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Isolated liver perfusion

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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
#1
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/28188296/effect-of-garlic-gingko-and-st-john-s-wort-extracts-on-the-pharmacokinetics-of-fexofenadine-a-mechanistic-study
#2
Jasmina Turkanovic, Jacobus P Gerber, Michael B Ward, Robert W Milne
The aim of this study was to determine the effects of garlic and ginkgo herbal extracts on the pharmacokinetics of the P-glycoprotein (P-gp)/Organic anion transporting polypeptides (Oatps) substrate fexofenadine. Male rats were dosed orally with garlic (120 mg/kg), ginkgo (17 mg/kg), St. John's wort (SJW; 1000 mg/kg; positive control) or milli Q water for 14 days. On day 15, rats were either administered fexofenadine (orally or intravenously), had their livers isolated and perfused with fexofenadine, or the small intestine divided into four segments (SI-SIV) and analysed for P-gp and Oatp1a5...
February 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28178721/chemosaturation-with-percutaneous-hepatic-perfusion-in-unresectable-hepatic-metastases
#3
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/28155130/rapid-isolation-of-murine-primary-hepatocytes-for-chromosomal-analysis
#4
Kentaro Ariyoshi, Yohei Fujishima, Tomisato Miura, Yi Shang, Shizuko Kakinuma, Shimada Yoshiya, Kosuke Kasai, Akifumi Nakata, Akira Tachibana, Mitsuaki A Yoshida
Primary hepatocyte culture is a crucial tool for investigations of liver function and for evaluating the toxic effects of drugs. In addition, chromosomal analysis of hepatocytes could also prove useful for understanding the mechanisms of hepatocarcinogenesis. However, cultivation of primary hepatocytes for chromosome analysis has been hampered by the specific equipment and skill required to perform the in situ perfusion step necessary for isolation of primary hepatocytes. In the present study, we aimed to establish a simple and efficient method of isolating hepatocytes suitable for chromosome analysis...
February 2, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28110582/the-effect-of-perfusate-buffering-on-toxicity-and-response-in-isolated-hepatic-perfusion-for-uveal-melanoma-liver-metastases
#5
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/28101459/venlafaxine-induced-cytotoxicity-towards-isolated-rat-hepatocytes-involves-oxidative-stress-and-mitochondrial-lysosomal-dysfunction
#6
Elham Ahmadian, Hossein Babaei, Alireza Mohajjel Nayebi, Aziz Eftekhari, Mohammad Ali Eghbal
Purpose: Depression is a public disorder worldwide. Despite the widespread use of venlafaxine in the treatment of depression, it has been associated with the incidence of toxicities. Hence, the goal of the current investigation was to evaluate the mechanisms of venlafaxine-induced cell death in the model of the freshly isolated rat hepatocytes. Methods: Collagenase-perfused rat hepatocytes were treated with venlafaxine and other agents. Cell damage, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential decline, lysosomal damage, glutathione (GSH) level were analyzed...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28024294/celecoxib-administration-reduced-mortality-mesenteric-hypoperfusion-aortic-dysfunction-and-multiple-organ-injury-in-septic-rats
#7
Erdem Kamil Ozer, Mustafa Tugrul Goktas, Ibrahim Kilinc, Hulagu Bariskaner, Ceyhan Ugurluoglu, Alper Bektas Iskit
BACKGROUND: The cyclooxygenase (COX)-2 overexpression is associated with vascular injury and multiple organ failure in sepsis. However, constitutive COX-1 and basal COX-2 expressions have physiological effects. We aimed to investigate the effects of partial and selective COX-2 inhibition without affecting constitutive COX-1 and basal COX-2 activities by celecoxib on mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries, and survival in septic rats accomplished by cecal ligation and puncture (CLP)...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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
#8
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
#9
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/27913845/mitogen-activated-protein-kinases-are-involved-in-hepatocanalicular-dysfunction-and-cholestasis-induced-by-oxidative-stress
#10
Flavia D Toledo, Cecilia L Basiglio, Ismael R Barosso, Andrea C Boaglio, Andrés E Zucchetti, Enrique J Sánchez Pozzi, Marcelo G Roma
In previous studies, we showed that the pro-oxidant model agent tert-butyl hydroperoxide (tBuOOH) induces alterations in hepatocanalicular secretory function by activating Ca(2+)-dependent protein kinase C isoforms (cPKC), via F-actin disorganization followed by endocytic internalization of canalicular transporters relevant to bile formation (Mrp2, Bsep). Since mitogen-activated protein kinases (MAPKs) may be downstream effectors of cPKC, we investigated here the involvement of the MAPKs of the ERK1/2, JNK1/2, and p38(MAPK) types in these deleterious effects...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27881031/cavitation-enhances-coagulated-size-during-pulsed-high-intensity-focussed-ultrasound-ablation-in-an-isolated-liver-perfusion-system
#11
Lu-Yan Zhao, Shan Liu, Zong-Gui Chen, Jian-Zhong Zou, Feng Wu
PURPOSE: To investigate whether cavitation enhances the degree of coagulation during pulsed high-intensity focussed ultrasound (HIFU) in an isolated liver perfusion system. METHODS: Isolated liver was treated by pulsed HIFU or continuous-wave HIFU with different portal vein flow rates. The cavitation emission during exposure was recorded, and real-time ultrasound images were used to observe changes in the grey scale. The coagulation size was measured and calculated...
November 24, 2016: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/27878478/liver-resection-after-selective-internal-radiation-therapy-with-yttrium-90-is-safe-and-feasible-a-bi-institutional-analysis
#12
G Paul Wright, J Wallis Marsh, Manish K Varma, Michael G Doherty, David L Bartlett, Mathew H Chung
BACKGROUND: Treatment with yttrium-90 (Y90) microspheres has emerged as a viable liver-directed therapy for patients with unresectable tumors and those outside transplantation criteria. A select number of patients demonstrate a favorable response and become candidates for surgical resection. METHODS: Patients who underwent selective internal radiation therapy (SIRT) with Y90 microspheres at two institutions were reviewed. Patients who underwent liver resection were included in the study...
November 22, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27860296/impact-of-subnormothermic-machine-perfusion-preservation-in-severely-steatotic-rat-livers-a-detailed-assessment-in-an-isolated-setting
#13
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
#14
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
#15
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/27720763/hemodynamic-responses-to-lachesis-muta-south-american-bushmaster-snake-venom-in-anesthetized-rats
#16
Lourdes Dias, Mariana A P Rodrigues, André L Rennó, Alessandra Stroka, Bruna R Inoue, Patrícia C Panunto, Anibal R Melgarejo, Stephen Hyslop
In this work, we examined the hemodynamic responses to Lachesis muta (South American bushmaster) venom in anesthetized male Wistar rats. Venom (1.5 mg/kg, i.v.) caused immediate hypotension that was followed by a gradual return towards baseline over 60 min; there were no significant changes in heart rate, ECG parameters and respiratory rate. A higher dose (3 mg/kg, i.v.) caused sustained hypotension, variable bradycardia, respiratory depression and fluctuations in ECG; death occurred within 10-60 min. Venom injected intramuscularly (15 mg/kg) produced a smaller decrease in blood pressure that was more persistent than with 1...
December 1, 2016: Toxicon: Official Journal of the International Society on Toxinology
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/27695064/studying-closed-hydrodynamic-models-of-in-vivo-dna-perfusion-in-pig-liver-for-gene-therapy-translation-to-humans
#18
Luis Sendra, Antonio Miguel, Daniel Pérez-Enguix, María José Herrero, Eva Montalvá, María Adelaida García-Gimeno, Inmaculada Noguera, Ana Díaz, Judith Pérez, Pascual Sanz, Rafael López-Andújar, Luis Martí-Bonmatí, Salvador F Aliño
INTRODUCTION: Expressing exogenous genes after naked DNA delivery into hepatocytes might achieve sustained and high expression of human proteins. Tail vein DNA injection is an efficient procedure for gene transfer in murine liver. Hydrodynamic procedures in large animals require organ targeting, and improve with liver vascular exclusion. In the present study, two closed liver hydrofection models employing the human alpha-1-antitrypsin (hAAT) gene are compared to reference standards in order to evaluate their potential clinical interest...
2016: PloS One
https://www.readbyqxmd.com/read/27688659/hepatocyte-isolation-from-resected-benign-tissues-results-of-a-5-year-experience
#19
Fan-Ying Meng, Li Liu, Jun Liu, Chun-You Li, Jian-Ping Wang, Feng-Hui Yang, Zhi-Shui Chen, Ping Zhou
AIM: To analyze retrospectively a 5-year experience of human hepatocyte isolation from resected liver tissues with benign disease. METHODS: We established a method of modified four-step retrograde perfusion to isolate primary human hepatocytes. Samples were collected from the resected livers of patients with intrahepatic duct calculi (n = 7) and liver hemangioma (n = 17). Only the samples weighing ≥ 15 g were considered suitable for hepatocyte isolation. By using the standard trypan blue exclusion technique, hepatocyte viability and yield were immediately determined after isolation...
September 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27643409/evaluating-the-role-of-drug-metabolism-and-reactive-intermediates-in-trazodone-induced-cytotoxicity-toward-freshly-isolated-rat-hepatocytes
#20
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
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