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Liver transplantation in rat

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https://www.readbyqxmd.com/read/28346882/determination-of-prodrug-treosulfan-and-its-biologically-active-monoepoxide-in-rat-plasma-liver-lungs-kidneys-muscle-and-brain-by-hplc-esi-ms-ms-method
#1
Michał Romański, Anna Kasprzyk, Artur Teżyk, Agnieszka Widerowska, Czesław Żaba, Franciszek Główka
A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance...
March 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28320485/mesenchymal-stem-cells-increase-expression-of-heme-oxygenase-1-leading-to-anti-inflammatory-activity-in-treatment-of-acute-liver-failure
#2
Zhi-Heng Zhang, Wei Zhu, Hao-Zhen Ren, Xin Zhao, Shuai Wang, Hu-Cheng Ma, Xiao-Lei Shi
BACKGROUND: Mesenchymal stem cells (MSCs) have been studied for the treatment of acute liver failure (ALF) for several years. MSCs may exert their effect via complex paracrine mechanisms. Heme oxygenase (HO) 1, a rate-limiting enzyme in heme metabolism, exerts a wide range of anti-inflammatory, anti-apoptotic and immunoregulatory effects in a variety of diseases. However, the relationship between MSCs and HO-1 in the treatment of ALF is still unclear. We investigated the preventive and therapeutic potential of intravenously administered BMSCs...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28320107/pre-conditioning-with-tanshinone-iia-attenuates-the-ischemia-reperfusion-injury-caused-by-liver-grafts-via-regulation-of-hmgb1-in-rat-kupffer-cells
#3
Xuanfei Li, Yakun Wu, Wenfeng Zhang, Jianping Gong, Yao Cheng
OBJECTIVE: We have evaluated the protective mechanism of tanshinone IIA in ischemia/reperfusion injury (IRI) induced by liver grafts, revealing novel supplementary immunotherapy for liver transplantation. METHODS: The tanshinone IIA preconditioning group (TP group) was pretreated with tanshinone IIA via intraperitoneal injection for 1 week before receiving orthotopic liver transplantation with hepatic arterial ischemia for 30min. The sham-operation group (SO group), control graft group (CG group) and IRI group were pretreated with an equivalent volume of normal saline...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28289017/activated-tafi-promotes-the-development-of-chronic-thromboembolic-pulmonary-hypertension-a-possible-novel-therapeutic-target
#4
Taijyu Satoh, Kimio Satoh, Nobuhiro Yaoita, Nobuhiro Kikuchi, Junichi Omura, Ryo Kurosawa, Kazuhiko Numano, Elias Al-Mamun, Mohammad Abdul Hai Siddique, Shinichiro Sunamura, Masamichi Nogi, Kota Suzuki, Satoshi Miyata, John Morser, Hiroaki Shimokawa
Rationale: Pulmonary hypertension (PH) is a fatal disease; however, its pathogenesis still remains to be elucidated. Thrombin-activatable fibrinolysis inhibitor (TAFI) is synthesized by the liver and inhibits fibrinolysis. Plasma TAFI levels are significantly increased in chronic thromboembolic PH (CTEPH) patients. Objective: To determine the role of activated TAFI (TAFIa) in the development of CTEPH. Methods and Results: Immunostaining showed that TAFI and its binding partner thrombomodulin (TM) were highly expressed in the pulmonary arteries (PA) and thrombus in patients with CTEPH...
March 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/28282906/gsk3%C3%AE-and-vdac-involvement-in-er-stress-and-apoptosis-modulation-during-orthotopic-liver-transplantation
#5
Mohamed Amine Zaouali, Arnau Panisello, Alexandre Lopez, Carlos Castro, Emma Folch, Teresa Carbonell, Anabela Rolo, Carlos Marques Palmeira, Agustin Garcia-Gil, René Adam, Joan Roselló-Catafau
We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia-reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured...
March 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28275217/identification-of-proteins-interacting-with-cytoplasmic-high-mobility-group-box-1-during-the-hepatocellular-response-to-ischemia-reperfusion-injury
#6
Tianjiao Zhang, Weiwei Wei, Olaf Dirsch, Thomas Krüger, Chunyi Kan, Chichi Xie, Olaf Kniemeyer, Haoshu Fang, Utz Settmacher, Uta Dahmen
Ischemia/reperfusion injury (IRI) occurs inevitably in liver transplantations and frequently during major resections, and can lead to liver dysfunction as well as systemic disorders. High-mobility group box 1 (HMGB1) plays a pathogenic role in hepatic IRI. In the normal liver, HMGB1 is located in the nucleus of hepatocytes; after ischemia reperfusion, it translocates to the cytoplasm and it is further released to the extracellular space. Unlike the well-explored functions of nuclear and extracellular HMGB1, the role of cytoplasmic HMGB1 in hepatic IRI remains elusive...
January 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28273635/nobiletin-ameliorates-ischemia-reperfusion-injury-by-suppressing-the-function-of-kupffer-cells-after-liver-transplantation-in-rats
#7
Yakun Wu, Wenfeng Zhang, Min Li, Ding Cao, Xiaoli Yang, Jianping Gong
This study aims to explore the protective effects of nobiletin against hepatic ischemia-reperfusion (IR) injury after liver transplantation. Kupffer cells (KCs) were activated and co-cultured with different concentration of nobiletin for 24h in vitro, inflammatory products and activity of TLR4/NF-κB signaling pathway were detected. Sprague-Dawley rats were selected and underwent orthotopic liver transplantation. Donors were injected intravenously with nobiletin (50mg/kg) or saline solution, once a day for 1 week before the surgery...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28271982/hepatic-mir-301a-as-a-liver-transplant-rejection-biomarker-and-its-role-for-interleukin-6-production-in-hepatocytes
#8
Toshiaki Nakano, I-Hsuan Chen, Shigeru Goto, Chia-Yun Lai, Hui-Peng Tseng, Li-Wen Hsu, King-Wah Chiu, Chih-Che Lin, Chih-Chi Wang, Yu-Fan Cheng, Chao-Long Chen
Acute rejection (AR) of liver transplantation remains a formidable challenge for diagnostic medicine and biomarker discovery. We characterized AR-related microRNAs (miRNAs) and the underlying AR mechanisms in liver transplantation. Using a rat model of orthotopic liver transplantation (OLT) as well as microarrays, we compared the miRNA expression profiles between naive and AR livers on day 7 after OLT with short- (<14 days, donor Dark Agouti [DA] liver into Lewis [LEW] recipient) and long-term (>60 days, donor DA liver into Piebald Virol Glaxo [PVG] recipient) survival fates...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28246131/the-effect-of-cortisol-in-rat-steatotic-and-non-steatoticliver-transplantation-from-brain-dead-donors
#9
Mónica Bibiana Jiménez-Castro, Elsa Negrete-Sánchez, Araní Casillas-Ramírez, Jose Gulfo, Ana I Álvarez-Mercado, Maria Eugenia Cornide-Petronio, Jordi Gracia-Sancho, Juan Rodés, Carmen Peralta
In this study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with upregulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were downregulated in steatotic liver grafts...
February 28, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28239866/influence-of-vasomodulators-and-tumor-transplantation-on-the-disposition-of-5-fluorouracil-after-application-to-the-liver-surface-in-rats
#10
Yukinobu Kodama, Miyuki Horishita, Ayako Tokunaga, Hirotaka Miyamoto, Shintaro Fumoto, Hitoshi Sasaki, Junzo Nakamura, Koyo Nishida
This study investigated the effect of epinephrine (a vasoconstrictor) and hydralazine (a vasodilator) on the hepatic disposition of 5-fluorouracil (5-FU) after application to the liver surface in rats. Normal livers were compared with a Walker 256 carcinoma cell tumor model. A cylindrical diffusion cell was attached to the liver surface. 5-FU was added into the diffusion cell in combination with vasomodulators or after pretreatment with epinephrine. After selected treatment times, 5-FU concentrations were assayed at three sites in the excised livers...
February 27, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28238806/rat-acute-gvhd-is-th1-driven-and-characterized-by-predominant-donor-cd4-t-cell-infiltration-of-skin-and-gut
#11
Margherita Boieri, Pranali Shah, Dasaradha Jalapothu, Olena Zaitseva, Lutz Walter, Bent Rolstad, Christian Naper, Ralf Dressel, Marit Inngjerdingen
Acute graft-versus-host disease (aGvHD) remains a significant hurdle to successful treatment of many hematological disorders. The disease is caused by infiltration of allo-activated donor T cells primarily into the gastrointestinal tract and skin. While cytotoxic T cells mediate direct cellular damage, T helper (Th) cells differentially secrete immunoregulatory cytokines. Acute GvHD is thought to be primarily initiated by Th1 cells but a consensus is still lacking regarding the role of Th2 and Th17 cells. The aim of this study was to determine the contribution of distinct T cell subsets to aGvHD in the rat...
February 23, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28223727/remote-ischemic-perconditioning-prevents-liver-transplantation-induced-ischemia-reperfusion-injury-in-rats-role-of-ros-rns-and-enos
#12
Ning He, Jun-Jun Jia, Jian-Hui Li, Yan-Fei Zhou, Bing-Yi Lin, Yi-Fan Peng, Jun-Jie Chen, Tian-Chi Chen, Rong-Liang Tong, Li Jiang, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng
AIM: To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS: Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (ΔΨm) and total nitric oxide (NO)...
February 7, 2017: World Journal of Gastroenterology: WJG
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
#13
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/28219600/tert-butylhydroquinone-protects-liver-against-ischemia-reperfusion-injury-in-rats-through-nrf2-activating-anti-oxidative-activity
#14
X-P Zeng, X-J Li, Q-Y Zhang, Q-W Liu, L Li, Y Xiong, C-X He, Y-F Wang, Q-F Ye
BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is a serious complication that occurs in surgical operations such as hepatectomy and liver transplantation. NF-E2-related factor 2 (Nrf2) is a transcription factor that has been proven against inflammatory and oxidative injury. Tert-butylhydroquinone (tBHQ), a widely used Nrf2 activator, is a common food preservative. In this study, we attempt to investigate the potential protective role of tBHQ in hepatic I/R injury. METHODS: Twenty adult male rats were randomly divided into four groups: (1) sham+vehicle group; (2) I/R+vehicle group; (3) sham+tBHQ group; and (4) I/R+tBHQ group...
March 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28207637/the-efficacy-of-a-prevascularized-retrievable-poly-d-l-lactide-co-%C3%AE%C2%B5-caprolactone-subcutaneous-scaffold-as-transplantation-site-for-pancreatic-islets
#15
Alexandra M Smink, Shiri Li, Don T Hertsig, Bart J de Haan, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally, this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here, we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) scaffold...
April 2017: Transplantation
https://www.readbyqxmd.com/read/28187520/exogenous-vegf-delivery-prior-to-endothelial-precursor-cell-transplantation-in-orthotopic-liver-transplant-induced-hepatic-ischemia-reperfusion-injury
#16
Ding Cao, Menghao Wang, Junhua Gong, Sidong Wei, Jianping Gong, Jinzheng Li
BACKGROUND: Vascular endothelial growth factor (VEGF) promotes angiogenesis in vivo. We hypothesized that exogenous delivery of VEGF prior to bone marrow-derived endothelial precursor cell (EPC) transplantation may improve orthotopic liver transplantation (OLT)-induced hepatic ischemia-reperfusion injury (HIRI). METHODS: OLT between Sprague Dawley donor rats and inbred LEW Wistar recipient rats was performed in six experimental groups to comparatively assess the effects of VEGF gene: an untreated normal control group, a surgical control group, a liposomal control group, a VEGF group receiving only the liposome-encapsulated VEGF plasmid, an EPC group receiving only EPCs, and an EPC+VEGF group receiving the liposome-encapsulated VEGF plasmid followed by EPCs...
February 10, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28187014/delayed-donor-bone-marrow-infusion-induces-liver-transplant-tolerance
#17
Yan Xie, Yang Wu, Kang Xin, Jiao-Jing Wang, Hong Xu, Suzanne T Ildstad, Joseph Leventhal, Guang-Yu Yang, Zheng Zhang, Josh Levitsky
BACKGROUND: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. METHODS: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls...
February 10, 2017: Transplantation
https://www.readbyqxmd.com/read/28174669/cell-therapy-for-liver-disease-using-bioimaging-rats
#18
REVIEW
Junko Haga, Shin Enosawa, Eiji Kobayashi
Advances in stem cell research suggest that cell therapy is a potential alternative to liver transplantation. The use of individualized and minimally invasive cell therapy is desirable to avoid rejection and reduce patient burden. While allo-hepatocyte transplantation has been performed for metabolic hepatic disease, auto-bone marrow transplantation (BMT) has shifted toward mesenchymal stem cells (MSCs) transplantation for liver cirrhosis. In this article, an overview of cell transplantation research for liver disease is provided through our recent rat studies...
January 8, 2017: Cell Medicine
https://www.readbyqxmd.com/read/28109058/in-vivo-construction-of-liver-tissue-by-implantation-of-a-hepatic-non-parenchymal-adipose-derived-stem-cell-sheet
#19
Mio Fujii, Kosho Yamanouchi, Yusuke Sakai, Zhassulan Baimakhanov, Izumi Yamaguchi, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Tamotsu Kuroki, Susumu Eguchi
Subcutaneous hepatocyte sheet implantation is an attractive therapeutic option for various liver diseases. However, this technique is limited by the availability of hepatocytes. Thus, the use of hepatic non-parenchymal cells (NPCs) containing small hepatocytes, which have the ability to proliferate more rapidly than mature hepatocytes, for transplantation has been suggested. The aim of our study was to construct liver tissue subcutaneously in rats by implanting NPC sheets co-cultivated with adipose-derived stem cells (ADSCs), which produce certain angiogenic factors...
January 21, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28105981/cryopreservation-of-hepatocyte-microbeads-for-clinical-transplantation
#20
Suttiruk Jitraruch, Anil Dhawan, Robin D Hughes, Celine Filippi, Sharon C Lehec, Leanne Glover, Ragai R Mitry
Intraperitoneal transplantation of hepatocyte microbeads is an attractive option for the management of acute liver failure. Encapsulation of hepatocytes in alginate microbeads supports their function and prevents immune attack of the cells. Establishment of banked cryopreserved hepatocyte microbeads is important for emergency use. The aim of this study was to develop an optimised protocol for cryopreservation of hepatocyte microbeads for clinical transplantation using modified freezing solutions. Four freezing solutions with potential for clinical application were investigated...
January 20, 2017: Cell Transplantation
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