Significantly fewer Ki67- and pH3-positive hepatocytes Depsipeptide purchase were detectable in Mdr2-/-c-MycΔ/Δ mice and regain of liver weight was significantly delayed. Similarly, Mdr2-/-c-MycΔ/Δ hepato-cytes transplanted into Fah-/—mice failed to repopulate the livers compared to c-Myc WT hepatocyte. Mechanistically, we provide evidence that c-Myc is required to maintain metabolic homeostasis in hepatocytes during chronic liver injury. Mechanistically, we provide evidence that loss of c-Myc significantly impaired oxidative phosphorylation in isolated hepatocytes. Accordingly, ATP levels were significantly

lower in Mdr2-/-c-MycΔ/Δ hepatocytes and the ATP/ADP ratio increased in Mdr2-/-c-MycΔ/Δ. Gene expression analysis identified several networks that were regulated by c-Myc including cellular assembly/organization, growth/proliferation GDC 973 and inflammatory response. Together, we provide evidence that c-Myc is a central regulator of liver homeostasis in mice with chronic liver injury in contrast to the only modest phenotype of WT mice with a deletion of c-Myc in liver. C-Myc is specifically required to prevent

liver injury and induce liver regeneration in mice with pre-existing chronic liver injury. Disclosures: Michael P. Manns – Consulting: Roche, BMS, Gilead, Boehringer Ingelheim, Novartis, Idenix, Achillion, GSK, Merck/MSD, Janssen, Medgenics; Grant/ Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis The following people have nothing to disclose: Stephanie Klett, Kristin Hanak, Bruno Guigas, Robert Geffers, Jessica Endig, Laura E. Buitrago, Silke Marhenke, Arndt Vogel Background: TIGAR is a bisphosphatase that has been linked to the inhibition of glycolysis and increased carbohydrate flux through the pentose-phosphate shunt (PPS). A PPS intermediate, xylulose-5-phosphate (X5P) has

been shown to suppress AKT phosphorylation by activating protein phosphatase 2A (PP2A). Increased AKT phosphorylation has been demonstrated to be an important determinant of sorafenib resistance in hepato-cellular carcinoma (HCC) cells. Hypothesis: Overexpression of TIGAR may improve chemosensitivity in sorafenib-resistant 上海皓元医药股份有限公司 HCC cells by inhibiting glycolysis, and promoting the formation of X5P that subsequently leads to diminished AKT phos-phorylation via PP2A activation. Methods: HepG2, Hep3B, FOCUS and HepaRG HCC cell lines were employed in this study to assess the correlation between AKT phosphorylation and TIGAR expression/chemosensitivity. Full-length human TIGAR cDNA was overexpressed in cells with low endogenous TIGAR levels (HepaRG and FOCUS). Overexpression was confirmed by real-time PCR, Western-blotting, subcellular localization studies, and biochemical assays. Cellular X5P content was assessed by HPLC-MS/MS. AKT phosphorylation was measured by Western-blotting.

We used paired biopsies to study patients who progressed to BGJ398 chemical structure bridging fibrosis (BF) or cirrhosis with patients who remained at early stages. Methods: Adult patients enrolled in one of the NASH CRN studies with 2 or more biopsies (excluding active treatment arms of the

PIVENS study) at least a year apart and in which the first biopsy had a fibrosis stage less than 3 were included. Laboratory and anthropometric data were included if available within 6 months of biopsy. All biopsies underwent blinded consensus review. The endpoint was progression to BF or cirrhosis from first to last biopsy. Chi-square, ANOVA, Kruskal-Wallis, and CochraneArmitage tests were used to assess difference between progressers and non-progressers at baseline. Multivariate logistic regression models were used to assess association with fibrosis progression. Results: 270 patients (mean age 46 years, 62% female) had at least 2 biopsies, with a mean time between first and last biopsies

of 4.4 years (range 1 to 17.3).43 (16%) showed progression to BF or cirrhosis.149 patients had laboratory data available at baseline. Patients who progressed were older, had higher ALT, AST and glucose, and were more often diabetic or had metabolic syndrome at baseline (all p<0.02). Initial biopsies of progressors had more ballooning, this website portal inflammation, Mallory Denk bodies, higher NAFLD Activity Scores, and more often showed steatohepatitis (all p≤0.02). The table shows the results of separate multivariate logistic regression models for the histological and clinical/demographic factors. Only features with p<0.05 are shown. Conclusion: Progression of NAFLD and NASH from early to late fibrosis stage is associated mainly with histological features of NASH, as well as age, higher transaminase levels and the presence of diabetes and metabolic syndrome at baseline. These data suggest that clinical models can be developed to identify patients with early stages of fibrosis at risk for progression to advanced 上海皓元医药股份有限公司 fibrosis. Baseline Findings OR 95% CI P Histological Model Portal Inflammation 2.14

1.01-4.53 0.047 Acidophil Bodies 2.30 1.03-5.16 0.04 Mallory Denk Bodies 4.91 1.68-14.37 0.004 Clinical Model Metabolic Syndrome 6.46 0.98-42.53 0.05 ALT (log U/L) 5.24 1.78-15.40 0.003 Disclosures: Elizabeth M. Brunt – Speaking and Teaching: Geneva Foundation Kris V. Kowdley – Advisory Committees or Review Panels: Abbott, Gilead, Merck, Novartis, Vertex; Grant/Research Support: Abbott, Beckman, Boeringer Ingelheim, BMS, Gilead Sciences, Ikaria, Janssen, Merck, Mochida, Vertex Arun J. Sanyal – Advisory Committees or Review Panels: Gore, Gilead, Abbott, Ikaria; Consulting: Salix, Immuron, Exhalenz, Bayer-Onyx, Genentech, Norgine, GalMed, Novartis, Echosens, Takeda; Grant/Research Support: Salix, Genentech, Genfit, Intercept, Ikaria, Takeda, Gilead; Independent Contractor: UpToDate Brent A.

Vascular endothelial growth factor (VEGF) depleted lipid-ordered membrane and increased fenestrations. The results are consistent with a sieve-raft interaction, where fenestrations form in non-raft lipid-disordered

regions of endothelial selleck cells once the membrane-stabilizing effects of actin cytoskeleton and membrane rafts are diminished. The endothelial cells are a specialized cell type that line blood and lymphatic vessels and form a monostratified layer called the endothelium. The endothelium may be continuous or discontinuous, and in some tissues the communication between the parenchyma and blood circulation can be finely tuned by the presence of special transcellular pores called fenestrations.1 Thanks to the pioneering Volasertib research buy work performed by Wisse et al.2, 3 on the ultrastructure of liver sinusoids, we know that the liver sinusoidal endothelial cells (LSECs) contain fenestrations with diameters of ∼20-250 nm and without diaphragms that are arranged in special structures called sieve plates. Several studies have stressed the importance of these special structural features of the LSEC in pathological conditions. For example, liver fibrosis and cirrhosis are associated with molecular and morphological changes of LSEC. Preclinical studies have demonstrated that LSECs undergo defenestration as an early event

that precedes liver fibrosis. This pathological change, collectively with the formation of a continuous lamina basal, is called capillarization and is thought to contribute to the increment of intrahepatic resistance, hepatocellular necrosis, and hepatic stellate cell activation.4, 5 Atherosclerosis is another clinical condition that has been associated with variability in the diameter and number of fenestrations existing in LSEC. The chylomicron-remnants, formed by the metabolism of dietary lipids, must pass through the LSEC to be metabolized by the liver parenchyma. However, only small chylomicrons (i.e., smaller than 250 nm in diameter) have access to the space

of Disse, a phenomenon referred to as sieving.3 The experimental evidence supporting this association derives MCE from studies performed in experimental models of nicotine dosage and partial hepatectomy in rats.6, 7 Other indirect evidence that seems to point in this direction is the association between fenestration variability and the susceptibility of species-dependent hypercholesterolemia after dietary manipulation. In this context, animals that more easily develop atherosclerosis and hyperlipoproteinemia are precisely those that exhibit fewer and smaller fenestrations, such as rabbits and chickens.1 Despite these clinical implications, the publications related to this field are not abundant, likely due to the technological complexity required to visualize fenestrations in LSEC.

MRI images from 21 fetuses at 16–26 weeks of gestation and eight embryos at Carnegie stage (CS)23 were investigated in the present study. Using the image data, the morphology of the liver as well

as its adjacent organs was extracted and reconstructed three-dimensionally. Morphometry of fetal liver growth was performed using simple regression analysis. The fundamental morphology was similar in all cases of the fetal livers examined. The liver tended to grow along the transversal axis. The four lobes were BMN 673 price clearly recognizable in the fetal liver but not in the embryonic liver. The length of the liver along the three axes, liver volume and four lobes correlated with the bodyweight (BW). The morphogenesis of the fetal liver on the dorsal and caudal sides was affected by the growth of the abdominal organs, such as the stomach, duodenum and spleen, and retroperitoneal organs, such as the right adrenal gland and right kidney. The main blood vessels such as inferior vena cava, portal vein and umbilical vein made a groove on the surface of the liver. Morphology of the fetal liver was different from that of the embryonic liver at CS23. The present data will be useful for evaluating the development of the fetal liver and the adjacent organs that affect its morphology. “
“Amplification of 1q is one of the most frequent chromosomal alterations in human hepatocellular

carcinoma (HCC). In this study we identified and characterized a novel oncogene, Maelstrom (MAEL), at 1q24. Amplification and overexpression of MAEL was frequently detected in HCCs BMS-907351 cell line and significantly associated with HCC recurrence 上海皓元医药股份有限公司 (P = 0.031) and poor outcome (P = 0.001). Functional study demonstrated that MAEL promoted cell growth, cell migration, and tumor formation in nude mice, all of which were effectively inhibited when MAEL was silenced with short hairpin RNA (shRNAs). Further study found that MAEL enhanced AKT

activity with subsequent GSK-3β phosphorylation and Snail stabilization, finally inducing epithelial-mesenchymal transition (EMT) and promoting tumor invasion and metastasis. In addition, MAEL up-regulated various stemness-related genes, multidrug resistance genes, and cancer stem cell (CSC) surface markers at the messenger RNA (mRNA) level. Functional study demonstrated that overexpression of MAEL increased self-renewal, chemoresistance, and tumor metastasis. Conclusion: MAEL is an oncogene that plays an important role in the development and progression of HCC by inducing EMT and enhancing the stemness of HCC. (Hepatology 2014;59:531–543) “
“Background and Aim:  Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) of unknown etiology. We aimed to identify the etiological agent of CD using a molecular cloning strategy that was particularly focused on identifying agents causing immune abnormalities and infectious agents.

This study was conducted to assess recent trends in negative appendectomy rates at our institution taking into account age, gender and ethnicity. Methods: A retrospective analysis was conducted using data from the Universitas Hospital Complex (Universitas and Pelonomi Hospitals, Bloemfontein, South Africa) from 2005 to 2009. All

patients who had undergone surgery for clinically suspected acute appendicitis at the Pelonomi and Universitas Hospitals from Ensartinib mouse 2005 to 2009 were included. Patients with incidental appendectomy were excluded, whilst those with other appendiceal pathologies, such as carcinoid and tuberculosis, who had presented as acute appendicitis, were included. The patients were stratified according to age, gender and ethnicity. Results: Between 2005 and 2009, 708 appendectomies were performed. Seven hundred and four (n = 704) of these were included in our study. Of these, 163 were negative appendectomies (23.3%). The age range was 4 to 84 years, with a median age of 20 (25th percentile 14 years and 75th percentile 29 years). The male : female ratio was 1.4 : 1. The percentage of negative appendectomies was greater this website amongst women than men (32.0% vs. 16.7%, respectively; p < 0.0001). The number of patients with negative appendices was higher in the childbearing age group (between 13 and 50) than in children (27.0% vs. 7.3%, respectively; p < 0.0001). The average rate of perforation was 32.8%

(231 of all patients). Ethnic distribution in our setting was 69.3% black patients, 11.2% white, 19.1% coloured and 0.4% other ethnic groups. When comparing negative appendectomies among patients by ethnicity, a statistically significant difference was found in the prevalence between black and white groups (18.4% vs. 39.2%, respectively; p < 0.0001). Other appendiceal histology was found in 0.9% of cases, with a prevalence of carcinoid tumour of the appendix found in 0.14% of our MCE study population. Conclusion: Negative appendectomy was found to have a relatively high prevalence, despite efforts to reduce the tendency. On the other hand, delays in referral and diagnosis may have led to an increase

of perforated appendicitis, with attendant increase in morbidity and mortality. More liberal use of imaging studies and laparoscopy should be assessed as means to improve diagnostic accuracy, particularly in children, the elderly and women of child-bearing age. Key Word(s): 1. appendicitis; 2. appendicectomy; 3. surgery; Presenting Author: WANG DAN Additional Authors: WANG JING, WANG LIBO, XU HONG Corresponding Author: XU HONG Affiliations: JiLin University Objective: To investigate the relationship between the multiple serum Helicobacter pylori antibodies and peptic ulcer or chronic gastritis, and evaluate the clinical application value of protein chip technique in detection of Helicobacter pylori infection. Methods: The antibodies CagA, VacA and Ure in 200 serum samples were detected by protein chip technique.

Little is known about chronic HBV and HCV infection and their sequelae among recent African immigrants in the United States. The aim of this study was to screen and characterize HBV and HCV infections in individuals of Somali descent in Minnesota using community-based, culturally and linguistically appropriate strategies. Methods: Individuals of Somali descent were enrolled in a prospective screening study for chronic HBV and HCV infection. Blood samples were collected and tested for hepatitis B surface antigen

(HBsAg), hepatitis B core antibody (HBcAb), hepatitis B surface antibody (HBsAb), and PS-341 molecular weight anti-hepatitis C virus antibody (anti-HCV). Follow-up testing, health education, counseling, and referral were provided to participants. Results: Overall, 425 Somalis enrolled in this study and specimens were collected from 402 individuals (94.5%) median age: 46; 55.2% Male). 16.4 participants were found to have chronic HBV infection (HBsAg+) while 33.3% had been exposed and spontaneously cleared HBV (HBsAb+ and HBcAb+). 9% participants had chronic HCV infection and 19.40% were negative for markers of HBV and HCV. Follow up and linkage to care were provided to participants with chronic infections; advice and referral were provided to those who were negative for both infections.

Conclusions: Based on our findings, chronic HBV and HCV are major health problems among Somalis immigrants Paclitaxel order and refugees. Community-based screening is an effective way to identify and provide health education and linkage to care for individuals with or at risk for viral hepatitis. Disclosures: Lewis R. Roberts – Grant/Research Support: Bristol Myers Squibb, ARIAD Pharmaceuticals, BTG, Wako Diagnostics, Inova Diagnostics, Gilead Sciences The following people have nothing to disclose: Nasra H. Giama, Abdirashid Shire, Hassan M. Shaleh, Essa A. Mohamed Introduction: Although liver diseases are an important cause of morbidity and mortality worldwide, there are few data on their

impact in Brazil. Aim: To estimate the burden of chronic viral hepatitis and liver cirrhosis in Brazil. Methods: In order to estimate the burden of chronic hepatitis and liver cirrhosis in Brazil for the year 2008, the indicator used was the disability-adjusted life year (DALY), which 上海皓元医药股份有限公司 corresponds to the sum of years of life lost due to premature mortality (YLL) and years lived with disability (YLD). To estimate YLL, deaths attributable to chronic hepatitis and cirrhosis from 2007 to 2009 were obtained from the Brazilian Mortality Information System. To obtain incidence and duration of the conditions for YLD estimates, prevalence, along with remission and mortality data were used for modeling of disease in Dismod II, a World Health Organization’s software tool. Liver cirrhosis was analyzed in three etiologic categories: “hepatitis C”, “hepatitis B” and “alcohol and other causes”.

The percentage of NK cells in the liver lymphocytes was markedly higher than that in peripheral blood (Fig. 7A). Hepatic NK cells also expressed higher levels of activation markers HLA-DR, CD38, and CD69 (Fig. 7B) and activation receptors NKp30,

NKp44, NKp46, NKG2A, and NKG2D but lower levels of inhibitory receptors CD158a and CD158b (Fig. 7C) in comparison with peripheral NK compartments. Furthermore, hepatic NK cells produced more CD107a than peripheral NK cells with all four stimulations, as described in Fig. 7D. In comparison with peripheral NK cells, hepatic NK cells produced higher levels of IFN-γ only upon PMA/ionomycin stimulation and produced less IFN-γ upon P815/anti-NCR stimulation. These data indicate that hepatic NK cells displayed higher levels of activation and cytotoxic functions than peripheral NK cells in these IA patients. We subsequently Everolimus cell line analyzed the associations between hepatic NK cell activation status and degranulation capacity and liver injury scores in IA patients. As GSK1120212 in vivo shown in Fig. 8A, the expression levels of HLA-DR and CD38 on freshly isolated

hepatic NK cells and CD107a degranulation in response to anti-ALS or anti-NCR were higher in IA patients with inflammation scores of G2 to G3 versus those with a score of G1. On the contrary, CD69 expression on liver NK cells and PMA/ionomycin

and K562 induction of CD107a degranulation were similar between these groups. The correlation medchemexpress analysis further illustrated that the expression of CD38, NKp30, and NCR-redirected CD107a on hepatic NK cells correlated positively with serum ALT levels (all P < 0.05; Fig. 8B). These data suggest that the presence of activated NK cells is closely associated with liver necroinflammation in IA patients. The current study has characterized hepatic and peripheral NK cells in HBV-infected subjects and has demonstrated that (1) activated NK cells preferentially accumulate in the livers of IA patients, in which they are skewed toward cytolytic activity dependent on increased hepatic IL-12, IL-15, and IL-18 expression and decreased IL-10 expression, and (2) the elevated NK cytolytic activity is associated with liver injury, whereas concomitant inefficient IFN-γ production may favor viral persistence in these IA patients. These findings clearly describe the immune status of NK cells in vivo and further define the potential roles of NK cells in liver injury in CHB patients. Although the hepatic NK cell frequency was reduced in IA patients, the total number of hepatic NK cells from these patients was significantly increased, as demonstrated by immunohistochemistry analyses.

32 Therefore, clopidogrel usage should be limited to those who required

double anti-platelet agents and should be restricted to a finite duration. As in the case of NSAIDs, prescription or discontinuation of aspirin and anti-platelet drugs in high-risk patients should always be a balance between harm and benefit. If these drugs were discontinued in patients who require cardio-protection or cerebrovascular protection because of peptic ulcer bleeding, would BAY 80-6946 chemical structure it jeopardize patient survival? How long should anti-platelet agents be discontinued in the post-acute phase of gastrointestinal bleeding to confer sufficient GI protection without exposing patients to risks of cardiovascular and cerebrovascular complications? In a randomized study comparing aspirin restarted on day 1 after endoscopy

versus withholding aspirin for 8 weeks until ulcer healing, elderly patients who required aspirin for coronary or cerebral vascular disease were enrolled.33 There was a trend of higher recurrent bleeding with early resumption of aspirin (18%) versus withholding aspirin (12%). However, the mortality rate was significantly higher (10-fold increase) with those who had discontinuation of aspirin for 8 weeks. The important lesson to learn is that anti-platelet agents should be restarted as soon as the patient’s bleeding ulcer

is hemodynamically stabilized and under control. Prolonged discontinuation of an anti-platelet agent will do more harm than good to these patients. As in this website the case of NSAID usage, a balance between the gastrointestinal risk and cardiovascular risk should be evaluated in patients who require long-term anti-platelet therapy. Table 2 is a suggested permutation for clinicians’ reference.34 The past two decades have witnessed tremendous advances in our understanding of peptic ulcer disease. Endoscopic therapy should always be the first-line therapy. Combination with potent acid suppressing agents adds further protection and benefit the control of bleeding. Eradication of H. pylori when medchemexpress found is an undisputable strategy. The use of NSAIDs, COX-2 inhibitors, aspirin and other anti-platelet agents poses new challenges to the management of peptic ulcer bleeding. Striking a balance between the benefit and risk of using these agents should be the most important rule of thumb. I wish to thank my team of physicians, surgeons and nurses at the Prince of Wales Hospital Hong Kong, whom I have been working closely with over the last 20 years for all of these fruitful results. The expedition of research on peptic ulcer bleeding management has been an exciting and rewarding experience.

32 Therefore, clopidogrel usage should be limited to those who required

double anti-platelet agents and should be restricted to a finite duration. As in the case of NSAIDs, prescription or discontinuation of aspirin and anti-platelet drugs in high-risk patients should always be a balance between harm and benefit. If these drugs were discontinued in patients who require cardio-protection or cerebrovascular protection because of peptic ulcer bleeding, would Dasatinib clinical trial it jeopardize patient survival? How long should anti-platelet agents be discontinued in the post-acute phase of gastrointestinal bleeding to confer sufficient GI protection without exposing patients to risks of cardiovascular and cerebrovascular complications? In a randomized study comparing aspirin restarted on day 1 after endoscopy

versus withholding aspirin for 8 weeks until ulcer healing, elderly patients who required aspirin for coronary or cerebral vascular disease were enrolled.33 There was a trend of higher recurrent bleeding with early resumption of aspirin (18%) versus withholding aspirin (12%). However, the mortality rate was significantly higher (10-fold increase) with those who had discontinuation of aspirin for 8 weeks. The important lesson to learn is that anti-platelet agents should be restarted as soon as the patient’s bleeding ulcer

is hemodynamically stabilized and under control. Prolonged discontinuation of an anti-platelet agent will do more harm than good to these patients. As in buy PLX4032 the case of NSAID usage, a balance between the gastrointestinal risk and cardiovascular risk should be evaluated in patients who require long-term anti-platelet therapy. Table 2 is a suggested permutation for clinicians’ reference.34 The past two decades have witnessed tremendous advances in our understanding of peptic ulcer disease. Endoscopic therapy should always be the first-line therapy. Combination with potent acid suppressing agents adds further protection and benefit the control of bleeding. Eradication of H. pylori when 上海皓元医药股份有限公司 found is an undisputable strategy. The use of NSAIDs, COX-2 inhibitors, aspirin and other anti-platelet agents poses new challenges to the management of peptic ulcer bleeding. Striking a balance between the benefit and risk of using these agents should be the most important rule of thumb. I wish to thank my team of physicians, surgeons and nurses at the Prince of Wales Hospital Hong Kong, whom I have been working closely with over the last 20 years for all of these fruitful results. The expedition of research on peptic ulcer bleeding management has been an exciting and rewarding experience.

9, 10 Although the effect of albumin on cardiac output is simply Gefitinib attributed, in current opinion, to its ability to increase cardiac preload, the action of albumin in this situation can be far more complex. First, albumin binds many substances such as NO, reactive oxygen species

(ROS), and proinflammatory cytokines,11-14 which may be involved in the pathogenesis of both the peripheral arterial vasodilatation and the cardiac dysfunction in cirrhosis and ascites. In addition, it can be hypothesized that in cirrhosis, as in sepsis, albumin can exert a positive inotropic effect in the cardiac tissue through an inhibitory effect on the expression and activity of iNOS.15 The aim of our study was to verify in an animal model of cirrhosis with ascites if albumin infusion can improve cardiac contractility through a mechanism that is independent of the increase of the preload, and to define its possible molecular basis. Adcy3, adenylate cyclase

3; β-AR, beta-adrenergic receptor; BDL, bile duct-ligated; BSA, bovine serum albumin; CCl4, carbon tetrachloride; DTT, dithiothreitol; find more EGTA, ethylene glycol tetraacetic acid; ELISA, enzyme-linked immunosorbent assay; Gαi2, Gαi2 protein; Gαs, Gαs protein; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HES, hydroxyethyl starch; HPRT, hypoxanthine guanine phosphoribosyl transferase; HRS, hepatorenal syndrome; iNOS, inducible nitric oxide synthase; LVDP, left ventricular developed pressure; NAD(P)H, nicotinamide adenine dinucleotide phosphate; NF-κB, nuclear factor-κB; NO, nitric oxide; PKA, protein kinase A; PMSF, phenylmethylsulfonylfluoride; PRA, plasma renin activity; ROS, reactive oxygen species; SBP, spontaneous bacterial peritonitis; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; TNF-α, tumor necrosis factor α. The study was performed in conscious, male, adult Wistar-Kyoto rats with cirrhosis and ascites, and in 上海皓元 conscious, male, adult Wistar-Kyoto control rats. The study was conducted in accordance with the principles and procedures outlined

in the National Institutes of Health Guide for the Care and Use of Laboratory Animals and was approved by the Italian Ministry of Health (approval on September 8th 2006 by the Italian Ministry of Health according to legislative decree no. 116/92). Cirrhosis was induced in adult (200-225 g) male Wistar-Kyoto rats (Charles River, Calco, Italy) by exposing the animals to the inhalation of carbon tetrachloride (CCl4) twice a week up to ascites appearance, as described.16 Thirty rats with cirrhosis and ascites and 30 control rats were housed in environmentally controlled facilities and allowed free access to chow and distilled water containing phenobarbital (Luminal 0.3 g/L, Bracco, Milan, Italy).