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Isolated Hepatic perfusion

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https://www.readbyqxmd.com/read/28412881/glutathione-s-transferase-a1-gsta1-as-a-marker-of-acetaminophen-induced-hepatocyte-injury-in-vitro
#1
Rui Li, Fangping Liu, Yicong Chang, Xin Ma, Minmin Li, Changwen Li, Chenxi Shi, Jingshan He, Ying Li, Zhi Li, Yuexia Lin, Qing Han, Yulin Zhao, Dening Wang
Acetaminophen (APAP) overdose causes serious hepatocyte injury, and new markers are needed to predict APAP-induced hepatic injury. Glutathione S-transferase A1 (GSTA1) plays a significant role in the metabolism of APAP. Primary mouse hepatocytes were isolated by a two-step perfusion in situ. An APAP-induced hepatocyte injury model was used to characterize GSTA1 in APAP treated cells and determine whether GSTA1 could be a prognostic marker in vitro. A significant increase (p<0.05) in GSTA1 in cell culture supernatant was detected at 6 h after APAP treatment, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) showed marked differences (p<0...
April 16, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28412296/impact-of-higher-order-heme-degradation-products-on-hepatic-function-and-hemodynamics
#2
Raphael A Seidel, Thierry Claudel, Franziska A Schleser, Navin K Ojha, Matthias Westerhausen, Sandor Nietzsche, Christoph Sponholz, Frans Cuperus, Sina M Coldewey, Stefan H Heinemann, Georg Pohnert, Michael Trauner, Michael Bauer
BACKGROUND& AIMS: While, traditionally, biliverdin and bilirubin are considered end products of heme catabolism, there is evidence for further degradation to diverse bioactive products. As such, Z-BOX A and Z-BOX B arise upon oxidation with unknown implications for hepatocellular function and integrity. We studied the impact of Z-BOX A and B on hepatic functions and explored their alterations in health and cholestatic conditions. METHODS: Functional implications and mechanisms were investigated in rats, hepatocytic HepG2 and HepaRG cells, human immortalized hepatocytes, and isolated perfused livers...
April 12, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28364696/differential-effects-of-liver-steatosis-on-pharmacokinetic-profile-of-two-closely-related-hepatoselective-no-donors-v-pyrro-no-and-v-proli-no
#3
Kamil Kus, Edyta Kus, Agnieszka Zakrzewska, Wojciech Jawien, Barbara Sitek, Maria Walczak, Stefan Chlopicki
PURPOSE: To analyze the effect of liver steatosis and obesity on pharmacokinetic profile of two structurally-related liver-selective NO-donors - V-PYRRO/NO and V-PROLI/NO. METHODS: C57BL/6 mice were fed control or high-fat diet for 15 weeks to induced liver steatosis and obesity (HFD mice). Pharmacokinetics and renal elimination studies were conducted in vivo following iv dosing of V-PYRRO/NO and V-PROLI/NO (0.03mmol/kg). Hepatic clearance was evaluated ex vivo in the isolated perfused mice liver and in vitro with the use of liver microsomes...
February 2, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28337244/rat-liver-enzyme-release-depends-on-blood-flow-bearing-physical-forces-acting-in-endothelium-glycocalyx-rather-than-on-liver-damage
#4
Julieta A Díaz-Juárez, Rolando Hernández-Muñoz
We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH), apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver "pool...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28328586/percutaneous-isolated-hepatic-perfusion-hemodynamic-monitoring-and-goal-directed-anesthetic-management-a-case-report
#5
Oscar Martin-Delgado, Miguel Rodriguez, Andres Lopez, Miguel A Reina, Emilio De Vicente, Yolanda Quijano, Antonio Echenagusia, Juan A Martinez
The percutaneous isolated hepatic perfusion utilizes a venovenous bypass to administer high-dose chemotherapy exclusively in the liver, getting depurated through a hemofilter before returning to the systemic circulation. The hepatic perfusion is managed under general anesthesia and invasive monitoring as a result of very abrupt changes in venous return and vascular resistances because of the isolation of the hepatic territory and absorption of circulating catecholamines by the hemofilter. We report a case in which we describe the technique, physiologic implications, anesthetic, and goal-directed hemodynamic management for this procedure...
March 15, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28317117/comparative-pharmacokinetic-evaluation-of-lopinavir-and-lopinavir-loaded-solid-lipid-nanoparticles-in-hepatic-impaired-rat-model
#6
Punna Rao Ravi, Rahul Vats
OBJECTIVE: Drug-induced hepatotoxicity is a major cause of concern in patients receiving HIV/TB co-treatment. Lopinavir (LPV), an anti-HIV drug, shows poor plasma exposure due to hepatic first-pass metabolism. In this study, we investigated the effect of hepatotoxicity on pharmacokinetics of free LPV and LPV-loaded solid lipid nanoparticles (LPV SLNs) in male Wistar rats. METHODS: Hepatic impairment model in rats was developed by injecting CCl4 (i.p., 2 ml/kg). Comparative pharmacokinetic (n = 5) and tissue distribution studies (n = 3) were conducted following oral administration (20 mg/kg) of free LPV and LPV SLNs in normal and hepatic impaired rats...
March 19, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28277163/predictions-of-bisphenol-a-hepatic-clearance-in-the-isolated-perfused-rat-liver-iprl-impact-of-albumin-binding-and-of-co-administration-with-naproxen
#7
Sara Bounakta, Michel Bteich, Marc Mantha, Patrick Poulin, Sami Haddad
1. This study aimed (i) to characterise hepatic clearance (CL) of bisphenol A (BPA) and naproxen (NAP) administered alone or in binary mixtures to highlight the influence of a binding to albumin (ALB) using an isolated perfused rat liver (IPRL) system; and (ii) to compare results of prediction algorithms with measured clearance rates. 2. The IPRL system and liver microsomes were used to determine the metabolic constants of BPA and NAP either in the presence or absence of ALB. In this study, the IPRL was used as proxy for the in vivo situation...
March 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28220319/cfd-assessment-of-the-effect-of-convective-mass-transport-on-the-intracellular-clearance-of-intracellular-triglycerides-in-macrosteatotic-hepatocytes
#8
Gabriel Yarmush, Lucas Santos, Joshua Yarmush, Srivathsan Koundinyan, Mubasher Saleem, Nir I Nativ, Martin L Yarmush, Francois Berthiaume, Timothy J Maguire, Chris Guaghan
Donor livers available to transplant for patients with end-stage liver disease are in severe shortage. One possible avenue to expand the donor pool is to recondition livers that would be otherwise discarded due to excessive fat content. Severely steatotic livers (also known as fatty livers) are highly susceptible to ischemia-reperfusion injury and as a result, primary liver non-function post-transplantation. Prior studies in isolated perfused rat livers suggest that "defatting" may be possible in a timeframe of a few hours; thus, it is conceivable that fatty liver grafts could be recovered by machine perfusion to clear stored fat from the organ prior to transplantation...
February 20, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28178721/chemosaturation-with-percutaneous-hepatic-perfusion-in-unresectable-hepatic-metastases
#9
REVIEW
Evan S Glazer, Jonathan S Zager
BACKGROUND: In patients with hepatic metastases from solid-organ malignancies, surgical resection may be a potentially curative option, but it is not possible in most cases. Chemosaturation with percutaneous hepatic perfusion was developed for the management of unresectable metastases to the liver. METHODS: Relevant medical literature was summarized with regard to the outcomes and limitations of chemosaturation with percutaneous hepatic perfusion. RESULTS: Six articles were identified that contained data on 91 individuals who received chemosaturation with percutaneous hepatic perfusion...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28144756/percutaneous-isolated-hepatic-perfusion-as-a-treatment-for-isolated-hepatic-metastases-of-uveal-melanoma-patient-outcome-and-safety-in-a-multi-centre-study
#10
Thomas J Vogl, Silvia A Koch, Gösta Lotz, Bernhard Gebauer, Winfried Willinek, Christoph Engelke, Roland Brüning, Martin Zeile, Frank Wacker, Arndt Vogel, Boris Radeleff, Jan-Erik Scholtz
PURPOSE: Percutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study. MATERIALS AND METHODS: Between 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1...
January 31, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28110582/the-effect-of-perfusate-buffering-on-toxicity-and-response-in-isolated-hepatic-perfusion-for-uveal-melanoma-liver-metastases
#11
Ilan Ben-Shabat, Valerio Belgrano, Christoffer Hansson, Bagge Roger Olofsson
BACKGROUND: Isolated hepatic perfusion (IHP) is a treatment option for patients with liver metastases. Previous studies have found that liver toxicity is one of the limiting factors, and in an attempt to reduce the toxicity a buffering agent was added to the perfusate. The aim was to retrospectively analyze if this buffering reduced toxicity and complication rates. METHODS: A retrospective review of 52 consecutive patients with uveal melanoma liver metastases treated with IHP between 2005-2013...
January 22, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28006924/in-vitro-and-in-vivo-experimental-hepatotoxic-models-in-liver-research-applications-to-the-assessment-of-potential-hepatoprotective-drugs
#12
H Farghali, M Kgalalelo Kemelo, L Wojnarová, N Kutinová Canová
This mini-review highlights our and others' experience about in vitro and in vivo models that are being used to follow up events of liver injuries under various hepatotoxic agents and potential hepatoprotective drugs. Due to limitations of the outcomes in each model, we focus primarily on two models. First, a developed perfusion method for isolated immobilized hepatocytes that improves the process of oxygenation and helps in end-product removal is of considerable value in improving cell maintenance. This cellular model is presented as a short-term research-scale laboratory bioreactor with various physiological, biochemical, molecular, toxicological and pharmacological applications...
December 21, 2016: Physiological Research
https://www.readbyqxmd.com/read/27975323/advanced-method-for-isolation-of-mouse-hepatocytes-liver-sinusoidal-endothelial-cells-and-kupffer-cells
#13
Jia Liu, Xuan Huang, Melanie Werner, Ruth Broering, Dongliang Yang, Mengji Lu
Separation of pure cell populations from the liver is a prerequisite to study the role of hepatic parenchymal and non-parenchymal cells in liver physiology, pathophysiology, and immunology. Traditional methods for hepatic cell separation usually purify only single cell types from liver specimens. Here, we describe an efficient method that can simultaneously purify populations of hepatocytes (HCs), liver sinusoidal endothelial cells (LSECs), and Kupffer cells (KCs) from a single mouse liver specimen. A liberase-based perfusion technique in combination with a low-speed centrifugation and magnetic-activated cell sorting (MACS) led to the isolation and purification of HCs, KCs, and LSECs with high yields and purity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27860296/impact-of-subnormothermic-machine-perfusion-preservation-in-severely-steatotic-rat-livers-a-detailed-assessment-in-an-isolated-setting
#14
Y Okamura, K Hata, H Tanaka, H Hirao, T Kubota, O Inamoto, S Kageyama, I Tamaki, N Yermek, J Yoshikawa, S Uemoto
The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS)...
November 10, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27800122/subnormothermic-perfusion-in-the-isolated-rat-liver-preserves-the-antioxidant-glutathione-and-enhances-the-function-of-the-ubiquitin-proteasome-system
#15
Teresa Carbonell, Norma Alva, Sergio Sanchez-Nuño, Shannamar Dewey, Aldrin V Gomes
The reduction of oxidative stress is suggested to be one of the main mechanisms to explain the benefits of subnormothermic perfusion against ischemic liver damage. In this study we investigated the early cellular mechanisms induced in isolated rat livers after 15 min perfusion at temperatures ranging from normothermia (37°C) to subnormothermia (26°C and 22°C). Subnormothermic perfusion was found to maintain hepatic viability. Perfusion at 22°C raised reduced glutathione levels and the activity of glutathione reductase; however, lipid and protein oxidation still occurred as determined by malondialdehyde, 4-hydroxynonenal-protein adducts, and advanced oxidation protein products...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27765937/neither-isolated-hepatic-arterial-clamping-nor-hepatic-arterial-ligation-induce-ischemic-type-biliary-lesions-in-rats
#16
Ulrich Keppler, Mohammed R Moussavian, Pascal Jeanmonod, Moritz J Strowitzki, Mathias Wagner, Claudia Scheuer, Michael D Menger, Maximilian von Heesen
BACKGROUND Ischemic type biliary lesions (ITBL) is a troublesome complication after liver transplantation. Little is known about its pathogenesis and there is particularly little data about morphological alterations. Prolonged warm and cold ischemia time and reduced hepatic arterial perfusion are risk factors leading to ITBL. There are only a few animal models described in literature. Therefore, we examined the effects of 3 h of hepatic artery ischemia-reperfusion (3 h I/R) and hepatic arterial ligation (HAL), both combined with ligation of the peribiliary plexus (PBP)...
October 21, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/27713829/equine-hepatocytes-isolation-cryopreservation-and-applications-to-in%C3%A2-vitro-drug-metabolism-studies
#17
Khaled A Shibany, Sabine Tötemeyer, Stefanie L Pratt, Stuart W Paine
Despite reports of the successful isolation of primary equine hepatocytes, there are no published data regarding the successful cryopreservation of these isolated cells. In this study, a detailed description of the procedures for isolation, cryopreservation, and recovery of equine hepatocytes are presented. Furthermore, the intrinsic clearance (Clint) and production of metabolites for three drugs were compared between freshly isolated and recovered cryopreserved hepatocytes. Primary equine hepatocytes were isolated using a two-step collagenase perfusion method, with an average cell yield of 2...
October 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/27643409/evaluating-the-role-of-drug-metabolism-and-reactive-intermediates-in-trazodone-induced-cytotoxicity-toward-freshly-isolated-rat-hepatocytes
#18
A Najibi, R Heidari, J Zarifi, A Jamshidzadeh, N Firoozabadi, H Niknahad
Background: Trazodone is an antidepressant agent widely administered for the treatment of depressive disorders. On the other hand, several cases of hepatic injury have been reported after Trazodone administration. Although the precise mechanism(s) of trazodone-induced liver injury is not known, some investigations proposed the role of reactive intermediates in this complication. This study was designed to investigate the role of reactive metabolites in hepatocytes injury induced by trazodone. Methods: Isolated rat hepatocytes were prepared by the method of collagenase enzyme perfusion via the portal vein...
November 2016: Drug Research
https://www.readbyqxmd.com/read/27548803/isolation-and-characterization-of-hepatic-mast-cells-from-cholestatic-rats
#19
Laura Hargrove, Allyson Graf-Eaton, Lindsey Kennedy, Jennifer Demieville, Jennifer Owens, Kyle Hodges, Brittany Ladd, Heather Francis
Mast cells (MCs) are immune cells that release histamine and other mediators. MC number increases after bile duct ligation (BDL) and blocking mast cell-derived histamine decreases biliary proliferation. We aimed to isolate and characterize MCs from cholestatic livers. Rats were subjected to BDL starting at 6 h and up to 14 days. MC infiltration was evaluated by toluidine blue. BDL rats were perfused using standard collagenase perfusion. Following enzymatic digestion, tissue was passed through a fine gauge needle...
November 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27513071/isolated-hypoxic-hepatic-perfusion-with-high-dose-chemotherapy-in-patients-with-unresectable-liver-metastases-of-uveal-melanoma-results-from-two-experienced-centres
#20
Eleonora M de Leede, Mark C Burgmans, Ellen Kapiteijn, Gre P M Luyten, Martine J Jager, Fred G J Tijl, Henk H Hartgrink, Dirk J Grünhagen, Joost Rothbarth, Cornelis J H van de Velde, Cornelis Verhoef, Alexander L Vahrmeijer
Uveal melanoma patients have a poor survival after the diagnosis of metastatic disease. Isolated hepatic perfusion (IHP) was developed to treat patients with unresectable metastases confined to the liver. This retrospective analysis focuses on treatment characteristics, complications, toxicity and survival after IHP. Patients with uveal melanoma metastases confined to the liver treated with IHP in two experienced hepato-pancreatic-biliary surgery centres (Erasmus MC Cancer Institute and Leiden University Medical Center) were included...
August 10, 2016: Melanoma Research
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