No stent migration was occurred in inoperable patients. Stent obstruction in inoperable patients was developed in 15.9% (7/44) during follow up period. Conclusion: The modified fully covered SEMS may be useful to prevent stent migration in patients with distal malignant biliary obstruction. Long-term STA-9090 mouse follow up and prospective comparative studies were demanded. Key Word(s): 1. distal malignant biliary obstruction; 2. covered self-expandable metallic stent Presenting Author: SOO KYUNG PARK Additional Authors: JONG HO MOON, HYUN JONG CHOI, YUN NAH

LEE, TAE HOON LEE, SANG WOO CHA, YOUNG DEOK CHO, SANG HEUM PARK, SUN JOO KIM Corresponding Author: SOO-KYUNG PARK Affiliations: Soonchunhyang University School of Medicine, Soonchunhyang University School of Medicine, Soonchunhyang University School of Medicine, Soonchunhyang University School of Medicine, Soonchunhyang University

School of Medicine, Soonchunhyang University School of Medicine, SoonChunHyang University School of Medicine, Soonchunhyang University School of Medicine Objective: Endoscopic bilateral metallic stenting has been introduced as feasible and effective palliative modality in patients with inoperable hilar malignant biliary strictures (MBS). However, repetitive endoscopic revision of occluded bilateral metallic stents may be challenging. The aim of this study was to GSK-3 signaling pathway evaluate the feasibility and efficacy of repetitive endoscopic revision after first endoscopic revision for hilar MBS previously managed by bilateral stent-in-stent placement with cross-wired metallic stents. Methods: Total 6 patients (5 cholangiocarcinoma and one gallbladder cancer) who had previously managed by bilateral stent-in-stent placement with cross-wired metallic

stents (BONASTENT-M Hilar, Standard Sci Tech., Seoul, Korea) were required repetitive biliary reintervention because of stent occlusion after first endoscopic revision during follow up. Results: Total 19 repetitive endoscopic revision were performed. The mean number of repetitive endoscopic revision for each patient was 3.2 (range 1–8). Technical and clinical success rate of repetitive endoscopic revision after first endoscopic revision was 100.0% (19/19) and 78.9% (15/19), respectively. Bilateral revision was performed in 8 (42.1%) MCE endoscopic sessions. Early and late complication rate was 15.8% (3/19, cholangitis; 1, pancreatits; 2) and 21.1% (4/19, liver abscess; 4), respectively. And, stent occlusion rate was 68.4% (13/19). Mean stent patency period was 75 days (20–265), and became shorter than when first stenting (216 days, 43–481) and first revision (126 days, 34–316) (p = 0.006). Conclusion: Repetitive endoscopic revision for hilar MBS previously managed by bilateral metallic stenting was feasible. Cross-wired metallic stents for hilar MBS may facilitate repetitive endoscopic revision after stent occlusion. Key Word(s): 1. Hilar malignant biliary stricture; 2.

4%) and T54S (4.9%). These variants were often present in combinations, with V36M+R155K (10.4%), T54S+R155K (2.2%) and V36M+T54S+R155K (1.2%) occurring most often. The combination of V36M+T54S was seen only in the triple variant, V36M+T54S+R155K. Q80 substitutions were seen in 34.2% of

GT1a patients and 1.3% of GT1b patients. Q80K, the most frequent substitution, was seen in 32.3% of GT1a patient samples, but only 0.1% of GT1b samples. The combination of Q80K+R155K was seen in GT1 a samples only, at a frequency of 6.0%. Conclusions: The analysis of TVR and BoC RAVs among the first 1500 samples tested is consistent with that of the first 500. Our findings demonstrate a higher prevalence of HCV PI RAVs among GT1a versus GT1b samples. For TPV and BOC RAVs Decitabine purchase this is consistent with a higher genetic barrier for GT1b viruses. Q80K substitutions were frequently observed, which may significantly impact treatment decisions utilizing SMV. These RAVs were also observed during clinical trials. These findings support the consideration of baseline NS3/4A resistance testing prior

to the initiation of SMVcontaining regimens. Disclosures: click here Sunny S. Choe – Employment: Monogram Biosciences Joseph M. Volpe – Employment: Monogram Biosciences Jacqueline D. Reeves – Employment: Monogram Biosciences Wei Huang – Employment: monogram biosciences Mojgan Haddad – Employment: Monogram Biosciences Christos J. Petropoulos – Employment: Monogram Biosciences, LabCorp; Management Position: Monogram Biosciences, LabCorp; Patent Held/Filed: Monogram Biosciences, LabCorp; Stock Shareholder: LabCorp Charles M. Walworth – Employment: Monogram Biosciences BACKGROUND: In 2009, IL28B genotype (gt) was identified as the 上海皓元 strongest baseline predictor of peginterferon+ribavirin (PR) response in HCV1. In 2013, a novel dinucleotide variant in interferon-lambda-4 (IFNL4, ss469415590,

ΔG/TT), in high linkage disequilibrium (LD) with IL28B polymorphism, was proposed to be the causal variant. IFNL4 gt was a better predictor of sustained virological response (SVR). We have performed the first independent validation study of the association between IFNL4 gt, IL28B gt, and PR treatment outcomes in Australian HCV1/3 patients. METHODS: HCV1/3 patients who received PR were included. IL28B (rs12979860) and IFNL4 (ss469415590) gts were determined (ĪaqMan allelic discrimination kit, custom designed primers where testing unsuccessful). IFNL4 gt was correlated with rapid virological response (RVR) and SVR, and compared to IL28B gt using logistic regression modeling and LD calculation. RESULTS: 270 PR treatment patients were included: 56% HCV1, 44% HCV3. Self-reported ethnicity for HCV1 was 79% Caucasian and 20% Asian, and for HCV3 was 90% Caucasian and 3% Asian. Overall SVR rates were 50% (HCV1) and 82% (HCV3). IFNL4 gt could not be determined in 31 patients, and DNA re-extraction +/- concentration was required.

Infectivity was determined through quantification of HIV-1 p24, an HIV capsid protein, in culture supernatants after infection. With progressive time in culture, there was a significant increase in the p24 concentration in culture supernatants of HSCs challenged with both strains of HIV-1, suggesting that HSCs are permissive to HIV infection in vitro (Fig. 1). HIV-IIIB infection of primary HSCs resulted in a four- to eight-fold increase in p24 levels compared with infection with HIV-BaL. Although this observed difference may result from

a specific donor susceptibility to X4, HIV-IIIB is a laboratory X4 isolate recognized by its increased efficiency relative to BaL and other R5 strains in vitro. Therefore, primary HSCs were also challenged with HIV-IIIB at a lower moi of 0.1, with resulting p24 levels comparable to HIV-BaL at a moi of 0.5 (data Ibrutinib not shown). To support the physiologic relevance of these findings, primary HSCs were also challenged with HIV primary isolates, both X4-tropic and R5-tropic (Fig. 1E,F). Although a higher p24 level was observed with the X4-tropic primary isolate compared with the R5-tropic virus, a much

larger panel of isolates would be needed to determine whether primary HSCs are more permissive to infection by X4-tropic viruses. To further confirm HIV entry and explore whether HSCs could INCB024360 manufacturer support HIV gene expression, LX-2 and primary HSCs were exposed to HIV-X4 and HIV-R5 expressing GFP.12 GFP expression indicates different stages of the infectious viral cycle (Fig. 2A). HIV NL-GI is a replication-competent virus carrying an enhanced 上海皓元 GFP gene in place of the nef start codon that reflects early gene expression. HIV Gag-iGFP is an infectious clone that carries the GFP gene in subdomains of Gag; expression of its Gag-GFP fusion during later stages of the HIV replication cycle are indicative of late viral gene expression.12 GFP expression was observed in primary HSCs 48-72 hours after exposure to both viral constructs, indicating viral entry and early and late gene expression. Furthermore, preincubation with AZT, a reverse-transcriptase

inhibitor, blocked HIV-GFP gene expression in HSCs (Fig. 2B). R5-tropic GFP viruses did not show efficient viral entry into HSCs though the available clones are less infectious, making direct comparisons difficult (data not shown). To quantify the percentage of HSCs infected by HIV NL-GI GFP, LX-2 and primary HSCs were analyzed by way of flow cytometry 72 hours after viral exposure. In three independent experiments, 22%-28% of infected cells were positive for GFP expression (Fig. 2C). AZT almost completely abolished GFP expression in HSCs, with levels comparable to noninfected cells by both fluorescence microscopy and flow cytometry (0%-2% positive cells). Cell viability in the presence of AZT was confirmed by bright field microscopy (Fig. 2E) and cell viability assay (Fig. 2F).

Resource utilization data

were elicited using expert opinion and multiplied with relevant unit costs from appropriate public sources. All costs and outcomes occurring beyond 1 year were discounted at 3%. Results demonstrated higher LY gained for sorafenib compared to BSC associated with higher total cost. The model calculated an overall incremental cost-effectiveness ratio for sorafenib, compared to BSC, of $US62 473/LY gained. Results were sensitive to changes in the discount rate, OS with sorafenib and BSC, and the TTP with sorafenib. The probabilistic sensitivity analysis accentuated the validity of the analysis, and showed that the probability of sorafenib providing a cost-effective alternative to BSC was 68% at $US75 000 click here and 86% Alvelestat at $US100 000.

The results indicate that sorafenib is cost-effective compared to BSC, with cost-effectiveness ratios within the established threshold that society is willing to pay, that is, $US50 000–$US100 000,29 and significantly lower than alternative thresholds that have been suggested in recent years ($US183 000–$US264 000/LY gained) for oncology products.30,31 In the USA, in a survey of 139 academic medical oncologists, the implied cost-effectiveness thresholds, derived from the hypothetical scenarios, averaged around $US300 000.31 In the UK, although £30 000 is the threshold for the National Institute of Health and Clinical Excellence for innovative treatments extending life in disease areas with short life-expectancy (using the end-of-life criteria), ICER such as £54 103 for sunitinib in renal cell carcinoma have also been accepted.32 Data constraints led to certain limitations and, as with most economic models, the analysis was based on multiple data sources and was reliant on certain analytical assumptions. First, in the absence of licensed therapies, a large percentage of this patient population is offered other therapies, such as doxorubicin. These treatment options were not incorporated due to the lack of effectiveness data in this population,

however they would probably increase the cost of the comparator arm significantly, while having limited impact on effectiveness. Thus, incorporating these treatments would further improve the 上海皓元 cost-effectiveness of sorafenib by decreasing the additional costs associated with the treatment, without any significant change in effectiveness. Second, because the SHARP trial demonstrated a clinically and statistically significant increase in OS at 72 weeks for a sorafenib-treated patient compared to a placebo-treated patient and was consequently stopped early, patient-level data were extrapolated by fitting a distribution to the patient-level data. The results were most sensitive to these efficacy data. For AE, the assumption of being constant throughout the model was made. In clinical practice, these AE are likely to occur in earlier stages of treatment as seen in clinical trials of sorafenib in patients with advanced renal-cell carcinoma.

Resource utilization data

were elicited using expert opinion and multiplied with relevant unit costs from appropriate public sources. All costs and outcomes occurring beyond 1 year were discounted at 3%. Results demonstrated higher LY gained for sorafenib compared to BSC associated with higher total cost. The model calculated an overall incremental cost-effectiveness ratio for sorafenib, compared to BSC, of $US62 473/LY gained. Results were sensitive to changes in the discount rate, OS with sorafenib and BSC, and the TTP with sorafenib. The probabilistic sensitivity analysis accentuated the validity of the analysis, and showed that the probability of sorafenib providing a cost-effective alternative to BSC was 68% at $US75 000 Saracatinib in vitro and 86% selleck at $US100 000.

The results indicate that sorafenib is cost-effective compared to BSC, with cost-effectiveness ratios within the established threshold that society is willing to pay, that is, $US50 000–$US100 000,29 and significantly lower than alternative thresholds that have been suggested in recent years ($US183 000–$US264 000/LY gained) for oncology products.30,31 In the USA, in a survey of 139 academic medical oncologists, the implied cost-effectiveness thresholds, derived from the hypothetical scenarios, averaged around $US300 000.31 In the UK, although £30 000 is the threshold for the National Institute of Health and Clinical Excellence for innovative treatments extending life in disease areas with short life-expectancy (using the end-of-life criteria), ICER such as £54 103 for sunitinib in renal cell carcinoma have also been accepted.32 Data constraints led to certain limitations and, as with most economic models, the analysis was based on multiple data sources and was reliant on certain analytical assumptions. First, in the absence of licensed therapies, a large percentage of this patient population is offered other therapies, such as doxorubicin. These treatment options were not incorporated due to the lack of effectiveness data in this population,

however they would probably increase the cost of the comparator arm significantly, while having limited impact on effectiveness. Thus, incorporating these treatments would further improve the 上海皓元 cost-effectiveness of sorafenib by decreasing the additional costs associated with the treatment, without any significant change in effectiveness. Second, because the SHARP trial demonstrated a clinically and statistically significant increase in OS at 72 weeks for a sorafenib-treated patient compared to a placebo-treated patient and was consequently stopped early, patient-level data were extrapolated by fitting a distribution to the patient-level data. The results were most sensitive to these efficacy data. For AE, the assumption of being constant throughout the model was made. In clinical practice, these AE are likely to occur in earlier stages of treatment as seen in clinical trials of sorafenib in patients with advanced renal-cell carcinoma.

Takah. & Nozaki sp. nov.) based on differences in cell shape and surface ornamentations of the vegetative cells under the field-emission scanning electron microscope. Molecular phylogenetic analyses

of P700 chl a apoprotein A2 (psaB) genes and internal transcribed spacer (ITS) regions of nuclear ribosomal DNA (rDNA), as well as a comparison of secondary structures of nuclear rDNA ITS-2 and genetic distances of psaB genes, supported the delineation of five morphological species of Cyanophora. “
“The family Microchaetaceae is a large group of heterocytous cyanobacteria, whose members bear typical morphological features of uniseriate heteropolar filaments never terminated by thin hairs and with simple false branching. However, phylogenetic analyses of the gene for 16S rRNA showed that members of this traditionally Selumetinib in vitro morphologically delimited family form several distant groups and therefore the current concept is hereafter indefensible. In this study, we provide

reassessment of the status of the family Microchaetaceae based on morphology, ecology, biogeography, and phylogeny of 16S rRNA gene. Thorough examination of strains of the nominate genus Microchaete revealed their affiliation to two groups, Nostocaceae and Rivulariaceae, and their distant position to other traditional members of Microchaetaceae such as Tolypothrix, Hassallia, and Coleodesmium. To reflect the phylogenetic relationships and to accommodate members of the traditional family Microchaetaceae that are clearly not GS-1101 solubility dmso related to any of the Microchaete representatives, we propose establishment of two new families, Tolypothrichaceae and Godleyaceae. Based on both molecular and morphological evidence, we also provide a description of three new species of the genus Fortiea. “
“Three populations of the freshwater filamentous cyanobacterium Lyngbya wollei (Farlow ex Gomont) Speziale and Dyck MCE have been putatively identified from north-eastern Australia and found to produce the potent cyanotoxin cylindrospermopsin (CYN) and its

analog deoxy-cylindrospermopsin (deoxy-CYN). We investigated the phylogeny and toxicology of strains and mats isolated from two of these populations using a combination of molecular and morphological techniques. Morphologically the strains corresponded to the type description, however, the frequency of false-branching was low, and variable over time. Strains and mat samples from both sites were positive for the cyrF and cyrJ genes associated with CYN biosynthesis. Phylogenetic analysis of these genes from Australian L. wollei sequences and comparable cyanobacterial sequences revealed that the genes in L. wollei were more closely related to homologous genes in Oscillatoria sp. PCC 6506 than to homologs in Nostocalean CYN-producers. These data suggest a common evolutionary origin of CYN biosynthesis in L. wollei and Oscillatoria. In both the 16S rRNA and nifH phylogenies, the Australian L. wollei strains formed well-supported clades with United States L.

Takah. & Nozaki sp. nov.) based on differences in cell shape and surface ornamentations of the vegetative cells under the field-emission scanning electron microscope. Molecular phylogenetic analyses

of P700 chl a apoprotein A2 (psaB) genes and internal transcribed spacer (ITS) regions of nuclear ribosomal DNA (rDNA), as well as a comparison of secondary structures of nuclear rDNA ITS-2 and genetic distances of psaB genes, supported the delineation of five morphological species of Cyanophora. “
“The family Microchaetaceae is a large group of heterocytous cyanobacteria, whose members bear typical morphological features of uniseriate heteropolar filaments never terminated by thin hairs and with simple false branching. However, phylogenetic analyses of the gene for 16S rRNA showed that members of this traditionally Sotrastaurin morphologically delimited family form several distant groups and therefore the current concept is hereafter indefensible. In this study, we provide

reassessment of the status of the family Microchaetaceae based on morphology, ecology, biogeography, and phylogeny of 16S rRNA gene. Thorough examination of strains of the nominate genus Microchaete revealed their affiliation to two groups, Nostocaceae and Rivulariaceae, and their distant position to other traditional members of Microchaetaceae such as Tolypothrix, Hassallia, and Coleodesmium. To reflect the phylogenetic relationships and to accommodate members of the traditional family Microchaetaceae that are clearly not Hydroxychloroquine related to any of the Microchaete representatives, we propose establishment of two new families, Tolypothrichaceae and Godleyaceae. Based on both molecular and morphological evidence, we also provide a description of three new species of the genus Fortiea. “
“Three populations of the freshwater filamentous cyanobacterium Lyngbya wollei (Farlow ex Gomont) Speziale and Dyck MCE公司 have been putatively identified from north-eastern Australia and found to produce the potent cyanotoxin cylindrospermopsin (CYN) and its

analog deoxy-cylindrospermopsin (deoxy-CYN). We investigated the phylogeny and toxicology of strains and mats isolated from two of these populations using a combination of molecular and morphological techniques. Morphologically the strains corresponded to the type description, however, the frequency of false-branching was low, and variable over time. Strains and mat samples from both sites were positive for the cyrF and cyrJ genes associated with CYN biosynthesis. Phylogenetic analysis of these genes from Australian L. wollei sequences and comparable cyanobacterial sequences revealed that the genes in L. wollei were more closely related to homologous genes in Oscillatoria sp. PCC 6506 than to homologs in Nostocalean CYN-producers. These data suggest a common evolutionary origin of CYN biosynthesis in L. wollei and Oscillatoria. In both the 16S rRNA and nifH phylogenies, the Australian L. wollei strains formed well-supported clades with United States L.

2C). Vector control cells (VC1 and VC2) formed bigger tumor masses than Lcn2-expressing cells (Fig. 2D, upper panels). Lcn2 immunoreactivity was found mainly in the cytoplasm and to a lesser extent in the nuclei of tumor tissues (Fig. 2D, lower panels). First, using transient expression of Lcn2 by adeno-associated virus transduction, we examined

whether Lcn2 influences the expression of EMT-associated markers in SH-J1 cells. Lcn2 effectively inhibited the expression of mesenchymal markers such as N-cadherin (N-cad), alpha-smooth muscle actin (α-SMA), vimentin (VIM), and fibronectin (FN), which are EMT marker genes. In contrast, Lcn2 treatment increased the expression of epithelial markers, including PF-02341066 datasheet cytokeratin 8 (CK8), cytokeratin 18 (CK18), and desmoplakin I/II (DesI/II) (Fig. 3A). Next, we performed knockdown of Lcn2 by small hairpin RNA (shRNA) lentiviral delivery in HKK-2 cells and observed the simultaneous up-regulation of mesenchymal markers and down-regulation of epithelial markers (Fig. 3B). These results are consistent with the results we obtained by overexpressing Lcn2 in SH-J1 cells by adenovirus infection. Growth see more factor signaling pathways, particularly EGF- and EGFR-driven signaling

pathways, have been shown to play a crucial role in cancer progression.[23] Overexpression of EGF and EGFR has been reported in various cancer types, including HCC.[24, 25] It has also been demonstrated that EGF treatment in vitro enhances the invasiveness and metastatic properties of several different cancer cells, including ovarian,[26] cervical,[27] epidermoid,[28] and breast cancer cells.[29] To investigate whether EGF is involved in the down-regulation of Lcn2 and the up-regulation of Twist1 in HCC and CC cells, we examined the effects of EGF on Lcn2 expression in HLK-5 and JCK cells, which strongly express Lcn2

(Fig. 3C). EGF treatment resulted in cells with a migratory and scattering phenotype and the down-regulation of Lcn2 and E-cad and up-regulation of Twist1. Furthermore, concomitant treatment of cells with the EGF receptor tyrosine kinase inhibitor, AG1478, substantially MCE blocked these EGF-mediated changes. It has also been demonstrated that loss of E-cadherin is a causal factor that promotes tumor progression.[30] In our study, EGF treatment remarkably reduced E-cadherin protein expression concurrent with a reduction in the protein level of Lcn2, accompanied by increased Twist1 expression. TGF-β1 treatment and EGF had similar effects on cell morphology and epithelial marker expression (Fig. 3D). Wound repair assays were performed using Lcn2-negative (SK-HEP1 and Huh7) or Lcn2-positive cell lines (HKK-2 and HLK-5, respectively) (Fig. 4A, left panels). The wound closure ability of Lcn2-positive cell lines was significantly lower than that of Lcn2-negative cell lines, even though the Lcn2-positive cell lines expressed much more endogenous EGF and TGF-β1 than the Lcn2-negative cell lines (Fig.

27 Both MAT1A and GNMT knockouts also support our findings.28, 29 In fact, deficiency of MATI/III enzyme is characterized by macrovesicular steatosis and increased expression of proliferative signals with decreased S-adenosylmethionine find more and increased methionine.28 By

contrast, GNMT deficiency leads to steatosis and hepatocellular carcinoma in mice characterized by increased S-adenosylmethionine but increased methionine.29 The definition of the role of Timp3 and TACE in the regulation of methionine metabolism will require further studies, although the observation of increased methionine levels in Timp3−/− mice is a common feature of both MAT1A and GNMT and suggests that these genes play a role in the phenotype described here.21 Among up-regulated signals we found FABP1; mice deficient in FABP1 are protected from liver steatosis induced by a HFD, consistent with the hypothesis that increased FABP1 expression, as found in Timp3−/− mice and in hepatocytes over expressing TACE, may contribute to an opposite phenotype.30 In conclusion, our data support the concept that TACE is a novel regulator of hepatic metabolism that is activated in the course of metabolic toxicity

induced by an HFD and contributes to the development of NAFLD through multiple mechanisms. Additional AZD8055 Supporting Information may be found in the online version of this article. “
“Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, MCE公司 mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects

and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC. "
“In areas of the world where tenofovir disoproxil fumarate is not marketed, adefovir (ADV) + lamivudine (LAM) is recommended and widely used for LAM-resistant chronic hepatitis B (CHB).

3,15 Further studies are required to define the diagnostic and prognostic role of testing adipokines in this context. In summary, the studies by Kimura, Manchanayake and their respective colleagues clearly demonstrate that insulin resistance is almost universal in patients with NAFLD. Around half of these patients have undiagnosed impaired glucose tolerance or diabetes. Post-challenge hyperglycemia is often associated with adverse clinical events and is amenable to treatment by lifestyle modification and insulin sensitizers. Before new biomarkers are ready for routine clinical use, OGTT should be considered in most NAFLD patients. “
“Systemic activation

of the inflammatory immune system contributes to the progression of cirrhosis with ascites. Immune cells become activated after interacting at the mesenteric lymph nodes (MLNs) Adriamycin with bacteria translocated from the gut, and thereafter reach the bloodstream through recirculation. Selleckchem RG-7388 It is unknown whether systemic activation of the immune system is present in pre-ascitic cirrhosis, in which gut bacterial translocation has not been described. The purpose of this study was to determine whether systemic activation of the immune system initiates in rats with compensated carbon tetrachloride (CCl4)-induced cirrhosis, and if so

to establish the activation site of immune cells. We studied the activation status of immune cells in peripheral blood, MLNs, and hepatic lymph nodes (HLNs). Systemic inflammation was present in rats with cirrhosis, as shown by expansion (P < 0.01) of circulating 上海皓元 total and inflammatory monocytes and recently activated CD134+ T helper (Th) cells. The same populations of cells were increased (P < 0.01) in MLNs and HLNs. Bacterial translocation was absent in rats with cirrhosis or control rats, but bacterial DNA fragments were present in the MLNs of 54% of rats with cirrhosis. The liver was the source of activated immune cells present in the blood, as shown by the direct correlation between activated Th cells in the blood and HLNs, but not in MLNs, and the normalization

by gut decontamination with antibiotics of activated cells in MLNs, but not in the blood or HLNs. Conclusion: In experimental cirrhosis, systemic activation of the immune system occurs before ascites development and is driven by recirculation of cells activated in HLNs. In addition, in compensated cirrhosis, bacterial DNA fragments reach the MLNs, where they elicit a local inflammatory response. (HEPATOLOGY 2010;52:2086-2095) The immune system is a complex network of cells and molecules that plays a relevant role in the defense against infections through its ability to recognize and develop a response against non–self-antigens.1 The effector defensive response is associated with the induction of an orchestrated cascade of events that involve activation of immune system cells and production of cytokines at the systemic and/or local level.