However, studies have not yet been conducted to ascertain its role in prevention of hepatotoxicity. Aim: This study was planned to elucidate the role of wheat grass if any on liver function tests (LFT), antioxidants enzymes and histoarchitecture in hepatotoxicity conditions induced by Carbon tetra chloride (CCl4). Methods: 42 female

Wistar rats were divided into 7 groups. Group 1 (Normal control): Rats were given normal saline subcutaneously (SC). Group 2: CCl4 was administered SC at a dose of 2 ml/kg b.wt twice/week for 4 weeks. Group 3–6: – Rats in these groups received orally wheatgrass dissolved in water at different doses of 20 mg, 40 mg, 60 mg and 80 mg/100 g b.wt and CCl4 as was given to group 2 animals. Wheatgrass was started 2 weeks prior to first injection of CCl4. Group 7- Animals in this group received wheatgrass alone Y27632 at a highest dose of 80 mg/100 g b.wt. The effects of different treatments were studied on LFT, Glutathione (GSH), lipid peroxidation (LPO), Catalase and superoxide dismutase (SOD) at end of 2 weeks and 4 weeks. Histological studies were also conducted. Results: The enzyme activity of ALP, Selleck LY2157299 AST, and ALT

were increased significantly at 2 and 4 weeks as compared to values in control group. Interestingly, supplementation of wheat grass at all doses brought down the already increased activity of ALT but there was more pronounced decrease with 80 mg dose of wheat grass at both the time duration s of 2 and 4 weeks. However, AST and ALP activity was found to be decreased significantly at 4 weeks following supplementation of wheat grass at doses Resminostat ranging from 40–80 mg. Also, it was found that GSH level significantly decreased while LPO increased in CCl4 treated rats as compared to group1 (control).

In wheat grass treated groups, GSH level was increased while LPO decreased as compared to group 2. Histologically, there was necrosis, portal triaditis & lobular inflammation in CCl4 group. Therefore, protection was observed with wheat grass which may not be significant at 2 weeks but values were significant at 4 weeks. Conclusion: Wheat grass supplementation at a dose of 80 mg/100 g is effective in controlling hepatotoxicity induced by CCl4. Wheat grass and its extracts can be boon in preventing liver diseases Key Word(s): 1. Wheatgrass; 2. Carbon Tetrachloride; 3. Prevention; 4. Hepatotoxicity; Presenting Author: TAMSINNAOMI CARGILL Additional Authors: PREYA PATEL, LYNFA LANZON-MILLER, SANDRO LANZON-MILLER Corresponding Author: TAMSINNAOMI CARGILL, PREYA PATEL Affiliations: Milton Keynes Hospital Objective: Nasal bridle use is claimed to enable uninterrupted delivery of enteral nutrition and prevent unnecessary percutaneous endoscopic gastrostomies (PEGs). This study assesses the outcomes of patients fitted with nasal bridles at Milton Keynes Hospital.

HBsAg levels <100 IU/mL may herald HBsAg clearance. Disclosures: Cihan Yurdaydin - Advisory Committees or Review Panels: Janssen, Roche, Merck, Gilead The following people have nothing to disclose: Onur Keskin, Mustafa Yakut, Cagdas Kalkan, Senem C. Karatayli, Ersin Karatayli, Ramazan Idilman, A Mithat Bozdayi Background/Aim: The study aimed to

investigate HBV ETV resistance profile of Chinese patients in clinical practice. Methods: Serum samples from 18,419 patients collected from July 2007 to June 2012 in Beijing 302 Hospital were screened. buy Hydroxychloroquine Genotypic resistance was detected by direct PCR sequencing and confirmed by clonal sequencing if necessary. Phenotypic resistance was analyzed by measuring HBV replication capacity under drug pressure in

HepG2 cells. Results: ETV-resistant mutations were detected from 646 samples and the incidence had been increased in the past five years (1.91%, 2.23%, 3.54%, 3.96%, and 4.77%). Mutational pattern analysis showed that concomitant with rtM204V/rtM204I, mutations at rt1 84, rt202, rt250, and two of rt1 84/rt202/rt250 sites were 57.4%, 22.4% and 14.1%, and 6.1%, LBH589 purchase respectively (Figure 1). Nineteen percent (123/646) of ETV-resistant samples harbored rtM204I±L80I/L180M-based pattern rather than rtL180M+M204V-based pattern. Among them 70 samples only harbored two resistant mutations (rtM204I+T184I × 39, rtM204I+M250L × 26, rtM204I+M250I × 5). All ETV-resistant SPTBN5 strains exhibited varied lower natural replication capacity compared to wild-type strains in vitro. ETV susceptibility of rtL180M+M204V-based ETV-resistant mutants

was usually lower than rtM204I-based ETV-resistant mutants. Replication of all tested ETV-resistant strains could be effectively suppressed by tenofovir and adefovir in vitro. In clinical practice, adding-on adefovir was more efficacious than switching-to adefovir as a rescue therapy for ETV-resistant patients. Conclusions: The occurrence of ETV-resistant HBV infection kept growing in the past five years in Chinese patients. ETV-resistant mutational pattern diversified and rtM204I-containing ETV-resistant strains occupied near 1/5 of the patients. ETV-resistant strains could be suppressed by tenofovir or adefovir in vitro; and currently, adding-on adefovir was a practical rescue therapy in clinical practice in China. Disclosures: The following people have nothing to disclose: Yan Liu, Zhihui Xu, Liming Liu, Xiaodong Li, Jiuzeng Dai, Zengtao Yao, Li Chen, Siyu Bai, Shaojie Xin, Dongping Xu Background: Hepatitis B virus (HBV) infection plays a crucial role in the pathogenesis of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Therefore, it is of prime importance to understand the mechanisms of HBV-host interactions during malignant transformation in chronic hepatitis B (CHB) infection to identify novel therapeutic anti-HBV targets.

22 In a study using 24-h ambulatory MII–pH, Sifrim et al. reported that GERD patients showed

more acid reflux and less non-acid reflux.6 The total rate of reflux episodes was similar in patients and healthy controls. However, GERD patients showed a higher proportion of acid reflux. One-third of reflux episodes were non-acid in both groups. Vela et al. reported that treatment with omeprazole resulted in a significantly decreased number of acid reflux episodes; however, non-acid reflux continued to occur and was responsible for some symptoms.23 When patients with NCCP were divided into GERD-related NCCP and non GERD-related NCCP groups based on MII–pH and upper endoscopy, there were no differences in age, sex, typical esophageal symptoms, improvement with PPI medication, or esophageal dysmotility between the two groups. Improvement of selleck inhibitor symptoms was achieved in 92% of patients when using PPI medication. As for the possible mechanisms for the improvement with PPI in GERD-unrelated NCCP, several mechanisms for NCCP, such as visceral hypersensitivity and psychological comorbidity, have been proposed.10 Although it requires further confirmation,

there are several hypotheses, such as abnormal mechanophysical properties of the esophagus, sustained longitudinal muscle contractions of the esophagus, altered central processing of selleck chemicals esophageal stimuli, and autonomic dysregulation. This suggests that both non GERD-related and GERD-related NCCP respond to PPI therapy and that PPI might be an alternative treatment for non GERD-related NCCP. There are some limitations to the present study. First, the pathological bolus exposure time in the postprandial period was not based on the normal values in healthy volunteers. Second, psychological aspects of NCCP were not sufficiently identified. Nevertheless, this study is important because it investigates the role of pathological

bolus exposure in patients with NCCP using impedance–pH monitoring. In conclusion, the combination of impedance and pH monitoring improves the detection and characterization of NCCP. This study suggests that pathological bolus exposure plays a check details significant role in eliciting NCCP. “
“Colorectal cancer is one of the commonest malignancies in the “developed” world. The liver constitutes the main host organ for its distant metastases which, when present, augur a bad prognosis for the disease. Kupffer cells (KCs) are macrophages that constantly reside within the liver and form an effective first line defence against multiple harmful agents which reach the hepatic sinusoids via the portal circulation. KCs remove chemical compounds and dead or damaged cells, eliminate bacteria and protect against invading tumour cells. They may play a crucial tumouricidal role, exerting cytotoxic and cytostatic functions through the release of multiple cytokines and chemokines.

With platelet-rich plasma, it is also possible to titrate the ristocetin effect using the ristocetin-induced platelet aggregation (RIPA) assay [11]. RIPA is most commonly used to differentiate between VWD type 2A (decreased RIPA) and 2B (increased RIPA). However, RIPA is also increased in platelet-type VWD [12] explained by gain-of-function mutations in the GPIBA gene that encodes the GPIbα receptor. BAY 73-4506 ic50 A major drawback of RIPA is the requirement to use the patient’s platelets, so the sample cannot be frozen and analysed at a remote centre. Alternative ristocetin-based assays use flow cytometry or ELISAs with recombinant GPIbα bound to a specific antibody, which capture VWF in plasma (Fig. 1) [10]. Pure

immunobinding assays, independent of ristocetin, are based on monoclonal antibodies directed against the functional epitope of VWF with the binding site for GPIbα. These can be performed by ELISA or as a fully automated latex immunoassay [13,14]. Novel, ristocetin-independent assays that only utilize GPIbα have been published [15,16]. These utilize gain-of-function mutated GPIbα constructs that bind VWF without the need of any modulator. Ristocetin-independent assays are unaffected by common polymorphisms that may result in false low VWF:RCo results [17]. There

are now commercial variants of this assay, including a latex particle find more enhanced agglutination assay reportedly easy to perform on common coagulometers, with good reproducibility and sensitivity [18]. If initial evaluation results are validated in clinical routine settings, ristocetin-free assays have the potential to eventually replace classical VWF:RCo [19]. Thus, ‘alternative’ VWF:RCo assays may measure binding to GPIbα, or fragments thereof, enough directly or indirectly through specific antibodies and with or without ristocetin as modulating agent. These activity assays have not been extensively validated and cannot currently be recommended to replace traditional VWF:RCo in routine clinical practice. Collagen binding

to the subendothelial matrix is another measurable adhesive activity of VWF (Fig. 1). VWF collagen binding activity (VWF:CB) assays, as well as VWF:RCo, both offer some selective discrimination of HMW-VWF, and are thus similarly useful for identification of types 2A and 2B VWD. The VWF:CB/VWF:Ag ratio is typically >0.7 in type 1, but <0.7 in types 2A and 2B VWD. The three test panel of VWF:CB, VWF:RCo and VWF:Ag assists both the identification and discrimination of most VWD types, and is more powerful and less error-prone than the combination of VWF:Ag and VWF:RCo alone [7,20,21]. VWF:CB was originally an ELISA assay [22], which is the system still most commonly used despite the early description of a flow cytometry method [23]. VWF:CB reproducibility is between that of VWF:Ag and VWF:RCo (interassay CVs 15–25% [7,20,21]) and its limit of VWF detection is similar to that of VWF:Ag, at around 0–5 U dL−1 [6].

Each measurement was repeated at least in triplicate and normalized

to the corresponding glyceraldehyde 3-phosphate dehydrogenase (GAPDH) content values. The optimized primers used for real-time PCR are listed Raf activity in Supporting Table 1. The ability of cell migration was evaluated using a Transwell system (Corning Coster, Cambridge, MA), which allows cells to migrate through a polycarbonate membrane (8-μm pore size). Briefly, the upper compartment was filled with DMEM containing 1% FBS, and the lower chamber contained DMEM plus 10% FBS. Cells were treated as indicated in Supporting Fig. S3, and then seeded in the upper compartment of the Transwell chamber and cultured for an additional 12 hours at 37°C. Nonmigrated cells on the upper surface of the filter membrane were removed and migrated cells attached to the bottom surface of the filter membrane were fixed in methanol, stained with Giemsa, and counted in five random fields. All

assays were performed in triplicate. Data are presented as mean values ± SE. Comparisons were made using Student t test. For all analyses, a two-sided P < 0.05 was considered to indicate statistical significance. Given the prominent role of TGF-β in EMT and fibrogenesis, https://www.selleckchem.com/products/Y-27632.html a number of strategies for blocking TGF-β signaling have been proposed.22–24 Small molecules targeting this signaling cascade have great therapeutic potential. To identify such candidates, a drug library screen was performed using (CAGA)12-Lux, a luciferase reporter that is activated in response to a wide range of TGF-β1 concentrations (Supporting Fig. S1). Interestingly, the activity of this reporter could be inhibited by treatment with sorafenib, but not with other clinical agents (Fig. 1A). The inhibitory effect of sorafenib on TGF-β-dependent gene transcription of the (CAGA)12-Lux reporter was dose-dependent (Fig. 1B). To further investigate the intracellular signal transduction mechanism, we treated cells with increasing doses of sorafenib under TGF-β1 stimulation. As shown in Fig. 1C, sorafenib abrogated TGF-β-mediated phosphorylation of Smad2 and Smad3, again in a dose-dependent manner. Moreover, sorafenib reduces the nuclear

localization of phosphorylated Smad2/3 (Supporting Fig. S2A), which are the central mediators of the TGF-β signaling pathway.5, BCKDHA 6 We next examined whether treatment with sorafenib impaired the endogenous expression of Smad7, a target gene that is transiently induced by TGF-β1 through a negative feedback mechanism.4–6 Indeed, the application of sorafenib markedly decreased the expression of Smad7 mRNA (Fig. 1D). Experiments similar to those shown in Fig. 1B were repeated in HEK 293T, NIH 3T3, and HeLa cells with essentially the same results (data not shown), indicating that sorafenib acts as an effective inhibitor of TGF-β signaling regardless of cell type. These findings prompted us to assess the impact of sorafenib on TGF-β-mediated physiological events.

As a number of candidate genes of Bmi1 were identified in this study, coordinated regulation of multiple Bmi1 targets might be needed to recapitulate Bmi1-mediated tumorigenesis in vivo. In this regard, knockdown of Sox17 or other candidate target genes in Ink4a/Arf−/−

Dlk+ cells would be intriguing to assess for their tumorigenic activity in vivo. Finally, our findings demonstrated Selleck GSK126 that Bmi1 regulates the self-renewal of hepatic stem/progenitor cells to a large extent through the suppression of Ink4a/Arf. However, it is evident that targets of Bmi1 other than the Ink4a/Arf locus are also responsible for the development of cancer. Further analyses are necessary to determine the roles of the genes listed here in liver development, regeneration, and cancer. The authors thank Dr. M. van Lohuizen for Bmi1+/− mice, Dr. W. Pear for the MIGR1 vector,

Dr. Valentina M. Factor for the anti-A6 antibody, Dr. N. Nozaki for the anti-Bmi1 antibody, Dr. A. Miyawaki for Kusabira orange, Y. Yamazaki for technical support with the flow cytometry, and M. Tanemura for laboratory assistance. Additional Supporting Information may be found in the online version of this article. “
“Aim:  The human hepatocellular carcinoma (HCC) cell line HepG2 can easily acquire resistance to doxorubicin. However, the mechanism of action is unclear. Methods:  In the present study, we used confocal microscopy, flow cytometry and other methods to reveal the mechanisms by which HepG2 cells acquire doxorubicin resistance. Pexidartinib cost Results:  Our results showed that R-HepG2 cells, a doxorubicin-resistant sub-line of HepG2, exhibited decreased intracellular accumulation of doxorubicin and increased expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 when compared with HepG2 cells. R-HepG2 cells also harbored higher levels of glutathione and increased expression of glutathione peroxidase. Furthermore, we demonstrated that the phosphorylation of mitogen-activated protein kinases (p38 and c-jun-N-terminal kinases), IkBα and CREB were increased

in R-HepG2 cells. Specific p38 inhibitor SB203580 decreased P-gp Cisplatin manufacturer expression. The multi-kinase inhibitor sorafenib tosylate also significantly suppressed the phosphorylation of these proteins and inhibited the expression of P-gp. Conclusion:  These findings reveal that the drug resistance could be acquired through mitogen-activated protein kinase-dependent upregulation of P-gp. This mechanism protects R-HepG2 cells from the anticancer action of doxorubicin. “
“See article in J. Gastroenterol. Hepatol. 2012; 27: 566–578. For patients with advanced liver fibrosis/cirrhosis, the development of hepatocellular carcinoma (HCC) is a cause of both significant morbidity and mortality. The often late presentation of HCC, alongside patient age and comorbidity, means that radiofrequency ablation (RFA), multikinase inhibitors, and transarterial chemo-embolization frequently have a limited role.

94 95%CI 1.38-2.73, p<0.001). ROC analysis showed that the FIB-4 index (AUC=0.72, 95%CI 0.67-0.77) was better to discriminate between Ishak 4 and Ishak 5/6 compared to APRI (AUC=0.66, 95%CI 0.60-0.72, p<0.001) or AST/ALT ratio (AUC=0.66, 95%CI 0.60-0.72, p<0.001, Figure). CONCLUSION Among chronic HCV patients with and biopsy-proven advanced liver disease, the diagnostic accuracy of the FIB-4 index for presence of Ishak score 5/6 was selleck inhibitor better as compared to the APRI score and AST/ALT ratio. Disclosures: Raoel Maan – Consulting:

AbbVie Adriaan J. van der Meer – Speaking and Teaching: MSD, Gilead Jordan J. Feld – Advisory Committees or Review Panels: Idenix, Merck, Janssen, Gilead, AbbVie, Merck, Theravance, Bristol Meiers Squibb; Grant/Research Support: AbbVie, Boehringer Ingelheim, Janssen, Gilead, Merck Heiner Wedemeyer – Advisory Committees or Review Panels: Transgene, MSD, Roche, Gilead, Abbott, BMS, Falk, Abbvie, Novartis, GSK; Grant/Research Support: MSD, Novartis, Gilead, Roche, Abbott; Speaking

and Teaching: BMS, MSD, Novartis, ITF, Abbvie, Gilead Jean-Francois J. DuFour – Advisory Committees or Review Panels: Bayer, Gilead, Janssen, BMS, Jennerex, Merck, Novartis, Roche; Speaking and Teaching: Bayer, Boehringer-Ingelheim, Novartis, Roche Andres Duarte-Rojo – Advisory Committees or Review Panels: Gilead Sciences; Grant/Research Support: Vital Therapies Michael P. Manns – Consulting: Roche, BMS, Gilead, Boehringer CAL-101 supplier Ingelheim, Novartis, Idenix, Achillion, GSK, Merck/MSD, Janssen, Medgenics; Grant/ Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS; Speaking and Teaching:

Merck/MSD, Roche, BMS, Gilead, Janssen, Lumacaftor mouse GSK, Novartis Stefan Zeuzem – Consulting: Abbvie, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Co., Gilead, Novartis Pharmaceuticals, Merck & Co., Idenix, Janssen, Roche Pharma AG, Vertex Pharmaceuticals Harry L. Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris Bart J. Veldt – Board Membership: GSK, Janssen Therapeutics Robert J. de Knegt – Advisory Committees or Review Panels: MSD, Roche, Norgine, Janssen Cilag; Grant/Research Support: Gilead, MSD, Roche, Janssen Cilag, BMS; Speaking and Teaching: Gilead, MSD, Roche, Janssen Cilag The following people have nothing to disclose: Frank Lammert, Wolf P. Hofmann, Bettina E. Hansen Predicting mortality in HIV/HCV coinfected patients (pts) is of crucial importance to determine the appropriate timing of inscription on the waiting-list of liver transplantation. Aim: To determine risk factors of mortality in HIV/HCV coinfected pts after a first episode of decompensation (DC). Methods: HIV/ HCV coinfected pts with a first episode of DC within 1 year (yr) before enrollments were prospectively followed.

Our findings emphasize that cirrhosis profoundly disturbs physiological defense

mechanisms, and this disturbance extends outside the peritoneal cavity. Table 1. Absolute risks and adjusted odds ratios (aOR) for complications after total hip and knee replacement in patients with or without cirrhosis. Cirrhosis patients Patients without cirrhosis aOR† †Adjusted for age, gender, Charlson Comorbidity Index, operation site (hip/ knee), anesthesia (general/ regional), and number of inpatient hospitalizations in the year preceding hip or knee replacement. Disclosures: Søren Overgaard – ABT-263 cost Grant/Research Support: Biomet The following people have nothing to disclose: Thomas Deleuran, Hendrik V. Vilstrup, Peter Jepsen Background: Endoscopic variceal band ligation (EVL) is an effective procedure to control and prevent variceal bleeding, but can be complicated by bleeding from post EVL ulcers. Several studies have reported that proton pump inhibitors

(PPI) decrease size of post-EVL Belinostat chemical structure ulcers. However, no evidence has been provided whether PPI reduce the actual risk of bleeding after EVL. The aim of this study was to analyze factors associated with bleeding after prophylactic EVL and to assess the effect of PPI. Methods: Liver cirrhosis patients with high-risk esophageal varices who received elective EVL to prevent variceal bleeding between January 1998 and April 2011 were Edoxaban included. High risk varices were defined as large esophageal varices with red color sign. Patients who had history of acute variceal bleeding were excluded. Post EVL bleeding was defined as; (1)decrease in hemoglobin by >20g/L, or (2) occurrence of active bleeding evidenced by melena or hematemesis after prophylactic EVL within 60 days. Results: 505 patients were included for this analysis.25 patients (5%) developed bleeding after prophylactic EVL.359 patients (71.1%) received PPI after EVL. Factors associated with bleeding included low serum Na [odds ratio (OR) 3.209, 95% Cl (confidence interval), 1.217-8.464,

p=0.018], high ALT [OR 2.582, 95% Cl: 1.075-6.200, p=0.034], high Child-Pugh score [OR 3.636, 95% CI: 1.499-8.820, p=0.004], gastric varix [OR 3.598, 95% Cl: 1.592-8.132, p=0.002, and no PPI medication [OR 7.09, 95% Cl: 2.89-17.24, p<0.001] by univariate analysis. In multivariate logistic analysis, no PPI therapy [OR 6.41, 95% Cl: 2.5-16.39, p<0.001] and presence of gastric varix [OR 4.61, 95% Cl: 1.82-11.62, p=0.001] were independent factors for bleeding. Subgroup analysis was performed after excluding patients with gastric varix, and low serum Na [odds ratio (OR) 4.144, 95% CI (confidence interval), 1.217-14.116, p=0.023], high ALT [OR 3.226, 95% Cl:1.021-10.187, p=0. O46], high Child-Turcotte-Pugh score [〇R 5.198, 95% CI: 1.624-16.638, p=0.005], and no PPI medication [〇R 8.55, 95% Cl: 2.31-31.25, p=0.001] were predictor factors of bleeding by univariate analysis.

2001; Pistorius and Bester 2002b; McMahon et al. 2003, 2005a, b; de Little et al. 2007). In the northern elephant seal, we have likewise found substantial variation in juvenile survivorship this website and annual fecundity (Huber et al. 1991, Reiter and Le Boeuf 1991, Le Boeuf et al. 1994, Crocker et al. 2006), suggesting ample opportunity for either to affect population growth. Except for pup mortality, however, density-dependent variation in survival and fecundity has not been demonstrated (Le Boeuf et al. 2011). On the other

hand, when compared to other large mammals, elephant seals are short-lived. Adult females of most large herbivores have survival rates >90%/yr (Gaillard et al. 1998), as do many pinnipeds (Cameron and Siniff 2004, Hastings et al. 2011). In gray seals (Halichoerus grypus), 95% of adult females survive annually (Harrison et al.

2006) and a 42 yr old has been observed (Bowen et al. 2006). Elephant seals must have higher fecundity than gray seals in order to sustain population growth with their relatively short lifespan. At least one pinniped, though, is similar to elephant seals: in monk seals (Monachus schauinslandi), survival declined starting at age 17 (Baker and Thompson 2007). Our next steps are to study fluctuations in vital rates over time by studying other cohorts, then to build models of the Año Nuevo colony and the entire population of northern elephant seals based on complete life tables. Given our current estimate of a 21 MK-2206 manufacturer yr life span and 86% annual survival of adult females, we will explore variation in juvenile survival to find a rate that would support

the rapid worldwide recovery in the 20th century. We can also use the observed life table at Año Nuevo to quantify the immigration rate needed to account for local population growth. Other pinniped species offer excellent precedents for this sort of modeling (Cameron and Siniff 2004, Harrison et al. 2006). With the northern elephant seal, we will soon have the bonus of observing the cessation of population growth, allowing us to document vital rates across the transition to stability and test hypotheses about environmental and demographic factors important in regulating the population. We thank colleagues and numerous assistants for observations at Año Nuevo, especially D. Costa and his students; Mirabegron D. Adams, J. Adams, H. Jensen, D. Press, and L. Ptak for work at Point Reyes; D. Lee for work at the Farallones; A. Huntley for the brands and much assistance in the field; Clairol for hair dye; the University of California Natural Reserve System for maintenance of the Año Nuevo Island Reserve; the U.C. Santa Cruz Institute for Marine Science, especially S. Davenport, for supporting the field operation; and the rangers at Año Nuevo State Reserve for providing help and access. The analysis was developed as part of the PCAD Marine Mammal Working Group, funded by the Office of Naval Research.

In this study of propranolol therapy, Child-Pugh class C, hyponatremia, and renal impairment were found to be independent variables of mortality in patients with cirrhosis with refractory ascites. As a result, the authors suggest that propranolol should be contraindicated in click here these patients. Although the authors did not report the cardiac status of the patients, we would like to discuss their findings in this regard, upon the findings of two recent articles.2, 3 Krag et al.2 evaluated 24 patients with cirrhosis with a cardiac index (CI) above or below 1.5 L/minute/m2, and they found that patients with low CI showed significantly poorer

survival than those with a higher CI. In addition, hyponatremia and renal impairment, which are independent variables of mortality in the study report by Serste et al., were found to be associated with lower CI.2 Krag et al. stated that a cardio-renal relation in cirrhosis is most likely the result of chronic circulatory stress combined with more acute events, such as bacterial translocation and systemic inflammatory response, which trigger a systemic response. This may lead to progression of a systolic failure with a decrease in CI, starting a vicious circle in which find more the decreased CI leads to accentuated arterial underfilling, decreased arterial pressure,

and renal perfusion, resulting in deterioration of the renal function, which further enhances cardiac and renal deterioration. Recently, Sharma et al.3 investigated the effects of propranolol on normotensive and hypertensive patients with cirrhosis; they showed

that CI significantly decreased after propranolol therapy in both groups. Based on these findings, we think that lowering effects of propranolol on CI and consecutively, development of hyponatremia and renal impairment, may explain the possible mechanism of deleterious effects of propranolol on survival in these Idoxuridine patients. Finally, the common usage of beta-blockers for the prevention of variceal bleeding may change in the near future, at least in patients with severe cirrhosis, and band ligation and/or therapies that improve CI may be considered as emerging treatment options to improve survival. Cumali Efe M.D.*, Tugrul Purnak M.D.†, Ersan Ozaslan M.D.†, * Departments of Internal Medicine, Numune Research and Education Hospital, Ankara, Turkey, † Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey. “
“A 50-year-old woman was admitted to hospital with hematemesis and hypotension. She had previously been well. Her hemoglobin was 7.9 g/dL (79 g/l) and she had a mild elevation of alanine aminotransferase (102 u/l) and alkaline phosphatase (187 u/l). At upper gastrointestinal endoscopy, oozing of blood from superficial gastric ulcers was treated with injections of adrenaline.