Many hypotheses were advanced and tested in numerous

Many hypotheses were advanced and tested in numerous selleck inhibitor taxa regarding possible direct and indirect fitness benefits that females might derive from polyandry (e.g. Keller & Reeve, 1995; Yasui, 1998; Jennions & Petrie, 2000; Möller & Jennions, 2001). Of course, multiple mating was recognized to have potential downsides as well (such as the risk of contracting sexually transmitted diseases), but overall the bulk of the research effort went into understanding why females (in addition to males) often take multiple mates. Recent

surveys of the literature on genetic parentage in ‘pregnant’ vertebrate and invertebrate animals (Avise & Liu, 2010, 2011; Avise, Tatarenkov & Liu, 2011) have confirmed that the majority of broods do indeed consist of multiple full-sib cohorts, meaning that a gestating parent typically had several successful mates. Much more surprising, however, were two additional genetic observations: (1) the overall numbers and frequency distributions click here of mates per brood proved to be remarkably similar across invertebrate and vertebrate taxa; and (2) numbers of mates per pregnancy (typically about 2–5) were much lower than they theoretically could have been given the resolving powers of the molecular markers employed and given the large brood sizes (often with dozens to thousands of embryos) in many of the species assayed. The authors

of these review articles concluded that the explanation probably has to do not only with the balance between the costs and benefits of multiple mating but also with the finite logistical opportunities for successful mating events during each breeding season or episode. Depending on the species, constraints on mate acquisition might include ecological and natural-history factors such as low population densities, short mating seasons, poor vagilities, lengthy courtships, and perhaps even post-copulatory phenomena such as sperm competition and cryptic female choice of sperm (Birkhead & Pizzari, 2002; Eberhard, 2009), the net effect

being to truncate mate numbers even in animal species with huge broods and high frequencies of polygamy. Such mating-constraint hypotheses can be viewed as null models for reproductive behaviors Liothyronine Sodium in nature (Hubbell & Johnson, 1987; Gowaty & Hubbell, 2009), in which case logistical considerations offer a different perspective on mating systems that might help to counterbalance traditional interpretations based on polyandry’s purported selective advantages. For example, before invoking a selective explanation for genetic polygamy in any focal species, an important question might be whether the mean number of successful mates per brooder statistically exceeds or does not exceed the suspected rate of mate encounters given each species’ particular biology and ecology.

The study protocol was approved by the Human Ethics Review Commit

The study protocol was approved by the Human Ethics Review Committee of the institution. Blood samples were frozen at −80°C within 4 hours of collection and were not thawed until used for testing. Anti-HCV, HCV RNA, HCV genotype, and aa substitutions of the HCV-1b core region were assayed using stored frozen sera. HCV genotype was determined by PCR using a mixed

primer set derived from nucleotide sequences of the NS5 region.24 HCV RNA quantitative click here analysis was measured by branched DNA assay v. 2.0 (Chiron), AMPLICOR GT HCV Monitor v. 2.0 using the 10-fold dilution method (Roche Molecular Systems, Pleasanton, CA), or COBAS TaqMan HCV test (Roche Diagnostics, Tokyo, Japan). High viral load of viremia levels was defined as branched DNA

assay ≥1.0 Meq/mL, AMPLICOR GT HCV Monitor ≥100 × 103 IU/mL, or COBAS TaqMan HCV test ≥5.0 log IU/mL. Low viral load was defined as branched DNA assay <1.0 Meq/mL, AMPLICOR GT HCV Monitor <100 × 103 IU/mL, or COBAS TaqMan HCV test <5.0 log IU/mL. In the present study, aa substitutions of the core region of HCV-1b were analyzed by direct sequencing. HCV RNA was extracted from serum samples Opaganib manufacturer and reverse transcribed with random primer and MMLV reverse transcriptase (Takara Syuzo, Tokyo, Japan). Nucleic acids of the core region were amplified by nested PCR using the following primers. The first-round PCR was performed with CE1 (sense, 5′-GTC TGC GGA ACC GGT GAG TA-3′, nucleotides: 134-153) and CE2 (antisense, 5′-GAC GTG GCG TCG TAT TGT CG-3′, nucleotides: 1096-1115) primers, and the second-round PCR with CC9 (sense, 5′-ACT GCT AGC CGA GTA GTG TT-3′, nucleotides: 234-253) and CE6 (antisense, 5′-GGA GCA GTC GTT CGT GAC AT-3′, nucleotides: 934-953) primers. All samples were initially denatured BCKDHB at 95°C for 2 minutes. The 35 cycles of amplification were set as follows: denaturation for 30 seconds at 95°C, annealing of primers for 30 seconds at 55°C, and extension for 1 minute at 72°C with an additional 7 minutes for extension. Then 1 μL of

the first PCR product was transferred to the second PCR reaction. Other conditions for the second PCR were the same as the first PCR, except that the second PCR primers were used instead of the first PCR primers. The amplified PCR products were purified by the QIA quick PCR purification kit (Qiagen, Tokyo, Japan) after agarose gel electrophoresis and then used for direct sequencing. Dideoxynucleotide termination sequencing was performed with the Big Dye Deoxy Terminator Cycle Sequencing kit (Perkin-Elmer, Tokyo, Japan). With the use of HCV-J (accession no. D90208) as a reference,25 the dominant sequence of 1-191 aa in the core protein of HCV-1b was determined by direct sequencing and then compared with the consensus sequence constructed on 50 clinical samples to detect substitutions at aa 70 of arginine (Arg70) or glutamine/histidine (Gln70/His70) and aa 91 of leucine (Leu91) or methionine (Met91).

Further exploration of molecular mechanisms of hedgehog signaling

Further exploration of molecular mechanisms of hedgehog signaling in modulating metastases will establish molecular targets for the therapeutic intervention of hepatoma metastases. Disclosures: The following people have nothing to disclose: Ya-Han Fan, Samantha Nguyen, Jia Ding, Jian Wu BACKGROUND: Sorafenib is the only systemic agent approved for the therapy of hepatocellular carcinoma (HCC). However, in spite of its efficacy, the investigation of alternative therapeutic

targets is urgently required. JNK is overexpressed in the majority of HCC and chemical induction of HCC is prevented byJNK inhibition. Notably, expression of JNK was recently shown to predict a poor response to sorafenib. Nevertheless, since no JNK inhibitor is currently undergoing investigation as therapy of HCC, JNK remains

a largely unexploited therapeutic target. CEP-1347 Torin 1 cost is a MLK/JNK inhibitor originally designed to prevent the progression of Parkinson’s disease, and underwent extensive Phase 3 clinical investigation proving Selleck LEE011 save and well tolerated. We aimed at assessing the potential efficacy of this compound as therapy of HCC. METHODS: the effect of CEP-1 347 was assessed in liver cancer cell lines by viability assays, FACS-based analysis of cell cycle and apoptosis and by western blot. In vivo, its effect was assessed in a model of xenograft tumor induction by daily intraperitoneal

injections of CEP-1347 or vehicle. RESULTS: Administration of CEP-1 347 Adenosine triphosphate in nanomolar range led to a dramatic loss of cell viability and enhanced the antiproliferative effect of sorafenib by causing G2/M cell cycle arrest and apoptosis. Concomitantly, caspase cleavage and the downregulation of apoptosis regulators Mcl-1 and Bcl-2 were observed. In vivo CEP-1347 strongly inhibited tumor growth of Huh7 cells. CONCLUSIONS: We provide preclinical in vitro and in vivo data showing the antitumor activity of CEP-1 347 and propose the utilization of this compound as experimental therapy of hepatocellular carcinoma. Disclosures: The following people have nothing to disclose: Shuai Lu, Johanna Liebl, Antonia Rizzani, Burkhard Göke, Eike Gallmeier, Alexander L. Gerbes, Angelika Vollmar, Enrico N. De Toni Background and aims: Double-stranded RNA-activated protein kinase R (PKR) is upregulated by hepatitis C virus (HCV) and overexpressed in hepatocellular carcinoma (HCC). We previously reported that PKR is overexpressed and activated in HCC with HCV infection, as compared with surrounding non-HCC tissues. However, the precise roles of PKR in HCC with HCV infection remain unclear. The present study aimed to identify the roles of PKR in HCC with HCV infection, and to determine whether overexpressed PKR in HCC has beneficial or malignant effects in patients with this disease.

The Bethesda assay detects inhibitors but is relatively insensiti

The Bethesda assay detects inhibitors but is relatively insensitive. Recently, a new fluorescence-based immunoassay (FLI) was developed for antibody detection. The aim of this study was to assess the prevalence of inhibitors as measured by FLI. Assays of FVIII, FVIII inhibitor by Bethesda assay with Nijmegen modification, and FVIII inhibitor by FLI were performed on adult patients Selleck Y27632 with haemophilia A. Data were complete for 46 patients (median age 39), of whom 72% were severe, 7% moderate and 22% mild. The Bethesda assay was positive in only two patients (4%), while FLI was positive in 23 of 46 patients (50%), with values ranging from 0.4 to 33.7 nm (median 3.5 nm). FLI titres exceeded 7.0 nm in 19.5% of patients,

all but one of whom had severe haemophilia. FLI antibody-positive patients were less likely to be HIV positive (30% vs. 70%, P = 0.02). The use of a prophylaxis regimen was associated with a lower incidence of antibody; only two of 23 patients with detectable antibody and none of those with antibody >7 nm were on a prophylaxis regimen, while nine of 23 patients without antibody were on prophylaxis, (P = 0.03). There was no difference in inhibitor presence in patients using recombinant versus plasma-derived factor. Antibodies detected by FLI are frequent in patients with haemophilia A, but are less common in those who are

HIV positive or are receiving regular FVIII prophylaxis.
“Musculoskeletal involvement in hemophilia, primarily synovitis and early arthropathy, continues as a hallmark finding. As comprehensive hemophilia treatment team members, physiotherapists focus on promoting joint health and maximizing functional ability. In hemophilia care, it is necessary for physiotherapists to combine clinical expertise with research findings to question and improve upon current practice standards.

The current trend in the health professions is to employ evidence-based practice, rather than continuing to rely solely on anecdotal evidence or merely following the same traditional methods. This chapter will explore two current practices and future trends in physiotherapy for the acute hemarthrosis, using an evidence-based approach. Teicoplanin The use of ice and recommendations for rest, as part of the traditional RICE protocol, will be addressed within the framework of the risk versus benefit model. The importance of the evaluation in identifying potential causative factors will also be highlighted, as will proactive physiotherapy intervention, focusing on prevention of musculoskeletal complications. “
“Summary.  Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co-morbidities in Italian persons with haemophilia (PWH).

4M075; where M is body mass in kg), and 3 ×  Kleiber Facing an

4M0.75; where M is body mass in kg), and 3 ×  Kleiber. Facing an increase in drag, an individual can: (1) maintain a characteristic velocity and exponentially increase energy expenditure to overcome added drag; or (2) swim at

a reduced speed in order to maintain Selleckchem Ganetespib the same power output as if under normal conditions (Jones et al. 2011). For the latter case, the decrease in velocity (Ured, m/s) to maintain the same power output in an entangled drag scenario (DT), is (12) To determine the additional power demands experienced by Eg 3911 while entangled, we compared PI,T for the drag conditions of a nonentangled whale, with surface drag factor γ following disentanglement (i.e., γ  =  1.0), to the conditions of an entangled whale, towing three gear configurations tested in this experiment, with surface drag factor g calculated for the mean ± SD dive

Compound Library in vitro depth prior to disentanglement (i.e., γ  =  1.6). Dive Parameters—Eg 3911 completed n = 152 dives over the 6 h deployment period, to a median (IQR) depth of 11.50 (10.97) m and duration of 98.7 (82.1) s (Fig. 5). Within the Sedation/Entangled phase, there was no significant difference between the depth or duration of dives completed in the 21 min prior to (n = 7) and the 50 min following (n = 45) sedative injection (Z = 0.402 and 0.188; P = 0.6876 and 0.8511, respectively; Table 3). Dive depth increased significantly with every phase (χ2 = 26.66, P < 0.0001; Fig. 6). Median

dive depth was significantly (138%) shallower in Sedation/Entangled compared to Disentangled (Z  =  −6.121, P < 0.0001). Significant increases in dive depth occurred between Disentangled and Recovery (Z = 4.607, P < 0.0001), though only by 19%. Even when considering increases in approximate regional Edoxaban water column depth with time, proportional dive depth was significantly shallower in Sedation/Entangled (by 95%) compared to following the removal of gear and buoys (i.e., in Disentangled; Z  =  −5.216, P < 0.0001; Fig. 6). Further, we observed no significant difference in proportional dive depth between Disentangled and Recovery phases (Z  =  −0.679, P = 0.497). Descent rates (m/s) during dives differed significantly between phases (χ2 = 49.87, P < 0.0001; Fig. 6), where descents during Sedation/Entanglement were 57% slower than in Disentangled (Z  =  −6.287, P < 0.0001). There was no significant difference between the descent rates in Disentangled and Recovery (Z = 0.535, P = 0.5927). Ascent rates (m/s) during dives also differed significantly between phases (χ2 = 46.22, P < 0.0001; Fig. 6), with significantly slower ascents (31%) during Sedation/Entanglement compared to in Disentanglement (Z  =  −5.948, P < 0.0001). Similar to descent rate, ascent rate did not differ between Disentanglement and Recovery (Z = 0.090, P = 0.9285). For Eg 3911 (h = 1 m, d = 2.20 m), wave drag is maximal within 0.

(2009) did for centrosaurine nasal horns However, in any case so

(2009) did for centrosaurine nasal horns. However, in any case social selection reduces to a kind of natural selection. Moreover, these authors do not accurately distinguish social selection and species recognition. They state (2009: 1394) that ‘species recognition traits are under selection only in the earliest stages of courtship during mating’, following West-Eberhard (1983); but species recognition is simply a matter of possessing traits that allow an individual to recognize others of its species, for many functions besides breeding. They also state that ‘species recognition traits are only expected to occur in closely related sympatric

species,’ as opposed to being DAPT ic50 able to ‘diverge in allopatric isolated populations,’ but in our view species recognition can begin at the population level selleck products and can easily diverge in populations of a single species, especially if the selective change is anagenetic. Contrary to West-Eberhard (1983), species recognition

does not entail ‘reproductive character displacement,’ or necessarily any features that relate to mating, reproduction, or competition among individuals of a species (Mayr, 1963). Those other terms are the provenance of mate recognition, social selection, and natural selection. She rightfully criticizes earlier work that attributed to species recognition many phenomena due to sexual selection or social selection (such as the hypothesis that signal distinctiveness should be reduced on islands and in isolated (allopatric) populations (West-Eberhard, 1983: 165). That was sorted out with further experimental work, but it does not nullify the concept of species recognition or imply that it is indistinguishable from these other processes. This confusion aside, it is possible to assess the predicted effects of species recognition and to separate them from those of other hypotheses. (iv) Species recognition– Under the explanation of species recognition, bizarre structures would have no apparent mechanical function and would not specifically evolve to

attract members of the opposite sex for mating (viz., Vrba, 1984; Paterson, 1993); rather, they make it easier for individuals to recognize others of the same (and different) species. That is, the bizarre structures communicate to other Methamphetamine individuals a variety of possible associational cues, including species identification, potential protection and social habits and the appropriateness of potential mates. They are positive indicators of beneficial social affiliations. There can be a strong ontogenetic component to this process: young neoceratopsians, pachycephalosaurs and lambeosaurs lacked the extent of cranial ornaments of fully grown individuals, although they had rudimentary development, and it appears that in many cases these ornaments were rather rapidly developed at or around the attainment of adult size.

Using western blot and quantitative real-time polymerase chain re

Using western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analysis, the expression of these biomarkers was validated in Sirt6−/− mouse hepatocytes and human hepatoma cell lines. Further, re-expression of SIRT6 in HepG2 cells restored sensitivity to apoptotic stimuli. Global transcriptomic analyses confirmed the prominent role of Sirt6 signaling in the regulation of key hepatocyte functions such as cell cycle, metabolism, and oxidative stress response. On the molecular level, genetic loss of Sirt6 caused changes in the methylation pattern of affected livers leading to a metabolic and pro-oncogenic phenotype. Together, our results indicate a clinical significance of SIRT6 and disrupted SIRT6 signaling during liver carcinogenesis. Mice of the strain 129-Sirt6tm1Fwa/J

were obtained from The Jackson Laboratory and interbred to obtain mice homozygous for the Sirt6tm1Fwa allele. Hepatocytes from Sirt6−/− and Sirt6+/+ mice were isolated from mouse livers via hepatic portal vein perfusion as described.[19] Mice were kept learn more in the central laboratory animal facility (ZVTE) of the Johannes Gutenberg University. Blood glucose levels were measured in whole blood with an Accu-Chek Sensor (Roche). For genomic DNA preparation, tissues were lysed at 37°C overnight in a buffer containing 75mM NaCl, 30 mM EDTA, 0.5% SDS and 250 μg/mL proteinase K (pH 8.0). After addition of NaCl to a final concentration of 2M, the lysate was centrifuged for 20 minutes at 10,000 rpm. Genomic DNA was precipitated, Cediranib (AZD2171) washed with 70% ethanol, air-dried, and resuspended in TE buffer. The global DNA methylation status of livers from Sirt6−/− and Sirt6+/+ mice was determined using the colorimetric MethylFlash Methylated DNA Quantification

Kit (Epigentek Inc.) according to the manufacturer’s instructions.[20] Relative quantification of 100 ng genomic DNA was performed on an enzyme-linked immunosorbent assay plate reader at 450 nm. All investigations were performed in triplicate using two independent replicates. Total RNA from isolated hepatocytes was extracted using Absolutely RNA Miniprep Kit (Agilent Technologies) following the instructions of the manufacturer. RNA quantity was estimated using a NanoDrop ND-1000 Spectrophotometer (NanoDrop Technologies, Wilmington, DE). Gene expression microarrays were performed using Affymetrix GeneChip Mouse Genome 430 2.0 arrays. The arrays were deposited at EMBL-EBI (accession number: E-MTAB-1477). Arrays were normalized based on mean intensity values across the chips. Changes in expression levels were calculated based on log2 ratio. Publically available microarray data (Gene Expression Omnibus accession number: GSE21965)[11] was downloaded from GEO, processed, and analyzed using BRB ArrayTools V3.3.

Good health perception, high level of albumin and white blood cel

Good health perception, high level of albumin and white blood cell had positive effect on multiple domains of SF-36. Conclusion: Patients with PBC had impaired HRQOL. Age, female gender, present ascites and prolonged prothrombin time are important factors reducing HRQOL. Good health perception and high level of albumin may improve HRQOL. Key Word(s): 1. quality of life; 2. PBC; 3. SF-36; 4. influencing factor; Presenting MK-8669 purchase Author: MAYING JIE Corresponding Author: MAYING JIE Affiliations: Zhengzhou institute of liver and gastrointestinal disease Objective: To compare the differences

in immune effect of dendritic cell (DC) and cytokine-induced killer cell (CIK), which activated by HBsAg, in chronic hepatitis B (CHB) and healthy people. To investigate the potential effect of CHB patients. Methods: DCs and CIK cells were cultured and amplified from CHB and healthy people peripheral blood. DCs was stimulated with pure HBsAg in cell culture medium prior to maturation. ELISA was used to detect the level of IL-12 in the supermatants of co-cultured DCs and CIK cells. The cell-killing activity of DC-induced CIK cell against HepG2.2.15 cells was

measured. DC-CIK activated by HBsAg were reinfusion. Virus serological and Liver function were measured before and after 4,8,12 and 24 weeks of treatment. Results: the positive rate of HBsAg-activated DC and CIK cells surface selleck compound marker in healthy people were significantly higher than in CHB. The cell-killing activity of HBsAg-activated DC/CIK was significantly higher than non-activated in (-)-p-Bromotetramisole Oxalate CHB or healthy people (P < 0.05). The level of IL-12 in

supermatants of co-cultured HBsAg activated DC-CIK cells form healthy people was much higher than that form CHB (P < 0.001). HBsAg activated DC-CIK cell therapy for CHB, can reduce the viral replication at 24 weeks, viral response rate was 63.6%. Conclusion: surface markers and immune effects of DCs / CIK cells HBsAg-activated and non-activated form healthy people were significantly higher than CHB; whether form healthy people or CHB, DCs and CIK cells immune effector were enhanced by HBsAg-pulsed. Transfusion of autologous DCs/CIK cells activated by HBsAg inhibits viral replication in patients with CHB Key Word(s): 1. dc; 2. CIK; 3. immunotherapy; 4. CHB; Presenting Author: METIN BASARANOGLU Additional Authors: FATMA KALEM Corresponding Author: METIN BASARANOGLU Affiliations: Ankara YIH; Konya Numune Hospital Objective: Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are very important infectious agents for public health. The aim of this retrospective study was to assess the seroprevalence of HBsAg, anti-HBs and anti-HCV test results of patients who admitted to first step health organizations in central and peripheral districts of Konya, the middle region of Turkey during the period 2005–2010.

1) Ceramide is metabolized to sphingosine by ceramidases, which

1). Ceramide is metabolized to sphingosine by ceramidases, which in turn is metabolized by sphingosine kinases to sphingosine-1-phosphate

(S1P). A host of cellular responses have been discovered for these three bioactive sphingolipids (e.g. cell senescence, differentiation, apoptosis and cell cycle arrest for ceramide; apoptosis and cell cycle arrest for sphingosine; and proliferation, mitogenesis, migration, angiogenesis, and protection from apoptosis for S1P). Reviews of sphingolipid metabolism, sphingolipid signaling, and the mechanisms of action of ceramide, sphingosine and S1P emphasize the complex web of interactions that occurs because of the intricately interconnected network of sphingolipid species and enzymes that

are involved.10,11 Lee et al.9 now show that in a mouse strain prone to gallstone formation, feeding a lithogenic diet is associated with elevated levels of ceramide in serum and bile. Furthermore, these ceramide levels are decreased by the addition of myoricin, a specific inhibitor of the first and rate-limiting step in the sphingolipid biosynthetic pathway catalyzed by SPT. After 6 weeks on the diets, 65% AG-014699 mw of mice on the lithogenic diet formed gallstones, compared with none in the control chow group and 15% in the lithogenic diet with myoricin group. Serum cholesterol and triglyceride levels were also elevated in the lithogenic diet group; these levels were reduced in the myoricin-treated mice. Gallbladder p38 mitogen-activated protein kinase phosphorylation was

increased in the lithogenic diet group, which was reduced with myoricin treatment. The findings reported are preliminary; the mechanisms by which inhibition of the sphingolipid biosynthetic pathway leads to cholesterol gallstone formation remain undefined. Nevertheless, Casein kinase 1 based on the extensive literature that has accumulated with respect to cholesterol gallstone pathogenesis on the one hand, and bioactive sphingolipid biology on the other, one can create a roadmap for future studies that will likely yield mechanistic insights. One potential mechanism involves effects on gallbladder inflammation. Gallstone formation in mouse models involves activation of an inflammatory response.12 Bioactive sphingolipids are known to modulate inflammatory mediators.13 Therefore, one possible mechanism involves downregulation of inflammatory mediators in the gallbladder by inhibition of the de novo sphingolipid biosynthetic pathway. This scenario is supported by the findings of a previous study by the same group.14 A high-cholesterol diet fed to Syrian Golden hamsters induced gallstones in association with sixfold elevations of biliary ceramide and S1P. Levels of gallbladder inducible nitric oxide synthase and phosphorylated signal transducer and activator of transcription 3, which have been linked to inflammation, were increased.

2 The immune system is abnormally activated at the systemic level

2 The immune system is abnormally activated at the systemic level in patients and experimental models

with cirrhosis and ascites.3-5 The alteration is characterized by expansion of activated lymphocytes and monocytes in peripheral blood and an increased production VX-770 ic50 of proinflammatory cytokines.3-5 It has been claimed that in cirrhosis with ascites, this systemic inflammatory response is mainly induced and maintained by the interaction of cells of the immune system with bacteria that have translocated from the intestinal lumen at the mesenteric lymph nodes (MLNs). Thereafter, recirculation of activated immune cells extends the inflammation response to the peripheral blood.5-7 Activated immune cells can migrate to the tissues and modify the function of somatic cells, such as vascular endothelial and brain cells, and contribute to the nonhepatic clinical expression of cirrhosis.3, 8-10 Despite the pivotal role of systemic activation of the immune system in cirrhosis, it is unknown whether this abnormality already exists in the compensated pre-ascitic stage of the disease. selleck chemicals It is possible to hypothesize that the liver, the main organ of inflammation in cirrhosis, has a crucial role as a source of abnormally activated monocytes and lymphocytes. Such a

particular role of the liver appears to be particularly relevant in rats with cirrhosis at the preascitic stage, in which gut bacterial translocation is not increased.11 The aim of this study was to investigate whether there is in fact systemic activation of the inflammatory immune system in rats with preascitic compensated carbon tetrachloride (CCl4)-induced cirrhosis, and if so to establish the pivotal site where immune system cells become activated.

APC, allophycocyanin; CCl4, carbon tetrachloride; FITC, fluorescein isothiocyanate; HLN, hepatic lymph node; IL-6, interleukin-6; MLN, mesenteric lymph node; PE, phycoerythrin; PerCP, peridinin chlorophyll protein; Tc, T cytotoxic; Th, T helper; TNFα, tumor necrosis factor α. Male Wistar rats (Harlan, Horst, The Netherlands) were used for all experiments. Animals were fed a standard laboratory diet with water and food provided ad libitum. All experiments were old approved by the Spanish animal welfare authorities and performed in accordance with the animal care guidelines of our institution. All studies were conducted according to the Guide for the Care and Use of Laboratory Animals (NIH publication 86-23, revised 1985) and in compliance with local regulations. Cirrhosis was induced by CCl4 feeding by gavage on a weekly basis, along with phenobarbital added to the drinking water. The initial 20-μL dose of CCl4 was subsequently increased, depending on the animal’s weekly change in body weight. Animals were sacrificed at 12 weeks, when cirrhosis without ascites is almost constantly present.