41, 42 A seminal study in the field identified centrilobular injury

as a consequence of hepatic oxygen demand in alcohol-fed rats that were briefly exposed to low atmospheric oxygen tension, and were able to demonstrate protection against this effect with the coadministration of the thioamide antihyperthyroid drug propylthiouracil.41 The diverse effects of chronic ethanol on cellular signaling, cellular metabolism, and organ physiology has been reviewed elsewhere.43 The development of hypoxia in alcohol-exposed liver has also been reviewed elsewhere.44 Over three decades ago, exposure of thin liver slices to acute ethanol was reported to increase oxygen consumption.45 Acute ethanol causes a rapid increase in liver metabolism, including rapid induction of alcohol detoxifying enzymes and hepatic oxygen consumption within 2-3 hours.46 More recently, CAL-101 concentration acute ethanol was found to result in increased areas of staining using the hypoxia-specific marker pimonidazole; this effect appeared to be at least partially dependent on selleck chemicals functional hepatic Kupffer cells, and was also apparent in a model of chronic ethanol treatment.47, 48 Recent gene array data from ethanol-fed and pair-fed mice demonstrated up-regulation of multiple genes in the glycolytic pathway, as well as genes in lipid metabolic pathways in the livers of chronically

alcohol fed mice.49 Although not explored in that publication, most, if not all of these genes may be regulated by HIF1α. An earlier report suggested an up-regulation of HIF1α messenger RNA (mRNA) in the livers of chronic alcoholics.50 One group offered some data to indicate that HIF1α mRNA is cyclically regulated

with the urinary alcohol cycle in a model on continuous, intragastric ethanol feeding.51 More recently, in the hypercholesterolemic Ketotifen ApoE(−/−) mouse, ethanol significantly increased HIF1α protein in liver, and a synergistic up-regulation with tobacco smoke was observed.52 Our own recent work has demonstrated that chronic alcohol administration increased HIF activation in the liver and that increased hepatic steatosis in the setting of alcohol developed in an HIF-dependent manner.53 It has been well established that alcoholic liver disease proceeds in part through a combination of prolonged metabolic insult coupled with activation of signaling through innate immune mechanisms. Given the role of HIFs in innate immunity, as described further below, it is quite possible that the contribution of HIFs to alcoholic liver disease proceeds both through pathways of innate immunity as well as through pathways in the hepatocyte, including hepatic lipid accumulation. A schematic illustrating the convergence of innate immune pathways with HIF1α in an experimental model of steatohepatitis is given in Fig. 2.

2% after five years among treatment-naïve subjects).47 The low resistance rate is related to both the profound viral suppression Roxadustat cell line as well as the requirement of at least three sites of genetic mutations in order to confer entecavir resistance. (Two of these three sites overlap with lamivudine resistance, both lamivudine and entecavir being nucleoside analogues.) This characteristic is referred to as “high genetic barrier”. Because of these merits, entecavir is now the first line agent for treatment-naïve CHB patients. However, it is not a drug of choice for patients with lamivudine-resistant

disease because of the common sharing of two out of the three required mutations between entecavir and lamivudine resulting in a high rate of development of entecavir resistant mutations.48,49 The chance of emergence

of entecavir-resistant HBV is as high as 51% in patients with pre-existing lamivudine resistant mutations after five years of entecavir treatment.47 ABT-263 molecular weight Because of this limitation, patients with lamivudine resistant HBV should be preferably treated by tenofovir which will be mentioned below, or adefovir if tenofovir is not widely available. HBsAg seroconversion occurs in 5.1% of patients after 96 weeks of entecavir.50 In patients who continue to receive entecavir, a further 1.4% have HBsAg seroconversion by year 5.45 While better treatment for lamivudine-resistant disease was still under investigation, telbivudine, another NA belonging to the L-nucleoside subgroup was approved for treatment for CHB in 2006. Telbivudine is more potent than lamivudine in reducing the HBV DNA levels by an addition of l log copies/mL after one year of therapy.51 The HBV DNA undetectable rates are 60% vs 40% for HBeAg-positive and 88% vs 71% for HBeAg-negative patients, respectively. Therefore the chance of drug resistance compared

to lamivudine-treated patients is lower in telbivudine-treated patients, although they share the same genetic mutation sites, and like lamivudine, a single mutation can cause resistance. However, the emergence of viral resistance to telbivudine (25% for HBeAg-positive patients and 11% for HBeAg-negative patients after two years)52 is still higher than adefovir and entecavir. The use of lamivudine and telbivudine has shown the OSBPL9 importance of selecting patients who achieve early potent HBV DNA suppression as a criterion for continuing therapy with these agents. Yuen et al. first demonstrate that HBV DNA levels after 24 weeks of lamivudine therapy is a reliable marker for predicting the chance of lamivudine resistance on continuous treatment.53 This concept of CHB treatment has also been proven in the GLOBE trial of telbivudine vs lamivudine.51,52 In addition to the measurement of HBV DNA treatment response at week 24, baseline HBV DNA levels and ALT levels are also important in selecting patients to be treated with these two agents. According to Zeuzem et al.

5%, p <0.05), better maintenance of MAP (93.8% vs. 72.5%, p=0.02) with cessation of vasopressor requirement (50% versus 25% p=0.03) at 48 hours, improved urine output at 24 hours (59% versus 36%, p=0.05) and no variceal

bleed (0% versus 15.45%, p=0.03) without significantly increased adverse effects (40.6% vs. 22.5%, p=0.12). Terlipressin use showed delayed resolution of Acute Kidney Injury on fifth day (59.4% vs. 16.75, p=0.08) with improved lactate clearance, Central Venus Oxygen saturation and CO2 gradient in Venous – arterial blood gases (p=NS). An early survival advantage was seen with the use of terlipressin (93.5% vs. 75%, p=0.02) in the first 48 hours, but not at 28 days. Conclusion: Terlip-ressin as a vasopressor is non-inferior to noradrenaline with greater hemodynamic stability, early survival benefit, improved urine output, reduced variceal bleed MDV3100 nmr and decreased incidence of nosocomial SBP with nonfatal and reversible adverse effects. Its use is recommended in decompensated

cirrhotics presenting with septic shock. Disclosures: The following people have nothing to disclose: Ashok K. Choudhury, Chitranshu Vashishtha, Deepak Saini, Sachin Kumar, Shiv K. Sarin Background and Aims: HRS-1 is a reversible form of acute kidney injury in cirrhotics with ascites. The aim of REVERSE was to define the efficacy and safety of terlipressin plus albumin versus Rucaparib in vitro albumin alone for the treatment of HRS-1. Methods: HRS-1 was defined as rapidly deteriorating renal function (SCr ≥2.5 mg/ dL and actual or projected doubling of SCr within 2 weeks) without improvement in renal function (<20% decrease in SCr and SCr ≥2.5 mg/dL) 48 hours after both diuretic withdrawal and albumin-fluid challenge in adult cirrhotics with ascites. Subjects were randomized to terlipressin (1 mg IV every 6 hours) or placebo, plus

albumin in both groups. Treatment was continued to Day 14 unless the following occurred: confirmed HRS reversal (CHRSR), renal replacement therapy (RRT), transplantation or SCr at or above baseline at Day 4. CHRSR was defined as 2 SCr values ≤1.5 mg/dL, at least 48 hours apart, on treatment, Ergoloid without RRT or liver transplant; HRS reversal was a decrease in SCr to ≤1.5 mg/dL. Results: 196 subjects were enrolled; 97 were randomized to terlipressin, 99 to placebo. Demographic and baseline clinical characteristics were similar between treatment groups. CHRSR, the primary endpoint, was observed in 19/97 patients (19.6%) in the terlipressin group vs. 13/99 patients (13.1%) in the placebo group (p = 0.2214); a higher percentage of patients in the terlipres-sin group achieved HRS reversal (23/97; 23.7%) compared with placebo (15/99; 15.2%) (p=0.1296). The change from baseline to end of treatment in SCr was significantly greater for terlipressin vs. placebo (terlipressin -1.2, placebo -0.6, ter-lipressin vs. placebo -0.6 mg/dL, p = 0.0003); there was significant correlation between improvement of SCr and survival (r2 = 0.7274, p=0.0035).

As implemented in this study, intermittent presentation of feedback is more effective than continuous presentation in promoting self-modulation of brain activity.

Furthermore, it appears that the process of evaluating feedback involves many brain regions that can be isolated using intermittent presentation. Real-time” functional MRI (RTfMRI) is used to describe the analysis of data while scans are being acquired, as opposed to the more common approach of analyzing data at some time following scanning. It has been proposed that such real-time analysis may be useful for quality monitoring, for brain-computer https://www.selleckchem.com/products/LDE225(NVP-LDE225).html interfaces, and for neurofeedback.1–5 RTfMRI feedback (RTfMRIf) provides individuals neurofeedback regarding their own brain function, thus theoretically allowing a subject or patient to dynamically self-manipulate brain activity during mental processes. There are a number of proposed research and clinical applications of RTfMRIf,4,6 yet fundamental questions surrounding the optimal procedures for RTfMRIf have not been systematically explored. Such questions include how to account for scanner signal drift and physiologic noise over time during a session, how best to select and quantify the signal to feedback, and,

perhaps most important, how to best provide the feedback to the subject.1–4,7–9 A variety of approaches have been used to present RTfMRIf, such as display of whole-brain activity,10 verbal feedback,7,11 a scrolling graph display,8,12 visual scales,13,14 and combinations of feedback display approaches.6,15 The first published report of RTfMRIf used intermittent feedback, NVP-BKM120 supplier updating a functional map after each rest-task block.10 Following EEG feedback findings,8,16 many RTfMRIf studies have used continuous feedback, in which the visual display is updated after each acquired volume.6,8,12,13,15

It is important to note that there are temporal differences between Edoxaban EEG and fMRI measurements of brain activity. The sampling rate of EEG (∼100 samples/second) is orders of magnitude faster than that of fMRI (∼.5 samples/second). Also, the EEG signal is tightly linked to neural activity in time, while fMRI measures a hemodynamic response that follows seconds after neural activity.17 The aim of this study was to directly compare an intermittent versus a continuous approach for providing feedback with RTfMRI to test whether this matters and to aid our group and others in future RTfMRIf study design. Continuous feedback theoretically may have some advantages. The more feedback that is given, the more opportunities are available to modify thoughts and brain activity to best manipulate brain function. Also, continuous feedback may provide greater interest or engagement in participating in the feedback paradigm and ensure greater attention. However, there may be some disadvantages to continuous feedback.

12 In selected experiments (see below), hepatocytes were cultured in minimal essential medium (MEM, Invitrogen, Breda, The Netherlands). Hepatocyte AUY-922 nmr viability and purity were over 90%. Primary rat hepatocytes were plated at a density of 1.0 × 105 cells/cm2. After a 24-hour attachment period, cells were incubated with 25, 100, or 300 μM [2,2,4,4-D]Cholic acid (D4CA; isotopic purity

98%, ISOTEC, Miamisburg, OH) for 0 to 24 hours. For taurine or glycine conjugation preference assays, hepatocytes were cultured in MEM, supplemented with 666 μM glycine (Sigma-Aldrich, St. Louis, MO) and/or 666 μM taurine (Sigma-Aldrich) in the presence of 100 μM D4CA. At indicated timepoints, media and cells were collected followed by subcellular fractionation or immediate storage at −20° C. The subcellular fractionation and isolation of peroxisomes from

rat liver was performed essentially as described13 using PEG1500-containing homogenization buffer (isolation medium-3). Peroxisomes were purified from the 500g supernatant (postnuclear supernatant [PNS]) using Nycodenz density gradient centrifugation according to the method described by Verheyden et al.14 Twelve mL PNS was loaded on top of a discontinuous Nycodenz gradient (2 mL 56%, 3 mL 45%, 15 mL 30%, and 5 mL 18%) and EPZ-6438 cell line spun in a vertical rotor (Sorvall, SV288, Thermo Fisher Scientific, Waltham, MA) at 20,000 rpm for 2 hours Phosphatidylethanolamine N-methyltransferase at 4°C in a slow acceleration/deceleration mode. Equal volumes of all supernatants, pellets, and gradient fractions were analyzed by western blotting or were further purified for mass spectrometry. Digitonin assays were performed essentially as described,11 with the basic difference that digitonin treatments were performed on rat hepatocytes attached to collagen-coated culture discs instead of treated in suspension. Equal volumes of supernatant and pellet fractions were analyzed by western blotting or further processed for mass spectrometry. Apoptotic cell death was visualized

by acridine orange nuclear staining15 and quantified by determining caspase-3 activity.16 The arbitrary fluorescence unit (AFU) was corrected for the amount of total protein in the cell lysate. Necrotic cell death was quantified by determining lactate dehydrogenase (LDH) leakage17 and Sytox green (Invitrogen) according to the supplier’s protocol. Protein samples were separated by SDS-PAGE and analyzed by western blotting according to established procedures.11 Protein concentrations were determined using the Bio-Rad Protein Assay system (Bio-Rad, Hercules, CA) using bovine serum albumin as standard. Primary antibody dilutions used in this study are shown in Supporting Table S1. Proteins signals were detected and quantified in a ChemiDoc XRS system (Bio-Rad). Protein band intensities were quantified using Quantity One software (Bio-Rad). Media samples (0.1-1.

I cannot overstate the value and importance of the support I have received from the VA system in my development as a physician-scientist. I believe that Dr. Montgomery

Bissell expressed this clearly in his Master’s Perspective article,13 when he said that at the beginning of a career as a physician-scientist, the young physician needs “80% of protected time for keeping a steady focus in research”. Thankfully, the VA Research Associate position permitted me 3-4 days a week in which I could focus on research. Because I was at the VA Medical Center, I was also free of certain university committee obligations that can consume much of a young researcher’s precious time. In 1979, I was promoted to Associate Cell Cycle inhibitor Professor of

Medicine, but by then my laboratory was well-established and I could afford the time that departmental duties took up. My opportunity for collaboration with physicians and scientists throughout the world began in earnest when I returned to Yale. I am proud to say that my good www.selleckchem.com/products/Staurosporine.html friends, Mario Chojkier, Andres Blei, and David Kravetz all collaborated with me in my laboratory at the West Haven Veterans Administration Hospital.14-17 We have remained close friends through all these years, meeting at every American Association for the Study of Liver Diseases (AASLD) and Digestive Disease Week meeting. Each now occupies a distinguished position in different medical

schools in this country; sadly, Andy Blei is no longer with us, and we miss him dearly By the late 1970s and for next three decades, the polyglot nature of my laboratory was established with a steady arrival of bright physicians coming from the United States, Argentina, Spain, Italy, Switzerland, Israel, India, Japan, Taiwan, South Korea, Brazil, Mexico, Turkey, and Germany. At times, the laboratory sounded like a “Tower of Babel”, where English was the common language spoken with many different accents (Fig. 3). It was a magnificent time not only as a scientific eltoprazine but also as a personal experience. Because of my past experience treating patients with arterial hypertension, it was clear to me that to make significant advances in the treatment of portal hypertension we needed to improve on the methods available to measure portal pressure. The only acceptable method available in the mid-1970s was the hepatic venous pressure gradient (HVPG) performed with a straight catheter that had to be advanced to the wedged position and withdrawn to obtain the free pressure in the hepatic vein. HVPG, the difference between the wedged hepatic venous pressure (WHVP) and the free hepatic venous pressure (FHVP) represents the gradient between portal vein and intra-abdominal vena cava pressure.

H. pylori expressing high Trx1 significantly induced cell apoptosis, decreased the expression of cyclin D1 and up-regulated p21 in GES-1. However, in BGC823, it increased cell proliferation, and up-regulated cyclin D1. These imply

that the effects of H. pylori were different in the developing stages of gastric cancer. In vivo, we found that H. pylori expressing high Trx1 was much more high pathogenic. Mongolian gerbils were infected by H. pylori expressing high Trx1 for 91 weeks, resulting Selleckchem BGB324 in significantly more serious pathological changes in the gastric mucosa, including gastric cancer and atypical hyperplasia. Conclusion: High Trx1 expression in H. pylori is associated with gastric carcinogenesis. In H. pylori, Trx1 likely participates in find more the pathogenesis of gastric cancer and might be a novel risk marker for highly toxic H. pylori. Key Word(s): 1. Helicobacter pylori; 2. gastric cancer; 3. thioredoxin; Presenting Author: YANYAN SHI Additional Authors: MO CHEN, LINNA LIU, JING ZHANG, YE WANG, SHIGANG DING Corresponding Author: SHIGANG DING Affiliations: Peking University Third Hospital Objective: Helicobacter pylori (H. pylori) maintains long-term persistence in the host and combats oxidative stress via diverse antioxidant proteins, which are expected to be relevant to bacterial-associated diseases. The antioxidant system

in H. pylori is complex and has not been clear. We aim to investigate the expression of three essential antioxidants in H. pylori isolated from patients of different clinical outcomes. Methods: Forty H. pylori strains were isolated from endoscopic biopsy specimens of gastric mucosa from ten patients displaying gastric cancer, twelve patients displaying peptic ulcer, and eleven patients displaying gastritis. After RNA isolation and reverse transcription, the expressions of arginase (RocF), alkyl hydroperoxide reductase (AhpC) and thioredoxin 1 (Trx1) in H. pylori 17-DMAG (Alvespimycin) HCl were

measured by real-time PCR. Comparisons between multiple sample sets were analyzed using a one-way ANOVA test. Pearson’s correlation test was used to assess relationships between multiple continuous variables. Results: RocF expression of H. pylori in gastric cancer tissues was higher than gastritis (P < 0.05). Trx1 expression of H. pylori in gastric cancer (P < 0.05) and peptic ulcer (P < 0.05) tissues was higher than gastritis. The expressions of RocF and Trx1 had positive correlation (r = 0.411, P < 0.05). These indicated that RocF and Trx1 might be related with each other and involved in gastric carcinogenesis. However, we did not find any difference of AhpC expression in different clinical outcomes and any correlation with other two genes. Conclusion: Trx1 and RocF expressions of H. pylori in clinical gastric cancer tissues were higher than in tissues with gastritis. In H. pylori, the members of antioxidant system likely correlate with each other and are relevant to gastric cancer. Key Word(s): 1.

As unexpected findings, they reported a significant

reduction of total circulating B-cell number in MC patients as compared with control populations. They concluded that, naive B cells being more prone to apoptosis and representing the largest fraction of the major B-cell compartment, their reduced frequency may contribute to the observed reduction in CD19+ B-cell number in these patients. These data, indeed, contradict many previously published observations showing an expanded number of PBLs in MC populations.2, 3 Stirred by these observations, we reassessed the results of immunophenotypic analyses of PBLs assessed in 100 HCV-related MC and in 100 HCV-infected patients without MC and in 50 healthy controls. In all patients, PBLs were obtained on the same day of liver biopsy and in no case were cells thawed after cryopreservation. All had selleck compound histological diagnosis of chronic hepatitis without cirrhosis. The patient groups had a comparable total

lymphocyte frequency of 1,435 ± 277 cells/μL in cryoglobulinemic and 1,280 ± 196 cells/μL in noncryoglobulinemic patients. As shown in Fig. 1, the results demonstrate a significant enrichment of circulating B cells in MC patients. As a measure of range values, MC patients showed a CD19+ B-cell frequency higher than 20% in almost 80%. These results are not in line with data reported by Holz et al., whose observations Epigenetics inhibitor may support the notion of compartmentalization of lymphocyte subpopulations. An altered trafficking of B cells with an increased number of naive phenotype in circulation may be proposed, in that activated B cells are selectively retained. HCV induces changes regulating lymphocyte homing, migration, or adhesion to the extracellular matrix. Furthermore, the sharp prevalence of male sex in Holz et al.’s population accounts for a distinct subgroup of cryoglobulinemic patients. They found a 2.4 male/female ratio, which is a very unusual finding. The

high prevalence of females in cryoglobulinemic patients is a long-standing observation. In Selleck Metformin this context remarkable differences in sex distribution within the patients considered by Holz et al. may suggest that hormone patterns may contribute to the modification of characteristics of the B-cell immune response. “
“Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 2010;327:198-201. (Reproduced with permission.) The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed.

Importantly, a few months later, the same protective HLA alleles were confirmed to be associated

with PBC in a large-scale case–control study from the UK.14 Because both these protective alleles are known to influence the penetrance of infectious agents, they have implications in light of the proposed infectious theory of PBC origin. However, the revived interest for HLA genes in PBC arising from these studies was soon overcome by three recent genome-wide Daporinad mouse association studies (GWAS) in PBC, which showed that the strongest associations are located in the HLA region.15-17 This review does not attempt to summarize the knowledge of the genetics of PBC, but will mainly focus on older and more recent associations with HLA

variants obtained with candidate-gene large-scale studies and GWAS, and on how these data may change the genetic landscape of PBC. CTLA-4, cytotoxic T-lymphocyte antigen-4; GWAS, genome-wide see more association studies; HLA, human leukocyte antigen; IL, interleukin; IKZF3, IKAROS family zinc finger 3; IRF5, interferon regulatory factor 5; ORMDL3, ORM1 like 2; PBC, primary biliary cirrhosis; SNP, single-nucleotide polymorphism; SPIB, SPi-B transcription factor; STAT4, signal transducer and activator of transcription 4; TNF, tumor necrosis factor. In the past, a number of reports have reported an increased risk

of developing PBC within family members of affected individuals, a scenario called “familial PBC”.18 The majority of these studies as well as population-based epidemiological reports were performed in the UK.19-22 In this geographical area, the former reported rates of PBC prevalence within family members were approximately 1%-2.4%.19, 20 Prevalence rates of familial PBC were later reported to be 6.4% in the UK22 and between 3.8% and 9.0% in a number of studies from North America, Europe, and Japan. A further estimate of the familial Teicoplanin prevalence of PBC, the sibling relative risk, was found to be 10.5% in a UK study.22 In addition, a recent large US study indicated that having a first-degree relative with PBC was significantly associated with increased risk of disease, with an odds ratio of 10.7.23 Of course, shared environmental factors by family members may well explain these findings, as suggested by data on prevalence and incidence of PBC. A role for genetics is also suggested by the frequent coexistence with other autoimmune diseases in more than one-third of patients who have PBC.23 Diseases that may coexist in patients with PBC or family members include rheumatoid arthritis, Sjögren syndrome, and autoimmune thyroid disease.

4), suggesting protection from cholestasis is a specific physiological function of endogenous serotonin. To investigate potential mechanisms underlying the action of serotonin in cholestasis, we assessed whether the serotonin-dependent protection relates to the elevated plasma bile acids in Tph1−/− mice or is rather due to a more general hepatoprotective role of the neurotransmitter. We first measured ALT levels in WT and Tph1−/− mice following exposure to CCl4.

No differences were observed at 24 and 48 hours after CCl4 treatment (Supporting Fig. 4), suggesting serotonin does not afford general protection from liver injury. To assess whether the serotonergic protection may associate with the bile pool perturbations, we next determined the hepatotoxicity of bile salts by analyzing the composition of plasma

and liver bile salts and adding corresponding Dabrafenib supplier mixtures to hepatocytic cultures. Mass spectrometry (Fig. 3A,B) revealed that about 85% GSI-IX chemical structure of the six analyzed bile salts and acids were taurine-conjugated. Exposure of rat hepatocyte cultures or mouse hepatoma cells to bile acid mixtures demonstrated that the bile acid composition as found in the plasma (about 500 μg/mL) is hepatotoxic in vitro (Fig. 3C,E). The bile acid mix found in the liver was hepatotoxic only in mouse hepatoma cells and at higher doses (Fig. 3D,F). As liver bile salts represent mostly intracellular pools, their extracellular testing may not adequately reveal their toxicity. However, bile salt toxicity was dose-dependent, suggesting the relative increase of bile acids in Tph1−/− mice is augmenting liver injury in vivo. Toxicities of individual bile salts are shown in Supporting Fig. 5. Given the toxicity of bile salts

and their ostensibly reduced clearance in Tph1−/− mice (Supporting Fig. 2), we next examined the expression of genes related to bile salt homeostasis in the liver. Three days of BDL altered the expression of most of the genes examined in the liver. However, no difference was noted between WT and Tph1−/− livers that could explain the increased bile salts and liver injury in Tph1−/− mice (Fig. 4 and Supporting Fig. 6). Notably, the major enzymes related to bile acid production (Fig. 4A), detoxification pheromone (Fig. 4B,C), and transport into plasma (Fig. 4D) were not differentially expressed between WT and Tph1−/− mice. We therefore conclude that serotonin does not affect hepatic bile salt homeostasis in cholestatic mice after 3 days of BDL. Since serotonin does not appear to regulate bile salt homeostasis in the cholestatic liver, we explored whether the kidney may account for the increased bile salt levels in Tph1−/− mice. We tested the expression of renal bile salt transporter genes after 3 days of BDL (Fig. 5).