7E). Last, starvation caused greater elevations of serum BOH levels in Jα18−/− mice, compared to WT mice (Fig. 7F). These data confirm that it was the deletion of NKT cells that rendered mice more susceptible to AILI. Our data demonstrate that NKT cell-deficient mice are more susceptible to AILI than WT mice. This is the result, in part, to starvation-induced up-regulation

of CYP2E1 protein selleck inhibitor expression and activity, which is associated with marked increases in hepatic APAP protein adduct formation. Starvation also caused greater elevations of ketone bodies in NKT cell-deficient mice, which may account for the increase in CYP2E1 protein levels. Upon activation, NKT cells rapidly produce cytokines, such as interleukin (IL)-4 and IFN-γ.9 Many studies have shown both protective and pathological functions of these PD0325901 cytokines in liver disease models.22, 23 Based on these findings, we examined whether differential production of these cytokines between WT and CD1d−/− mice may explain the increased susceptibility of NKT cell-deficient mice to AILI. However, message levels of a number of cytokines were similar in liver tissues and isolated liver mononuclear cells (in which NKT cells are enriched) from APAP-treated WT and CD1d−/− mice (data not shown). These results suggest that APAP treatment does not trigger NKT cells to produce protective cytokines. It is established that

APAP Carbohydrate metabolism to NAPQI and its covalent modification of liver proteins are essential in triggering hepatocyte damage.16 Because a series of downstream events, such as mitochondrial dysfunction, ATP depletion, and DNA damage, take place before

ALT release, there is a delay between NAPQI generation and increase of serum ALT levels. Compared to WT mice, CD1d−/− mice had significantly higher levels of APAP protein adducts as early as 2 hours post-APAP (Fig. 2); however, depending on the dose of APAP, a significantly higher ALT level was not observed until 8 (Supporting Fig. 2) or 24 hours after APAP challenge (Fig. 1). GSH plays a pivotal role in AILI through scavenging of NAPQI. It has been demonstrated that mice deficient in both IL-10 and IL-4 (IL-10/4−/− mice) are more susceptible to AILI, compared to WT mice. This appears to be the result of lower GSH levels in IL-I0/4−/− mice before, and more dramatically after, APAP challenge.24 We observed no differences in total GSH levels in livers of naïve or starved WT and CD1d−/− mice (Fig. 4). Although there appears to be a slight delay in GSH rebound in the CD1d−/− mice at 8 hours, GSH levels were similar in WT and CD1d−/− mice at 19 hours after APAP treatment. Furthermore, we did not observe significant differences in expression and holoenzyme formation of glutamate cysteine ligase, the rate-limiting enzyme for GSH synthesis (data not shown).

7E). Last, starvation caused greater elevations of serum BOH levels in Jα18−/− mice, compared to WT mice (Fig. 7F). These data confirm that it was the deletion of NKT cells that rendered mice more susceptible to AILI. Our data demonstrate that NKT cell-deficient mice are more susceptible to AILI than WT mice. This is the result, in part, to starvation-induced up-regulation

of CYP2E1 protein phosphatase inhibitor library expression and activity, which is associated with marked increases in hepatic APAP protein adduct formation. Starvation also caused greater elevations of ketone bodies in NKT cell-deficient mice, which may account for the increase in CYP2E1 protein levels. Upon activation, NKT cells rapidly produce cytokines, such as interleukin (IL)-4 and IFN-γ.9 Many studies have shown both protective and pathological functions of these 3-MA order cytokines in liver disease models.22, 23 Based on these findings, we examined whether differential production of these cytokines between WT and CD1d−/− mice may explain the increased susceptibility of NKT cell-deficient mice to AILI. However, message levels of a number of cytokines were similar in liver tissues and isolated liver mononuclear cells (in which NKT cells are enriched) from APAP-treated WT and CD1d−/− mice (data not shown). These results suggest that APAP treatment does not trigger NKT cells to produce protective cytokines. It is established that

APAP mafosfamide metabolism to NAPQI and its covalent modification of liver proteins are essential in triggering hepatocyte damage.16 Because a series of downstream events, such as mitochondrial dysfunction, ATP depletion, and DNA damage, take place before

ALT release, there is a delay between NAPQI generation and increase of serum ALT levels. Compared to WT mice, CD1d−/− mice had significantly higher levels of APAP protein adducts as early as 2 hours post-APAP (Fig. 2); however, depending on the dose of APAP, a significantly higher ALT level was not observed until 8 (Supporting Fig. 2) or 24 hours after APAP challenge (Fig. 1). GSH plays a pivotal role in AILI through scavenging of NAPQI. It has been demonstrated that mice deficient in both IL-10 and IL-4 (IL-10/4−/− mice) are more susceptible to AILI, compared to WT mice. This appears to be the result of lower GSH levels in IL-I0/4−/− mice before, and more dramatically after, APAP challenge.24 We observed no differences in total GSH levels in livers of naïve or starved WT and CD1d−/− mice (Fig. 4). Although there appears to be a slight delay in GSH rebound in the CD1d−/− mice at 8 hours, GSH levels were similar in WT and CD1d−/− mice at 19 hours after APAP treatment. Furthermore, we did not observe significant differences in expression and holoenzyme formation of glutamate cysteine ligase, the rate-limiting enzyme for GSH synthesis (data not shown).

Results:  The crude rate of CC in HK increased from 29.6/100 000 in 1983 to 57.1/100 000 in 2006. Age standardized

rate (ASR) increased by less than 20%. It was markedly smaller than the 190% increase in crude rate. ASR progressively increased in males. In females, ASR peaked in 1994 and declined Stem Cell Compound Library in the last decade. In most countries, the risk of CC was higher and increasing in males, but stable or decreasing in females. With respect to age, increasing risk was noted in males above 60 years old and females above 70 years old. However, a declining rate was noted in those below 50 years old. The decrease was over 40% in the 30–34 years group over the past two decades. Conclusions:  Increasing incidence of CC in HK was mostly in the older and

male population, but not in the younger age group. Increasing incidences of colorectal cancer (CC) have been noted in Asian countries.1–4 The overall prevalence of advanced colorectal neoplasm in asymptomatic Asians was also comparable to other developed countries.5 Some studies had shown a recent decrease in age-standardized rate (ASR), especially in the younger population, in some countries.6,7 Only the rising incidence over the last two decades, but Cyclopamine nmr not the recent decrease of ASR in some Asian countries, was reported in the recent Asia Pacific Consensus.8 It is thus important to re-examine the local ASR using reliable data to determine whether there is a rising risk of colorectal cancer locally and furthermore, the

age groups that are responsible for the increase, if present. For this reason, a study examining the ASR and the actual incidence of colorectal cancer in different age groups in the last two decades in Hong Kong was conducted. The trends of colorectal cancer in Hong Kong and some other countries were compared. Data of patients with newly diagnosed colorectal cancer during the period 1983–2006 was obtained from the Hong Kong Cancer Registry.9 The cases of colorectal cancer corresponded to the C18–C21 code of the tenth revision of the International Classification of Disease (ICD-10). The Hong Kong Cancer Registry is population-based and is a member of the International Association of Cancer Registries. It has a series of comprehensive cross-checking programs to ensure the accuracy of the Fossariinae data. This registry has access to practically all hospital/laboratory cancer data in both private and public sectors. The sources of information include: all clinical oncology centers and pathology departments in public hospitals and departments of health, discharge summaries from all public hospitals, case summaries from all radiotherapy departments in the private sector, most pathology departments/institutes in the private sector, registered deaths from the government births, deaths and marriages registry, and voluntary notification from medical practitioners. Population data during the corresponding period were obtained from the Hong Kong Census and Statistics Department.

Results:  The crude rate of CC in HK increased from 29.6/100 000 in 1983 to 57.1/100 000 in 2006. Age standardized

rate (ASR) increased by less than 20%. It was markedly smaller than the 190% increase in crude rate. ASR progressively increased in males. In females, ASR peaked in 1994 and declined http://www.selleckchem.com/products/AZD6244.html in the last decade. In most countries, the risk of CC was higher and increasing in males, but stable or decreasing in females. With respect to age, increasing risk was noted in males above 60 years old and females above 70 years old. However, a declining rate was noted in those below 50 years old. The decrease was over 40% in the 30–34 years group over the past two decades. Conclusions:  Increasing incidence of CC in HK was mostly in the older and

male population, but not in the younger age group. Increasing incidences of colorectal cancer (CC) have been noted in Asian countries.1–4 The overall prevalence of advanced colorectal neoplasm in asymptomatic Asians was also comparable to other developed countries.5 Some studies had shown a recent decrease in age-standardized rate (ASR), especially in the younger population, in some countries.6,7 Only the rising incidence over the last two decades, but Selleck Dactolisib not the recent decrease of ASR in some Asian countries, was reported in the recent Asia Pacific Consensus.8 It is thus important to re-examine the local ASR using reliable data to determine whether there is a rising risk of colorectal cancer locally and furthermore, the

age groups that are responsible for the increase, if present. For this reason, a study examining the ASR and the actual incidence of colorectal cancer in different age groups in the last two decades in Hong Kong was conducted. The trends of colorectal cancer in Hong Kong and some other countries were compared. Data of patients with newly diagnosed colorectal cancer during the period 1983–2006 was obtained from the Hong Kong Cancer Registry.9 The cases of colorectal cancer corresponded to the C18–C21 code of the tenth revision of the International Classification of Disease (ICD-10). The Hong Kong Cancer Registry is population-based and is a member of the International Association of Cancer Registries. It has a series of comprehensive cross-checking programs to ensure the accuracy of the Amisulpride data. This registry has access to practically all hospital/laboratory cancer data in both private and public sectors. The sources of information include: all clinical oncology centers and pathology departments in public hospitals and departments of health, discharge summaries from all public hospitals, case summaries from all radiotherapy departments in the private sector, most pathology departments/institutes in the private sector, registered deaths from the government births, deaths and marriages registry, and voluntary notification from medical practitioners. Population data during the corresponding period were obtained from the Hong Kong Census and Statistics Department.

Other specific amino acid residues in the DRβchain appear to contribute to susceptibility or resistance to PBC. Genome-wide analysis and resequencing of the entire HLA region will be necessary to provide more precise genetic information on susceptibility to PBC in Japan. The authors thank Yuki Akahane and Asami Yamazaki for their technical assistance, and Trevor Ralph for his editorial assistance. Additional Supporting Information may be found in the online version of this article. “
“Aim:  This study was conducted to clarify the incidence of hepatocellular carcinoma (HCC) and the factors contributing to its occurrence by following chronic hepatitis C patients who received pegylated interferon (PEG-IFN) α-2b

plus

ribavirin (RBV) combination therapy. Methods:  Patients who received PEG-IFN GSK2126458 nmr α-2b and RBV combination therapy with no history of HCC or HCC within 3 months after the start of treatment were observed for the onset of HCC at 67 centers. Results:  Sustained virological response (SVR) was observed in 999 (53.5%) of 1865 patients eligible for analysis. During the observation period (median duration: 4 years and 3 months), HCC developed in 59 patients (3.1%). A significant difference was observed in the 5-year cumulative incidence of HCC between SVR and non-SVR patients (1.1% vs. 7.1%). Factors contributing to HCC selected in multivariate analysis were therapeutic efficacy, sex, age, alanine aminotransferase (ALT) level at 24 weeks

after the end of treatment, and platelet count. Non-SVR patients with Y-27632 in vitro ALT improvement after the end of treatment had a significantly Small molecule library in vitro lower 5-year cumulative incidence of HCC than those without (3.4% vs. 11.0%). HCC developed in 10 patients who achieved SVR, and multivariate analysis indicated that ALT level at 24 weeks after the end of treatment was the only significant factor contributing to HCC. Conclusion:  Several known risk factors for HCC contributed to HCC in patients who received PEG-IFN α-2b and RBV combination therapy, and ALT abnormality after the end of treatment contributes to the onset of HCC in both non-SVR and SVR patients. “
“Sphincter of Oddi dysfunction (SOD) refers to a motor abnormality of the sphincter of Oddi, typically resulting in a hypertonic sphincter, and may be manifested clinically by chronic abdominal pain, pancreatitis, or abnormal liver function tests. In this review, we discuss the classification systems typically used in SOD, as well as the epidemiology of this controversial disease. The diagnostic criteria for SOD are presented, and the evaluation of patients with suspected SOD is reviewed. Both non-invasive and invasive diagnostic methods are discussed. Sphincter of Oddi manometry (SOM) is the only available method to measure motor activity directly, and is considered to be the gold standard for evaluating patients for SOD. Indications, performance, and complications of this technique are reviewed.

2, 5, 20 Here we describe an Arab-Iranian family in which several

individuals developed cirrhosis of unknown etiology. Homozygosity mapping was used to identify homozygous regions of genomic DNA that were shared by two affected cousins but not by an unaffected family member. The two affected individuals in the family who were available for sampling were homozygous for an inactivating mutation in HSD3B7. The family is remarkable for the variability in age of onset and clinical severity of the disease among affected members. ALT, alanine aminotransferase; ALKP, alkaline phosphatase; AST, aspartate aminotransferase; CT, computerized tomography; FAB-MS, fast atom bombardment ionization mass spectrometry; GGT, gamma glutamyl transferase; SNP, single nucleotide polymorphism. LY2606368 molecular weight The study protocol was approved by the University of Texas Southwestern Institutional Review Board. Fasting blood samples were collected after written informed consent was obtained. Plasma and serum were isolated, aliquoted, and stored at −80°C. Fasting serum levels of glucose, lipids/lipoproteins, and liver enzymes were

measured using an automated analyzer and genomic DNA was extracted from blood using an AutopureLS DNA Extractor (Qiagen, Germantown, MD). To detect candidate genomic regions of extended homozygosity, DNA from the proband (III.14), an affected first cousin (III.5), and an unaffected first cousin (III.6) was very assayed for 2.4 million single nucleotide polymorphisms (SNPs) using the HumanOmni 2.5BeadChip microarray (Illumina, San Diego, CA). Briefly, genomic DNA was denatured and amplified Idasanutlin datasheet overnight at 37°C. The amplified DNA was enzymatically fragmented and then incubated overnight at 48°C with the BeadChip containing locus-specific 50-mer

probes. The array was then washed and a single-base extension reaction was performed using labeled nucleotides to extend the captured DNA template. The BeadChip was imaged using the iScan system and visualized using GenomeStudio software (v. 2010.2). The genotypes from the microarrays were exported from GenomeStudio and analyzed using Partek Genomics Suite software (Partek, St. Louis, MO). All samples were successfully genotyped for >99.4% of all SNPs. Genotypes were analyzed using a Hidden Markov Model to identify extended regions of homozygosity. Homozygosity was compared between the samples using custom Perl scripts. The nine exons of HSD3B7 were amplified by polymerase chain reaction (PCR) from genomic DNA of the proband using flanking oligonucleotides exactly as described.3 Negative ion FAB-MS was used to analyze the bile acids in the serum (0.5 mL) exactly as previously described.21 A 24-year-old Arab woman (III.14) from the southwestern region of Iran (Khuzestan) presented with cirrhosis of unknown etiology complicated by portal hypertension, varices, ascites, and hypersplenism.

couchii is an intermediate host. This host-parasite relationship indicates that fin whales probably also feed on N. couchii in the NEA (Gregori et al. 2012). The diet of humpback whales in the NEA is poorly studied, although they are known to be generalists feeding on amphipods, capelin, clupeids and krill (Piatt et al. 1989, Skern-Mauritzen et al. 2011). They have been observed foraging in association with fin whales in the CS (Whooley et al. 2011). In the CS, fin and humpback whales associate with a seasonal inshore movement of spawning herring (Clupea harengus) (Whooley et al. 2011). These herring comprise

two stocks targeted by a single fishery. Historically, these stocks have collapsed possibly as a result of a combination click here of over-exploitation and environmental factors (Lynch et al. 2011, Harma et al. 2012). Sprat (Sprattus sprattus) is a major bycatch component of other fisheries in the CS (e.g., for groundfish and herring), but there is also a targeted fishery that is not currently managed or assessed by the Intergovernmental Counsel for the Exploration

of the Seas (ICES) for which there is an open quota (Enever et al. 2007). Moreover, sprat are recognized as an important prey for several predators in the CS ecosystem (Trenkel et al. 2005, Chivers et al. 2012). In order to effectively conserve fin and humpback whales in the CS, their basic requirements and roles in the ecosystem must be identified, so that threats to their habitat, survival, CH5424802 and population

http://www.selleck.co.jp/products/CAL-101.html growth can be identified and alleviated. Towards achieving this goal, the present study aims to estimate relative contributions of krill and clupeid fish in the diet of fin whales and humpback whales that occur sympatrically in the Celtic Sea (CS) using stable isotope Bayesian mixing models. It is hoped that this information may aid the development of ecosystems based approach to fisheries management. The study area comprised the CS and coastal waters to the south of Ireland (Fig. 1). A literature review and photographic evidence of surface active feeding were used to identify a priori the most likely prey (sources) contributing to the diet of both fin and humpback whales (mixture) in the CS. Herring (C. harengus) and sprat (S. sprattus) were caught by pelagic trawl during dedicated herring fisheries surveys and plankton samples were collected in a ring net (1 m diameter, 360 μm mesh) using vertical tows. Plankton samples were collected during February 2010 and fish samples were collected on 18 October 2010 from the RV Celtic Explorer. Skin biopsies were collected from whales between November 2009 and July 2011. Species identification of zooplankton was carried out under the microscope. Skin biopsies were collected from fin and humpback whales from small boats (5–12 m) using modified bolts (CETA-DART) fired from a crossbow (150 lb draw-strength).

Demographic characteristics in each fibrosis stage group were evenly distributed, including race, gender, HIV status, and HBsAg status, although persons with more severe fibrosis were generally older (P < 0.01). We observed that SBA (mU/mL) decreased with increasing liver disease stage (Fig. 4B). For reference, serum albumin, bilirubin, and APRI levels were compared at contemporaneous timepoints (Fig 4C-E) and were similarly found to have significant

AZD6244 purchase changes with advanced liver disease. The role of BCHE in the pathogenesis of liver fibrosis is contingent on its decreased expression before the onset of advanced liver fibrosis. To test the temporal relationship of BCHE expression with liver fibrosis, SBA was measured in fibrosis progressors and nonprogressors at four regularly spaced timepoints that spanned the progression of fibrosis from minimal disease to cirrhosis in the progressors (Table 2). The median (range) time between visits was 4 (1.5–6) years in progressors, and 4.4 DMXAA supplier (1.6–6.2) years in non-progressors.

Median SBA was lower in progressors compared with nonprogressors at timepoint 1 (adj. P = 0.04), timepoint 3 (adj. P = 0.04), and timepoint 4 (adj. P = 0.00057). Indeed, all intermediate timepoints showed steady and significant decreases of SBA except between timepoints 1 and 2 (Fig. 5A). These results were compared with serum albumin, a well-characterized clinical marker of impaired liver synthetic function in persons with advanced liver disease. Serum albumin was only significantly lower in progressors compared with nonprogressors Smad inhibitor after the establishment of cirrhosis (Fig. 5b). To confirm that earlier decreases of SBA compared with albumin were not simply due to methodologic differences in the performance of those assays, serum bilirubin was tested in the longitudinal cohort; bilirubin was not different

between and within the two groups at any stage (data not shown). Interestingly, SBA in nonprogressors was significantly lower at timepoint 3 (adj. P = 0.007) and timepoint 4 (adj. P = 0.0001) compared with timepoint 1, confirming that decreased BCHE expression occurs before the onset of significant fibrosis. In contrast, serum albumin levels were not different between any timepoints in the nonprogressors, confirming that its decrease is a result of impaired liver function. In the setting of chronic viral hepatitis, the portal tracts become chronically inflamed and contain mononuclear cells including B cells, T cells, and monocytes. The hepatic lobules also have chronic inflammation in chronic HCV, but generally less so. To confirm enrichment of cellular inflammation in portal tracts, 18 segments from portal tract transcriptomes of the original nine subjects were compared with 54 hepatocyte transcriptomes from the same subjects, yielding 801 differentially expressed genes: 71 genes were up-regulated in portal tracts, whereas 730 genes were up-regulated in hepatocytes.

Then the labeled cells were washed and incubated with anti-FITC-conjugated magnetic beads (Miltenyi Biotec). Positive cells were sorted using columns and a MACS kit (Miltenyi Biotec). Finally, the purities were tested (>90%). The purified γδ T cells were stimulated

with either IL-1β or IL-23 or the combination for 48 hours. The supernatants were collected for measurement of IL-17A. The remaining cells were directly stained for intracellular IL-17A either without additional stimulation or with phorbol-12-myristate-13-acetate (PMA, 50 ng/mL; Sigma-Aldrich), ionomycin (1 μg/mL; Sigma-Aldrich), and monensin (5 μg/mL; Sigma-Aldrich) for 5 hours. To measure IL-23 secretion by macrophages stimulated with HMGB1, peritoneal macrophages were harvested from TLR4+/+ mice or TLR4−/− mice 3 days after treatment with Linsitinib 3% sodium thioglycolate. The cells were stimulated with HMGB1 (20 ng/mL, eBioscience) for 18 hours and the supernatant was see more collected for IL-23 measurement. The concentrations of IL-17A, IL-23, IL-23p40, and HMGB1 were measured by a standard enzyme-linked immunosorbent

assay (ELISA). The following ELISA kits were used: IL-17A and IL-23p40 (Dakewe Biotech, Shenzhen, China); IL-23 (Biolegend, USA); and HMGB1 (Yanhui Biotech, Shanghai, China). To isolate hepatic leukocytes, livers were pressed through a 200G stainless steel mesh and suspended in PBS. The suspension was centrifuged at 50g for 1 minute. PDK4 The supernatant was then transferred into a new tube and centrifuged at 800g for 10 minutes. The pellets were resuspended in 40% Percoll and centrifuged at 1,260g for 15 minutes at room temperature. The pellets were resuspended and the cell number was determined. To detect hepatic neutrophils, 1 × 106 cells were stained with specific mAb against mouse FITC-CD11b (M1/70, BD Bioscience, USA), PE-Ly6G (1A8, BD Bioscience), Percp-Cy5.5-CD45.2 (104, BD Bioscience), and APC-Gr-1 (RB6-8C5, BD Bioscience). To detect

γδ T cells, 1 × 106 cells were stained with specific mAb against mouse FITC-γδTCR (GL3, eBioscience), PE-CD3 (145-2C11, BD Bioscience), and Percp-Cy5.5-CD45.2 (104, BD Bioscience). To detect IL-17A+ cells, 1 × 106 cells were stimulated with PMA (50 ng/mL), ionomycin (1 μg/mL), and monensin (5 μg/mL) for 4 hours. The cells were stained with FITC-CD4 (RM4-5, BD Bioscience), Percp-Cy5.5-CD3 (145-2C11, BD Bioscience), APC-γδTCR (GL3, eBioscience), and PE-CY7-NK1.1 (PK136, BD Bioscience), and then intracellularly stained with PE-IL-17A (BD Bioscience) after fixation and permeabilization. Finally, the stained cells were analyzed using a FACSCalibur (BD Biosciences) or BD LSR II (BD Biosciences) flow cytometer. The acquired data were analyzed using FlowJo software. Data are presented as the mean ± standard error of the mean (SEM). The significance of differences was determined using a two-tailed unpaired t test; the significance levels are marked *P < 0.05; **P < 0.01; ***P < 0.005.

Indeed, by attenuating adenosine uptake, and concomitant increases of spontaneously formed extracellular adenosine levels, endogenously generated levels of extracellular

adenosine could become sufficient to trigger immunosuppressive adenosine receptor signaling events within the inflamed liver tissue microenvironments in vivo.[16, 17] In other words, the molecular concept is that pathophysiologically induced elevations of extracellular adenosine can provide better liver protection, if they are elevated over a longer time period, which can be achieved by adenosine uptake inhibitors, or by genetically targeting individual adenosine transporters. Therefore, we combined Idelalisib chemical structure studies of ENT transcript and protein levels in biopsy samples obtained from patients undergoing liver transplantation with pharmacologic and genetic studies in a previously described model of murine partial hepatic ischemia and reperfusion.[8, 9, 18] These studies demonstrated a selective role for ENT1 in elevating hepatic adenosine levels and conveying liver protection from ischemia and reperfusion injury. Liver samples were obtained from patients undergoing orthotopic

liver transplantation (Supporting Table 1). Liver biopsies (I) were taken at the conclusion of cold ischemia time (CIT) during find more back table preparation of the cadaveric liver allograft (Fig. 1A). A second biopsy (R) was taken immediately prior to closure of the abdomen following

drain placement (Fig. 1A). Importantly, total reperfusion time is defined as the time from portal vein perfusion to abdominal closure at the conclusion of the procedure. All animal protocols were in accordance with the University of Colorado, Denver guidelines. Idoxuridine Ent1 on the C57BL/6J strain were generated, validated, and characterized as described.[19] Ent2-deficient mice were obtained from Taconic Farms. Conditional hypoxia-inducible factor 1 alpha (HIF1α)loxP/loxP Albumin Cre+ mice were obtained by crossing HIF1αloxP/loxP with Albumin Cre+ mice (Jackson Laboratory). In all control experiments, age-, gender-, and weight-matched littermate controls were used. In an effort to avoid mesenteric congestion, a murine model of partial liver ischemia was employed using a hanging-weight system as described.[18] Ent1 and Ent2 transcript levels were measured by reverse-transcription polymerase chain reaction (RT-PCR) (iCycler, Bio-Rad Laboratories) as described.[20] In both human and mouse tissues Ent1 and Ent2 protein content was determined at different timepoints as described.[20] Liver preparation was performed as described in detail by Wei and colleagues.[21] IFN-γ, IL-6 (R&D Systems), and neutrophil sequestration was quantified according to the manufacturer’s instructions. Livers were removed and immediately snap-frozen after 45 minutes of liver ischemia without reperfusion. Adenosine was measured as described.