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Transplantation,ischemia reperfusion injury

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https://www.readbyqxmd.com/read/28447976/method-of-direct-segmental-intra-hepatic-delivery-using-a-rat-liver-hilar-clamp-model
#1
Eliza W Beal, Curtis Dumond, Jung-Lye Kim, Khalid Mumtaz, Don Hayes, Ken Washburn, Bryan A Whitson, Sylvester M Black
Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ischemia/reperfusion (I/R) injury with myriad negative consequences. Potential I/R injury in marginal organs destined for liver transplantation contributes to the current donor shortage secondary to a decreased organ utilization rate. A significant need exists to explore hepatic I/R injury in order to mediate its impact on graft function in transplantation. Rat liver hilar clamp models are used to investigate the impact of different molecules on hepatic I/R injury...
April 2, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28444847/complement-dependence-of-murine-costimulatory-blockade-resistant-cellular-cardiac-allograft-rejection
#2
Nicholas Chun, Robert L Fairchild, Yansui Li, Jinhua Liu, Ming Zhang, William M Baldwin, Peter S Heeger
Building upon studies showing that ischemia/reperfusion-(IR)-injury is complement-dependent, we tested links among complement activation, transplant associated ischemia-reperfusion injury, and murine cardiac allograft rejection. We transplanted BALB/c hearts subjected to 8h cold ischemic storage (CIS) into CTLA4Ig-treated WT or c3(-/-) B6 recipients. Whereas allografts subjected to 8h CIS rejected in WT recipients with a median survival time (MST) of 37d, identically treated hearts survived >60d in c3(-/-) mice (p<0...
April 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28441386/graft-derived-cell-free-dna-a-noninvasive-early-rejection-and-graft-damage-marker-in-liver-transplantation-a-prospective-observational-multicenter-cohort-study
#3
Ekkehard Schütz, Anna Fischer, Julia Beck, Markus Harden, Martina Koch, Tilo Wuensch, Martin Stockmann, Björn Nashan, Otto Kollmar, Johannes Matthaei, Philipp Kanzow, Philip D Walson, Jürgen Brockmöller, Michael Oellerich
BACKGROUND: Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection...
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28440739/featured-article-pharmacological-postconditioning-with-delta-opioid-attenuates-myocardial-reperfusion-injury-in-isolated-porcine-hearts
#4
Maria Seewald, James A Coles, Daniel C Sigg, Paul A Iaizzo
Ischemic preconditioning has been utilized to protect the heart from ischemia prior to ischemia onset, whereas postconditioning is employed to minimize the consequences of ischemia at the onset of reperfusion. The underlying mechanisms and pathways of ischemic pre- and postconditioning continue to be investigated as therapeutic targets. We evaluated the administration of a delta opioid agonist or cariporide on various parameters associated with myocardial reperfusion injury upon reperfusion of isolated porcine hearts...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28438069/emerging-graft-protective-strategies-in-clinical-liver-transplantation
#5
Arash Nickkholgh, Daniel Maluf
There have been remarkable efforts to characterize the key responsible pathophysiologic mechanisms, as well as to ameliorate the organ preservation and ischemia reperfusion injury with the ultimate goal of expanding the donor pool and further improvement of the outcomes of the liver transplantation. Attempts to translate the experimental results from bench to bedside have yielded no valid protective concepts in the field of clinical liver transplantation yet. Nonetheless, there has been a considerable amount of ongoing clinical research to develop clinically relevant graft protective strategies...
April 24, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28429535/a-cross-circulated-bicephalic-model-of-head-transplantation
#6
Peng-Wei Li, Xin Zhao, Yun-Long Zhao, Bing-Jian Wang, Yang Song, Zi-Long Shen, Hong-Jun Jiang, Hai Jin, Sergio Canavero, Xiao-Ping Ren
AIMS: A successful cephalosomatic anastomosis ("head transplant") requires, among others, the ability to control long-term immune rejection and avoidance of ischemic events during the head transference phase. We developed a bicephalic model of head transplantation to study these aspects. METHODS AND RESULTS: The thoracic aorta and superior vena cava of a donor rat were anastomosed with the carotid artery and extracorporeal veins of a recipient rat by vascular grafts...
April 21, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28426449/temperature-and-oxygenation-during-organ-preservation-friends-or-foes
#7
Nicholas Gilbo, Diethard Monbaliu
PURPOSE OF REVIEW: The liberalization of donor selection criteria in organ transplantation, with the increased use of suboptimal grafts, has stimulated interest in ischemia-reperfusion injury prevention and graft reconditioning. Organ preservation technologies are changing considerably, mostly through the reintroduction of dynamic machine preservation. Here, we review the current evidence on the role of temperature and oxygenation during dynamic machine preservation. RECENT FINDINGS: A large but complex body of evidence exists and comparative studies are few...
April 19, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28422872/effect-of-hsp27-and-cofilin-in-the-injury-of-hypoxia-reoxygenation-on-hepatocyte-membrane-f-actin-microfilaments
#8
Yafei Zhang, Jiazhong Wang, Hong Ji, Hongwei Lu, Le Lu, Jinlong Wang, Yiming Li
Hypoxia-reoxygenation (H/R) injury hepatocyte models were established to simulate the ischemia/reperfusion injury of transplanted organ. Through the study of the molecular mechanism of H/R on the F-actin damage of the liver cytomembrane, the mechanism of F-actin damage induced by ischemia and reperfusion was studied from the level of cell and molecule.The hypoxic environment of cells in vitro was simulated by chemical hypoxia agent CoCl2. Liver cells were detected by MTT, H/R group was subdivided into 3 subgroups: H/R 2, 4, and 6 h...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28414974/bilirubin-nanoparticle-preconditioning-protects-against-hepatic-ischemia-reperfusion-injury
#9
Jin Yong Kim, Dong Yun Lee, Sukmo Kang, Wenjun Miao, Hyungjun Kim, Yonghyun Lee, Sangyong Jon
Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver transplantation and resection, despite continuing efforts to prevent it. Accumulating evidence suggests that bilirubin possesses antioxidant, anti-inflammatory and anti-apoptotic properties. However, despite obvious potential health benefits of bilirubin, its clinical applications are limited by its poor solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate whether BRNPs protect against IRI in the liver by preventing oxidative stress...
April 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28407626/exogenous-mirna-146a-enhances-the-therapeutic-efficacy-of-human-mesenchymal-stem-cells-by-increasing-vascular-endothelial-growth-factor-secretion-in-the-ischemia-reperfusion-injured-heart
#10
Hyang-Hee Seo, Se-Yeon Lee, Chang Youn Lee, Ran Kim, Pilseog Kim, Sekyung Oh, Hojin Lee, Min Young Lee, Jongmin Kim, Lark Kyun Kim, Ki-Chul Hwang, Woochul Chang
Adult stem cells have been studied as a promising therapeutic modality for the functional restoration of the damaged heart. In the present study, a strategy for enhancing the angiogenic efficacy of human mesenchymal stem cells (hMSCs) using micro-RNA was examined. We investigated whether micro-RNA-146a (miR-146a) influences the secretion of vascular endothelial growth factor (VEGF) and angiogenesis of MSCs. Our data indicated that miR-146a-transfected hMSCs (hMSCmiR-146a) decreased the expression of neurofibromin 2, an inhibitor of p21-activated kinase-1 (PAK1)...
April 14, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28407355/extracellular-vesicles-from-bone-marrow-derived-mesenchymal-stem-cells-protect-against-murine-hepatic-ischemia-reperfusion-injury
#11
Hiroaki Haga, Irene K Yan, David Borelli, Akiko Matsuda, Mansi Parasramka, Neha Shukla, David D Lee, Tushar Patel
Hepatic ischemia-reperfusion injury (IRI) and associated inflammation contributes to liver dysfunction and complications after liver surgery and transplantation. Mesenchymal stem cells (MSC) have been reported to reduce hepatic IRI because of their reparative immunomodulatory effects in injured tissues. Recent studies have highlighted beneficial effects of extracellular vesicles from MSCs (MSC-EV) on tissue injury. The effects of systemically administered mouse bone marrow derived MSC-EV were evaluated in an experimental murine model of hepatic IRI induced by cross clamping the hepatic artery and portal vein for 90 minutes followed by reperfusion for periods of upto 6 hours...
April 13, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28403128/an-oxygenated-and-transportable-machine-perfusion-system-fully-rescues-liver-grafts-exposed-to-lethal-ischemic-damage-in-a-pig-model-of-dcd-liver-transplantation
#12
Philippe Compagnon, Eric Levesque, Hassen Hentati, Mara Disabato, Julien Calderaro, Cyrille Feray, Anne Corlu, José Laurent Cohen, Ismail Ben Mosbah, Daniel Azoulay
BACKGROUND: Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. METHODS: Cardiac arrest was induced in female large white pigs by IV injection of potassium chloride...
April 11, 2017: Transplantation
https://www.readbyqxmd.com/read/28395520/ischemic-conditioning-in-kidney-transplantation
#13
Kristin Veighey, Raymond MacAllister
Ischemia-reperfusion injury is a composite of the injury sustained during a period of reduced or absent blood flow to a tissue or organ and the additional insult sustained on reperfusion, which limits the amount of tissue that can be salvaged. Ischemia-reperfusion injury is the predominant insult during kidney transplantation, contributing to graft dysfunction, increased rates of acute rejection, and reduced rejection-free graft survival. In this review, we discuss the potential therapeutic benefits of a cost-effective and low-risk intervention, ischemic preconditioning, and its potential for improving kidney function following transplantation...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28389406/simultaneous-overexpression-of-human-e5nt-and-entpd1-protects-porcine-endothelial-cells-against-h2o2-induced-oxidative-stress-and-cytotoxicity-in-vitro
#14
Elisa Chisci, Marco De Giorgi, Elisa Zanfrini, Angela Testasecca, Elena Brambilla, Alessandro Cinti, Laura Farina, Barbara Kutryb-Zajac, Cristina Bugarin, Chiara Villa, Emanuela Grassilli, Romina Combi, Giuseppe Gaipa, Maria Grazia Cerrito, Ilaria Rivolta, Ryszard Tomasz Smolenski, Marialuisa Lavitrano, Roberto Giovannoni
Ischemia-reperfusion injury (IRI) and oxidative stress still limit the survival of cells and organs in xenotransplantation models. Ectonucleotidases play an important role in inflammation and IRI in transplantation settings. We tested the potential protective effects derived by the co-expression of the two main vascular ectonucleotidases, ecto-5'-nucleotidase (E5NT) and ecto nucleoside triphosphate diphosphohydrolase 1 (ENTPD1), in an in vitro model of H2O2-induced oxidative stress and cytotoxicity. We produced a dicistronic plasmid (named pCX-DI-2A) for the co-expression of human E5NT and ENTPD1 by using the F2A technology...
April 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28388830/the-release-of-microrna-122-during-liver-preservation-is-associated-with-early-allograft-dysfunction-and-graft-survival-after-transplantation
#15
Jasmijn W Selten, Cornelia J Verhoeven, Veerle Heedfeld, Henk P Roest, Jeroen de Jonge, Jacques Pirenne, Jos van Pelt, Jan N M IJzermans, Diethard Monbaliu, Luc J W van der Laan
INTRODUCTION: Early allograft dysfunction (EAD) after liver transplantation is associated with inferior graft survival. EAD is more prevalent in grafts from donation after circulatory death (DCD). However, accurate prediction of liver function remains difficult due to the lack of specific biomarkers. Recent experimental and clinical studies highlight the potential of hepatocyte-derived microRNAs (miRNAs) as sensitive, stable and specific biomarkers of liver injury. The aim of this study was to determine whether miRNAs in graft preservation fluid are predictive for EAD after clinical liver transplantation and in an experimental DCD model...
April 7, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28388574/over-expression-of-growth-differentiation-factor-15-gdf15-preventing-cold-ischemia-reperfusion-i-r-injury-in-heart-transplantation-through-foxo3a-signaling
#16
Yixin Zhang, Lisa A Moszczynski, Qing Liu, Jifu Jiang, Duo Zhao, Douglas Quan, Tina Mele, Vivian McAlister, Anthony Jevnikar, Seung Joon Baek, Kexiang Liu, Xiufen Zheng
Ischemia reperfusion (I/R) injury which inevitably occurs during heart transplantation is the major factor leading to organ failure and graft rejection. In order to develop new therapies to prevent I/R injury, we used both a murine heart transplantation model with 24 hour cold I/R and an in vitro cell culture system to determine whether growth differentiation factor 15 (GDF15) is a protective factor in preventing I/R injury in heart transplantation and to further investigate underlying mechanisms of I/R injury...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386315/protective-benefits-of-amp-activated-protein-kinase-in-hepatic-ischemia-reperfusion-injury
#17
REVIEW
Min Zhang, Dan Yang, Xianqiong Gong, Pu Ge, Jie Dai, Ling Lin, Li Zhang
Hepatic ischemia-reperfusion injury (HIRI) is a major cause of hepatic failure and death after liver trauma, haemorrhagic shock, resection surgery and liver transplantation. AMP-activated protein kinase (AMPK) is an energy sensitive kinase that plays crucial roles in the regulation of metabolic homeostasis. In HIRI, ischemia induces the decline of ATP and the increased ratio of AMP/ATP, which promotes the phosphorylation and activation of AMPK. Three AMPK kinases, liver kinase B1 (LKB1), Ca(2+)/calmodulin-depedent protein kinase kinase β (CaMKKβ) and TGF-β-activated kinase-1 (TAK1), are main upstream kinases for the phosphorylation of AMPK...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28378341/nlrp3-inflammasome-induced-liver-graft-injury-through-activation-of-telomere-independent-rap1-kc-axis
#18
Hui Liu, Oscar Wai Ho Yeung, Chang Xian Li, Xiao Bing Liu, Xiang Qi, Kevin Tak Pan Ng, Jiang Liu, Yuen Yuen Ma, Yin Fan Lam, Qizhou Lian, See Ching Chan, Chung Mau Lo, Kwan Man
Acute phase inflammation plays a critical role in liver graft injury. Inflammasomes, multi-molecular complexes in the cytoplasm, are responsible for initiating inflammation. Here, we aimed to explore the role of inflammasomes in liver graft injury and further to investigate the regulatory mechanism. In a clinical liver transplant cohort, we found that intragraft expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes was significantly up-regulated post-transplantation...
April 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28371289/prolonged-cold-ischemia-time-results-in-local-and-remote-organ-dysfunction-in-a-murine-model-of-vascularized-composite-transplantation
#19
Néha Datta, Sean G Devaney, Ronald W Busuttil, Kodi Azari, Jerzy W Kupiec-Weglinski
Vascularized composite allotransplantation (VCA) is a viable reconstructive option for complex tissue defects. Although grafts with large muscular component may be uniquely susceptible to ischemia/reperfusion (I/R) syndrome, the safe cold ischemia time in VCA has not been established. We investigated the effects of cold ischemia on innate immune response and recipient survival in a murine orthotopic hindlimb transplantation model. Surprisingly, mice receiving grafts exposed to 6h or longer of cold storage demonstrated reduced survival and massive elevations in serum creatinine, BUN and creatine kinase, as compared to 1h of cold storage recipients...
March 30, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28370484/graft-derived-macrophage-migration-inhibitory-factor-correlates-with-hepatocellular-injury-in-patients-undergoing-liver-transplantation
#20
Joanna Baron-Stefaniak, Judith Schiefer, Edmund J Miller, Walter Plöchl, Claus G Krenn, Gabriela A Berlakovich, David M Baron, Peter Faybik
Experimental studies suggest that macrophage migration inhibitory factor (MIF) mediates ischemia/reperfusion injury during liver transplantation. This study assessed whether human liver grafts release MIF during preservation, and whether the release of MIF is proportional to the extent of hepatocellular injury. Additionally, the association between MIF and early allograft dysfunction (EAD) after liver transplantation was evaluated. Concentrations of MIF, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) were measured in effluents of 38 liver grafts, and in serum of recipients...
April 1, 2017: Clinical Transplantation
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