A comprehensive screen for liver disease was collected in all patients with deranged liver biochemistry. The likelihood of volatile anaesthetic related liver injury was determined by an experienced hepatologist. Results: Thirty three patients were recruited with adequate laboratory data to permit interim analysis. Twenty four experienced deranged liver biochemistry post-operatively – 7 involved a pure hepatitic picture, whilst 5 and 12 involved Erismodegib supplier a cholestatic or mixed picture respectively. There were no cases of

acute hepatic failure, although peak ALT/AST values exceeded 200 IU/L in 6 cases. Three patients experienced probable VA related liver injury. No risk factors for this outcome were identified. The most frequent aetiologies of deranged liver biochemistry NVP-BEZ235 concentration included drug reactions (18), sepsis (4), and acute alcohol ingestion (3). Causes of deranged liver biochemistry could not be determined in 3 cases. No adverse outcomes were identified. Conclusion: Deranged liver biochemistry following surgery is a common event, although progression to symptomatic liver injury is rare. The most common aetiology

is drug reactions. Probable volatile anaesthetic related liver injury is more common in this cohort than previously reported, possibly skewed by the small numbers, however risk factors for its severity and incidence remain unknown. E GANE,1 G DICKINSON,2 J WYETH,3 JJ FLAHERTY,4 B MASSETTO,4 P DINH,4 J CUSTODIO,4 M SUBRAMANIAN,4 S FUNG5 1Auckland General Hospital, Auckland, New Zealand; 2Waikato Hospital, Hamilton, New Zealand; 3Wellington Hospital, Wellington, New Zealand; 4Gilead Sciences, Foster City, CA, USA; 5University of Toronto, Toronto, ON, Canada. Background and aims: TDF has demonstrated sustained HBV suppression and a favourable safety profile through 6 years; however, data are limited in CHB patients with mild renal impairment (MRI) as they are excluded from most trials. MRI patients (CrCL 50 – <80 mL/min by Cockroft-Gault) were included in a 5 year prospective, randomized,

double-blind trial of TDF vs. FTC/TDF in lamivudine-resistant patients (Study 121) wherein no differences were observed in efficacy or safety between treatments (Fung click here S. AASLD 2012, #20). Methods: Post-hoc, interim analysis of Study 121 which compared MRI patients (74/280; 26%) and normal renal function (NRF; CrCL ≥80 mL/min) patients (206/280; 74%). Safety, including bone mineral density (BMD) monitoring by DXA, pharmacokinetics (PK; MRI patients only), and efficacy were assessed over 96 weeks. Results: At baseline (BL), mean (SD) CrCL was 67 (9) mL/min for the MRI group and 104 (18) mL/min for the NRF group. Both groups (MRI vs. NRF) were well matched except: mean age 58 vs.43 yrs (p < 0.001), males 59% vs. 81% (p < 0.001), prior IFN 18% vs. 32% (p = 0.015), and prior ADV 14% vs. 25% (p = 0.044).

g., Plaut & Shallice, 1993). Despite, however, the fruits of such epistemic changes (Lambon Ralph, 2004) to this day many cognitive neuropsychologists adhere to the original epistemological principles of the field either implicitly (see Harley, 2004 for a critical review), or explicitly

(Caramazza & Coltheart, 2006). Moreover, while some neuropsychologists welcome the insights of other neuroscientific methods, such as functional neuroimaging (e.g., Cooper & Shallice, 2010), others reject their application to neuropsychology as a neo-localizationist attempt to elucidate Panobinostat clinical trial the mind–brain relation (Coltheart, 2006; Harley, 2004; Page, 2006). This adherence to outdated principles of mental and brain functioning, and the associated reluctance to engage fully with recent methodological developments in the neurosciences may be at least partly responsible for the non-prominent position of neuropsychology among the contemporary neurosciences. Although it would be a mistake to assume that cognitive neuroscience shares no epistemological assumptions with cognitive neuropsychology (see below), cognitive neuroscientists differ from traditional cognitive neuropsychologists in both the ‘what’ and the ‘how’ they study the mind–brain interface. The advent of powerful methods of investigating the

AZD3965 neural basis of the mind in vivo have allowed cognitive neuroscientists to expand their enquiries to topics that far exceeded the traditional topics of neuropsychology, e.g., language, semantic processing and memory. Instead, topics such as emotion and empathy are now considered mainstream areas of cognitive neuroscience research. At the theoretical level, the assumption prevailing until the early 90s to the effect that the human mind can be understood by examining exclusively cognitive functions has undergone considerable criticism (see for example Fotopoulou, 2010; Fotopoulou, Conway & Pfaff, 2012). Following some extraordinary discoveries, e.g., mirror neurons in the macaque click here monkey (Di Pellegrino, Fadiga, Fogassi, Gallese & Rizzolatti, 1992), and other similar insights, a diverse and growing community of researchers views

mental abilities as defined also by emotions and motivation, as embedded in the acting, sensing and feeling body, and as subject to intricate couplings between organisms and their interpersonal, social and technological environments (e.g., Benedetti, 2010; Damasio, 1994; Decety & Ickes, 2009; Frith & Frith, 2010; Knoblich, Thornton, Grosjean & Shiffrar, 2006; LeDoux, 1996; Panksepp, 1998; Rizzolatti & Craighero, 2004). Perhaps more important to the change that took place in ‘what’ cognitive neuroscientists study, is the dramatic developments in ‘how’ they study the brain, and thus what kind of knowledge about brain–mind relations they can arrive at. Cognitive neuroscience does not need to depend on insights from the injured brain as neuropsychology does.

Conclusions:  FG-4592 clinical trial There was no significant difference in delta polyp size between the examinees with gallbladder polyps and cholelithiasis and those with gallbladder polyps only. Hence, a small proportion of subjects with gallbladder polyps and cholelithiasis, such as those with thickened gallbladder walls and an interval increase in the size of the gallbladder polyps are candidates for prophylactic cholecytectomy. “
“Transient elastography (TE) is increasingly employed in clinical practice for the noninvasive detection of tissue fibrosis in patients with chronic liver disease (CLD), and particularly chronic hepatitis C virus (HCV)-related hepatitis. The present study was designed to provide

a definitive characterization of the “confounding” increase in liver stiffness (LS) following a standardized meal in a consecutive population of 125 patients with chronic HCV infection at different stages of fibrotic evolution. LS values were obtained after overnight fasting and 15, 30, 45, 60, and 120 minutes following the onset of a standardized liquid meal (400 mL, 600 Kcal, 16.7% protein, 53.8% carbohydrates, 29.5% fat). An evident increase in LS values was observed 15 to 45 minutes after the onset of the meal with return to baseline premeal

levels within 120 minutes in all patients. The peak postmeal delta increase in LS was progressively more marked with increasing stages of fibrosis (P < 0.001), becoming maximal in patients with cirrhosis. However, the probability of identifying the Metavir stage see more of fibrosis, the Child-Pugh class, or the presence/absence of esophageal check details varices with the postmeal delta increase in LS was inferior to that obtained with baseline LS values. Conclusion: The results of the present study provide definitive evidence of the confounding effect of a meal on the accuracy of LS measurements for the prediction of fibrosis stage in patients with chronic HCV hepatitis and suggest that a fasting period of 120 minutes should be observed before the performance of TE. (HEPATOLOGY 2013;) Transient elastography

(TE) is increasingly employed in clinical practice for the noninvasive detection of tissue fibrosis in patients with chronic liver disease (CLD), and particularly chronic hepatitis C virus (HCV)-related hepatitis.1 In this clinical setting, TE has been shown to be able to discriminate between at least three stages of fibrotic evolution: the absence of significant fibrosis, the presence of advanced fibrosis/cirrhosis, and an intermediate stage, often defined as a “gray area.” This distinction is useful in everyday practice for directing the need of liver biopsy,2 and overall, the use of TE, alone or in association with other noninvasive means, considerably reduces the number of liver biopsies necessary for correct patient management.

977) with dispensing accuracy for each dosage strength group. Among Groups 1, 2 and 3, 23.0%, 44.9% and 73.4% of patients, respectively, had at least one single vial option dispensed selleck chemicals llc (P < 0.0001). A broader selection of rFVIII dosage strengths and more actual rFVIII potencies were associated with improved dispensing accuracy and more

single-vial users. This may translate into less waste, cost savings, increased convenience and improved adherence to physician-prescribed regimens. “
“Platelet function defects (PFD) are reported to occur frequently in adult women with heavy menstrual bleeding (HMB). Few studies on adolescent HMB report varying incidence rates (2–44%) for PFD. We reviewed our institutional experience in detecting and managing PFD in adolescent HMB.

Postmenarchial girls and adolescents with HMB seen at our institution undergo a comprehensive bleeding disorder work-up by paediatric haematology and paediatric gynaecology providers. Whole blood platelet aggregometry (WBPA) is performed as a second tier test after excluding thrombocytopaenia, coagulation factor PLX-4720 mouse deficiencies and Von Willebrand disease (VWD). We retrospectively reviewed the medical records of adolescents with HMB seen between June 2009 and November 2010, as approved by the Institutional Review Board. Patient demographics, clinical features, laboratory results, therapy details and patient outcome information were analysed. Overall, 114 postmenarchial girls and adolescents with HMB were evaluated; 68 patients (59%) had WBPA study performed. Nineteen patients (28%) had at least one aggregation or secretion click here defect; 12 (18%) had two or more such defects. Treatment included hormonal therapy (13/19; 68%), antifibrinolytic agents (8/19; 42%) and intra-nasal DDAVP

(3/19; 16%). Thirteen patients (81%) had improved outcome (median follow-up – 15.6 months; range of 1–66 months). In this study, PFD were identified in nearly one-third of girls with HMB, with the majority of these having two or more defects as identified by WBPA. Further prospective studies are needed to better define the prevalence and address appropriate management of HMB and other bleeding complications of PFD in adolescents. “
“Secondary factor VIII (FVIII) prophylaxis converts severe haemophiliacs (FVIII:C < 1 IU dL−1) to a moderate phenotype (FVIII:C ≥ 1 IU dL−1), however, plasma FVIII:C is a poor predictor of bleeding risk. This study used thromboelastography (TEG) and thrombin generation assay (TGA) to quantify coagulation across a 48 h rFVIII prophylaxis period. 10 severe haemophiliacs with varying clinical bleeding phenotypes received their standard rFVIII prophylaxis dose and blood samples were obtained over 48 h. Measured parameters included FVIII:C, TEG and TGA at each time point. FVIII:C pharmacokinetics (PK) and correlation between global assay parameters was performed. The FVIII:C PK parameters were consistent with previous literature.

Disclosures: John P. Sabo – Employment: Boehringer Ingelheim Pharmaceuticals, Inc. Benjamin find more Lang – Employment: Boehringer Ingelheim Pharma GmbH & Co. KG Mabrouk Elgadi – Employment: Boehringer Ingelheim Fenglei Huang – Employment: Boehringer Ingelheim Pharmaceuticals, Inc Aim: To evaluate the effect of faldaprevir at steady-state on the pharmacokinetics

and pharmacodynamics of methadone or buprenorphine/naloxone in subjects on stable opioid maintenance therapy. Methods: This was an open-label study in subjects receiving a stable dose regimen of methadone (up to a maximum of 180 mg/day) or buprenorphine/naloxone (up to a maximum of 24 mg/6 mg per day). On Day 2, subjects received 480 mg faldaprevir (loading dose) followed by 240 mg QD faldaprevir on Days 3 to 9. Blood samples were taken on Days 1 and 9 for pharmacokinetic analysis for methadone and buprenorphine/naloxone (up to 24 h post-dose) and faldaprevir (up to 96 h post-dose). Pharmacodynamics of the opioid

maintenance regimens were evaluated by the objective RG-7388 clinical trial opioid withdrawal scale (OOWS) and subjective opioid withdrawal scale (SOWS). Results: Thirty four subjects entered and completed the study; 15 on methadone, 19 on buprenorphine/naloxone. Co-administration of faldaprevir with methadone or buprenorphine/naloxone resulted in geometric mean ratios for AUC0-24,ss″, Cmax,SS

and C24,SS of si.2 for R-methadone and S-methadone, and ≤1.1 for buprenorphine and naloxone (Table 1). Similar faldaprevir exposures were observed in both the methadone and buprenorphine/naloxone treated subjects. There was no evidence of symptoms of withdrawal as evaluated by the validated OOWS or SOWS scores following co-administration of this website faldaprevir with methadone or buprenorphine/naloxone. Conclusions: No dose adjustment is required for methadone or buprenorphine/naloxone when co-administered with faldaprevir. Disclosures: Michael J. Schobelock – Employment: Boehringer Ingelheim Pharmaceuticals Inc. Lynn R. Webster – Advisory Committees or Review Panels: AstraZeneca, Boehringer Ingelheim, Covidien Mallinckrodt, Nektar Therapeutics, Orexo; Consulting: CVS Caremark, Jazz Pharmaceuticals, Neura Therapeutik, Quintiles, Ther-avance Mabrouk Elgadi – Employment: Boehringer Ingelheim Fenglei Huang – Employment: Boehringer Ingelheim Pharmaceuticals, Inc The following people have nothing to disclose: David Joseph, Robert A. Riesen-berg, Bradley Vince, Abidemi Adeniji Background: Peginterferon Lambda-1a (Lambda), a Type III interferon (IFN), exerts potent antiviral activity through a unique receptor complex with limited cellular distribution outside the liver, and is expected to have a differentiated safety profile compared to peginterferon alfa (alfa).

CT angiography has become the

primary imaging method in many centers during the past few decades, partially because of its speed in scanning, which is especially suitable for acute subarachnoid hemorrhage patients. The main disadvantages include radiation, skull base artifacts in imaging and potential harm from iodine used in the scanning.[19, 20] In our institution, CTA is not recommended for a routine. The advent of MRA may challenge the role of traditional imaging methods. MRA, requiring no radiation or iodine, is the best method especially for screening anomalies or aneurysms of intracranial arteries. With GS-1101 concentration MRA, especially with VR reconstruction, it is possible to evaluate the whole anterior circulation at one time, allowing more accurate differentiation of Az from other ACA anomalies, and easier identification of the associated aneurysms. Furthermore, the specificity and sensitivity of 3-D-TOF MRA in detecting intracranial aneurysm is comparable to DSA, as proved in our previous work in which the patient based specificity and sensitivity of 3-D-TOF R788 MRA is reported up to 94.4% and 99.2%, respectively.[21]

So, 3-D-TOF-MRA at 3.0 T may replace DSA as a contrast-free, noninvasive, and nonradiation-based modality for the diagnosis and screening of intracranial aneurysms and other vascular anomalies.[21] To our knowledge, this study has reported for the first time the use of 3-D-TOF MRA with VR in screening and diagnosing Az and associated aneurysms with high imaging quality and feasibility. However, it should be noted that image quality might be degraded by some artifacts, including equipment vibration and patient movement.[22] 3-D-TOF MRA may overestimate blood turbulence or overlook small or slow-flowing vessels.[7, 23] Therefore, it is important

for us that the thin slice of source of MRI images and MIP images must be reviewed for confirmation of the anomaly. It should take a longer selleck time to scan than CT angiography and it is unsuitable for patients with metal implants or pacemakers.[7] The higher demand for MRA scanners and workstation software may be an obstacle for its application and popularization. Despite these limitations, we still strongly recommend MRA as an initial method to either screen or preoperatively evaluate ACA anomalies with or without associated aneurysms. 3-D-TOF MRA with VR has been shown to be feasible for screening and diagnosing Az and associated aneurysms with high imaging quality. This study has been supported by the National Natural Scientific Fund of China (Contract number: 30970793). “
“This study aims to investigate the regional changes in the early onset of blindness using the deformation-based morphometry (DBM) method. A total of 15 early blindness and 30 gender- and age-matched sighted control subjects were recruited for the study.

3, 4 Intrahepatic chemokines, such as the CCR5 ligands, RANTES (regulated on activation normal T cell expressed and secreted), macrophage

inflammatory protein (MIP)-1β and MIP-1α, and the CXCR3 ligand, IP-10, are elevated in HCV patients, and the levels of some of them are reported to correlate with the severity of liver inflammation.3-5 However, the cellular source and underlying mechanism of chemokine induction during HCV infection remain elusive.2 Toll-like receptor-3 (TLR3) and the retinoic inducible gene I (RIG-I)-like receptors (RLRs; RIG-I and melanoma differentiation-associated gene 5; MDA5) constitute two parallel classes of cellular sensors

click here that recognize viral pathogen-associated molecular patterns (PAMPs) and initiate innate immune responses. Despite operating HM781-36B mouse via distinct adaptors and mechanisms, both pathways culminate in the activation of interferon regulatory factor-3 (IRF3)-dependent interferon (IFN) antiviral response and the production of nuclear factor kappa B (NF-κB)-dependent proinflammatory mediators. TLR3 and RLRs sense viral double-stranded RNA (dsRNA), a major viral PAMP, in endosomal and cytoplasmic compartments, respectively. RIG-I also recognizes viral RNAs bearing 5′-triphosphates.6 The importance of RLR and TLR3 pathways in innate immunity to HCV is suggested

by the fact that HCV encodes a serine protease, nonstructural protein (NS)3/4A, which inactivates both pathways by cleaving two adaptor proteins, mitochondrial antiviral signaling protein (MAVS) and Toll-interleukin (IL)-1 receptor homology domain containing adaptor-inducing interferon β (TRIF).7-10 Though much has been learned concerning how TLR3 and RIG-I pathways act to control see more HCV replication through activating IRF3 and antiviral interferon-stimulated gene (ISG) expression,8, 11-13 little is known about the mechanisms governing the chemokine and proinflammatory cytokine response to HCV infection. A better understanding of the latter is crucial to broadening our knowledge on immune response to, and pathogenesis of, HCV and to design new effective immunotherapies for HCV. Here, we demonstrate that TLR3 senses HCV infection in cultured hepatocytes, leading to NF-κB activation and production of proinflammatory chemokines/cytokines previously reported in hepatitis C patients. Our study also defines the molecular features of HCV dsRNA that serves as the PAMP for TLR3.

This was accomplished by measuring the incorporation of [3H]acetate into TG (Fig. 2A), and in vivo hepatic TG secretion following inhibition of VLDL metabolism with poloxamer (P-407) (Fig. 2B). We also determined ketone bodies in serum (Fig. 2C) and the in vitro secretion of acid-soluble metabolites (Krebs cycle metabolites and ketones) (Fig. 2D), as a measure of FA β-oxidation. Whereas lipogenesis and FA β-oxidation were barely altered in hepatocytes from Gnmt−/− mice (Fig. 2A,C,D), the hepatic TG secretion rate in GNMT-depleted livers was elevated compared to livers from WT animals (Fig. 2B). Consistent with these studies, a comprehensive gene expression analysis showed that, overall, the expression

of genes that supply NADPH and acyl-CoA FK228 mw for lipid synthesis was unaltered in mice JQ1 supplier without GNMT (Fig. 2E). Despite the marked hepatic steatosis, mice without GNMT did not show insulin resistance or changes in serum FA concentrations (Supporting Fig. 1a,b). Depletion of GNMT in mice did not alter food intake or body weight (Supporting Fig. 1c,d). The greater liver weight in Gnmt−/− mice was not accompanied by differences in body weight, which may be explained by the reduced mass of the white adipose tissue in these animals (Supporting Fig. 1d-f). Based on the results depicted in Fig. 2, which demonstrate that Gnmt−/− mice have increased lipid secretion without affecting lipid synthesis or

oxidation, it is not obvious how to explain the presence of fatty livers in these animals. We reasoned that an elevation of SAMe in Gnmt−/− mice

would activate the flux from PE to PC via PEMT, which would lead to increased PC catabolism and the corresponding augmentation of hepatic DG and TG production (Fig. 2). To confirm this hypothesis, we measured the incorporation of [3H]ethanolamine into PE and PC this website in hepatocytes isolated from 3-month-old Gnmt−/− mice and calculated the radioactivity incorporated into PC as a percentage of the radiolabel incorporated into PC+PE (Fig. 3A). Because PC formed via PEMT primarily contains long-chain polyunsaturated FA (PUFA), such as docosahexaenoic acid (22:6n-3), whereas PC synthesized by the CDP-choline route do not, we also determined the PC(22:6n-3) to total PC ratio in GNMT-depleted and WT livers as a marker of hepatic PEMT activity.[21] Given that PEMT activity is primarily located in the endoplasmic reticulum,[22] we measured the content of PE and PC in whole liver microsomes (Fig. 3B,C). As shown in Fig. 3, high SAMe levels in Gnmt−/− hepatocytes associated with a 2.5-fold increase in the flux from PE to PC (P < 0.001) (Fig. 3A), and an increase in the PC(22:6)/PC ratio (from 0.18 ± 0.005 in WT to 0.25 ± 0.005 in GNMT-depleted livers, P = 3.23E-06). Also as predicted, the content of PE was reduced ∼2-fold in microsomes isolated from GNMT-depleted livers (P < 0.05), whereas the amount of PC was increased 2-fold (P < 0.05) (Fig. 3B,C).

Dates of death were obtained from the Danish Civil Registration System, which is continuously updated with dates of birth, death, and emigration.22 Causes of death were ascertained from the Danish Cause of Death Registry, with review of registry data to determine whether deaths were from cirrhosis or other causes. Death from liver failure, variceal bleeding,

bacterial infection, or hepatocellular carcinoma counted as death from cirrhosis. Data linkage across data sources was made possible by the Palbociclib unique personal identifier issued to all Danish citizens at birth or immigration and used in all national databases and record systems. At the time of inclusion into the study cohort, patients with alcoholic cirrhosis were classified into five categories

according to the presence and type of cirrhosis complications: no complications; ascites alone; variceal bleeding alone; ascites and variceal bleeding; hepatic encephalopathy with or without ascites and variceal bleeding. Patients who developed complications during follow-up were Decitabine in vivo reclassified into another category if appropriate. Based on our clinical experience and a previous Danish study,23 we assumed that a given complication carried the same prognosis whether it had been present at the time of cirrhosis diagnosis or developed later. selleck In all analyses follow-up ended at death or at censoring at the end of follow-up, on 31 August 2006. Analyses were conducted separately for the five complication categories and were based on the Aalen-Johansen estimator of the probability of having died or being in a particular category of cirrhosis complications at a particular point in time during follow-up.24, 25 Ninety-five percent

confidence intervals were bootstrapped. We conducted three types of analyses which differed in the handling of complications during follow-up. In the first analysis complications were ignored, hence the Aalen-Johansen method was simplified to a Kaplan-Meier analysis yielding the cumulative mortality and the median survival time, i.e., the time to reach a cumulative mortality of 50%. In the second analysis complications were taken into account, but follow-up continued when they developed. On that basis we estimated the distribution of cirrhosis complication categories after 1 and 5 years of follow-up using the following categorization: alive without more complications; alive with more complications; dead without more complications; and dead with more complications. In the third analysis follow-up ended whenever complications developed, whereby the Aalen-Johansen method amounted to estimating the 1-and 5-year cumulative incidence (i.e., risk) of complications or death as competing events.

Physiologically, vitamins K1 and K2 (VK) act as co-factors for γ-carboxylation of prothrombin and other coagulation factors. In previous studies, VK analogs have been found to have potent negative effects on the survival of various cancer cells. We hypothesized that the well-tolerated and naturally occurring VK1

and VK2 may be used to inhibit pancreatic cancer cell survival. Methods:  Four pancreas cancer cell lines were tested. Two of these (MiaPaCa2 and PL5) were found to be sensitive check details to VK1 and VK2 (IC50 values ≤150 µM). To address the mechanisms of this effect on cell survival, we performed cell cycle and apoptosis studies using VK2 (the more potent compound). Results:  We found that VK induced caspase-dependent apoptosis in over 60% of cells in the sensitive lines at the half maximal inhibitory concentration (IC50) range. Further, this induction in apoptosis Everolimus chemical structure was antagonized by a caspase inhibitor. Accompanying apoptosis, a dose- and time-dependent

induction of extracellular signal-regulated kinase (ERK) phosphorylation occurred when sensitive lines were treated with either VK1 or VK2 at inhibitory doses. Simultaneous co-treatment of cells with a MEK1 inhibitor and VK prevented both the induction of ERK phosphorylation and the apoptosis, showing that the mitogen-activated protein (MAP) kinase pathway is central for VK-mediated apoptosis in pancreatic cancer cells. Conclusion:  These data show that naturally-occurring, non-toxic K vitamins can inhibit the survival of some pancreatic cancer cell lines. These novel, safe and clinically-utilized agents initiate a caspase-dependent

apoptosis via the MAP kinase pathway and could potentially benefit patients with pancreatic cancer either as a single agent or in combination with chemotherapy for treatment, or for prevention of recurrence of pancreas cancer post resection. “
“Ischemia and reperfusion-elicited tissue injury contributes to morbidity and mortality of hepatic surgery and during liver transplantation. Previous studies implicated extracellular adenosine signaling in liver protection. Based on the notion that extracellular adenosine signaling is terminated by uptake from the extracellular towards the intracellular compartment by selleck products way of equilibrative nucleoside transporters (ENTs), we hypothesized a functional role of ENTs in liver protection from ischemia. During orthotopic liver transplantation in humans, we observed higher expressional levels of ENT1 than ENT2, in conjunction with repression of ENT1 and ENT2 transcript and protein levels following warm ischemia and reperfusion. Treatment with the pharmacologic ENT inhibitor dipyridamole revealed elevations of hepatic adenosine levels and robust liver protection in a murine model of liver ischemia and reperfusion. Studies in gene-targeted mice for Ent1 or Ent2 demonstrated selective protection from liver injury in Ent1−/− mice.