 kU/L.12 We formed three AFP groups for univariate analysis: pre-TACE-1 AFP ≥200 kU/L with response versus pre-TACE-1 AFP ≥200 kU/L and no response versus pre-TACE-1 AFP levels <200 kU/L. We recently demonstrated15 that elevated C-reactive protein (CRP) values have a strong prognostic significance for patients with HCC. Thus, CRP values (<1 mg/dL and ≥1 mg/dL) prior the second TACE were included into statistical analysis. Adverse events that occurred within 4 weeks after TACE or were unequivocally TACE-related were documented according to the Common Terminology Criteria for Adverse Events v. 3.0 (CTCAE).

The particular time interval between injections in these cases sh

The particular time interval between injections in these cases should be tailored to the individual patient’s response pattern. The medication used for injection can also be a factor in choice of treatment intervals. Bupivacaine can potentially cause myotoxicity at the site of injection, and some injectors will limit its use accordingly, although its incidence is not well established.[9] Corticosteroid injection may R788 in vivo be associated with both local and systemic AEs,

such as alopecia, cutaneous atrophy, hyperpigmentation, and Cushing’s syndrome, especially with frequent injections at high doses of the drug.[10, 11] Therefore, more caution is warranted in these cases, and injections may need to be performed less frequently to minimize systemic or local AEs. Reports have suggested that corticosteroids may be beneficial in certain headache diagnoses including CH, headache related to sexual activity, cervicogenic headaches, episodic migraine with and without aura, hemiplegic migraine with prolonged aura, chronic migraine, hemicrania continua, and post-traumatic headache.[4, 7, 8, 12-18] Corticosteroids may be beneficial in GON blocks in reducing dynamic mechanical allodynia in migraine patients.[12]

Triamcinolone, methylprednisolone, dexamethasone, betamethasone (dipropionate long-acting salt and disodium phosphate rapid-acting salt), and cortivazol are the most commonly reported corticosteroids used in the management of patient with headache disorders.[4, 7, 8, buy Z-VAD-FMK 12, 14, 16, 17] Clinically, corticosteroids used in GON blockade for the management of headache disorders are usually used in combination

with a local anesthetic. However, treatment of migraine with GON blocks using only corticosteroids has been reported.[19] Table 3 lists the commonly used corticosteroids as well as their half-life and equivalence to triamcinolone. Although the dose range of corticosteroids in GON blocks varies, with dosages as high as 160 mg of methylprednisolone reported, triamcinolone 40-60 mg, or an equivalent dose of a different steroid, in combination with a local anesthetic, may be adequate for headache disorders.[12, 14, 16, 19-21] Study results for the use of corticosteroids in GON blocks have been mixed. This may N-acetylglucosamine-1-phosphate transferase be due to the different doses and steroid types used in the different studies, as well as the variability in headache disorders evaluated. In a controlled study of patients with transformed migraine, GON block using the combination of triamcinolone and local anesthetics was not significantly more effective than injecting local anesthetic alone.[20] In a randomized controlled study of CH patients, however, the suboccipital injection of betamethasone and lidocaine was significantly more effective than saline and lidocaine in inducing headache remission.

3, 4 Besides medical management of organ dysfunction there are no

3, 4 Besides medical management of organ dysfunction there are no specific approaches to treat patients with ACLF. The use of liver transplantation check details in this context is hampered by the shortage of organs5 as well as by the high frequency of concomitant conditions that contraindicate the procedure. The use of extracorporeal albumin dialysis by the molecular adsorbent recirculating system (MARS) has been shown to remove protein-bound substances

and decrease the plasma concentrations of bilirubin, ammonium, and creatinine in patients with ACLF. In these patients, treatment with MARS was also associated with relevant hemodynamic and clinical effects, such as a decrease in portal pressure,6, 7 improvement of the hyperdynamic circulation,8 and hepatic encephalopathy.9, 10 Beneficial effects of MARS

have also been observed in other clinical settings such as refractory pruritus,11-13 acute Wilson’s disease,14 and intoxications. Furthermore, small randomized clinical trials have suggested that albumin dialysis may improve survival in ACLF.17-19 Therefore, we conducted a large, multicenter randomized controlled clinical trial to determine whether albumin dialysis using the MARS device improves survival and relevant clinical outcomes in patients with ACLF. ACLF, acute on chronic liver failure; CI, Selleckchem Abiraterone confidence interval; HE, hepatic encephalopathy; HRS, hepatorenal syndrome; INR, international normalized ratio; ITT, intention-to-treat; MARS, molecular adsorbent recirculating system; MELD, Model for Endstage Liver Disease; OR, odds ratio; PP, per protocol;

SMT, standard medical therapy. We enrolled patients at 19 European centers between April 2003 and March 2009. Eligible patients had acutely decompensated cirrhosis as defined by the existence of a presumptive diagnosis of cirrhosis with an identifiable triggering event, an increase of serum bilirubin greater than 5 mg/dL and at least one of the following findings: hepatorenal syndrome (HRS) as defined by International Ascites Club criteria; hepatic encephalopathy (HE) equal or greater than grade II as defined by the HE scoring algorithm9 (an adaptation of the West Haven Criteria); rapidly progressive hyperbilirubinemia (defined as a more than 50% increase from bilirubin levels at admission) greater than 20 mg/dL at the time of randomization. Exclusion criteria were progressive jaundice as a consequence of the natural course of cirrhosis or extrahepatic cholestasis, platelet count less than 50,000/mm3, international normalized ratio (INR) >2.

31)8 were synthesized in the

Medicinal Chemistry Laborato

31)8 were synthesized in the

Medicinal Chemistry Laboratory of the Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences, with a purity over 99.0%. The compound structure was confirmed with 1H-NMR and MS spectra. Interferon-α-2b (Intron A) was from Schering Plough (Brinny) (Kenilworth, NJ). BILN2061, a known NS3-4A protease inhibitor, was provided by Shanghai Lechen International Trading (Shanghai, China). Plasmid pcDNA3.1-Vif coding for HIV-1 full-length Vif was created by insertion of Vif (amplified BVD-523 nmr by polymerase chain reaction [PCR] from HIV-1 plasmid SVC21.BH10) into pcDNA3.1; the plasmids hA2, hA3B, hA3C, hA3F, and hA3G that express wildtype forms of hA2, hA3B, hA3C, hA3F, and hA3G, respectively, possess a fused HA tag at the C-terminus. The above-mentioned plasmids were gifts from Dr. Shan Cen at the Lady Davis Institute for Medical Research and McGill University AIDS Centre. The plasmid pFL-J6/JFH/JC1 containing the full-length chimeric

HCV cDNA was kindly provided by Vertex Pharmaceuticals (Boston, MA). Production of infectious HCV in hepatocytes was done as described.14 The plasmid pFL-J6/JFH/JC1 was restricted with XbaI and treated with Mung Bean nuclease (New England Biolabs) to generate the according HCV cDNA with T7 promotor. The cDNAs were purified and used as templates for RNA synthesis. HCV RNA was synthesized DCLK1 in vitro using a MEGAscript T7 kit (Ambion). The synthesized RNA was treated

with DNase I (New England Biolabs) and purified with Wizard Erastin cell line SV Gel and PCR Clean-Up System (Promega). The synthesized HCV RNA was used to transfect naïve Huh7.5 cells with the addition of Lipofectamine 2000 (Invitrogen). The culture medium was collected and cleaned with centrifugation at 3,000 rpm for 10 minutes. The supernatants were stored at −70°C as HCV viral stock and quantified with the Diagnostic Kit for Quantification of Hepatitis C Virus RNA (Shanghai Kehua Bio-Engineering). Huh7.5 cells 24 hours after HCV infection with viral stock (45 IU per cell) were transfected with different concentrations of APOBEC- or Vif-containing plasmids in the FuGENE HD Transfection Reagent (Roche), with pcDNA3.1 as plasmid control. Then, 72 hours later the culture medium was removed and total intracellular proteins were extracted using CytoBuster Protein Extraction Reagent (Novagen) with 1 mM protease inhibitor cocktail (Roche Applied Science). HCV Core, NS3, and hA3G protein (or APOBEC proteins with HA tag) was detected with western blot. A similar procedure was used for the experiment using GS4.3 cells, except the infection step. Huh7.5 cells were planted into the 6-well plate with 3 × 105 cells per well in the complete growth medium and infected with HCV viral stock (45 IU per cell).

Disclosures: The following people have nothing to disclose: Chris

Disclosures: The following people have nothing to disclose: Christy E. Trussoni, Patrick L. Splinter, James H. Tabibian, Steven P. O’Hara The secretin dependent biliary secretion of ions and water by transporters and/or channels is essential for the regulation of biliary flow. The cystic fibrosis transmembrane conductance regulator (CFTR) see more plays a key role in the chloride secretion into the bile. In the cystic fibrosis (CF) patients, totally 5 to 10% of patients develop the progressive biliary fibrosis resembling primary sclerosing cholangitis. The loss of CFTR in mice also leads to the liver failure. ERM (ezrin-radixin-moesin)

proteins are identified as cross-linkers between plasma membrane proteins and actin cytoskeleton. Ezrin interacts with Na+/ H+ exchanger regulatory factor-1 (NHERF1) via its N-terminal

binding domain and with actin cytoskeleton via its C-terminal actin-binding domain. CFTR is associated with NHERF1 via its c-terminal PDZ binding motif. In the liver, ezrin, but not radixin or moesin, is exclusively expressed in the cholangiocytes and colocalizes with CFTR and NHERF1 at apical membrane of cholangiocyte. In the STI571 chemical structure present study, we have found that ezrin knockdown (Vil2kd/kd) mice develop severe hepatic failure characterized by extensive bile duct proliferation, periductular fibrosis, and intrahepatic bile acid accumulation. In these mice, apical membrane localizations of CFTR and NHERF1 were disturbed in the bile ducts. Stable expression of a dominant negative form of ezrin in immortalized mouse cholangiocytes also led to the reduction of the surface expression of CFTR. Furthermore, the surface expressions of other transport proteins, which are required for the apical ion and water transport in bile duct including Anion exchanger 2 (AE-2) and aquaporin 1 (AQP1), were also disturbed in Florfenicol cholangiocytes.

Reduced surface expression of these transport proteins was accompanied by reduced CFTR-mediated Cl- efflux activity. These data suggest that dysfunction of ezrin mimics important aspects of the pathological mechanisms responsible for cholangiopathies via the regulation of apical membrane transport in bile ducts. Disclosures: The following people have nothing to disclose: Ryo Hatano, Kaori Akiyama, Shinji Asano Background. Cholangiocytes release a variety of inflammatory mediators in response to injury. Cholangiocyte release of IL-6 is of particular importance, since it is necessary for liver regeneration. However, the mechanisms regulating IL-6 in cholangiocytes are largely unknown. Since adenosine is increasingly recognized as a potent mediator of liver injury, we tested the hypothesis that extracellular adenosine induces upregulation of IL-6 in cholangiocytes in a physiologically relevant fashion. Specific Aims.