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https://www.readbyqxmd.com/read/28088582/ripk1-protects-hepatocytes-from-kupffer-cells-mediated-tnf-induced-apoptosis-in-mouse-models-of-pamp-induced-hepatitis
#1
Aveline Filliol, Claire Piquet-Pellorce, Céline Raguénès-Nicol, Sarah Dion, Muhammad Farooq, Catherine Lucas-Clerc, Peter Vandenabeele, Mathieu J M Bertrand, Jacques Le Seyec, Michel Samson
BACKGROUND & AIMS: The severity of liver diseases is exacerbated by the death of hepatocytes, which can be induced by the sensing of Pathogen Associated Molecular Patterns (PAMPs) derived from the gut microbiota. The molecular mechanisms regulating these cell death pathways are poorly documented. In this study, we investigated the role of the Receptor Interacting Protein Kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of PAMP-induced hepatitis...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28088461/changes-in-the-prevalence-of-hepatitis-c-virus-infection-non-alcoholic-steatohepatitis-and-alcoholic-liver-disease-among-patients-with-cirrhosis-or-liver-failure-on-the-waitlist-for-liver-transplantation
#2
David Goldberg, Ivo C Ditah, Kia Saeian, Mona Lalehzari, Andrew Aronsohn, Emmanuel C Gorospe, Michael Charlton
BACKGROUND & AIMS: Concurrent to development of more effective drugs for treatment of hepatitis C virus (HCV), infection, there has been an increase in the incidence of non-alcoholic fatty liver disease (NAFLD). Data indicate that liver transplantation prolongs survival times of patient with acute hepatitis associated with alcoholic liver disease (ALD). We compared data on disease prevalence in the population with data from liver transplantation waitlists to evaluate changes in the burden of liver disease in the United States...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28088395/lactate-and-lactate-pyruvate-ratio-in-the-diagnosis-and-outcomes-of-pediatric-acute-liver-failure
#3
Amy G Feldman, Ronald J Sokol, Regina M Hardison, Estella M Alonso, Robert H Squires, Michael R Narkewicz
OBJECTIVES: To assess the accuracy of blood lactate and lactate: pyruvate molar ratio (L:P) as a screen for mitochondrial, respiratory chain, or fatty acid oxidation disorders in children with pediatric acute liver failure (PALF); to determine whether serum lactate ≥ 2.5 mmol/L or L:P  ≥ 25 correlated with biochemical variables of clinical severity; and to determine whether lactate or L:P is associated with clinical outcome at 21 days. STUDY DESIGN: Retrospective review of demographic, clinical, laboratory, and outcome data for PALF study group participants who had lactate and pyruvate levels collected on the same day...
January 12, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28087208/-child-langerhans-cell-histiocytosis
#4
Jean Donadieu, Sébastien Héritier
DEFINITION: Langerhans cell histiocytosis (LCH) is defined by the association of a clinical and radiological involvement and a biopsy of a pathological tissue. Extension: it can affect any organ or system of the body but most commonly the bone (80% of cases), the skin (33%) and the pituitary (25%). Other organs are concerned such as liver, spleen, hematopoietic system and the lungs (15% each), lymph nodes (5-10%) and central nervous system (CNS) excluding the pituitary (2-4%). Natural history: the natural history of the disease is very heterogeneous, ranging from auto-regressive lesions to a disease affecting multiple organs with fatal consequences, while some lesions may be responsible for permanent sequels...
January 10, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28086800/relevance-of-fxr-p62-sqstm1-pathway-for-survival-and-protection-of-mouse-hepatocytes-and-liver-especially-with-steatosis
#5
Sanae Haga, Yimin, Michitaka Ozaki
BACKGROUND: Liver injury and regeneration involve complicated processes and are affected by various physio-pathological conditions. Surgically, severe liver injury after surgical resection often leads to fatal liver failure, especially with some underlying pathological conditions such as steatosis. Therefore, protection from the injury of hepatocytes and liver is a serious concern in various clinical settings. METHODS: We studied the effects of the farnesoid X receptor (FXR) on cell survival and steatosis in mouse hepatocytes (AML12 mouse liver cells) and investigated their molecular mechanisms...
January 13, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28079821/febuxostat-induced-agranulocytosis-in-an-end-stage-renal-disease-patient-a-case-report
#6
Xue Er Poh, Chien-Te Lee, Sung-Nan Pei
INTRODUCTION: Febuxostat, a nonpurine xanthine oxidase inhibitor, is approved as the first-line urate-lowering therapy in gout patients with normal renal function or mild to moderate renal impairment. The most common adverse effects of febuxostat are liver function test abnormalities, diarrhea, and skin rash. However, there is insufficient data in patients with severe renal impairment and end-stage renal disease (ESRD). We report the first case, to our knowledge, in which agranulocytosis developed after febuxostat treatment in an ESRD patient...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28079670/impact-of-genetic-variation-in-the-vasopressin-1a-receptor-on-the-development-of-organ-failure-in-patients-admitted-for-acute-decompensation-of-liver-cirrhosis
#7
Annarein J C Kerbert, Jelte J Schaapman, Johan J van der Reijden, Àlex Amorós Navarro, Aiden McCormick, Bart van Hoek, Vicente Arroyo, Pere Ginès, Rajiv Jalan, Victor Vargas, Rudolf Stauber, Hein W Verspaget, Minneke J Coenraad
BACKGROUND: Vasopressin receptor-mediated vasoconstriction is considered to be involved in the pathogenesis of organ failure in acute-on-chronic liver failure (ACLF). PATIENTS AND METHODS: We studied the association between six single nucleotide polymorphisms (SNPs) of the vasopressin 1a receptor gene and the development of organ failure in 826 patients admitted for acute decompensation of liver cirrhosis (n=641) or ACLF (n=185). RESULTS: No associations were found for SNPs with the presence of circulatory or renal failure...
January 10, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28079252/outcomes-of-surgical-shunts-and-transjugular-intrahepatic-portasystemic-stent-shunts-for-complicated-portal-hypertension
#8
I Hosokawa, R Adam, M-A Allard, G Pittau, E Vibert, D Cherqui, A Sa Cunha, H Bismuth, M Miyazaki, D Castaing
BACKGROUND: Transjugular intrahepatic portasystemic stent shunt (TIPSS), instead of surgical shunt, has become the standard treatment for patients with complicated portal hypertension. This study compared outcomes in patients who underwent TIPSS or surgical shunting for complicated portal hypertension. METHODS: This was a retrospective study of all consecutive patients who received portasystemic shunts from 1994 to 2014 at a single institution. Patients who underwent surgical shunting were compared with those who had a TIPSS procedure following one-to-one propensity score matching...
January 12, 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28079174/alleviating-liver-failure-conditions-using-an-integrated-hybrid-cryogel-based-cellular-bioreactor-as-a-bioartificial-liver-support
#9
Apeksha Damania, Mohsin Hassan, Nana Shirakigawa, Hiroshi Mizumoto, Anupam Kumar, Shiv K Sarin, Hiroyuki Ijima, Masamichi Kamihira, Ashok Kumar
Conventionally, some bioartificial liver devices are used with separate plasmapheresis unit to separate out plasma from whole blood and adsorbent column to detoxify plasma before it passes through a hepatocytes-laden bioreactor. We aim to develop a hybrid bioreactor that integrates the separate modules in one compact design improving the efficacy of the cryogel based bioreactor as a bioartificial liver support. A plasma separation membrane and an activated carbon cloth are placed over a HepG2-loaded cryogel scaffold in a three-chambered bioreactor design...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079146/nitrosative-stress-induced-disruption-of-baroreflex-neural-circuits-in-a-rat-model-of-hepatic-encephalopathy-a-dti-study
#10
Ching-Yi Tsai, Chia-Hao Su, Julie Y H Chan, Samuel H H Chan
The onset of hepatic encephalopathy (HE) in liver failure is associated with high mortality; the underlying mechanism is undecided. Here we report that in an acute liver failure model employing intraperitoneal administration of thioacetamide in Sprague-Dawley rats, diffusion weighted imaging revealed a progressive reduction in apparent diffusion coefficient in the brain stem. Diffusion tensor imaging further showed that the connectivity between nucleus tractus solitarii (NTS), the terminal site of baroreceptor afferents in brain stem and rostral ventrolateral medulla (RVLM), the origin of sympathetic innervation of blood vessels, was progressively disrupted until its disappearance, coincidental with the irreversible cessation of baroreflex-mediated sympathetic vasomotor tone signifying clinically the occurrence of brain death...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078736/investigation-of-underlying-comorbidities-as-risk-factors-for-symptomatic-human-hepatitis-e-virus-infection
#11
S Zhang, C Chen, J Peng, X Li, D Zhang, J Yan, Y Zhang, C Lu, J Xun, W Li, Y Ling, Y Huang, L Chen
BACKGROUND: Symptomatic Hepatitis E virus (HEV) infection occurs in few infected subjects, and the risk factors are not completely known. AIMS: To explore the risk factors for adverse clinical outcomes in acute HEV infections. METHODS: A large retrospective study was conducted. The baseline characteristics, clinical outcomes, and laboratory data of 512 acute HEV infection cases were analysed using logistic regression models. RESULTS: All patients exhibited autochthonous sporadic HEV infections, and most were elderly...
January 12, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28078470/appropriate-timing-to-start-and-optimal-response-evaluation-of-high-dose-corticosteroid-therapy-for-patients-with-acute-liver-failure
#12
Keisuke Kakisaka, Kojiro Kataoka, Yuji Suzuki, Hidekatsu Kuroda, Yasuhiro Takikawa
BACKGROUND: Corticosteroid therapy has been commonly administered to patients with acute liver injury (ALI)/acute liver failure (ALF) in Japan to prevent the development of hepatic encephalopathy, but the appropriate timing to start corticosteroid therapy has not been determined and optimal response evaluation of the therapy has not been conducted. We prospectively investigated the optimal timing to start therapy on the established severity indication: the Japan Hepatic Encephalopathy Prediction Model (JHEPM) and prothrombin time (PT)...
January 11, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#13
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28076676/use-of-metformin-for-cardiometabolic-risks-in-psychiatric-practice-need-to-know-safety-issues
#14
Chittaranjan Andrade
Metformin, a biguanide drug, is emerging as an important treatment option for the prevention or treatment of weight gain, type 2 diabetes mellitus, and the metabolic syndrome in psychiatric patients, especially those who require or receive antipsychotic drugs. Metformin treatment is commonly associated with gastrointestinal adverse effects; the risk of these is reduced by gradual dose uptitration, administration of the drug with meals, and use of a time-release formulation. Lactic acidosis, a potentially fatal complication of biguanide therapy, is very rare with metformin; the risk can be reduced by avoidance of its prescription in patients with impaired renal function, impaired liver function, cardiac failure, and certain other conditions...
November 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28076501/evaluating-the-best-time-to-intervene-acute-liver-failure-in-rat-models-induced-by-d-galactosamine
#15
Lígia Patrícia de Carvalho Batista Éboli, Alcides Augusto Salzedas Netto, Ramiro Antero de Azevedo, Valéria Pereira Lanzoni, Tatiana Sugayama de Paula, Alberto Goldenberg, Adriano Miziara Gonzalez
PURPOSE: To describe an animal model for acute liver failure by intraperitoneal d-galactosamine injections in rats and to define when is the best time to intervene through King's College and Clichy´s criteria evaluation. METHODS: Sixty-one Wistar female rats were distributed into three groups: group 1 (11 rats received 1.4 g/kg of d-galactosamine intraperitoneally and were observed until they died); group 2 (44 rats received a dose of 1.4 g/kg of d-galactosamine and blood and histological samples were collected for analysis at 12 , 24, 48 , 72 and 120 hours after the injection); and the control group as well (6 rats) ...
December 2016: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28076451/survival-benefits-of-interferon-based-therapy-in-patients-with-recurrent-hepatitis-c-after-orthotopic-liver-transplantation
#16
L P Zanaga, A G Vigani, R N Angerami, A Giorgetti, C A F Escanhoela, E C Ataíde, I F S F Boin, R S B Stucchi
Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013...
January 9, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28076340/telomere-length-assessment-for-prediction-of-organ-transplantation-outcome-future-or-failure-a-review-of-the-literature
#17
Karolina Kłoda, Leszek Domański, Artur Mierzecki
Telomeres are located at each end of eukaryotic chromosomes. Their functional role is genomic stability maintenance. The protective role of telomeres depends on various factors, including number of nucleotides repeats, telomere-binding proteins, and telomerase activity. Organ transplantation is the preferred replacement therapy in the case of chronic kidney disease and the only possibility of sustaining recipients' life in the case of advanced liver failure. While the prevalence of acute rejection is constantly decreasing, prevention of transplanted organ long-term function loss is still challenging...
January 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28076311/biomarkers-of-acute-kidney-injury-the-pathway-from-discovery-to-clinical-adoption
#18
Kianoush Kashani, Wisit Cheungpasitporn, Claudio Ronco
Acute kidney injury (AKI) is a common complication of critical illnesses and has a significant impact on outcomes, including mortality and morbidities. Unfortunately, apart from prophylactic measures, no effective treatment for this syndrome is known. Therefore, early recognition of AKI not only can provide better opportunities for preventive interventions, but also opens many gates for research and development of effective therapeutic options. Over the last few years, several new AKI biomarkers have been discovered and validated to improve early detection, differential diagnosis, and differentiation of patients into risk groups for progressive renal failure, need for renal replacement therapy (RRT), or death...
January 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28075444/the-role-of-lncrna-malat1-in-the-regulation-of-hepatocyte-proliferation-during-liver-regeneration
#19
Cuicui Li, Lei Chang, Zhiquan Chen, Zhongzhong Liu, Yanfeng Wang, Qifa Ye
Exploring the biological functions of long non-coding RNAs (lncRNAs) has come to the foreground in recent years. Studies have indicated that the lncRNA metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) not only regulates tumorigenesis in hepatocellular carcinoma, but also controls cell cycle progression in hematopoietic cells. The present study was designed to investigate the biological role of lncRNA MALAT1 in liver regeneration. We carried out a series of assays during liver regeneration following 2/3 partial hepatectomy in mice...
January 11, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28074467/systems-pharmacology-modeling-of-drug-induced-hyperbilirubinemia-differentiating-hepatotoxicity-and-inhibition-of-enzymes-transporters
#20
Kyunghee Yang, Christina Battista, Jeffrey L Woodhead, Simone H Stahl, Jerome T Mettetal, Paul B Watkins, Scott Q Siler, Brett A Howell
Elevations in serum bilirubin during drug treatment may indicate global liver dysfunction and a high risk of liver failure. However, drugs also can increase serum bilirubin in the absence of hepatic injury by inhibiting specific enzymes/transporters. We constructed a mechanistic model of bilirubin disposition based on known functional polymorphisms in bilirubin metabolism/transport. Using physiologically-based pharmacokinetic model-predicted drug exposure and enzyme/transporter inhibition constants determined in vitro, our model correctly predicted indinavir-mediated hyperbilirubinemia in humans and rats...
January 11, 2017: Clinical Pharmacology and Therapeutics
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