In this investigation we found a novel gene, BCHE, which was down-regulated years before the onset of cirrhosis. BCHE is the dominant enzyme that metabolizes cocaine, accounting for 95% of its metabolism.18-22 Although the natural function of this enzyme remains unclear, it has

been proposed as a treatment for cocaine overdose and addiction in humans.23 This finding was possible because of the use of LCM to differentiate tissue compartments, and was twice-validated in a cohort of HCV-infected persons at different stages of liver disease. If more broadly confirmed, the finding might shed light on the pathogenesis of HCV-related fibrosis in IDUs, the largest HCV risk group, and may represent a diagnostically useful disease

marker. The BCHE gene product is an abundant PLX4032 ic50 circulating enzyme that has been implicated in liver disease.24 In an animal model of cocaine intoxication, BCHE-/- knockout mice developed significant hepatic necrosis compared with wildtype mice,25 a finding that is consistent with our detection of lower BCHE expression in human HCV-infected liver tissue taken from IDUs. BCHE is highly polymorphic in its expression, and variants of BCHE have been historically associated with prolonged recovery from anesthetic agents such as succinyl choline.26 The ALIVE cohort members all have exposure to cocaine and/or heroin, which LDE225 ic50 is the major transmission route of HCV in industrialized countries. Because BCHE is important in the metabolism of cocaine and heroin, its progressive loss with hepatic fibrosis may potentiate the progression of liver disease. Other studies have examined transcriptional

patterns in whole liver from persons with chronic HCV infection. Using expression microarrays, Smith et al.27 found that liver tissue from persons with chronic HCV and progressive fibrosis had up-regulated expression of markers of myofibroblasts and myofibroblasts-like cells compared with HCV-infected persons without liver disease. Similarly, Takahara et al.28 found that fibrotic liver tissue had higher levels of genes related to inflammation and extracellular matrix compared with normal liver in a cohort of chronically infected persons. A major Metformin manufacturer difference between the present study and earlier ones is the use of LCM to directly compare hepatocytes, rather than pooled hepatic tissue from heterogeneous cellular inputs. This distinction is important because with advancing fibrosis the cellular components of the liver change: inflammatory cells infiltrate the liver, whereas hepatocytes are decreased in number. Indeed, in the present study differences in BCHE expression would not have been detected if high fibrosis transcriptomes were compared in bulk to low fibrosis transcriptomes.

Primary antibodies against ErbB2 (C-18; sc-284), phospho-ErbB2 (Tyr1248; sc-12352-R), ErbB1 (1005; sc-03), and phospho-ErbB1 (Tyr1173; sc-12351)

were purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA). Primary antibodies against phospho-Akt (Ser 473; #9271), Akt (#9272), phospho-p42/44 mitogen-activated protein kinase (MAPK) (Thr202/Thr204; #4377), p42/44 MAPK (#9102), caspase-3 (#9662), and cyclin D1 (#2926) were purchased from Cell Signaling Technology (Beverly, MA). Anti-actin (A 2066) was obtained from Sigma Aldrich Co. http://www.selleckchem.com/products/FK-506-(Tacrolimus).html (St. Louis, MO). Tryphostin AG879 and tryphostin AG1517 were purchased from Calbiochem-Novabiochem Corp. (San Diego, CA). Lapatinib was kindly provided by GlaxoSmithKline, Inc. (Research Triangle Park, NC). The rat cholangiocarcinoma cell lines C611B and BDEneu were each generated in our laboratory and have been previously described.3-5 The human cholangiocarcinoma cell line, HuCCT1, was purchased from Acalabrutinib in vitro the Japan Health Science Foundation (Osaka, Japan). TFK1, the other human cholangiocarcinoma cell line used in this study, was purchased from the German Collection of Microorganisms and

Cell Cultures (Braunschweig, Germany). All of the cholangiocarcinoma cell lines used in this study, with the exception of the HuCCT1 cell line, were cultured in Dulbecco’s modified Eagle medium (DMEM) supplemented according to our standard culture conditions.3 HuCCT1 cells were cultured under comparable conditions in Roswell Park Memorial Institute 1640 (RPMI-1640) medium. In vitro drug treatments with tryphostins AG879 and AG1517, alone and in combination, as well as with lapatinib,

were carried out against the various rat and human cholangiocarcinoma cell lines maintained in culture in either DMEM or RPMI-1640 medium in the presence of 2.5% fetal bovine serum. A range of concentrations of each TK GABA Receptor dissolved in dimethyl sulfoxide (DMSO; final DMSO concentration per culture = 0.1%) were added to the culture medium of the drug-treated cultures, beginning at 16-24 hours after initial cell plating and then continuing daily for up to an additional 72 hours, depending on the experimental design. Vehicle control cultures were exposed to 0.1% DMSO only. In vitro cell growth was assessed using the CellTiter 96 Aqueous Non-Radioactive Cell Proliferation Assay Kit from Promega Corp. (Madison, WI), as described.4, 6 Western blot analysis of total protein in cell lysates prepared from vehicle control and ErbB TK inhibitor–treated cholangiocarcinoma cell lines was also performed as described,4, 7 using commercially available antibodies that had been validated by us for reactivity and specificity.

Feeding a Western diet for 5 months, compared to a low fat control diet, resulted in 100% panlobular

macrosteatosis with some microvesicular steatosis, a 75% increase in peri-portal inflammation and 88% increase in lipogranuloma formation, and peri-portal and zone 1 sinusoidal fibrosis extending into zones 2 & 3 in places in 100% of the mice. When mice on a Western diet were treated with INT-767, there were marked and significant decreases in macrosteatosis (63%), microsteatosis Gefitinib (88%), inflammation (76%) and fibrosis (37%). These histopathological changes were accompanied by significant decreases in the lipogenic transcription factor SREBP-1c ( 25±1.4 in LF vs. 35±2.6 in WD, p<0.01 vs. 26±2.3 in WD+INT-767, p<0.05), pro-inflammatory mediator MCP-1(0.04±0.01 in LF vs. 0.38±0.07

in WD, p<0.01 vs. 0.11 ±0.04 in WD+INT-767, p<0.05), and profibrotic matrix protein Col1a1(2.4±0.6 in LF vs. 50±6.5 in WD, p<0.01 vs. 7.7±2.5 in WD+INT-767, p<0.01). The dual FXR-TGR5 agonist is therefore able to markedly and significantly arrest and revert progression of liver disease even when treatment is started in the presence of obesity, insulin resistance, and NAFLD/NASH. Disclosures: Luciano Adorini - Consulting: Intercept Pharmaceuticals Moshe Levi - Grant/Research Support: Intercept, Genzyme-Sanofi The following people have nothing to disclose: Xiaoxin Wang, Yuhuan Luo, Cherelle Parker, XL765 Rachel McMahan, Hugo R. Rosen, David J. Orlicky Excessive alcohol consumption leads to chronic alcoholic liver disease that ranges from fatty liver, to steatohepatitis, cirrhosis and in some cases hepatocellular carcinoma. Research evidence has suggested that elderly are more prone to severe liver injury due to excessive alcohol consumption, when compared to young adults. However, the mechanism is still unclear. We hypothesize Sinomenine that increased levels of neutrophils, which is a characteristic of human alcoholic liver disease can be affected by aging. Our current study uses female C57BL/6 mice from 18-month to 2 years of

age weighing from 20 g to 40g. These mice were fed with Lieber-DeCarli liquid diets containing eth-anol (5 % v/v) for 10 days, following a single ethanol binge (NIAAA model). Livery injury, demonstrated by elevated levels of alanine transaminase (ALT) and aspartate amino transfer-ase (AST) in middle age mice (18-month to 19-month) when compared to younger (6-month) or old mice (2 yr. old). The protocol used for chronic-plus-single-binge ethanol feeding induces, liver injury, inflammation and fatty liver, which mimic acute-on-chronic alcoholic liver injury in patients. Preliminary results from liver histological analysis revealed that there was a greater degree of steatosis and larger lipid droplets in eth-anol-fed livers from old mice when compared to the younger mice.

Methods: Six-week-old Alvelestat (n = 12) and 14-week-old (n = 12) homozygous mutant

rats at the white spotting locus (Ws/Ws rat) were used. Rats were handled daily by the same person and submitted to water avoidance stress (WAS) daily for 13 days. Rats were exposed to stress session for 1 hr/day in the morning for 13 days and their fecal pellet output (FPO) were counted during WAS or sham WAS. Rats were euthanized after completion of stress experiment and whole colon was collected. Immunohistochemistry for mast cell tryptase and PAR-2 were performed in the proximal and distal click here part of colon. Results: There was no difference in body weight change during stress experiment

between WAS and sham WAS group. WAS group exhibited increased FPO during 13 days compared to sham stress. This effect was significant for both aged Ws/Ws rat. MC were nearly absent in the colonic mucosa of 14-week-old Ws/Ws rat. In 6-week-old Ws/Ws rats, number of MC in the colonic mucosa were statistically increased by WAS compared to sham WAS. PAR-2 cells were statistically increased by WAS only in the 14-week-old Ws/Ws rat. Increased MC and PAR-2 cells by WAS were observed mainly in the proximal colon. Conclusion: Chronic psychological stress increased colonic motility independently to the presence

of mast cell in the colonic mucosa. And psychological stress increased not only mast cells but also other inflammatory cells preferentially in the proximal colon. Key Inositol monophosphatase 1 Word(s): 1. Psychological stress; 2. mast cell; 3. colon; 4. Ws/Ws rat; Presenting Author: WANGZHI MO Additional Authors: HOUXIAO HUA Corresponding Author: HOUXIAO HUA Affiliations: Division of Gastroenterology, Union Hospital, Tongji Medical College Objective: To explore the role of SRF-IEG on the formation of visceral hypersensitivity induced by acute restraint stress. Methods: 12 male Sprague-Dawley rats were randomly divided into control group and acute restraint stress group (model group). Visceral hypersensitivity was made by acute restraint stress for 2 h. The colorectal distension (CRD) with different pressure were performed and abdominal withdrawal reflex (AWR) scores were observed during CRD. The visceral hypersensitivity was determined by AWR scores.

Epidemiologic findings that women have higher rates of headache-related disability and psychiatric

comorbidity have not been replicated regularly among selleckchem treatment-seeking headache samples. Awareness of these differences may stimulate further research and enhance therapeutic opportunities for headache patients. “
“Objective.— To evaluate the pharmacokinetic profile and tolerability of single doses of rizatriptan oral disintegrating tablets (ODTs) in pediatric migraineurs. Background.— Acute migraine treatment options for children are limited despite a rising migraine prevalence. No triptans are approved in those under 12, and only sumatriptan nasal spray (European Union) and almotriptan tablets (USA) are approved for those aged 12-17. Appropriate dose selection based on body weight may be a factor in establishing treatment efficacy in this population. Methods.— Randomized, double-blind, placebo-controlled, parallel group, single-dose study in 6- to 17-year-old migraineurs. The study was performed between acute migraine attacks. Subjects were allocated to 1 of 2 groups based on body weight: (1) those weighing <40 kg received rizatriptan 5-Fluoracil manufacturer ODT 5 mg or placebo; (2) those weighing ≥40 kg received

rizatriptan 10 mg ODT or placebo. Pharmacokinetic data were compared with historical data on rizatriptan ODT 10 mg in healthy adults. Results.— The geometric mean area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)) (hours·ng/mL) and maximum peak plasma concentration (Cmax) (ng/mL) were 56.68 (95% confidence interval [CI]: 48.60, 66.09) and 22.39 (95% CI: 17.90, 28.02), respectively, for the <40 kg group and 78.49 (95% CI: 68.93, 89.38) and 22.27 (95% CI: 18.43, 26.92), respectively, for the ≥40 kg group. For the comparison of children vs adults, the geometric mean

ratios for rizatriptan AUC(0-∞) and Cmax were 0.85 (90% CI: 0.73, 0.98) and 1.07 (90% CI: 0.86, 1.34), respectively, for the <40 kg group vs historical adult data and 1.17 (90% CI: 1.02, 1.34) Metalloexopeptidase and 1.06 (90% CI: 0.87, 1.30), respectively, for the ≥40 kg group vs historical adult data. There were no serious adverse events, and rizatriptan was generally well tolerated. Conclusions.— In pediatric migraineurs, a weight-based dosing scheme generated plasma rizatriptan AUC(0-∞) and Cmax values that were generally similar to those historically observed in adults administered a 10-mg dose of rizatriptan ODT (a proven effective dose). The data support further evaluation of the safety, tolerability, and efficacy of this rizatriptan dosing scheme in larger scale clinical trials in the pediatric migraineur population. “
“(Headache 2011;51:632-636) Seventeenth-century English closets were books containing a wide repertoire of household supplies targeted at female readers. Such volumes typically included medical recipes, as early modern women also used to be responsible for preserving and restoring the health of relatives and close neighbors.

Epidemiologic findings that women have higher rates of headache-related disability and psychiatric

comorbidity have not been replicated regularly among ABT-888 manufacturer treatment-seeking headache samples. Awareness of these differences may stimulate further research and enhance therapeutic opportunities for headache patients. “
“Objective.— To evaluate the pharmacokinetic profile and tolerability of single doses of rizatriptan oral disintegrating tablets (ODTs) in pediatric migraineurs. Background.— Acute migraine treatment options for children are limited despite a rising migraine prevalence. No triptans are approved in those under 12, and only sumatriptan nasal spray (European Union) and almotriptan tablets (USA) are approved for those aged 12-17. Appropriate dose selection based on body weight may be a factor in establishing treatment efficacy in this population. Methods.— Randomized, double-blind, placebo-controlled, parallel group, single-dose study in 6- to 17-year-old migraineurs. The study was performed between acute migraine attacks. Subjects were allocated to 1 of 2 groups based on body weight: (1) those weighing <40 kg received rizatriptan learn more ODT 5 mg or placebo; (2) those weighing ≥40 kg received

rizatriptan 10 mg ODT or placebo. Pharmacokinetic data were compared with historical data on rizatriptan ODT 10 mg in healthy adults. Results.— The geometric mean area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)) (hours·ng/mL) and maximum peak plasma concentration (Cmax) (ng/mL) were 56.68 (95% confidence interval [CI]: 48.60, 66.09) and 22.39 (95% CI: 17.90, 28.02), respectively, for the <40 kg group and 78.49 (95% CI: 68.93, 89.38) and 22.27 (95% CI: 18.43, 26.92), respectively, for the ≥40 kg group. For the comparison of children vs adults, the geometric mean

ratios for rizatriptan AUC(0-∞) and Cmax were 0.85 (90% CI: 0.73, 0.98) and 1.07 (90% CI: 0.86, 1.34), respectively, for the <40 kg group vs historical adult data and 1.17 (90% CI: 1.02, 1.34) Megestrol Acetate and 1.06 (90% CI: 0.87, 1.30), respectively, for the ≥40 kg group vs historical adult data. There were no serious adverse events, and rizatriptan was generally well tolerated. Conclusions.— In pediatric migraineurs, a weight-based dosing scheme generated plasma rizatriptan AUC(0-∞) and Cmax values that were generally similar to those historically observed in adults administered a 10-mg dose of rizatriptan ODT (a proven effective dose). The data support further evaluation of the safety, tolerability, and efficacy of this rizatriptan dosing scheme in larger scale clinical trials in the pediatric migraineur population. “
“(Headache 2011;51:632-636) Seventeenth-century English closets were books containing a wide repertoire of household supplies targeted at female readers. Such volumes typically included medical recipes, as early modern women also used to be responsible for preserving and restoring the health of relatives and close neighbors.

These two miRNAs, together with the two most up-regulated miRNAs, miR-96 and miR-182, require further study for understanding their relevance in HCC. Down-regulated miRNAs are of interest because they can act as tumor suppressors.39 Cellular miRNAs can also act as oncogenes,47 and their up-regulation in cancer will cause down-regulation of their tumor-suppressive targets.

In general, these miRNAs are potentially relevant for HCC therapy: tumor suppressor miRNAs can be introduced back in a cancer PI3K inhibitor cell, thereby repressing tumorigenesis, and oncogenic miRNAs can be inhibited by using synthetic miRNA antagonists or virally-delivered sponge-like sequences.48, 49 This brings exciting possibilities for the use of miRNAs as therapeutics. In the current study we experimentally verified 13 predicted miRNAs targets in five ABC genes using luciferase reporter assays. We were able to prove that the miRNA effect was sequence-specific by mutating the targets in the reporters and by cotransfecting miRNAs not having targets in ABC genes (data not shown). Except for ABCC4, our mutational analysis revealed some new miRNA targets in ABC genes. Strikingly, we were able to show that for several miRNA-ABC pairs, a very high proportion of the

analyzed tumors have an increased ABC gene expression level together with a reduced level of miRNA. Thus far the only evidence selleck chemical of miRNA-mediated regulation of ABC gene expression in HCC has been provided by Furuta et al.,27 who showed that miR-203 regulates the expression of ABCE1, which is involved in translation initiation, but has not been linked to multidrug resistance. With this perspective, we are currently working on in vitro validation of the miRNA-mediated regulation of endogenous ABC gene expression with a special focus on the ABCC subfamily. Future research will concentrate on delivery of these miRNAs as gene therapy, either in miRNA-replacement therapy for HCC

or as a novel indirect strategy to induce down-regulation of ABC transporters instead of direct short hairpin RNA (shRNA)- or artificial miRNA-mediated 3-mercaptopyruvate sulfurtransferase gene therapy approaches.50 The focus should be on ABCB6, ABCC1, ABCC4, ABCC5, ABCC10, and ABCC12 as these genes were up-regulated in more than 50% of the patients. The authors thank Françoise Degos, Bruno Clément, Bruno Turlin, and the Centre de Ressources Biologiques Foie (France) for providing clinical samples and data, and Cees B.M. Oudejans (Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands) for kindly providing access to the ABI 7900HT. Additional Supporting Information may be found in the online version of this article. “
“Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) widely used in human immunodeficiency virus (HIV) infection therapy. It has been associated with hepatotoxic effects and alterations in lipid and body fat composition.

(HEPATOLOGY 2011;) See Editorial on Page 1427 This work was undertaken to address two issues raised in an editorial about our previous article16: (1) testing the accuracy of HCC immunomarkers in a homogeneous series of HCCs up to 2 cm in size and (2) improving the accuracy of the panel with additional markers. To this end, we retrospectively evaluated a series of HCCs consecutively diagnosed

on core biopsy samples with a 20- to 21-gauge needle; with this material, we tested the diagnostic accuracy of a refined panel of markers (CHC, GPC3, HSP70, and GS). The performance of the panel was also evaluated according to HCC grading [grade 1 (G1) versus grade 2 (G2)/grade 3 (G3)] and sizes (≤2 versus >2 cm). 3M, three-marker; 4M, four-marker; AASLD, American Selleckchem Vismodegib Association for the Study selleck products of Liver Diseases; CHC, clathrin heavy chain; G1, grade 1; G2, grade 2; G3, grade 3; GPC3, glypican 3; GS, glutamine synthetase; H&E, hematoxylin and eosin; HCC, hepatocellular carcinoma; HGDN, high-grade dysplastic nodule; HSP70, heat shock protein 70; LGDN, low-grade dysplastic nodule. The series

under study was composed of 20- to 21-gauge needle core biopsy samples from 86 HCCs with a cirrhotic background. They were obtained from the files of the Policlinico General Hospital (Milan, Italy) and Melegnano General Hospital (Melegnano, Italy) and were collected from 2005 to 2009. The diagnosis of HCC was made in all the cases according to AASLD guidelines.17 The diagnostic process included routine laboratory tests, serum alpha-fetoprotein measurements, and abdominal ultrasound, contrast-enhanced spiral computed tomography, or magnetic resonance imaging. The diagnosis of cirrhosis was based on histology or concordant laboratory and imaging findings. The tumor size was the largest diameter measured by imaging. The histopathological diagnosis of HCC Leukotriene-A4 hydrolase was originally made mostly after hematoxylin and eosin (H&E) staining supplemented by routine histochemical stains such as Gomori staining for reticulin, Perls’ staining for iron, and Masson trichrome staining. All the slides were preliminary revised by two expert pathologists (M.R.

and L.D.T.), and the diagnosis of HCC was confirmed after accurate morphological analysis in all cases. HCC grading was based on the available material according to Edmondson and Steiner,18 and cases were divided into two groups: well-differentiated histology (G1) and moderately to poorly differentiated histology (G2/G3). The main pathological criteria for identifying well-differentiated HCCs and distinguishing them from high-grade dysplastic nodules (HGDNs) are reported in Supporting Table 1. The series included only cases with a tumor core and material available for immunocytochemical analyses (at least five recuts from the original block). Figure 1 shows a paradigmatic G1 HCC with an extralesional sample, which well represents the material under study.

218 Although a strong rationale remains for the use of anti-TNF therapy in alcoholic hepatitis, there is also a theoretical basis for minimizing

TNF inhibition, because it plays a role in liver regeneration as well as apoptosis.219 Thus, in light of the poor clinical outcomes observed in the largest of the infliximab trials and the etanercept study, the use of these parenteral TNF inhibitors should be confined to clinical trials, and recommendations regarding specific therapy will need to await the results of these trials. There are no substantive clinical data comparing the use of steroids or nutrition to specific anti-TNF therapies. Although it is assumed that each Veliparib datasheet of these different treatments may operate via independent mechanisms, there are only minimal data regarding the comparative benefit of sequential therapies or combined approaches. One study tested the use of pentoxifylline in 29 patients with severe AH (MDF > 32) who did not respond to steroids based on a drop in bilirubin level after 1 week of prednisolone treatment. Compared to previously treated patients (who were continued on steroids despite lack of bilirubin response), there was no improvement in 2-month survival, thus arguing against a two-step strategy with MAPK Inhibitor Library an early switch to pentoxifylline.220 Several older studies had examined the role of anabolic steroids with nutritional interventions

(based on the presumption that both interventions acted via a similar mechanism, i.e., correction of protein calorie malnutrition).221 One pilot study evaluated the role of steroids in combination with enteral nutrition in 13 patients with severe AH, and found an overall mortality of 15%—possibly an improvement from expected.222 With the advent of new therapies, it is necessary to reconsider the risk-benefit

ratio of medical treatment. It has been suggested that it may be possible to use less toxic therapies at a lower threshold of disease severity.223 However, the exact role of these new therapies, and IKBKE the threshold for their use, is still undefined. Many other therapeutic interventions have been studied in alcoholic hepatitis, but have not been able to show convincing benefit, including trials of antioxidants (vitamin E, silymarin, combination antioxidants), antifibrotics (colchicine), antithyroid drugs (propylthiouracil [PTU]), promoters of hepatic regeneration (insulin and glucagons), anabolic steroids (oxandrolone and testosterone), as well as calcium channel blockers (amlodipine), polyunsaturated lecithin, and a number of complementary and alternative medicines (reviewed in O’Shea and McCullough224). In addition to medical treatment directed at the underlying pathophysiologic abnormalities, several studies have tested other aggressive interventions in patients with AH, such as a molecular adsorbent recirculating system.

218 Although a strong rationale remains for the use of anti-TNF therapy in alcoholic hepatitis, there is also a theoretical basis for minimizing

TNF inhibition, because it plays a role in liver regeneration as well as apoptosis.219 Thus, in light of the poor clinical outcomes observed in the largest of the infliximab trials and the etanercept study, the use of these parenteral TNF inhibitors should be confined to clinical trials, and recommendations regarding specific therapy will need to await the results of these trials. There are no substantive clinical data comparing the use of steroids or nutrition to specific anti-TNF therapies. Although it is assumed that each selleck screening library of these different treatments may operate via independent mechanisms, there are only minimal data regarding the comparative benefit of sequential therapies or combined approaches. One study tested the use of pentoxifylline in 29 patients with severe AH (MDF > 32) who did not respond to steroids based on a drop in bilirubin level after 1 week of prednisolone treatment. Compared to previously treated patients (who were continued on steroids despite lack of bilirubin response), there was no improvement in 2-month survival, thus arguing against a two-step strategy with Navitoclax purchase an early switch to pentoxifylline.220 Several older studies had examined the role of anabolic steroids with nutritional interventions

(based on the presumption that both interventions acted via a similar mechanism, i.e., correction of protein calorie malnutrition).221 One pilot study evaluated the role of steroids in combination with enteral nutrition in 13 patients with severe AH, and found an overall mortality of 15%—possibly an improvement from expected.222 With the advent of new therapies, it is necessary to reconsider the risk-benefit

ratio of medical treatment. It has been suggested that it may be possible to use less toxic therapies at a lower threshold of disease severity.223 However, the exact role of these new therapies, and SSR128129E the threshold for their use, is still undefined. Many other therapeutic interventions have been studied in alcoholic hepatitis, but have not been able to show convincing benefit, including trials of antioxidants (vitamin E, silymarin, combination antioxidants), antifibrotics (colchicine), antithyroid drugs (propylthiouracil [PTU]), promoters of hepatic regeneration (insulin and glucagons), anabolic steroids (oxandrolone and testosterone), as well as calcium channel blockers (amlodipine), polyunsaturated lecithin, and a number of complementary and alternative medicines (reviewed in O’Shea and McCullough224). In addition to medical treatment directed at the underlying pathophysiologic abnormalities, several studies have tested other aggressive interventions in patients with AH, such as a molecular adsorbent recirculating system.