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Isolated liver perfusion

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
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...
October 5, 2016: Toxicon: Official Journal of the International Society on Toxinology
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
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
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
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...
September 19, 2016: Drug Research
Fabien Cusin, Liliana Fernandes Azevedo, Pierre Bonnaventure, Jules Desmeules, Youssef Daali, Catherine M Pastor
Peroperative imaging with indocyanin green (ICG) is developing to increase safety in dissecting anatomical structures during hepatobiliary surgery. Images obtained with the fluorescence camera rely on concentrations measured in liver regions of interest. However, how ICG sinusoidal uptake and hepatocyte elimination rates generate ICG hepatocyte concentrations is largely unknown. To investigate such issue and better understand the role of membrane transporters in generating ICG hepatocyte concentrations, we perfused ICG in livers isolated from normal livers...
September 14, 2016: Basic & Clinical Pharmacology & Toxicology
Yi Li, Yujia Wang, Qiong Wu, Li Li, Yujun Shi, Hong Bu, Ji Bao
Successful porcine hepatocyte isolation is crucial for the development of bioartificial liver devices and hepatocyte transplantation. Serva collagenase NB grades are formulated collagenases that are suitable for various tissue isolation applications. N-acetylcysteine (NAC) can improve the viability of human hepatocytes. The aim of this study was to compare the effectiveness of two collagenases and effect of NAC on hepatocyte isolation from porcine liver tissue. Porcine hepatocytes were isolated using the perfusion method from Bama mini pigs assigned to the Serva NB 4 group (n=6), the Serva NB 8 group (n=6), or the NB 8+NAC group (n=6)...
September 2016: Xenotransplantation
Olivia B Yu, Leggy A Arnold
Calcitroic acid was isolated and characterized almost four decades ago, but little is known about this important vitamin D metabolite. Four reported synthetic strategies to generate calcitroic acid are presented that highlight the scientific progress in the field of chemistry directed to vitamin D analog synthesis. The most recent synthesis described the generation of calcitroic acid with an overall yield of 12.8% in 13 steps. The endogenous formation of calcitroic acid has been demonstrated in perfused rat kidney using 24,25,26,27-tetranor-1,23(OH)2D3...
October 21, 2016: ACS Chemical Biology
Cintia Zimmermann Meireles, Marcos Pasarin, Juan Jose Lozano, Héctor García-Calderó, Jordi Gracia-Sancho, Juan Carlos García-Pagán, Jaime Bosch, Juan G Abraldes
Liver function deterioration is a major cause of death in variceal bleeding. The effects of bleeding on intrahepatic microvascular dysfunction, which contributes to liver injury in cirrhosis, are largely unknown. The aims of this study were to evaluate the impact of hemorrhage/resuscitation (H/R) on cirrhotic microcirculation, and whether simvastatin, a drug that improves liver microcirculation, has hepatoprotective effects. The study was performed in three groups of rats: controls, rats with biliary cirrhosis (CBDL) and CBDL rats pre-treated with 3 doses (5 mg*Kg-1*day-1) of simvastatin...
August 24, 2016: Shock
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...
August 22, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Wee Ling Koh, Phoebe Huijun Tham, Hanry Yu, Hwa Liang Leo, James Chen Yong Kah
AIM: We examined the impact of aggregation and protein corona formation of gold nanoparticles (AuNPs) on the cytotoxicity, uptake and metabolism, specifically urea and albumin synthesis, of primary rat hepatocytes. MATERIALS & METHODS: The AuNPs were synthesized via citrate reduction and the human serum protein corona was preformed on the AuNPs. Primary hepatocytes were isolated from male Wistar rats via two-step in situ collagenase perfusion method, and were dosed with both citrate-capped (AuNP-Cit) and protein corona coated AuNPs (AuNP-Cor)...
September 2016: Nanomedicine
Toshiaki Kashiwadate, Shigehito Miyagi, Yasuyuki Hara, Yorihiro Akamatsu, Satoshi Sekiguchi, Naoki Kawagishi, Noriaki Ohuchi, Susumu Satomi
Transplantation using grafts obtained after cardiac death (CD) is considered a promising solution for graft shortages. However, no standard criteria for organ preservation have been established for CD donors. High-mobility group box 1 (HMGB1) is a DNA-binding protein that is released from dying hepatocytes as an early mediator of inflammation and organ tissue damage. HMGB1 stimulates immunocytes to produce inflammatory cytokines, thereby amplifying the inflammatory response. Thrombomodulin is an integral membrane protein that functions as an endothelial anticoagulant cofactor, and it binds HMGB1 through the extracellular domain...
2016: Tohoku Journal of Experimental Medicine
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
Eleonora M de Leede, Mark C Burgmans, Christian H Martini, Fred G J Tijl, Arian R van Erkel, Jaap Vuyk, Ellen Kapiteijn, Cornelis Verhoef, Cornelis J H van de Velde, Alexander L Vahrmeijer
Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects...
2016: Journal of Visualized Experiments: JoVE
P Roman, G Budziński, A Suszka-Świtek, A Caban, G Oczkowicz, R Wiaderkiewicz, F Ryszka, Z Smorąg, L Cierpka
BACKGROUND: Transgenic animals may serve as organ donors in human organ transplantation. However, the number of the studies addressing all doubts related to this issue is currently insufficient for the clinical application of this approach. The aim of this study was to analyze the hepatic tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) synthesis during a 24-hour cold preservation of the transgenic pig liver, depending on the type of transgenesis. MATERIALS AND METHODS: The study was carried out on wild-type and transgenic pig livers with transferred human α1,2-fucosyltransferase (FUT) and/or α-galactosidase (GAL) gene (four groups; n = 6)...
June 2016: Transplantation Proceedings
Jurandir Fernando Comar, Denise Silva de Oliveira, Livia Bracht, Fumie Suzuki Kemmelmeier, Rosane Marina Peralta, Adelar Bracht
There are several claims about the beneficial effects of supplementing L-glutamine to both type 1 and type 2 diabetes. The purpose of the present study was to provide detailed knowledge about the fate of this amino acid in the liver, the first organ that receives the compound when ingested orally. The study was done using the isolated perfused rat liver, an experimental system that preserves the microcirculation of the organ and that allows to measured several parameters during steady-state and pre steady-state conditions...
2016: PloS One
Kellie A Fay, Patrick N Fitzsimmons, Alex D Hoffman, John W Nichols
Isolated hepatocytes and liver S9 fractions have been used to collect in vitro biotransformation data for fish as a means of improving modeled estimates of chemical bioaccumulation. To date, however, there have been few direct comparisons of these 2 methods. In the present study, cryopreserved trout hepatocytes were used to measure in vitro intrinsic clearance rates for 6 polycyclic aromatic hydrocarbons (PAHs). These rates were extrapolated to estimates of in vivo intrinsic clearance and used as inputs to a well stirred liver model to predict hepatic clearance...
August 2, 2016: Environmental Toxicology and Chemistry
Cathal Harmon, Mark W Robinson, Ronan Fahey, Sarah Whelan, Diarmaid D Houlihan, Justin Geoghegan, Cliona O'Farrelly
The adult human liver is enriched with natural killer (NK) cells, accounting for 30-50% of hepatic lymphocytes, which include tissue-resident hepatic NK-cell subpopulations, distinct from peripheral blood NK cells. In murine liver, a subset of liver-resident hepatic NK cells have altered expression of the two highly related T-box transcription factors, T-bet and eomesodermin (Eomes). Here, we investigate the heterogeneity of T-bet and Eomes expression in NK cells from healthy adult human liver with a view to identifying human liver-resident populations...
September 2016: European Journal of Immunology
Zhi-Yu Wei, Bai-Ri Cui, Xun Cui, Yan-Ling Wu, Yang Fu, Li-Ping Liu, Hu-Ri Piao
In the present study, four novel series of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties were designed, synthesized and evaluated for negative inotropic activity by measuring the left atrium stroke volume in isolated rabbit heart preparations. Almost all of the compounds showed an ability to moderate the cardiac workload by decreasing the heart rate and contractility. Among them, 7h was found to be the most potent with a change in stroke volume of -48.22 ± 0.36% at a concentration of 3×10(-5) mol/L (metoprolol: -9...
July 28, 2016: Chemical Biology & Drug Design
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