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  1. Autophagy and Liver Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Raffaele Cursio

    2015-01-01

    Full Text Available Liver ischemia-reperfusion (I-R injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS, leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R.

  2. Effects of different periods of renal ischemia on liver as a remote organ

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    Mehri Kadkhodaee; Fereshteh Golab; Maryam Zahmatkesh; Rana Ghaznavi; Mehdi Hedayati; Hossein Ali Arab; Seyed Naser Ostad; Manoocher Soleimani

    2009-01-01

    AIM: To assess the hepatic changes after induction of different periods of renal ischemia. METHODS: Rats were subjected to either sham operation or ischemia (30, 45 and 60 rain) followed by 60 rain reperfusion. Liver and renal functional indices were measured. Hepatic glutathione (GSH) and ferric reducing antioxidant power levels and the concentration of interleukin (IL)-10 and tumor necrosis factor (TNF-α) were evaluated. Portions of liver and kidney tissues were fixed for histological evaluation.RESULTS: Forty-five minutes renal ischemia followed by 60 rain reperfusion caused significant changes in liver structure and a significant reduction in renal function. These rats showed a significant decrease inliver GSH, as well as a significant increase in TNF-α and IL-10 concentrations. These results demonstrated that renal ischemia caused changes in liver histology, function, oxidative stress and inflammatory status,which led to a reduction in hepatic antioxidant capacity. With 30 min ischemia, the magnitude of these changes was less than those with 45 or 60 min ischemia.CONCLUSION: A minimum of 45 min ischemia is needed to study the effects of renal injury on the liver as a remote organ.

  3. Melatonin protects liver from intestine ischemia reperfusion injury in rats

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    Jian-Yi Li; Hong-Zhuan Yin; Xi Gu; Yong Zhou; Wen-Hai Zhang; Yi-Min Qin

    2008-01-01

    AIM:To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats.METHODS:One hundred and fifty male Wistar rats,weighing 190-210 g,aged 7 wk,were randomly divided into melatonin exposure group,alcohol solvent control group and normal saline control group.Rats in the melatonin exposure group received intraperitoneal (IP) melatonin (20 mg/kg) 30 min before intestinal ischemia-reperfusion (IR),rats in the alcohol solvent control group received the same concentration and volume of alcohol,and rats in the normal saline control group received the same volume of normal saline.Serum samples were collected from each group 0.5,1,6,12,and 24 h after intestinal IR.Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured with an auto-biochemical analyzer.Serum TNF-a was tested by enzyme-linked immunosorbent assay (ELISA).Malondialdehyde (MDA) in liver was detected by colorimetric assay.Pathological changes in liver and immunohistochemical straining of ICAM-1 were observed under an optical microscope.RESULTS:The levels of ALT measured at various time points after intestinal IR in the melatonin exposure group were significantly lower than those in the other two control groups (P<0.05).The serum AST levels 12 and 24 h after intestinal IR and the ICAM-1 levels (%) 6,12 and 24 h after intestinal IR in the melatonin exposure group were also significantly lower than those in the other two control groups (P<0.05).CONCLUSION:Exotic melatonin can inhibit the activity of ALT,AST and TNF-a decrease the accumulation of MDA,and depress the expression of ICAM-1 in liver after intestinal IR injury,thus improving the liver function.

  4. Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats.

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    Fouad, Amr A; Jresat, Iyad

    2011-11-16

    The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5mg/kg, i.v.) was given 1h following the procedure and every 24h thereafter for 2 days. Ischemia/reperfusion caused significant elevations of serum alanine aminotransferase and hepatic malondialdehyde, tumor necrosis factor-α and nitric oxide levels, associated with significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters mediated by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced liver damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin protein in ischemic/reperfused liver tissue. These results emphasize that cannabidiol represents a potential therapeutic option to protect the liver against hypoxia-reoxygenation injury.

  5. Intestinal microflora in rats with ischemia/reperfusion liver injury

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    XING Hui-chun; LI Lan-juan; XU Kai-jin; SHEN Tian; CHEN Yun-bo; SHENG Ji-fang; YU Yun-song; CHEN Ya-gang

    2005-01-01

    Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin,intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied. Results: Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion: I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function,which contributes to endotoxemia and bacterial translocation to kidney.

  6. Can the rat donor liver tolerate prolonged warm ischemia ?

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    Ji Qi Yan; Hong Wei Li; Wei Yao Cai; Ming Jun Zhang; Wei Ping Yang

    2000-01-01

    The last two decades of the twentieth century have witnessed increasingly successful rates of liver transplantation. The number of liver transplantations has increased steadily while the number of organ donors has remained relatively constant. Thus a great disparity has developed between the demand and supply of donor organs and remains a major limiting factor for further expansion of liver transplantation. Although many procedures, such as split liver[1] , living-related transplantation[2] , and xenotransplantation[3], have been attempted clinically to overcome the shortage, it is hoped that livers harvested from non-heart-beating donors (NHBDs) would alleviatethe problem of organ shortage, which again becomes the focus of attention[4-9]. However, sensitivity of the liver to warm ischemia remains a major worry for use of theNHBDs. The aim of this animal study was to assess if murine liver could tolerate prolonged period of warm ischemia and to determine the optimum timing of intervention in the cadaver donor in order to preserve liver viability.

  7. Intermittent Ischemia but Not Ischemic Preconditioning Is Effective in Restoring Bile Flow After Ischemia Reperfusion Injury in the Livers of Aged Rats

    NARCIS (Netherlands)

    Schiesser, Marc; Wittert, Anna; Nieuwenhuijs, Vincent B.; Morphett, Arthur; Padbury, Robert T. A.; Barritt, Greg J.

    2009-01-01

    BackgroundlAims. Ischemic preconditioning (IPC) and intermittent ischemia (INT) reduce liver injury following ischemia reperfusion in liver resections. Aged livers are at higher risk for ischemia reperfusion injury, but little is known of the effectiveness of IPC and INT in aged livers. The aim of t

  8. Dynamical changing pattems of glycogen and enzyme histochemical activities in rat liver graft undergoing warm ischemia injury

    Institute of Scientific and Technical Information of China (English)

    Xiao-Shun He; Yi Ma; Lin-Wei Wu; Jin-Lang Wu; Rui-De Hu; Gui-Hua Chen; Jie-Fu Huang

    2005-01-01

    AIM: To investigate the changing patterns of glycogen and enzyme histochemical activities in rat liver graft under a dif ferent warm ischemia time (WIT) and to predict the tolerant time limitation of the liver graft to warm ischemia injury.METHODS: The rats were randomized into five groups, WTT was 0, 15, 30, 45, 60 min, respectively, and histochemical staining of liver graft specimens was observed. The recovery changes of glycogen and enzyme histochemistry activities were measured respectively 6 and 24 h following liver graft implantation.RESULTS: The activities of succinic dehydrogenase, cytochrome oxidase, apyrase (Mg++-ATPase) and content of glycogen were decreased gradually after different WIT in a time-dependent manner. The changes were significant when WIT was over 30 min.CONCLUSION: Hepatic injury is reversible within 30 min of warm ischemia injury. Glycogen and enzyme histochemistry activities of liver grafts and their recovery potency after reperfusion may serve as criteria to evaluate the quality of liver grafts.

  9. Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver

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    Fahrettin Yildiz; Alpaslan Terzi; Sacit Coban; Mustafa Ares,; Nurten Aksoy; Hale Cakir; Ali Riza Ocak; Muharrem Bitiren,

    2008-01-01

    AIM:To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver.METHODS:Thirty rats were divided into three groups as sham(Group 1),control(Group 2),and Nigella sativa(NS)treatment group(Group 3).All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion.Rats were intraperitoneally infused with only 0.9% saline solution in group 2.Rats in group 3 received NS(0.2 mL/kg)intraperitoneally,before ischemia and before reperfusion.Blood samples and liver tissues were harvested from the rats,and then the rats were sacrificed.Serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),and lactate dehydrogenase(LDH)Ievels were determined.Total antioxidant capacity(TAC),catalase(CAT),total oxidative status(TOS),oxidative stress index(OSI)and myeloperoxidase(MPO)in hepatic tissue were measured.Also liver tissue histopathology was evaluated by light microscopy.RESULTS:The levels of liver anzymes in group 3 were significantly lower than those in the group 2.TAC in liver tissue was significantly higher in group 3 than in group 2.TOS,OSI and MPO in hepatic tissue were significantly lower in group 3 than the group 2.Histo logical tissue damage was milder in the NS treatment group than that in the control group.CONCLUSION:Our results suggest that Nigella sativa treatment protects the rat liver against to hepatic ischemia-reperfusion injury.(C)2008 The WJG Press.All rights reserved.

  10. Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors

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    Xiao-Shun He; Yi Ma; Lin-Wei Wu; Wei-Qiang Ju; Jin-Lang Wu; Rui-De Hu; Gui-Hua Chen; Jie-Fu Huang

    2004-01-01

    AIM: To explore the dynamical changes of histology,histochemistry, energy metabolism, liver microcirculation,liver function and posttransplant survival of liver graft in rats under different warm ischemia times (WIT) and predict the maximum limitation of liver graft to warm ischemia.METHODS: According to WIT, the rats were randomized into 7 groups, with WIT of 0, 10, 15, 20, 30, 45, 60 min,respectively. The recovery changes of above-mentioned indices were observed or measured after liver transplantation. The graft survival and postoperative complications in each subgroup were analyzed.RESULTS: Liver graft injury was reversible and gradually resumed normal structure and function after reperfusion when WIT was less than 30 min. In terms of graft survival,there was no significant difference between subgroups within 30 min WIT. When WIT was prolonged to 45 min,the recipients' long-term survival was severely insulted,and both function and histological structure of liver graft developed irreversible damage when WIT was prolonged to 60 min.CONCLUSION: The present study indicates that rat liver graft can be safely subjected to warm ischemia within 30 min.The levels of ATP, energy charge, activities of glycogen,enzyme-histochemistry of liver graft and its recovery potency after reperfusion may serve as the important criteria to evaluate the quality of liver graft.

  11. The protective effect of niacinamide on ischemia-reperfusion-induced liver injury.

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    Chen, C F; Wang, D; Hwang, C P; Liu, H W; Wei, J; Lee, R P; Chen, H I

    2001-01-01

    Reperfusion of ischemic liver results in the generation of oxygen radicals, nitric oxide (NO) and their reaction product peroxynitrite, all of which may cause strand breaks in DNA, which activate the nuclear enzyme poly(ADP ribose)synthase (PARS). This results in rapid depletion of intracellular nicotinamide adenine dinucleotide and adenosine 5'-triphosphate (ATP) and eventually induces irreversible cytotoxicity. In this study, we demonstrated that niacinamide, a PARS inhibitor, attenuated ischemia/reperfusion (I/R)-induced liver injury. Ischemia was induced by clamping the common hepatic artery and portal vein of rats for 40 min. Thereafter, flow was restored and the liver was reperfused for 90 min. Blood samples collected prior to I and after R were analyzed for methyl guanidine (MG), NO, tumor necrosis factor (TNF-alpha) and ATP. Blood levels of aspartate transferase (AST), alanine transferase (ALT) and lactate dehydrogenase (LDH) which served as indexes of liver injury were measured. This protocol resulted in elevation of the blood NO level (p niacinamide (10 mM), liver injury was significantly attenuated, while blood ATP content was reversed. In addition, MG, TNF-alpha and NO release was attenuated. These results indicate that niacinamide, presumably by acting with multiple functions, exerts potent anti-inflammatory effects in I/R-induced liver injury.

  12. Melatonin treatment protects liver of Zucker rats after ischemia/reperfusion by diminishing oxidative stress and apoptosis.

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    Kireev, Roman; Bitoun, Samuel; Cuesta, Sara; Tejerina, Alejandro; Ibarrola, Carolina; Moreno, Enrique; Vara, Elena; Tresguerres, Jesus A F

    2013-02-15

    Fatty livers occur in up to 20% of potential liver donors and increase cellular injury during the ischemia/reperfusion phase, so any intervention that could enable a better outcome of grafts for liver transplantation would be very useful. The effect of melatonin on liver ischemia/reperfusion injury in a rat model of obesity and hepatic steatosis has been investigated. Forty fa/fa Zucker rats were divided in 4 groups. 3 groups were subjected to 35 min of warm hepatic ischemia and 36 h of reperfusion. One experimental group remained untreated and 2 were given 10mg/kg melatonin intraperitoneally or orally. Another group was sham-operated. Plasma ALT, AST and hepatic content of ATP, MDA, hydroxyalkenals, NOx metabolites, antioxidant enzyme activity, caspase-9 and DNA fragmentation were determined in the liver. The expression of iNOS, eNOS, Bcl2, Bax, Bad and AIF were determined by RT-PCR Melatonin was effective at decreasing liver injury by both ways as assessed by liver transaminases, markers of apoptosis, of oxidative stress and improved liver ATP content. Melatonin administration decreased the activities or levels of most of the parameters measured in a beneficial way, and our study identified also some of the mechanisms of protection. We conclude that administration of melatonin improved liver function, as well as markers of pro/antioxidant status and apoptosis following ischemia/reperfusion in obese rats with fatty liver. These data suggest that this substance could improve outcome in patients undergoing liver transplantation who receive a fatty liver implant and suggest the need of clinical trials with it in liver transplantation. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Prolonged Ischemia Triggers Necrotic Depletion of Tissue-Resident Macrophages To Facilitate Inflammatory Immune Activation in Liver Ischemia Reperfusion Injury.

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    Yue, Shi; Zhou, Haoming; Wang, Xuehao; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Zhai, Yuan

    2017-05-01

    Although mechanisms of immune activation against liver ischemia reperfusion (IR) injury (IRI) have been studied extensively, questions regarding liver-resident macrophages, that is, Kupffer cells (KCs), remain controversial. Recent progress in the biology of tissue-resident macrophages implicates homeostatic functions of KCs. This study aims to dissect responses and functions of KCs in liver IRI. In a murine liver partial warm ischemia model, we analyzed liver-resident versus infiltrating macrophages by FACS and immunofluorescence staining. Our data showed that liver immune activation by IR was associated with not only infiltrations/activations of peripheral macrophages, but also necrotic depletion of KCs. Inhibition of receptor-interacting protein 1 (RIP1) by necrostatin-1s protected KCs from ischemia-induced depletion, resulting in the reduction of macrophage infiltration, suppression of proinflammatory immune activation, and protection of livers from IRI. The depletion of KCs by clodronate liposomes abrogated the effect of necrostatin-1s. Additionally, liver reconstitutions with KCs postischemia exerted anti-inflammatory/cytoprotective effects against IRI. These results reveal a unique response of KCs against liver IR, that is, RIP1-dependent necrosis, which constitutes a novel mechanism of liver inflammatory immune activation in the pathogenesis of liver IRI. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. Nebivolol and chrysin protect the liver against ischemia/reperfusion-induced injury in rats

    Directory of Open Access Journals (Sweden)

    Sayed M. Mizar

    2015-03-01

    Full Text Available Oxidative stress plays a key role in the pathogenesis of hepatic ischemia/reperfusion (I/R-induced injury, one of the leading causes of liver damage post-surgical intervention, trauma and transplantation. This study aimed to evaluate the protective effect of nebivolol and chrysin against I/R-induced liver injury via their vasodilator and antioxidant effects, respectively. Adult male Wister rats received nebivolol (5 mg/kg and/or chrysin (25 mg/kg by oral gavage daily for one week then subjected to ischemia via clamping the portal triad for 30 min then reperfusion for 30 min. Liver function enzymes, alanine transaminase (ALT and aspartate transaminase (AST, as well as hepatic Myeloperoxidase (MPO, total nitrate (NOx, glutathione (GSH and liver malondialdehyde (MDA were measured at the end of the experiment. Liver tissue damage was examined by histopathology. In addition, the expression levels of nitric oxide synthase (NOS subtypes, endothelial (eNOS and inducible (iNOS in liver samples were assessed by Western blotting and confirmed by immunohistochemical analysis. Both chrysin and nebivolol significantly counteracted I/R-induced oxidative stress and tissue damage biomarkers. The combination of these agents caused additive liver protective effect against I/R-induced damage via the up regulation of nitric oxide expression and the suppression of oxidative stress. Chrysin and nebivolol combination showed a promising protective effect against I/R-induced liver injury, at least in part, via decreasing oxidative stress and increasing nitric oxide levels.

  15. Ischemia and reperfusion injury of the rat liver: the role of nimodipine.

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    Chávez-Cartaya, R E; Pino DeSola, G; Ramirez-Romero, P; Calne, R Y; Jamieson, N V

    1996-01-01

    The protective effect of the calcium channel blocker nimodipine on liver ischemia and reperfusion was studied in the rat. The homeostasis of intracellular calcium ions seems to be a determinant factor in the cell injury that appears after ischemia and reperfusion. Nimodipine was used to downregulate the calcium levels in the cytosol of the ischemic cell, the hypothetical role of Ca2+ in the pathogenesis of ischemia and reperfusion injury. The experimental procedure consisted of the temporary interruption of blood flow to the left lateral and medial lobes of the rat liver and subsequent reperfusion after a period of 45 min of ischemia. Nimodipine (10 micrograms/kg body wt) was administered either before or after the onset of ischemia. The postischemic liver blood flow and liver oxyhemoglobin saturation were recorded using a He-Ne laser Doppler flowmeter and photometer, which showed, in the pretreated group, a recovery of reperfusion blood flow (58.1%) and liver reflectance (85.5%) significantly better (P flow (32.8%) and reflectance (70.5%). In the group that received nimodipine after ischemia, the recovery of the blood flow and the postreperfusion liver reflectance were not significantly better than those in the untreated control group. ALT levels (P < 0.05), galactose elimination capacity (P < 0.001), and histological studies also showed a protective effect of calcium antagonist nimodipine when administered before ischemia.

  16. Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury

    NARCIS (Netherlands)

    Olthof, Pim B.; Golen, van Rowan F.; Meijer, Ben; Beek, van Adriaan A.; Bennink, Roelof J.; Verheij, Joanne; Gulik, van Thomas M.; Heger, Michal

    2017-01-01

    Background

    Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse

  17. Biliary tract injury caused by different relative warm ischemia time in liver transplantation in rats

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    Hong-Feng Zhao; Guo-Wei Zhang; Jie Zhou; Jian-Hua Lin; Zhong-Lin Cui; Xiang-Hong Li

    2009-01-01

    BACKGROUND: There is a controversy over the degree of liver and biliary injury caused by the period of secondary warm ischemia. A liver autotransplantation model was adopted because it excludes the effects of infection and immunological rejection on bile duct injury. This study was undertaken to assess biliary tract injury caused by relative warm ischemia (secondary warm ischemia time in the biliary tract) and reperfusion. METHODS: One hundred and two rats were randomly divided into 5 groups: groupⅠ (control); groupsⅡ toⅤ, relative warm ischemia times of 0 minute, 30 minutes, 1 hour and 2 hours. In addition to the levels of serum alkaline phosphatase, and total bilirubin, pathomorphology assessment and TUNEL assay were performed to evaluate biliary tract damage. RESULTS: Under the conditions that there were no signiifcant differences in warm ischemia time, cold perfusion time and anhepatic phase, group comparisons showed statistically signiifcant differences. The least injury occurred in groupⅡ (portal vein and hepatic artery reperfused simultaneously) but the most severe injury occurred in groupⅤ (biliary tract relative warm ischemia time 2 hours). CONCLUSIONS: Relative warm ischemia is one of the factors that result in bile duct injury, and the relationship between relative warm ischemia time the bile injury degree is time-dependent. Simultaneous arterial and portal reperfusion is the best choice to avoid the bile duct injury caused by relative warm ischemia.

  18. Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver

    DEFF Research Database (Denmark)

    Møller, Lin Nanna Okholm; Knudsen, Anders Riegels; Andersen, Kasper Jarlhelt

    2015-01-01

    , high dose dexamethasone, low dose dexamethasone or placebo intravenously 18 h before laparotomy with subsequent 60 min of liver ischemia. After reperfusion for 24 h the animals had their liver removed. Bloods were drawn 30 min and 24 h post ischemia induction. Liver cell apoptosis and necrosis were...

  19. Oleanolic acid attenuates liver ischemia reper-fusion injury by HO-1/Sesn2 signaling pathway

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    Bao-Bin Hao; Xiong-Xiong Pan; Ye Fan; Ling Lu; Xiao-Feng Qian; Xue-Hao Wang; Feng Zhang; Jian-Hua Rao

    2016-01-01

    BACKGROUND: Ischemia reperfusion injury (IRI) is unavoid-able in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI. METHODS: Mice were randomly divided into 6 groups based on different treatment. IRI model: The hepatic artery, portal vein, and bile duct to the left and median liver lobes (70% of the liver) were occluded with an atraumatic bulldog clamp for 90 minutes and then the clamp was removed for reperfusion. The mice were sacriifced 6 hours after reperfusion, and blood and liver tissues were collected. Liver injury was evaluated by biochemical and histopathologic examinations. The expressions of Sesn2, PI3K, Akt and heme oxygenase-1 (HO-1) were mea-sured with quantitative real-time RT-PCR and Western blotting. RESULTS: The serum aminotransferases level and scores of he-patic histology were increased after reperfusion. The increase was attenuated by pretreatment with OA (P CONCLUSIONS: Our results demonstrate that OA can attenu-ate hepatic IRI. The protective mechanism may be related to the OA-induced HO-1/Sesn2 signaling pathway.

  20. Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?

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    Peter Onody

    Full Text Available INTRODUCTION: Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury. MATERIAL AND METHODS: Levosimendan was administered to male Wistar rats 1 hour (early pretreatment or 24 hours (late pretreatment before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured. RESULTS: In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (p early = 0.02; p late = 0.005, AST (p early = 0.02; p late = 0.004 and less DNA damage by TUNEL test (p early = 0.05; p late = 0.034 and PAR positivity (p early = 0.02; p late = 0.04. Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment. CONCLUSION: Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection.

  1. Protective effect of salvianolate on lung injury induced by ischemia reperfusion injury of liver in mice

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    Zheng-xin WANG

    2011-11-01

    Full Text Available Objective To evaluate the protective effect of salvianolate on lung injury induced by hepatic ischemia reperfusion(IR injury in mice and its underlying mechanisms.Methods A hepatic IR model of mice was reproduced,and 24 animals were assigned into 3 groups(8 each: sham operation(SO group,control group and salvianolate(SV group.Just before ischemia induction,animals in SV group received salvianolate injection at a dose of 60 mg/kg via tail vein,while in control group the mice received normal saline with an equal volume,and in SO group the mice received the same operation as in SV group but without producing liver ischemia.Four hours after reperfusion,the serum,liver and lung tissue were collected.The alanine aminotransferase(ALT and aspartate aminotransferase(AST levels in serum were detected and the histological changes in liver and lung were examined.The wet-to-dry weight ratio of pulmonary tissue was measured.The contents of tumor necrosis factor α(TNF-α,interleukin(IL-6,IL-1β and IL-10 in bronchoalveolar lavage fluid(BALF were detected by enzyme linked immunosorbent assay(ELISA,and the relative mRNA levels of TNF-α,IL-6,IL-1β and IL-10 in pulmonary tissue were analyzed by real-time reverse transcription PCR(RT-PCR.The activaty of transcription factor NF-κB was measured with Western blotting analysis.Results No significant pathologic change was found in mice of SO group.Compared with the mice in control group,those in SV group exhibited lower levels of ALT and AST(P < 0.01,lighter histological changes in liver and lung(P < 0.05,lower levels of wet-to-dry weight ratio of lung tissue(P < 0.05,lower expression levels of TNF-α,IL-6,IL-1β and IL-10 in BALF and lung tissue(P < 0.05 or P < 0.01.Further examination demonstrated that the activity of NF-κB in SV group was significantly down-regulated as compared with that in control group.Conclusion Salvianolate can attenuate lung injury induced by hepatic IR in mice,the mechanism may inclade

  2. Effects of isoflurane on ICAM-1 expression and neutrophils infiltration in rats with liver ischemia and reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Xu Guangmin; Tao Guocai

    2009-01-01

    Objective: To establish a rat model of warm partial hepatic ischemia-reperfusion (IR), and investigate the protective and anti-inflammatory effects of isoflurane on warm hepatic ischemia-reperfusion injury (IRI) in rats. Methods: Thirty-two female Sprague-Dawley rots were divided equally into 4 groups (n=8): PB-Sham group in which the rats were anesthetized by intraperitoneal injection of pentobarbital sodium (1.0%, 40 mg/kg, PB) and received a sham operation without occlusion of liver blood flow; PB-IR group whose rats underwent partial hepatic IR after anesthesia; Iso-Sham group in which inhalation of 1.0 MAC isoflurane and sham operation was performed; Iso-IR group in which 1.0 MAC isoflurane was inhaled for 4 h and IR was performed. Rat model of warm partial hepatic IR was established by clamping the hepatic arteries and hilar vessels distributing to the left and median lobes to induce partial hepatic ischemia (70%) for 60 min followed by reperfusion for 3 h. The rats were killed 3 h after declamping, and specimens of liver tissue and blood were obtained. The serum ALT and AST were detected as liver damage markers. Viability of myeloperoxidase (MPO) in liver was measured. The protein level of ICAM-1 in the liver was detected by immunohistochemistry and Western blotting. Results: Rats treated with 1.0 MAC isoflurane during warm partial (70%) hepatic ischemia 60 min and 3 h reperfusion had significantly lower serum ALT and AST compared with rats anesthetized with pentobarbital sodium subjected to hepatic IRI. The expression of ICAM-1 in hepatic tissue was significantly increased by hepatic IRI after pentobarbital sodium anesthesia. Isoflurane significantly inhibited protein expression of ICAM-1 in hepatic IR injury compared with pentobarbital sodium anesthesia. Viability of liver MPO was significantly increased by hepatic IRI after pentobarbital sodium anesthesia; Isoflurane can significantly inhibit MPO alteration in rat liver ischemia-reperfusion injury

  3. Myeloid PTEN deficiency protects livers from ischemia reperfusion injury by facilitating M2 macrophage differentiation.

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    Yue, Shi; Rao, Jianhua; Zhu, Jianjun; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

    2014-06-01

    Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in regulating cell proliferation is well established, its function in immune responses remains to be fully appreciated. In the current study, we analyzed myeloid-specific PTEN function in regulating tissue inflammatory immune response in a murine liver partial warm ischemia model. Myeloid-specific PTEN knockout (KO) resulted in liver protection from ischemia reperfusion injury (IRI) by deviating the local innate immune response against ischemia reperfusion toward the regulatory type: expression of proinflammatory genes was selectively decreased and anti-inflammatory IL-10 was simultaneously increased in ischemia reperfusion livers of PTEN KO mice compared with those of wild-type (WT) mice. PI3K inhibitor and IL-10-neutralizing Abs, but not exogenous LPS, recreated liver IRI in these KO mice. At the cellular level, Kupffer cells and peritoneal macrophages isolated from KO mice expressed higher levels of M2 markers and produced lower TNF-α and higher IL-10 in response to TLR ligands than did their WT counterparts. They had enhanced Stat3- and Stat6-signaling pathway activation, but diminished Stat1-signaling pathway activation, in response to TLR4 stimulation. Inactivation of Kupffer cells by gadolinium chloride enhanced proinflammatory immune activation and increased IRI in livers of myeloid PTEN KO mice. Thus, myeloid PTEN deficiency protects livers from IRI by facilitating M2 macrophage differentiation.

  4. Effects of a Preconditioning Oral Nutritional Supplement on Pig Livers after Warm Ischemia

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    Arash Nickkholgh

    2012-01-01

    Full Text Available Background. Several approaches have been proposed to pharmacologically ameliorate hepatic ischemia/reperfusion injury (IRI. This study was designed to evaluate the effects of a preconditioning oral nutritional supplement (pONS containing glutamine, antioxidants, and green tea extract on hepatic warm IRI in pigs. Methods. pONS (70 g per serving, Fresenius Kabi, Germany was dissolved in 250 mL tap water and given to pigs 24, 12, and 2 hrs before warm ischemia of the liver. A fourth dose was given 3 hrs after reperfusion. Controls were given the same amount of cellulose with the same volume of water. Two hours after the third dose of pONS, both the portal vein and the hepatic artery were clamped for 40 min. 0.5, 3, 6, and 8 hrs after reperfusion, heart rate (HR, mean arterial pressure (MAP, central venous pressure (CVP, portal venous flow (PVF, hepatic arterial flow (HAF, bile flow, and transaminases were measured. Liver tissue was taken 8 hrs after reperfusion for histology and immunohistochemistry. Results. HR, MAP, CVP, HAF, and PVF were comparable between the two groups. pONS significantly increased bile flow 8 hrs after reperfusion. ALT and AST were significantly lower after pONS. Histology showed significantly more severe necrosis and neutrophil infiltration in controls. pONS significantly decreased the index of immunohistochemical expression for TNF-α, MPO, and cleaved caspase-3 (<0.001. Conclusion. Administration of pONS before and after tissue damage protects the liver from warm IRI via mechanisms including decreasing oxidative stress, lipid peroxidation, apoptosis, and necrosis.

  5. Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver.

    Science.gov (United States)

    Flendrig, L M; Calise, F; Di Florio, E; Mancini, A; Ceriello, A; Santaniello, W; Mezza, E; Sicoli, F; Belleza, G; Bracco, A; Cozzolino, S; Scala, D; Mazzone, M; Fattore, M; Gonzales, E; Chamuleau, R A

    1999-10-01

    Aim of the study was to evaluate treatment efficacy and safety of a scaled-up version of our porcine hepatocytes based BAL system in pigs with complete liver ischemia (LIS). Thirty-one pigs underwent total devascularization of the liver (LIS) by termino-lateral porta-caval shunts and sutures around the bile duct, the common hepatic and gastroduodenal arteries and their accessory branches. The hepato-duodenal ligament was completely transected. Four experimental groups were studied: the first control group (LIS Control, n = 10) received glucose infusion only, the second control group (LIS Plasmapheresis, n = 8) was connected to a centrifugal plasma-separator with a bottle representing the bioreactor volume, the third control group (LIS Empty-BAL, n = 5) received BAL treatment without cells, and the treated group (LIS Cell-BAL, n = 8) was connected for a maximum period of 24 hours to our scaled-up BAL seeded with around 14 billion viable primary porcine hepatocytes. BAL treatment significantly prolonged life in large animals (approximately 35 kg) with complete LIS (Controls, mean +/- SEM: 33.1 +/- 3 h, Cell-BAL: 51.1 +/- 3.4 h; p = 0.001; longest survivor 63 h). In addition, blood ammonia and total bilirubin levels decreased significantly, indicating metabolic activity of porcine hepatocytes in the bioreactor. No significant differences were noticed among the three control groups, indicating that there was no device effect and that the plasmapheresis procedure was well tolerated. No important adverse effects were observed.

  6. Gastric ischemia after epinephrine injection in a patient with liver cirrhosis

    Science.gov (United States)

    Kim, Su Young; Han, Seung-Hee; Kim, Kyung Han; Kim, Sang Ock; Han, Sang-Young; Lee, Sung-Wook; Baek, Yang Hyun

    2013-01-01

    Endoscopic epinephrine injection is relatively easy, quick and inexpensive. Furthermore, it has a low rate of complications, and it is widely used for the management of nonvariceal upper gastrointestinal bleeding. There have been several case reports of gastric ischemia after endoscopic injection therapy. Inadvertent intra-arterial injection may result in either spasm or thrombosis, leading to subsequent tissue ischemia or necrosis, although the stomach has a rich vascular supply and the vascular reserve of the intramural anastomosis. In addition to endoscopic injection therapy, smoking, hypertension and atherosclerosis are risk factors of gastric ischemia. We report a case of gastric ischemia after submucosal epinephrine injection in a 51-year-old woman with hypertension and liver cirrhosis. PMID:23372366

  7. Prolonging warm ischemia reduces the cold preservation limits of liver grafts in swine

    Institute of Scientific and Technical Information of China (English)

    De-Ke Qing

    2006-01-01

    BACKGROUND:The critical shortage of transplantable organs necessitates utilization of unconventional donors. But the safe time limits of cold preservation of liver grafts subjected to warm ischemia (WI) for up to 30 minutes from non-heart-beating-donors (NHBDs) has not been delineated. In this study, we investigated how the limits of cold ischemia (CI) in University of Wisconsin (UW) solution are changed in liver grafts subjected to WI from 10 to 30 minutes. METHODS:A simple porcine NHBD liver transplantation (LT) model was developed. In donors, livers were subjected to 10, 20 or 30 minutes of WI and subsequent different times of CI in UW solution. Animals were divided into three groups (WI 10 min, WI 20 min, WI 30 min, n=13 in each group) and nine subgroups (from CI 6 h to CI 28 h). One-week survival rates of recipients, hepatic function, liver energy metabolism, grafted liver microcirculation and pathological observations of the liver were compared. RESULTS:In the WI 10 min group, the one-week survival rate of the CI 20 h subgroup was signiifcantly higher than in the other two subgroups (CI 24 h and CI 28 h) (P CONCLUSIONS: The cold preservation limits of the liver grafts shortened from 20 to 12 to 6 hours when WI time was prolonged from 10 to 20 to 30 minutes. Only the liver grafts within these time limits could be safely transplanted.

  8. Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of resveratrol on liver ischemia/reperfusion (I/R) injury in rats. METHODS: A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups often: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats underwent liver ischemia for 45 min followed by reperfu-sion for 45 min; (4) I-R/Resveratrol group: rats pretreat-ed with resveratrol (10 μmol/L, iv). Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS: Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratrol-treated livers.CONCLUSION: These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusion-related liver injury.

  9. S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver

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    Wellington Andraus

    2010-01-01

    Full Text Available BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC, an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8, IR in normal liver; II (n=8, IR in normal liver with SNAC; III (n=9, IR in steatotic liver; IV (n=9, IR in steatotic liver with SNAC; and V (n=10, SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70% liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA, and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02. CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

  10. Short fasting does not protect perfused ex vivo rat liver against ischemia-reperfusion. On the importance of a minimal cell energy charge.

    Science.gov (United States)

    Papegay, Bérengère; Stadler, Michaela; Nuyens, Vincent; Kruys, Véronique; Boogaerts, Jean G; Vamecq, Joseph

    2017-03-01

    Dietary restriction or reduced food intake was supported to protect against renal and hepatic ischemic injury. In this vein, short fasting was recently shown to protect in situ rat liver against ischemia-reperfusion. Here, perfused ex vivo instead of in situ livers were exposed to ischemia-reperfusion to study the impact of disconnecting liver from extrahepatic supply in energetic substrates on the protection given by short-term fasting. Perfused ex vivo livers using short (18 h) fasted compared with fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate. Energetic stores are differently available in time and cell energetic charges (ratio of adenosine triphosphate plus half of the adenosine diphosphate concentrations to the sum of adenosine triphosphate + adenosine diphosphate + adenosine monophosphate concentrations), adenosine phosphates, and glycogen, which were further measured at different time points in livers. Short fasting versus feeding failed to protect perfused ex vivo rat livers against ischemia/reperfusion, increasing the release of cytolysis markers (potassium, cytochrome c, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) in the perfusate during reoxygenation phase. Toxicity of short fasting versus feeding was associated with lower glycogen and energetic charges in livers and lower lactate levels in the perfusate. High energetic charge, intracellular content in glycogen, and glycolytic activity may protect liver against ischemia/reperfusion injury. This work does not question how much the protective role previously demonstrated in the literature for dietary restriction and short fasting. In fact, it suggests that exceeding the energy charge threshold value of 0.3 might trigger the effectiveness of this protective role. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Erythropoietin reduces ischemia-reperfusion injury after liver transplantation in rats.

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    Schmeding, Maximilian; Hunold, Gerhard; Ariyakhagorn, Veravoorn; Rademacher, Sebastian; Boas-Knoop, Sabine; Lippert, Steffen; Neuhaus, Peter; Neumann, Ulf P

    2009-07-01

    Human recombinant Erythropoietin (rHuEpo) has recently been shown to be a potent protector of ischemia- reperfusion injury in warm-liver ischemia. Significant enhancement of hepatic regeneration and survival after large volume partial hepatic resection has also been demonstrated. It was the aim of this study to evaluate the capacities of rHuEpo in the setting of rat liver transplantation. One-hundred-and-twenty Wistar rats were used: 60 recipients received liver transplantation following donor organ treatment (60 donors) with either 1000 IU rHuEpo or saline injection (controls) into portal veins (cold ischemia 18 h, University of Wisconsin (UW) solution). Recipients were allocated to two groups, which either received 1000 IU rHuEpo at reperfusion or an equal amount of saline (control). Animals were sacrificed at defined time-points (2, 4.5, 24, 48 h and 7 days postoperatively) for analysis of liver enzymes, histology [hematoxylin-eosin (HE) staining, periodic acid Schiff staining (PAS)], immunostaining [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Hypoxyprobe] and real-time polymerase chain reaction (RT-PCR) of cytokine mRNA (IL-1, IL-6). Lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) values were significantly reduced among the epo-treated animals 24 and 48 h after liver transplantation (LT). The TUNEL and Hypoxyprobe analyses as well as necrotic index evaluation displayed significant reduction of apoptosis and necrosis in rHuEpo-treated graft livers. Erythropoietin reduces ischemia-reperfusion injury after orthotopic liver transplantation in rats.

  12. The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury

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    Zhijie Xu

    2016-04-01

    Full Text Available Background: Propofol and sevoflurane are widely used in clinical anesthesia, and both have been reported to exert a protective effect in organ ischemia/reperfusion (IR. This study aims to investigate and compare the effects of propofol and sevoflurane on liver ischemia/reperfusion and the precise molecular mechanism. Methods and Materials: Rats were randomized into four groups: the sham group, I/R group, propofol treatment group (infused with 1% propofol at 500 µg· kg-1· min-1, and sevoflurane treatment group (infused with 3% (2 L/min sevoflurane. The liver ischemia/reperfusion model was used to evaluate the hepatoprotective effect on ischemic injury. Liver enzyme leakage, liver cytokines and histopathological examination were used to evaluate the extent of hepatic ischemia/reperfusion injury. Oxidative stress was investigated by evaluating the levels of Malondialdehyde(MDA, Superoxide Dismutase(SOD and NO. The terminal dexynucleotidyl transferase(TdT-mediated dUTP nick end labeling (TUNEL assay and western blot were applied to detect apoptosis in the ischemic liver tissue and its mechanism. Results: Both propofol and sevoflurane attenuated the extent of hepatic ischemia/reperfusion injury which is evident from the hisopathological studies and alterations in liver enzymes such as AST and LDH by inhibiting Nuclear factor kappa B (NFκB activation and subsequent alterations in inflammatory cytokines interleukin-1(IL-1, interleukin-6(IL-6, tumor necrosis factor-alpha (TNF-a and increased IL10 release. Propofol exhibited a similar protective effect and a lower IL-1 release, while sevoflurane decreased TNF-a leakage more significantly. Meanwhile, oxidative stress was attenuated by reduced MDA and NO and elevated SOD release. The expression of antiapoptotic protein Bcl-2 and Bcl-xl were enhanced while that of apoptotic protein Bax and Bak were reduced by both propofol and sevoflurane to regulate hepatic apoptosis. In addition, propofol

  13. Nitrite enhances liver graft protection against cold ischemia ...

    African Journals Online (AJOL)

    Amani Cherif-Sayadi

    2017-03-30

    Mar 30, 2017 ... Introduction: Nitrite has been found to protect liver graft from cold preservation injury. However, ..... Relevance of epidermal growth factor to improve stea- totic liver ... [19] Li H, Sun -J-J, Chen G-Y, et al. Carnosic acid nanoparti ...

  14. Ischemia

    Science.gov (United States)

    Byeon, Suk Ho; Kim, Min; Kwon, Oh Woong

    "Ischemia" implies a tissue damage derived from perfusion insufficiency, not just an inadequate blood supply. Mild thickening and increased reflectivity of inner retina and prominent inner part of synaptic portion of outer plexiform layer are "acute retinal ischemic changes" visible on OCT. Over time, retina becomes thinner, especially in the inner portion. Choroidal perfusion supplies the outer portion of retina; thus, choroidal ischemia causes predominant change in the corresponding tissue.

  15. Drag reducing polymers decrease hepatic injury and metastases after liver ischemia-reperfusion

    Science.gov (United States)

    Yazdani, Hamza O.; Sud, Vikas; Goswami, Julie; Loughran, Patricia; Huang, Hai; Simmons, Richard L.; Tsung, Allan

    2017-01-01

    Introduction Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment. We hypothesize that DRP can potentially be used to ameliorate metastatic capture of tumor cells and tumor growth within the I/R liver. Methods Experiments were performed utilizing a segmental ischemia model of mice livers. Five days prior or immediately prior to ischemia, murine colon adenocarcinoma cells (MC38) were injected into the spleen. DRP (polyethylene oxide) or a control of low-molecular-weight polyethylene glycol without drag reducing properties were administered intraperitoneally at the onset of reperfusion. Results After three weeks from I/R, we observed that liver I/R resulted in an increased ability to capture and foster growth of circulating tumor cells; in addition, the growth of pre-existing micrometastases was accelerated three weeks later. These effects were significantly curtailed when mice were treated with DRPs at the time of I/R. Mechanistic investigations in vivo indicated that DRPs protected the livers from I/R injury as evidenced by significant decreases in hepatocellular damage, neutrophil recruitment into the liver, formation of neutrophil extracellular traps, deposition of platelets, formation of microthrombi within the liver sinusoids and release of inflammatory cytokines

  16. Drag reducing polymers decrease hepatic injury and metastases after liver ischemia-reperfusion.

    Science.gov (United States)

    Tohme, Samer; Kameneva, Marina V; Yazdani, Hamza O; Sud, Vikas; Goswami, Julie; Loughran, Patricia; Huang, Hai; Simmons, Richard L; Tsung, Allan

    2017-08-29

    Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment. We hypothesize that DRP can potentially be used to ameliorate metastatic capture of tumor cells and tumor growth within the I/R liver. Experiments were performed utilizing a segmental ischemia model of mice livers. Five days prior or immediately prior to ischemia, murine colon adenocarcinoma cells (MC38) were injected into the spleen. DRP (polyethylene oxide) or a control of low-molecular-weight polyethylene glycol without drag reducing properties were administered intraperitoneally at the onset of reperfusion. After three weeks from I/R, we observed that liver I/R resulted in an increased ability to capture and foster growth of circulating tumor cells; in addition, the growth of pre-existing micrometastases was accelerated three weeks later. These effects were significantly curtailed when mice were treated with DRPs at the time of I/R. Mechanistic investigations in vivo indicated that DRPs protected the livers from I/R injury as evidenced by significant decreases in hepatocellular damage, neutrophil recruitment into the liver, formation of neutrophil extracellular traps, deposition of platelets, formation of microthrombi within the liver sinusoids and release of inflammatory cytokines. DRPs significantly attenuated

  17. U-74389G PRETREATMENT ATTENUATING WARM ISCHEMIA INJURY IN LIVER TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    严佶祺; 李宏为; 张明钧; 杨卫平; 蔡伟耀; 林言箴

    2002-01-01

    Objective To investigate the protective role of lazaroid U-74389G pretreatment against warm ischemia injury of rat liver transplantation from non-heart-beating donors. Methods Rat othortopic liver transplantation was perfomed in 4 groups (N-45, N-60 , pN-45 and pN-60 ), according to pretreatrnent with U-74389G or not, and the non-heart-beating time 45min or 60min before donor liver harvested. Survival rates, liver functions, MDA values and graft pathology of each group were compared. Results The oneweek survival rates ofGroupN-45, N-60 , pN-45 and pN-60 were25% (2/8), 0% (0/8), 58.3% (7/12)and 33.3% ( 4/12 ), respectively. U-74389G pretreatment significantly increased survival rate of rat liver transplantation from non-heart-beating donors, but also improved liver functions atd graft pathologies, as well as decreased MDA expression. Conclusion U-74389G pretreatment could attenuate warm ischemia reperfusion injury of rat liver transplantation from non-heart-beating donors.

  18. Retinol binding protein 4 and retinol in steatotic and nonsteatotic rat livers in the setting of partial hepatectomy under ischemia/reperfusion.

    Science.gov (United States)

    Elias-Miró, Maria; Massip-Salcedo, Marta; Raila, Jens; Schweigert, Florian; Mendes-Braz, Mariana; Ramalho, Fernando; Jiménez-Castro, Mónica B; Casillas-Ramírez, Araní; Bermudo, Raquel; Rimola, Antoni; Rodes, Juan; Peralta, Carmen

    2012-10-01

    Steatotic livers show increased hepatic damage and impaired regeneration after partial hepatectomy (PH) under ischemia/reperfusion (I/R), which is commonly applied in clinical practice to reduce bleeding. The known function of retinol-binding protein 4 (RBP4) is to transport retinol in the circulation. We examined whether modulating RBP4 and/or retinol could protect steatotic and nonsteatotic livers in the setting of PH under I/R. Steatotic and nonsteatotic livers from Zucker rats were subjected to PH (70%) with 60 minutes of ischemia. RBP4 and retinol levels were measured and altered pharmacologically, and their effects on hepatic damage and regeneration were studied after reperfusion. Decreased RBP4 levels were observed in both liver types, whereas retinol levels were reduced only in steatotic livers. RBP4 administration exacerbated the negative consequences of liver surgery with respect to damage and liver regeneration in both liver types. RBP4 affected the mobilization of retinol from steatotic livers, and this revealed actions of RBP4 independent of simple retinol transport. The injurious effects of RBP4 were not due to changes in retinol levels. Treatment with retinol was effective only for steatotic livers. Indeed, retinol increased hepatic injury and impaired liver regeneration in nonsteatotic livers. In steatotic livers, retinol reduced damage and improved regeneration after surgery. These benefits of retinol were associated with a reduced accumulation of hepatocellular fat. Thus, strategies based on modulating RBP4 could be ineffective and possibly even harmful in both liver types in the setting of PH under I/R. In terms of clinical applications, a retinol pretreatment might open new avenues for liver surgery that specifically benefit the steatotic liver.

  19. Difference in hepatic tissue oxygenation between total vascular exclusion and inflow occlusion of the liver and the possible role of hepatic venous blood under liver ischemia.

    Science.gov (United States)

    Sato, T; Asanuma, Y; Kusano, T; Sasaki, N; Shindo, Y; Koyama, K

    1998-01-01

    The difference between total vascular exclusion (TVE) and inflow occlusion (IO) of the liver was assessed by the extent of DNA injury in rats and by hepatic tissue oxygen saturation (SahtO2) in pigs. Moreover, the role of hepatic venous blood under liver ischemia was discussed. Seventy percent of the rat livers were exposed to complete IO (hepatic artery + portal vein) or to TVE (IO + hepatic vein) for 30 or 60 min. DNA strand breaks following blood flow interception were measured using the in situ nick translation technique as an indicator of liver damage. IO/TVE were performed on pigs as well under portosystemic bypass, and the oxygen saturation of the hepatic venous blood (SahvO2) was altered by changing the fraction of inspiratory oxygen or by oxygenating the inferior caval blood using an extracorporeal membrane oxygenator. The changes in SahtO2 were measured sequentially using near-infrared spectroscopy. The results were as follows: (1) DNA injury occurred more severely under TVE than under IO of the rat liver at the end of ischemia, as well as 30 min after revascularization. (2) SahtO2 during TVE was significantly lower than that during IO. (3) The increase in SahvO2 by oxygenation of the inferior caval blood resulted in the elevation of SahtO2 under IO. In conclusion, TVE could cause greater damage to the liver than IO due to the lack of the hepatic venous blood. Hepatic venous blood might play an important role in hepatic tissue oxygenation in the case of hepatic blood flow interception.

  20. Increasing Cycles of Intermittent Ischemia Can Effectively Maintain Liver Function during the Acute Phase of Ischemia Reperfusion Injury by Promotion of Bile Flow and Reduction in Bile Salt Toxicity

    NARCIS (Netherlands)

    Peters, J.; Nieuwenhuijs, V. B.; Morphett, A.; Porte, R. J.; Padbury, R. T. A.; Barritt, G. J.

    2009-01-01

    Background/Aims: Intermittent ischemia (INT) can improve liver function following inflow occlusion. The aim was to test whether the number of cycles of INT can be increased without impairing liver function. Methods: Liver function in the acute phase of ischemia reperfusion injury was assessed by mea

  1. Remote ischemic preconditioning protects against liver ischemia-reperfusion injury via heme oxygenase-1-induced autophagy.

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    Yun Wang

    Full Text Available BACKGROUND: Growing evidence has linked autophagy to a protective role of preconditioning in liver ischemia/reperfusion (IR. Heme oxygenase-1 (HO-1 is essential in limiting inflammation and preventing the apoptotic response to IR. We previously demonstrated that HO-1 is up-regulated in liver graft after remote ischemic preconditioning (RIPC. The aim of this study was to confirm that RIPC protects against IR via HO-1-mediated autophagy. METHODS: RIPC was performed with regional ischemia of limbs before liver ischemia, and HO-1 activity was inhibited pre-operation. Autophagy was assessed by the expression of light chain 3-II (LC3-II. The HO-1/extracellular signal-related kinase (ERK/p38/mitogen-activated protein kinase (MAPK pathway was detected in an autophagy model and mineral oil-induced IR in vitro. RESULTS: In liver IR, the expression of LC3-II peaked 12-24 h after IR, and the ultrastructure revealed abundant autophagosomes in hepatocytes after IR. Autophagy was inhibited when HO-1 was inactivated, which we believe resulted in the aggravation of liver IR injury (IRI in vivo. Hemin-induced autophagy also protected rat hepatocytes from IRI in vitro, which was abrogated by HO-1 siRNA. Phosphorylation of p38-MAPK and ERK1/2 was up-regulated in hemin-pretreated liver cells and down-regulated after treatment with HO-1 siRNA. CONCLUSIONS: RIPC may protect the liver from IRI by induction of HO-1/p38-MAPK-dependent autophagy.

  2. Inflammation, complement, ischemia and amoebic survival in acute experimental amoebic liver abscesses in hamsters.

    Science.gov (United States)

    Olivos-García, A; Nequiz-Avendaño, M; Tello, E; Martínez, R D; González-Canto, A; López-Vancell, R; García de León, M C; Montfort, I; Pérez-Tamayo, R

    2004-08-01

    We have examined the role of inflammatory cells, ischemia and serum complement on the development of acute experimental amoebic liver abscess in hamsters (AEALAH). In hamsters made leukopenic by whole body radiation (800 rad) and daily intraperitoneal glycogen injections, the absence of inflammatory cells and liver tissue damage surrounding the parasites resulted in their rapid (24 h) disappearance from the liver, which showed no lesions. Focal liver ischemia, always present in control AEALAH with inflammation and tissue destruction, was reproduced in radiated hamsters by injection of amoebae mixed with Superdex microspheres, but again in the absence of inflammation, amoebae caused no liver damage and disappeared in 24 h. In hamsters made hypocomplementemic by injection of purified cobra venom factor (CVF), amoebae caused AEALA indistinguishable from controls, but in leukopenic + hypocomplementemic hamsters, amoebae were unable to produce lesions and disappeared from the liver in 48 h. We conclude that inflammation and tissue damage are required for the survival of amoebae in AEALAH and for the progression of the experimental disease.

  3. Pretreatment with mangafodipir improves liver graft tolerance to ischemia/reperfusion injury in rat.

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    Ismail Ben Mosbah

    Full Text Available Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP, a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging

  4. Global MicroRNA Expression Profiling of Mouse Livers following Ischemia-Reperfusion Injury at Different Stages.

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    Weisheng Zheng

    Full Text Available Hepatic ischemia-reperfusion injury is a dynamic process consisting of two stages: ischemia and reperfusion, and triggers a cascade of physiological and biochemical events. Given the important role of microRNAs in regulating gene expression, we analyzed gene expression changes in mouse livers at sham control, ischemia stage, and reperfusion stage. We generated global expression profiles of microRNA and mRNA genes in mouse livers subjected to ischemia-reperfusion injury at the three stages, respectively. Comparison analysis showed that reperfusion injury had a distinct expression profile whereas the ischemia sample and the sham control were clustered together. Consistently, there are 69 differentially expressed microRNAs between the reperfusion sample and the sham control whereas 28 differentially expressed microRNAs between the ischemia sample and the sham control. We further identified two modes of microRNA expression changes in ischemia-reperfusion injury. Functional analysis of both the differentially expressed microRNAs in the two modes and their target mRNAs revealed that ischemia injury impaired mitochondrial function, nutrient consumption, and metabolism process. In contrast, reperfusion injury led to severe tissue inflammation that is predominantly an innate-immune response in the ischemia-reperfusion process. Our staged analysis of gene expression profiles provides new insights into regulatory mechanisms of microRNAs in mouse hepatic IR injury.

  5. Butyrate protects rat liver against total hepatic ischemia reperfusion injury with bowel congestion.

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    Bin Liu

    Full Text Available Hepatic ischemia/reperfusion (I/R injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation.

  6. Ischemia-Reperfusion Injury and Ischemic-Type Biliary Lesions following Liver Transplantation

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    Raffaele Cursio

    2012-01-01

    Full Text Available Ischemia-reperfusion (I-R injury after liver transplantation (LT induces intra- and/or extrahepatic nonanastomotic ischemic-type biliary lesions (ITBLs. Subsequent bile duct stricture is a significant cause of morbidity and even mortality in patients who underwent LT. Although the pathogenesis of ITBLs is multifactorial, there are three main interconnected mechanisms responsible for their formation: cold and warm I-R injury, injury induced by cytotoxic bile salts, and immunological-mediated injury. Cold and warm ischemic insult can induce direct injury to the cholangiocytes and/or damage to the arterioles of the peribiliary vascular plexus, which in turn leads to apoptosis and necrosis of the cholangiocytes. Liver grafts from suboptimal or extended-criteria donors are more susceptible to cold and warm I-R injury and develop more easily ITBLs than normal livers. This paper, focusing on liver I-R injury, reviews the risk factors and mechanisms leading to ITBLs following LT.

  7. Nuclear factor-κB decoy oligodeoxynucleotides attenuates ischemia/reperfusion injury in rat liver graft

    Institute of Scientific and Technical Information of China (English)

    Ming-Qing Xu; Xiu-Rong Shuai; Mao-Lin Yan; Ming-Man Zhang; Lu-Nan Yan

    2005-01-01

    AIM: To evaluate the protective effect of NF-κB decoy oligodeoxynucleotides (ODNs) on ischemia/reperfusion (I/R) injury in rat liver graft.METHODS: Orthotopic syngeneic rat liver transplantation was performed with 3 h of cold preservation of liver graft in University of Wisconsin solution containing phosphorothioated double-stranded NF-κB decoy ODNs or scrambled ODNs. NF-κB decoy ODNs or scrambled ODNs were injected intravenously into donor and recipient rats 6 and 1 h before operation,respectively. Recipients were killed 0 to 16 h after liver graft reperfusion. NF-κB activity in the liver graft was analyzed by electrophoretic mobility shift assay (EMSA). Hepatic mRNA expression of TNF-α, IFN-γand intercellular adhesion molecule-1 (ICAM-1) were determined by semiquantitative RT-PCR. Serum levels of TNF-α and IFN-γ were measured by enzyme-linked immunosorbent assays (ELISA). Serum level of alanine transaminase (ALT) was measured using a diagnostic kit. Liver graft myeloperoxidase (MPO) content was assessed.RESULTS: NF-κB activation in liver graft was induced in a time-dependent manner, and NF-κB remained activated for 16 h after graft reperfusion. NF-κB activation in liver graft was significant at 2 to 8 h and slightly decreased at 16 h after graft reperfusion. Administration of NF-κB decoy ODNs significantly suppressed NF-κB activation as well as mRNA expression of TNF-α, IFN-γ and ICAM-1 in the liver graft. The hepatic NF-κB DNA binding activity [presented as integral optical density (IOD) value] in the NF-κB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (2.16±0.78 vs 36.78±6.35 and 3.06±0.84 vs 47.62± 8.71 for IOD value after 4 and 8 h of reperfusion, respectively, P<0.001).The hepatic mRNA expression level of TNF-α, IFN-y and ICAM-1 [presented as percent of β-actin mRNA(%)] in the NF-κBdecoy ODNs treatment group rat was significantly lower than that of the I/R group rat (8.31 ±3.48 vs 46.37±10

  8. Identification of differentially expressed genes after partial rat liver ischemia/reperfusion by suppression subtractive hybridization

    Institute of Scientific and Technical Information of China (English)

    Christine Fallsehr; Christina Zapletal; Michael Kremer; Resit Demir; Magnus von Knebel Doeberitz; Ernst Klar

    2005-01-01

    AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs.METHODS: We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays)to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WT/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70,Hsp27, Gadd45a and IL-1rl).RESULTS: Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context.CONCLUSION: This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70and Gadd45a might represent promising new candidates indicating WI/R liver damage.

  9. Histological and biochemical alterations in early-stage lobar ischemia-reperfusion in rat liver

    Institute of Scientific and Technical Information of China (English)

    Hossein Ali Arab; Farhang Sasani; Mohammad Hossein Rafiee; Ahmad Fatemi; Abbas Javaheri

    2009-01-01

    AIM: To investigate the structural and biochemical changes in the early stage of reperfusion in the rat livers exposed to lobar ischemia-reperfusion (IR).METHODS: The median and left lobes of the liver were subjected to 60 min ischemia followed by 5, 10,30, 45, 60 and 120 min reperfusion. Blood samples were taken at different time intervals to test enzyme activities and biochemical alterations induced by reperfusion. At the end of each reperfusion period, the animals were killed by euthanasia and tissue samples were taken for histological examination and immunohistochemistry.RESULTS: Cell vacuolation, bleb formation and focal hepatitis were the most important changes occur during ischemia. While some changes including bleb formation were removed during reperfusion, other alterations including portal hepatitis, inflammation and the induction of apoptosis were seen during this stage. The occurrence of apoptosis, as demonstrated by apoptot i c cel l s and bodies , was the mos t important histological change during reperfusion. The severity of apoptosis was dependent on the time of reperfusion, and by increasing the time of reperfusion,the numbers of apoptotic bodies was significantly enhanced. The amounts of lactate dehydrogenase,alanine aminotransferase, aspartate aminotransferase,creatinine and urea were significantly increased in serum obtained from animals exposed to hepatic IR.

  10. Iloprost donor treatment reduces ischemia-reperfusion injury in an isolated extracorporeal pig liver perfusion model.

    Science.gov (United States)

    Schoening, Wenzel N; Feige, Ines; Schubert, Thomas; Olschewski, Peter; Buescher, Niklas; Helbig, Michael; Schmitz, Volker; Neuhaus, Peter; Pratschke, Johann; Puhl, Gero

    2015-02-01

    Iloprost has the potential to protect the liver transplant graft before and during cold ischemia. We studied iloprost administration during organ procurement and reperfusion in an extracorporeal pig liver perfusion model. German Landrace pigs (n = 7/group; 22-26 kg each) were used as donors. Preservation was performed by aortic perfusion with 2 L Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK and cold ischemia time (4°C) 20 hours followed by normothermic extracorporeal perfusion for 8 hours. Untreated controls (1) were compared to iloprost (2) donor bolus-treatment (1 μg/kg body weight), (3) addition of iloprost to Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK (0.0125 μg/mL), (4) continuous infusion during reperfusion (2 ng/kg/min), and (5) combined treatment (2) and (4). Iloprost donor treatment led to significantly higher bile production. Addition of iloprost to the preservation solution significantly improved hepatic artery perfusion and was accompanied by improvements of microcirculation and bile production. Iloprost reperfusion treatment alone significantly improved bile production. Enzyme levels were positively affected by all treatment regimens. Combined use of iloprost before and after ischemia improved hepatic artery flow and microcirculation and showed significantly lower hypoxia staining versus controls. Iloprost donor treatment and use of iloprost in the preservation solution significantly improved graft perfusion and function. The effects of graft treatment seemed greater before than after reperfusion. Combined treatment did not reveal a synergistic advantage.

  11. Protective effect of prednisolone on ischemia-induced liver injury in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of prednisolone on cell membrane bleb formation, calpain μ activation and talin degradation during hepatic ischemia-reperfusion injury in rats. METHODS: The hilar area of the left lateral and median lobes of rat liver (68%) was clamped for 60 min and followed by 120 min reperfusion. Prednisolone was administered at 1.0, 3.0, or 10 mg/kg at 30 min before ischemia. In addition to biochemical and microscopic analyses, activation of calpain μ was determined using specific antibodies against the intermediate (activated) form of calpain μ. Degradation of talin was also studied by Western blotting.RESULTS: In the control and prednisolone (1.0 mg/kg) groups, serum aspartate transaminase (AST) and alanine transaminase (ALT) level were elevated, and cell membrane bleb formation was observed after 120 min of reperfusion. Moreover, calpain μ activation and talin degradation were detected. Infusion of prednisolone at 3.0 or 10 mg/kg significantly suppressed serum AST and ALT, and prevented cell membrane bleb formation. At 10 mg/kg, prednisolone markedly suppressed calpain μ activation and talin degradation. CONCLUSION: Prednisolone can suppress ischemia- reperfusion injury of the rat liver. Its cytoprotective effect is closely associated with the suppression of calpain μ activation and talin degradation.

  12. Effect of recombinant erythropoietin on ischemia-reperfusion-induced apoptosis in rat liver.

    Science.gov (United States)

    Shawky, Heba M; Younan, Sandra M; Rashed, Leila A; Shoukry, Heba

    2012-03-01

    Ischemia-reperfusion (I/R) cannot be avoided in liver transplantation procedures, and apoptosis is a central mechanism of cell death after liver reperfusion. Protective effect of recombinant erythropoietin (rhEPO) on liver apoptosis has not been clearly investigated. This work investigated intraportal (IP) rhEPO-protective effect in a rat model of hepatic I/R-induced apoptosis and its appropriated time and dose of administration. Eight groups were included (n = 10/group): sham-operated, I/R (45 min ischemia and 2 h reperfusion), preconditioned rhEPO I/R (24 h or 30 min before ischemia), and postconditioned rhEPO I/R (before reperfusion) using two different rhEPO doses (1,000 and 5,000 IU/kg). When compared with the sham-operated group, the I/R group showed significant increase of serum levels of aspartate and alanine aminotransferases (AST, ALT), hepatic caspase-9 activity(894.99 ± 176.90 relative fluorescence units (RFU)/mg/min versus 458.48 ± 82.96 RFU/mg/min), and Fas ligand (FasL) expression, histopathological damages, and significant decrease in the antiapoptotic Bcl-xL/apoptotic Bax ratio(0.38 ± 0.21 versus 3.35 ± 0.77) rhEPO-improved ALT and AST but failed to reduce FasL expression in all groups compared with the I/R group. Thirty minutes and 24 h preconditioning with rhEPO (1,000 IU/kg) increased Bcl-xL/Bax ratio and reduced caspase-9 activity, and the same effect was observed when higher dose was given 24 h before ischemia. Preconditioning was more effective than postconditioning in improving caspase-9 activity, and no dose-dependent effect was observed. In conclusion, single IP rhEPO injection 30 min before ischemia has an advantage over rhEPO postconditioning in improving post-hepatic I/R-induced apoptosis with no additional time- and dose-dependent effects which may provide potentially useful guide in liver transplantation procedures.

  13. Protective effects of apocynin and allopurinol on ischemia/reperfusion-induced liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    Ping-Guo Liu; Song-Qing He; Yan-Hong Zhang; Jian Wu

    2008-01-01

    AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Nice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX)inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-αlevels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: AIIopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generation of superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.

  14. Relevance of Endoplasmic Reticulum Stress Cell Signaling in Liver Cold Ischemia Reperfusion Injury

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    Emma Folch-Puy

    2016-05-01

    Full Text Available The endoplasmic reticulum (ER is involved in calcium homeostasis, protein folding and lipid biosynthesis. Perturbations in its normal functions lead to a condition called endoplasmic reticulum stress (ERS. This can be triggered by many physiopathological conditions such as alcoholic steatohepatitis, insulin resistance or ischemia-reperfusion injury. The cell reacts to ERS by initiating a defensive process known as the unfolded protein response (UPR, which comprises cellular mechanisms for adaptation and the safeguarding of cell survival or, in cases of excessively severe stress, for the initiation of the cell death program. Recent experimental data suggest the involvement of ERS in ischemia/reperfusion injury (IRI of the liver graft, which has been considered as one of major problems influencing outcome after liver transplantation. The purpose of this review is to summarize updated data on the molecular mechanisms of ERS/UPR and the consequences of this pathology, focusing specifically on solid organ preservation and liver transplantation models. We will also discuss the potential role of ERS, beyond the simple adaptive response and the regulation of cell death, in the modification of cell functional properties and phenotypic changes.

  15. Adenovirus-mediated eNOS expression augments liver injury after ischemia/reperfusion in mice.

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    Arun P Palanisamy

    Full Text Available Hepatic ischemia/reperfusion (l/R injury continues to be a critical problem. The role of nitric oxide in liver I/R injury is still controversial. This study examines the effect of endothelial nitric oxide synthase (eNOS over-expression on hepatic function following I/R. Adenovirus expressing human eNOS (Ad-eNOS was administered by tail vein injection into C57BL/6 mice. Control mice received either adenovirus expressing LacZ or vehicle only. Sixty minutes of total hepatic ischemia was performed 3 days after adenovirus treatment, and mice were sacrificed after 6 or 24 hrs of reperfusion to assess hepatic injury. eNOS over expression caused increased liver injury as evidenced by elevated AST and ALT levels and decreased hepatic ATP content. While necrosis was not pervasive in any group, TUNEL demonstrated significantly increased apoptosis in Ad-eNOS infected livers. Western blotting demonstrated increased levels of protein nitration and upregulation of the pro-apoptotic proteins bax and p53. Our data suggest that over-expression of eNOS is detrimental in the setting of hepatic I/R.

  16. The protective effects of dexmedetomidine on liver injury-induced myocardial ischemia reperfusion.

    Science.gov (United States)

    Erer, D; Ozer, A; Arslan, M; Oktar, G L; Iriz, E; Elmas, C; Zor, M H; Tatar, T; Goktas, G

    2014-01-01

    The aim of this study was to evaluate the effect of dexmedetomidine (100 µg/kg-ip) on liver injury-induced myocardial ischemia and reperfusion (IR) in rats. Twenty-four Wistar Albino rats were separated into four groups. There were four experimental groups (Group C (Control; n = 6), Group IR (ischemia-reperfusion, n = 6), Group D (Dexmedetomidine; n = 6) that underwent left thoracotomy and received ip dexmedetomidine without IR administered via 100 µg/kg ip route 30 minutes before ligating the left coronary artery, and Group IR-D (IR-Dexmedetomidine; n = 6). A small plastic snare was threaded through the ligature and placed in contact with the heart. To produce IR, a branch of the left coronary artery was occluded for 30 min followed by two hours of reperfusion. However, after the above procedure, the coronary artery was not occluded or reperfused in the control rats. At the end of the study, liver tissue was obtained for histochemical and immunohistochemical determination.Some part of tissue samples were stained with Masson-trichrome for the evaluation of ultrastructural changes and inducible nitric oxide synthase (iNOS) expression was evaluated in other part of samples for immunohistochemical examination. Histopathological changes were detected in Group IR when compared with Group C. iNOS expression was found to be increased and stronger particularly in the vascular wall, perisinusoidal space and hepatocytes around vena centralis in this group compared to the control group. Perivascular oedema was detected to be decreased in Group IR-D compared to Group IR. It was also observed that the impairment in the radial arrangement of hepatocytes significantly recovered in Group IR-D. The immunoreactivity was found to be significantly decreased in the assessment of iNOS expression in the same group when compared with Group IR. Administration of dexmedetomidine ameliorates liver injury induced by myocardial ischemia and reperfusion (Fig. 8, Ref. 33).

  17. Reduction of ischemia reperfusion injury after liver resection and hepatic inflow occlusion by α-lipoic acid in humans

    Institute of Scientific and Technical Information of China (English)

    Fritz Dünschede; Kirsten Erbes; Achim Kircher; Stefanie Westermann; Joachim Seifert; Arno Schad; Kempski Oliver; Alexandra K Kiemer; Junginger Theodor

    2006-01-01

    AIM:To evaluate the protective effects of preconditioning by α-lipoic acid (LA) in patients undergoing hepatic resection under inflow occlusion of the liver.METHODS:Twenty-four patients undergoing liver resection for various reasons either received 600 mg LA or NaCl 15 min before transection performed under inflow occlusion of the liver. Blood samples and liver wedge biopsy samples were obtained after opening of the abdomen immediately after inflow occlusion of the liver, and 30 min after the end of inflow occlusion of the liver.RESULTS:Serum levels of aspartate transferase and alanine transferase were reduced at all time points in patients who received LA in comparison to those who received NaCL. This was accompanied by reduced histomorphological features of oncosis. We observed TUNELpositive hepatocytes in the livers of the untreated patients, especially after 30 min of ischemia. LA attenuated this increase of TUNEL-positive hepatocytes. Under preconditioning with LA, ATP content was significantly enhanced after 30 min of ischemia and after 30 min of reperfusion.CONCLUSION:This is the first report on the potential for LA reducing ischemia/reperfusion injury (IRI) of the liver in humans who were undergoing liver surgery.Beside its simple and rapid application, side effects did not occur. LA might therefore represent a new strategy against hepatic IRI in humans.

  18. IMPACT OF SEVOFLURANE AND ACETYLCYSTEINE ON ISCHEMIA-REPERFUSION INJURY OF THE LIVER FROM BRAIN-DEAD DONOR

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    A. E. Shcherba

    2013-01-01

    Full Text Available Aim. The purpose of our work was to estimate the impact of preconditioning with acetylcysteine and sevoflurane on ischemia-reperfusion injury of cadaveric donor liver with marginal features. Methods and results. In this prospective randomized controlled trial we recruited 21 heart beating donors with brain death. We assigned 11 donors to the study group, and 10 donors to the control group. Morphological characteristics of ischemia- reperfusion injury in both groups were analyzed. Conclusion. Use of pharmacological preconditioning with acetylcysteine and sevoflurane resulted in necrosis and hepatocyte apoptosis reduction as compared to the control group, thereby had a protective effect against ischemia-reperfusion injury. 

  19. Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury

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    Edith Hochhauser

    2015-07-01

    Full Text Available Background/Aims: Ischemia/reperfusion (I/R injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC, a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC (0.002mg/kg in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults. Methods: C57Bl Mice were studied in in vivo model of hepatic segmental (70% ischemia for 60min followed by reperfusion for 6 hours. Results: THC administration 2h prior to the induction of hepatic I/R was associated with significant attenuated elevations of: serum liver transaminases ALT and AST, the hepatic oxidative stress (activation of the intracellular signaling CREB pathway, the acute proinflammatory response (TNF-α, IL-1α, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway activation. This was followed by cell death (the cleavage of the pro-apoptotic caspase 3, DNA fragmentation and TUNEL after 6 hours of reperfusion. Significantly less hepatic injury was detected in the THC treated I/R mice and fewer apoptotic hepatocytes cells were identified by morphological criteria compared with untreated mice. Conclusion: A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury. THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma.

  20. Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the effect of sulforaphane (SFN) on regulation of NF-E2-related factor-2 (Nrf2)-antiox-idant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R). METHODS: Rats were divided randomly into four ex-perimental groups: control, SFN control, intestinal I/R and SFN pretreatment groups (n = 8 in each group). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h and 2 h reperfu-sion. In the SFN pretreatment group, s...

  1. Glycine blunts transplantative liver ischemia-reperfusion injury by downregulating interleukin 1 receptor associated kinase-4

    Institute of Scientific and Technical Information of China (English)

    Zuo-jin LIU; Lu-nan YAN; Shen-wei LI; Hai-bo YOU; Jian-ping GONG

    2006-01-01

    Aim: To determine whether glycine could downregulate interleukin 1 receptor associated kinase-4 (IRAK-4) expression to interfere with lipopolysaccharides (LPS) signal transduction and blunt transplantative liver ischemia-reperfusion injury (I/RI). Methods: SD rats were randomly divided into two groups: donor animals of the glycine group (n=40) were given glycine (1.5 mL; 300 mmol/L, iv) 1 h before harvest, and the control group were treated with 1.5 mL physiological saline (n= 40). Orthotropic liver transplantation was then performed according to the Kamada technique. Ten animals in each group were followed up for 7 d after surgery to assess survival. The remaining animals in each group were divided into 3 subgroups (n=10) at 1h, 2 h and 6 h after portal vein reperfusion. Levels of LPS, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin in portal circulation, as well as IRAK-4 and TNF-α expression, NF-кB transcriptional activity and morphological study of liver tissues were analyzed. Results: Reperfusion resulted in a significant elevation of LPS concentrations in each group persisting to the end of our study. However, glycine, which led to improved survival rate and liver function, significantly alleviated liver parenchyma cell damage by downregulating IRAK-4, TNF-α expression and NF-кB transcriptional activity compared with the control group. Conclusion: Glycine can attenuate hepatic I/RI by downregulating IRAK-4 to interfere with LPS signal transduction.

  2. Effect of matrine on Kupffer cell activation in cold ischemia reperfusion injury of rat liver

    Institute of Scientific and Technical Information of China (English)

    Xin-Hua Zhu; Yu-Dong Qiu; Hao Shen; Ming-Ke Shi; Yi-Tao Ding

    2002-01-01

    AIM: To study the effect of matrine on activation of Kupffer cell during cold ischemia and reperfusion injury in rat orthotopic liver transplantation (OLT).METHODS: 168 syngeneic SD rats were randomly divided into four groups: untreated group, small-dose treated group, large-dose treated group and sham operation group. After 5 hours of preservation in Ringer's (LR) solution, orthotopic implantation of the donor liver was performed. At 1 h, 2 h, 4 h and 24 h after reperfusion of the portal vein, 6 rats were killed in each group to collect the serum and the liver for assay and pathology.RESULTS: Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF). TNF cytotoxicity level at 2 h decreased significantly by matrine treatment (7.94±0.42, 2.39±0.19 and 2.01±0.13 U/ml,respectively; P<0.01), so did the other three time points. The level of hylluronic acid (HA) and alanine transaminase (ALT) decreased significantly in both treated groups, and matrine treatment markedly ameliorated focal necrosis of hepatocytes, inflammatory cells aggregating, rounding and detachment of sinusoidal endothelial cells (SEC). And no significant difference was observed between the treated groups.CONCLUSION: Matrine can inhibit the activation of Kupffer cell and prevent the donor liver from cold preservation and reperfusion injury in rat orthotopic liver transplantation.

  3. Effect of ONO-4057 and tacrolimus on ischemia-reperfusion injury of the liver

    Institute of Scientific and Technical Information of China (English)

    Takayuki Takeichi; Shinji Uemoto; Sachiko Minamiguchi; Izumi Takeyoshi; Yukihiro Inomata; Koichi Tanaka; Eiji Kobayashi

    2009-01-01

    AIM: To investigate the effects of a novel Leukotriene B4 receptor antagonist and/or tacrolimus on ischemiareperfusion in a rat liver model.METHODS: Male Lewis rats were pretreated with ONO-4057 (100 mg/kg) and/or tacrolimus (1 mg/kg) orally, and divided into four experimental groups; group 1 (control), group 2 (ONO-4057), group 3 (tacrolimus),group 4 (ONO-4057 + tacrolimus).RESULTS: There was a tendency for long survival in the groups treated with tacrolimus alone and ONO-4057 plus tacrolimus. Post-reperfusion serum aspartate aminotransferase levels decreased more significantly in ONO-4057 plus tacrolimus group ( P < 0.01), than in the tacrolimus alone group ( P < 0.05), compared to controls. CONCLUSION: This study demonstrated that pretreatment with ONO-4057 in combination with tacrolimus produced additive effects in a rat model of liver ischemia- reperfusion injury.

  4. Xanthohumol suppresses inflammatory response to warm ischemia-reperfusion induced liver injury.

    Science.gov (United States)

    Dorn, Christoph; Massinger, Sabine; Wuzik, Andreas; Heilmann, Jörg; Hellerbrand, Claus

    2013-02-01

    Liver ischemia/reperfusion (I/R) leads to formation of reactive oxygen species (ROS), which cause hepatic injury and initiate an inflammatory response, which is a critical problem after liver surgery and transplantation. Xanthohumol, the major prenylated chalcone found in hops, has been discussed for its anti-inflammatory and ROS-scavenging properties, and thus, we aimed to investigate the effect of xanthohumol in a model of warm I/R liver injury. Xanthohumol was applied to BALB/c mice orally at a dose of 1 mg/g body weight for 5 days before I/R-injury was induced by clamping the vascular blood supply to the median and left lateral liver lobe for 1 h followed by a 6 h period of reperfusion. At this time, HPLC analysis revealed hepatic xanthohumol levels of approximately 2 μM, a concentration which has been shown to inhibit inflammatory effects in vitro. Assessment of hepatic HMOX1 expression, hepatic glutathione content and immunohistochemical analysis for proteins conjugated with the reactive aldehyde 4-hydroxynonenal indicated that I/R-induced oxidative stress was significantly inhibited in xanthohumol-fed compared to control mice. Histological analysis, TUNEL staining and determination of transaminase serum levels revealed no significant effects of xanthohumol on acute hepatocellular injury. However, at the same time point, pretreatment with xanthohumol almost completely blunted the I/R-induced AKT and NFκB activation and the expression of the proinflammatory genes IL-1alpha, IL-6, MCP-1 and ICAM-1, which are known to play a crucial role in the subacute phase of I/R-induced liver damage. In conclusion, these data indicate the potential of xanthohumol application to prevent adverse inflammatory responses to I/R-induced liver damage such as after surgical liver resection or transplantation.

  5. Failure of P-selectin blockade alone to protect the liver from ischemia-reperfusion injury in the isolated blood-perfused rat liver

    Institute of Scientific and Technical Information of China (English)

    Samuel Wyllie; Neal R Barshes; Feng-Qin Gao; Saul J Karpen; John A Goss

    2008-01-01

    AIM: To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS: The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution.RESULTS: In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 min of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-κB was found between control and P-selectin antibody-treated livers.CONCLUSION: In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.

  6. The role of hepatic ischemia-reperfusion injury and liver parenchymal quality on cancer recurrence.

    Science.gov (United States)

    Orci, Lorenzo A; Lacotte, Stéphanie; Oldani, Graziano; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-09-01

    Hepatic ischemia/reperfusion (I/R) injury is a common clinical challenge. Despite accumulating evidence regarding its mechanisms and potential therapeutic approaches, hepatic I/R is still a leading cause of organ dysfunction, morbidity, and resource utilization, especially in those patients with underlying parenchymal abnormalities. In the oncological setting, there are growing concerns regarding the deleterious impact of I/R injury on the risk of post-surgical tumor recurrence. This review aims at giving the last updates regarding the role of hepatic I/R and liver parenchymal quality injury in the setting of oncological liver surgery, using a "bench-to-bedside" approach. Relevant medical literature was identified by searching PubMed and hand scanning of the reference lists of articles considered for inclusion. Numerous preclinical models have depicted the impact of I/R injury and hepatic parenchymal quality (steatosis, age) on increased cancer growth in the injured liver. Putative pathophysiological mechanisms linking I/R injury and liver cancer recurrence include an increased implantation of circulating cancer cells in the ischemic liver and the upregulation of proliferation and angiogenic factors following the ischemic insult. Although limited, there is growing clinical evidence that I/R injury and liver quality are associated with the risk of post-surgical cancer recurrence. In conclusion, on top of its harmful early impact on organ function, I/R injury is linked to increased tumor growth. Therapeutic strategies tackling I/R injury could not only improve post-surgical organ function, but also allow a reduction in the risk of cancer recurrence.

  7. In vivo estimation of optical properties of rat liver using single-reflectance fiber probe during ischemia and reperfusion

    Science.gov (United States)

    Akter, Sharmin; Tanabe, Tomoki; Maejima, Satoshi; Kawauchi, Satoko; Sato, Shunichi; Hinoki, Akinari; Aosasa, Suefumi; Yamamoto, Junji; Nishidate, Izumi

    2016-04-01

    To quantify the changes in optical properties of in vivo rat liver tissue, we applied diffuse reflectance spectroscopy (DRS) system using single-reflectance fiber probe during ischemia and reperfusion evoked by hepatic portal occlusion (hepatic artery, portal vein and bile duct). Changes in the reduced scattering coefficient μ s', the absorption coefficient μ a, the tissue oxygen saturation StO2, and the oxidation of heme aa3 in cytochrome c oxidase (C cO) OHaa3 of in vivo rat liver (n = 6) were evaluated. Heme aa3 in C cO were significantly reduced (P ischemia, which indicates a sign of mitochondrial energy failure induced by oxygen insufficiency of liver tissue. We found that OHaa3 obtained from the proposed method was unchanged immediately after the onset of ischemia and started gradually decreasing at 2 min after the onset of ischemia. Difference in the time course between OHaa3 and the conventional ratio metric analysis with μ a(605)/ μ a(620) reported in literature demonstrates that the proposed method is effective in reduction of optical cross talk between hemoglobin and heme aa3. Our results suggest that DRS technique is applicable and useful for assessing in vivo tissue viability and hemodynamics in liver intraoperatively.

  8. Dynamical changing patterns of histological structure and ultrastructure of liver graft undergoing warm ischemia injury from non-heart-beating donor in rats

    Institute of Scientific and Technical Information of China (English)

    Yi Ma; Guo-Dong Wang; Lin-Wei Wu; Rui-De Hu

    2006-01-01

    AIM: To investigate the histological and ultra-structural characteristics of liver graft during different of warm ischemia time (WIT) in rats and to predict the maximum limitation of liver graft to warm ischemia. METHODS: The rats were randomized into 7 groups undergoing warm ischemia injury for 0, 10, 15, 20, 30,45 and 60 min, respectively. All specimens having undergone warm ischemia injury were investigated dynamically by light and electron microscopy, and histochemistry staining. After orthotopic liver transplantation (OLT), the recovery of morphology of liver grafts after 6, 24 and 48 h was observed. RESULTS: The donor liver from non-heart-beating donors (NHBD) underwent ischemia injury both in the warm ischemia period and in the reperfusion period. Morphological changes were positively related to warm ischemia injury in a time-dependent manner during the reperfusion period. The results demonstrated that different degrees of histocyte degeneration were observed when WIT was within 30 min, and became more severe with the prolongation of WIT, no obvious hepatocyte necrosis was noted in any specimen. In the group undergolng warm ischemia injury for 45 min, small focal necrosis occurred in the central area of hepatic lobule first. In the group undergoing warm ischemia injury for 60 min, patchy or diffused necrosis was observed and the area was gradually extended, while hepatic sinusoid endothe lial cells were obviously swollen. Hepatic sinusoid was obstructed and microcirculation was in disorder. CONCLUSION: The rat liver graft undergoing warm ischemia injury is in the reversible stage when the WIT is within 30 min. The 45 min WIT may be a critical point of rat liver graft to endure warm ischemia injury. When the WIT is over 60 min, the damage is irreversible.

  9. Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver.

    Science.gov (United States)

    Møller, Lin Nanna Okholm; Knudsen, Anders Riegels; Andersen, Kasper Jarlhelt; Nyengaard, Jens Randel; Hamilton-Dutoit, Stephen; Okholm Møller, Elise Marie; Svendsen, Pia; Møller, Holger Jon; Moestrup, Søren Kragh; Graversen, Jonas Heilskov; Mortensen, Frank Viborg

    2015-12-01

    The Pringle maneuver is a way to reduce blood loss during liver surgery. However, this may result in ischemia/reperfusion injury in the development of which Kupffer cells play a central role. Corticosteroids are known to have anti-inflammatory effects. Our aim was to investigate whether a conjugate of dexamethasone and antibody against the CD163 macrophage cell surface receptor could reduce ischemia/reperfusion injury in the rat liver. Thirty-six male Wistar rats were used for the experiments. Animals were randomly divided into four groups of eight receiving anti-CD163-dexamethasone, high dose dexamethasone, low dose dexamethasone or placebo intravenously 18 h before laparotomy with subsequent 60 min of liver ischemia. After reperfusion for 24 h the animals had their liver removed. Bloods were drawn 30 min and 24 h post ischemia induction. Liver cell apoptosis and necrosis were analyzed by stereological quantification. After 24 h' reperfusion, the fraction of cell in non-necrotic tissues exhibiting apoptotic profiles was significantly lower in the high dose dexamethasone (p = 0.03) and anti-CD163-dex (p = 0.03) groups compared with the low dose dexamethasone and placebo groups. There was no difference in necrotic cell volume between groups. After 30 min of reperfusion, levels of haptoglobin were significantly higher in the anti-CD163-dex and high dose dexamethasone groups. Alanine aminotransferase and alkaline phosphatase were significantly higher in the high dose dexamethasone group compared to controls after 24 h' reperfusion. We show that pharmacological preconditioning with anti-CD163-dex and high dose dexamethasone reduces the number of apoptotic cells following ischemia/reperfusion injury.

  10. Cardioprotective proteins upregulated in the liver in response to experimental myocardial ischemia.

    Science.gov (United States)

    Liu, Shu Q; Tefft, Brandon J; Roberts, Derek T; Zhang, Li-Qun; Ren, Yupeng; Li, Yan Chun; Huang, Yong; Zhang, Di; Phillips, Harry R; Wu, Yu H

    2012-12-15

    Myocardial ischemia (MI) activates innate cardioprotective mechanisms, enhancing cardiomyocyte tolerance to ischemia. Here, we report a MI-activated liver-dependent mechanism for myocardial protection. In response to MI in the mouse, hepatocytes exhibited 6- to 19-fold upregulation of genes encoding secretory proteins, including α-1-acid glycoprotein (AGP)2, bone morphogenetic protein-binding endothelial regulator (BMPER), chemokine (C-X-C motif) ligand 13, fibroblast growth factor (FGF)21, neuregulin (NRG)4, proteoglycan 4, and trefoil factor (TFF)3. Five of these proteins, including AGP2, BMPER, FGF21, NRG4, and TFF3, were identified as cardioprotective proteins since administration of each protein significantly reduced the fraction of myocardial infarcts (37 ± 9%, 34 ± 7%, 32 ± 8%, 39 ± 6%, and 31 ± 7%, respectively, vs. 48 ± 7% for PBS at 24 h post-MI). The serum level of the five proteins elevated significantly in association with protein upregulation in hepatocytes post-MI. Suppression of a cardioprotective protein by small interfering (si)RNA-mediated gene silencing resulted in a significant increase in the fraction of myocardial infarcts, and suppression of all five cardioprotective proteins with siRNAs further intensified myocardial infarction. While administration of a single cardioprotective protein mitigated myocardial infarction, administration of all five proteins furthered the beneficial effect, reducing myocardial infarct fractions from PBS control values from 46 ± 6% (5 days), 41 ± 5% (10 days), and 34 ± 4% (30 days) to 35 ± 5%, 28 ± 5%, and 24 ± 4%, respectively. These observations suggest that the liver contributes to cardioprotection in MI by upregulating and releasing protective secretory proteins. These proteins may be used for the development of cardioprotective agents.

  11. PREVENTION AND TREATMENT OF ISCHEMIA-REPERFUSION INJURY IN LIVER TRANSPLANTATION-POSSIBLE WAY TO EXPAND THE DONOR POOL

    Directory of Open Access Journals (Sweden)

    D. L. Tsoy

    2013-01-01

    Full Text Available The shortage of donor organs results in the search for alternative ways to increase the donor pool. One of these is the expansion of marginal donor criteria. The use of liver grafts from donors in this group is associated with a high risk of primary non-functioning graft which lies at the basis of ischemia-reperfusion injury of the liver. In this regard, in this review, we examined the main stages of the pathogenesis of liver disturbances as well as modern methods of prevention and treatment. 

  12. Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Sung, E-mail: Jae.Kim@surgery.ufl.edu; Wang, Jin-Hee, E-mail: jin-hee.wang@surgery.ufl.edu; Biel, Thomas G., E-mail: Thomas.Biel@surgery.ufl.edu; Kim, Do-Sung, E-mail: do-sung.kim@surgery.med.ufl.edu; Flores-Toro, Joseph A., E-mail: Joseph.Flores-Toro@surgery.ufl.edu; Vijayvargiya, Richa, E-mail: rvijayvargiya@ufl.edu; Zendejas, Ivan, E-mail: ivan.zendejas@surgery.ufl.edu; Behrns, Kevin E., E-mail: Kevin.Behrns@surgery.ufl.edu

    2013-12-15

    Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: • A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. • Impaired autophagy is a key event contributing to lethal reperfusion injury. • The importance of autophagy is extended and confirmed in an in vivo model. • CBZ is a potential

  13. Effect of liver regeneration after partial hepatectomy and ischemia-reperfusion on expression of growth factor receptors

    Institute of Scientific and Technical Information of China (English)

    P Baier; G Wolf-Vorbeck; S Hempel; UT Hopt; E von Dobschuetz

    2006-01-01

    AIM: To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration.This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration.METHODS: For partial hepatectomy (PH) 80% of the liver mass was resected in Sprague Dawley rats.Ischemia and reperfusion (I/R) were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury.Quantitative RT-PCR was performed at the time point of minimal receptor expression (24 h).RESULTS: In immunohistochemistry, EGFR, HGFR,FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control.CONCLUSION: At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore,a therapeutic use of growth factors to stimulate liver regeneration 24 h after the damage might be not successful.

  14. Hepatic ischemia

    Science.gov (United States)

    ... or oxygen, causing injury to liver cells. Causes Low blood pressure from any condition can lead to hepatic ischemia. ... leading to reduced blood flow (vasculitis) Symptoms If low blood pressure continues for a long time, you may feel ...

  15. Pentoxifylline enhances the protective effects of hypertonic saline solution on liver ischemia reperfusion injury through inhibition of oxidative stress Pentoxifylline enhances the protective effects of hypertonic saline solution on liver ischemia reperfusion injury through inhibition of oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Vinicius Rocha-Santos; Estela RR Figueira; Joel A Rocha-Filho; Ana MM Coelho; Rafael Soraes Pinheiro; Telesforo Bacchella; Marcel CC Machado; Luiz AC D'Albuquerque

    2015-01-01

    BACKGROUND:Liver ischemia reperfusion (IR) injury trig-gers a systemic inlfammatory response and is the main cause of organ dysfunction and adverse postoperative outcomes after liver surgery. Pentoxifylline (PTX) and hypertonic saline solution (HTS) have been identiifed to have beneifcial effects against IR injury. This study aimed to investigate if the addi-tion of PTX to HTS is superior to HTS alone for the preven-tion of liver IR injury. METHODS:Male Wistar rats were allocated into three groups. Control rats underwent 60 minutes of partial liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5%NaCl 15 minutes before reperfusion, and HPTX group were treated with 7.5% NaCl plus 25 mg/kg of PTX 15 minutes be-fore reperfusion. Samples were collected after reperfusion for determination of ALT, AST, TNF-α, IL-6, IL-10, mitochondrial respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase. RESULTS:HPTX signiifcantly decreased TNF-α 30 minutes after reperfusion. HPTX and HTS signiifcantly decreased ALT, AST, IL-6, mitochondrial dysfunction and pulmonary myelo-peroxidase 4 hours after reperfusion. Compared with HTS only, HPTX signiifcantly decreased hepatic oxidative stress 4 hours after reperfusion and pulmonary permeability 4 and 12 hours after reperfusion. CONCLUSION:This study showed that PTX added the beneifcial effects of HTS on liver IR injury through decreases of hepatic oxidative stress and pulmonary permeability.

  16. Raman and UV-Vis Spectroscopy Applied to the Analysis of Liver Tissues from Rats with Myocardial Ischemia Induced by Isoproterenol

    Institute of Scientific and Technical Information of China (English)

    GAO Hai-cheng; ZOU Ying-gang; HUANG Yu-xin; GAO Hai-mei; CHEN Lei; PEI Jin

    2011-01-01

    The application of the laser Raman spectroscopic(LRS) technique for the analysis of liver tissues from rats with myocardial ischemia induced by isoproterenol(ISO) was described.Animal model of myocardial ischemia was established for rats induced by ISO.Rats were randomly divided into four groups as normal group and myocardial ischemia groups.We observed the successful myocardial ischemia model via serum enzymes levels and hematoxylin-eosin(HE) staining,and detected the liver tissue of the rats from normal group and liver tissue of the rats from myocardial ischemia groups via UV-Vis spectroscopy(UV-Vis) and LRS,and the changes of the absorbance spectra were compared in the above four different groups.The results show that ISO can induce rat myocardial ischemia successfully.The spectrum of normal liver tissue supernatant exhibits a strong absorption band at 968 nm,but no absorption band appears in the spectra of liver tissue supernatant solutions from the rats with myocardial ischemia induction after 2,12 and 72 h presented at 968 nm.LRS results show that Raman intensities of the precipitates suffered from ISO-treatment after 2,12 and 72 h were obviously increased compared with that of the precipitate of the liver tissue of the normal rats suffered from 0.9 g/L normal saline(NS) treatment.These results indicate that LRS and UV-Vis can be harmless,nondestructive,rapid and effective methods for analyzing different pathological specimens of liver tissue from myocardial ischemia rats.

  17. Prostacyclin analog-suppressed ischemia-reperfusion injury of the rat liver: evaluation by calpain mu activation.

    Science.gov (United States)

    Wang, M; Sakon, M; Miyoshi, H; Umeshita, K; Kishimoto, S; Taniguchi, K; Gotoh, M; Imajoh-Ohmi, S; Monden, M

    1997-12-01

    Prostaglandin I2 has a protective effect on hepatic ischemia-reperfusion injury. However, the exact intracellular mechanisms of this effect have not been elucidated. Calpain micro, a Ca2+-dependent protease, has been found to play a role in the ischemia-reperfusion injury of various organs. The hilar area of the left lateral and median lobes of rat livers was clamped for 60 min. A prostaglandin I2 analog (OP2507, C35H41NO4) was intravenously administered at 0.1, 0.32, or 1.0 microg/kg/min from 20 min before the ischemia. In addition to biochemical and microscopic analyses, the activation of calpain mu was investigated using specific antibodies against the intermediate (activated) and preactivated forms of calpain mu. The degradation of talin was also studied by Western blotting. When OP2507 was infused at 0.32 and 1.0 microg/kg/min, bile flow significantly increased after reperfusion compared with the control group, consistent with the decrease in serum transaminase levels. Membrane bleb formation and the appearance of the intermediate form of calpain mu were observed at 60 min of ischemia in the control and OP2507 (0.1 microg/kg/min) groups and remained present until 120 min after reperfusion. OP2507 (1.0 microg/kg/min) markedly suppressed not only membrane bleb formation but also calpain mu activation and the degradation of talin. In conclusion, OP2507 suppresses ischemia-reperfusion injury of the rat liver, and its cytoprotective effect is closely associated with the inhibition of calpain mu activation.

  18. Carnosic acid nanoparticles suppress liver ischemia/reperfusion injury by inhibition of ROS, Caspases and NF-κB signaling pathway in mice.

    Science.gov (United States)

    Li, Hui; Sun, Jian-Jun; Chen, Guo-Yong; Wang, Wei-Wei; Xie, Zhan-Tao; Tang, Gao-Feng; Wei, Si-Dong

    2016-08-01

    Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can lead to early graft injury. However, the detailed molecular mechanism of I/R injury remains unclear. Carnosic acid, as a phenolic diterpene with function of anti-inflammation, anti-cancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, is produced by many species from Lamiaceae family. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions. Administration of carnosic acid nanoparticles was thought to be sufficient to lead to considerable inhibition of liver injury progression induced by ischemia/reperfusion. In our study, liver ischemia/reperfusion injury was established successfully with C57BL/6 animal model. 10 and 20mg/kg carnosic acid nanoparticles were injected to mice for five days prior to ischemia. After liver ischemia/reperfusion, the levels of serum AST, ALT and APL were increased, which was attenuated by pre-treatment with carnosic acid nanoparticles. In addition, carnosic acid nanoparticles inhibited ROS production via its related signals regulation. And carnosic acid nanoparticles also suppressed the ischemia/reperfusion-induced up-regulation in the pro-apoptotic protein and mRNA levels of Bax, Cyto-c, Apaf-1 and Caspase-9/3 while increased ischemia/reperfusion-induced decrease of anti-apoptotic factor of Bcl-2. Further, ischemia/reperfusion-induced inflammation was also inhibited for carnosic acid nanoparticles administration via inactivating NF-κB signaling pathway, leading to down-regulation of pro-inflammatory cytokines releasing. In conclusion, our study suggested that carnosic acid nanoparticles protected against liver ischemia/reperfusion injury via its role of anti-oxidative, anti-apoptotic and anti-inflammatory bioactivity.

  19. Short-term starvation attenuates liver ischemia-reperfusion injury (IRI) by Sirt1-autophagy signaling in mice

    Science.gov (United States)

    Qin, Jianjie; Zhou, Junjin; Dai, Xinzheng; Zhou, Haoming; Pan, Xiongxiong; Wang, Xuehao; Zhang, Feng; Rao, Jianhua; Lu, Ling

    2016-01-01

    Calorie restriction or starvation (fasting) has some beneficial effects in terms of prolonging life and increasing resistance to stress. It has also been shown that calorie restriction has a protective role during ischemia-reperfusion injury (IRI) in several organs, but the underlying mechanism has not been elucidated. In this study we investigated the effects and molecular mechanisms of short-term starvation (STS) on liver IRI in a mouse liver IRI model. We found that STS significantly attenuated liver IRI in this model, as evidenced by inhibition of serum aminotransferase levels, and decreased pathological damage and hepatocellular apoptosis, especially after 2- or 3-day starvation. Furthermore, we found that 2- or 3-day starvation induced expression of hepatocellular autophagy in vivo and in vitro. Further experiments provided support for the notion that STS-induced autophagy played a key role during starvation-regulated protection against liver IRI via autophagy inhibition with 3-methyladenine. Interestingly, the longevity gene Sirt1 was also significantly up-regulated in liver after STS. Importantly, inhibition of Sirt1 by sirtinol abolished STS-induced autophagy and further abrogated STS-mediated protection against liver IRI. In conclusion, our results indicate that STS attenuates liver IRI via the Sirt1-autophagy pathway. Our findings provide a rationale for a novel therapeutic strategy for managing liver IRI. PMID:27648127

  20. Alleviation of Ischemia-Reperfusion Injury in Liver Steatosis by Augmenter of Liver Regeneration Is Attributed to Antioxidation and Preservation of Mitochondria.

    Science.gov (United States)

    Weng, Junhua; Li, Wen; Jia, Xiaowei; An, Wei

    2017-10-01

    Fatty liver is one of the major impediments to liver surgery and liver transplantation because steatotic hepatocytes are more susceptible to ischemia-reperfusion injury (IRI). In this study, the effects of augmenter of liver regeneration (ALR) on hepatic IRI in steatotic mice were investigated. In vivo, liver steatosis of mice was induced by feeding a methionine-choline-deficient diet for 2 weeks. Three days before hepatic partial warm IRI, mice were transfected with the ALR-containing adenovirus. In an in vitro study, the protective effect of ALR on steatotic HepG2 cells was analyzed after hypoxia/reoxygenation (HR) treatment. The transfection of the ALR gene into steatotic mice attenuated liver injury, inhibiting hepatic oxidative stress, increasing antioxidation capacities, promoting liver regeneration, and consequently suppressing cell apoptosis/death. Furthermore, resistance to HR injury was notably increased in ALR-transfected cells compared with the vector-transfected cells. The HR-induced rise in the mitochondrial reactive oxygen species was reduced, and cellular antioxidant activities were enhanced. The ALR transfection prevented cells from apoptosis, which can be attributed to the preservation of the mitochondrial membrane potential, enhancement of oxygen consumption rate and production of adenosine triphosphate. ALR protects steatotic hepatocytes from IRI by attenuating oxidative stress and mitochondrial dysfunction, as well as improving antioxidant effect. ALR may be used as a potential therapeutic agent when performing surgery and transplantation of steatotic liver.

  1. Age dependence of rat liver function measurements

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

    1989-01-01

    Changes in the galactose elimination capacity, the capacity of urea-N synthesis and antipyrine clearance were studied in male Wistar rats at the age of 8, 20 and 44 weeks. Further, liver tissue concentrations of microsomal cytochrome P-450, microsomal protein and glutathione were measured. All...... liver function measurements increased from the age of 8 to 44 weeks when expressed in absolute values. In relation to body weight, these function measurements were unchanged or reduced from week 8 to week 20. At week 44, galactose elimination capacity and capacity of urea-N synthesis related to body...... weight were increased by 10% and 36%, respectively, and antipyrine plasma clearance was reduced to 50%. Liver tissue concentrations of microsomal cytochrome P-450 and microsomal protein increased with age when expressed in absolute values, but were unchanged per g liver, i.e., closely related to liver...

  2. Interaction of L-Arginine-methyl ester and Sonic hedgehog in liver ischemia-reperfusion injury in the rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the role of Sonic hedgehog (Shh) on the course of liver ischemia and repeffusion (I/R) in rats,and the interaction between treatment with nitric oxide donor L-Arginine-methyl ester (L-Arg) and up-regulation of Shh expression.METHODS: A total of 30 male Sprague-Dawley rats weighing 220-240 g were used in this study. Sham-control group (G1, n = 10): a sham operation was performed (except for liver I/R). I/R-untreated group (G2,n = 10): rats underwent liver ischemia for 1 h followed by reperfusion for 45 min. I/R-L-Arg group (G3, n =10): after performing the same surgical procedure as in group 2, animals were treated with L-Arg. Liver tissues were taken for determination of malondialdehyde (MDA)levels, and biochemical and histological evaluations were made.RESULTS: Plasma alanine aminotransferase (ALT),aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and γ-glutamyltranspeptidase (GGT) activities were higher in group 2 than in group 3. MDA values and the hepatic injury score decreased in the L-Arg treated group compared to the I/R-untreated group. In group 2,the hepatocytes were swollen with marked vacuolization.Group 3 rats showed well-preserved liver parenchyma,with hepatocytes extending from the central vein. The morphology of the hepatocytes and the sinusoidal structures was normal, without any signs of congestion.Mild Shh positive immunostaining was detected in group 2 animals. The expression of immunoreactive cells was increased markedly in liver tissue from I/R-L-Arg rats.CONCLUSION: Our findings suggest that Shh molecules are critical factors in the pathophysiology of inflammatory liver injury induced by I/R. In addition, NO plays an important role in the immunohistochemical expression of these molecules.

  3. Effect of Leukocytes Transfer on the Induction of Liver Damage after Renal Ischemia- Reperfusion in Inbred Mice

    Directory of Open Access Journals (Sweden)

    Hossein Khastar

    2012-07-01

    Full Text Available Introduction: Renal ischemia-reperfusion (IR induces organ damage in remote organs such as liver, brain and lung. The aim of this study was to assess the role of leukocytes in the induction of liver damage after renal IR injury.Methods: Inbred mice were subjected to either sham operation or bilateral renal IR injury (60 min ischemia followed by 3h reperfusion. Mice were then anesthetized for collection of leukocytes by heart puncture. Isolated leukocytes were transferred to two other groups: intact recipient mice that received leukocytes from IR mice and intact recipient mice that received leukocytes from sham-operated control mice. After 24h, recipient mice were anesthetized and blood and hepatic samples were collected.Results: Alanine aminotransferase (ALT, aspartate aminotransferase (AST and hepatic malondialdehyde (MDA increased significantly in intact recipient mice that received leukocytes from IR mice in comparison to intact recipient mice receiving leukocytes from sham-operated control mice. In addition, loss of normal liver architecture, cytoplasmic vacuolization and focal infiltration of leukocytes were observed.Conclusion: These results suggest that leukocytes are one of the possible factors that contribute to liver damage after renal IR injury and this damage is partly due to the induction of oxidative stress.

  4. Comparison Analysis of Dysregulated LncRNA Profile in Mouse Plasma and Liver after Hepatic Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Chen, Zhenzhen; Luo, Yanjin; Yang, Weili; Ding, Liwei; Wang, Junpei; Tu, Jian; Geng, Bin; Cui, Qinghua; Yang, Jichun

    2015-01-01

    Long noncoding RNAs (LncRNAs) have been believed to be the major transcripts in various tissues and organs, and may play important roles in regulation of many biological processes. The current study determined the LncRNA profile in mouse plasma after liver ischemia/reperfusion injury (IRI) using microarray technology. Microarray assays revealed that 64 LncRNAs were upregulated, and 244 LncRNAs were downregulated in the plasma of liver IRI mouse. Among these dysregulated plasma LncRNAs, 59-61% were intergenic, 22-25% were antisense overlap, 8-12% were sense overlap and 6-7% were bidirectional. Ten dysregulated plasma LncRNAs were validated by quantitative PCR assays, confirming the accuracy of microarray analysis result. Comparison analysis between dysregulated plasma and liver LncRNA profile after liver IRI revealed that among the 308 dysregulated plasma LncRNAs, 245 LncRNAs were present in the liver, but remained unchanged. In contrast, among the 98 dysregulated liver LncRNAs after IRI, only 19 were present in the plasma, but remained unchanged. LncRNA AK139328 had been previously reported to be upregulated in the liver after IRI, and silencing of hepatic AK139328 ameliorated liver IRI. Both microarray and RT-PCR analyses failed to detect the presence of AK139328 in mouse plasma. In summary, the current study compared the difference between dysregulated LncRNA profile in mouse plasma and liver after liver IRI, and suggested that a group of dysregulated plasma LncRNAs have the potential of becoming novel biomarkers for evaluation of ischemic liver injury.

  5. Effects of melatonin on liver function and lipid peroxidation in a rat model of hepatic ischemia/reperfusion injury.

    Science.gov (United States)

    Deng, Wen-Sheng; Xu, Qing; Liu, Y E; Jiang, Chun-Hui; Zhou, Hong; Gu, Lei

    2016-05-01

    The present study aimed to investigate the effects of melatonin (MT) on liver function and lipid peroxidation following hepatic ischemia-reperfusion injury (IRI). A total of 66 male Sprague-Dawley rats were randomly assigned into three groups: Normal control (N) group, ischemia-reperfusion (IR) group and the MT-treated group. A hepatic IRI model was developed by blocking the first porta hepatis, and subsequently restoring hepatic blood inflow after 35 min. Following reperfusion, changes in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were detected by a chemical method at various time points. In the MT group, the MDA levels were significantly reduced (PLDH were significantly reduced in the MT group at each time point, as compared with that of the IR group (Pfunction following IRI.

  6. Oxidation of HMGB1 causes attenuation of its pro-inflammatory activity and occurs during liver ischemia and reperfusion.

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    Anding Liu

    Full Text Available High mobility group box 1 (HMGB1 is a nuclear transcription factor. Once HMGB1 is released by damaged cells or activated immune cells, it acts as danger molecule and triggers the inflammatory signaling cascade. Currently, evidence is accumulating that posttranslational modifications such as oxidation may modulate the pro-inflammatory potential of danger signals. We hypothesized that oxidation of HMGB1 may reduce its pro-inflammatory potential and could take place during prolonged ischemia and upon reperfusion.Liver grafts were cold preserved for 24 h and flushed with saline in hourly intervals to collect the effluent. Liver grafts, cold-preserved for 6 h, were transplanted into syngeneic recipients to obtain serum and liver samples 24 h after initiation of reperfusion. Addition of the effluent to a macrophage culture induced the synthesis of tumor necrosis factor-alpha (TNF-α and interleukin (IL-6. The stimulatory activity of graft effluent was reduced after depletion of HMGB1 via immunoprecipitation. Oxidation of the effluent HMGB1 using H(2O(2 attenuated its stimulatory activity as well. Liver transplantation of cold preserved grafts caused HMGB1 translocation and release as determined by immunohistochemistry and ELISA-assay, respectively. Using Western blot with non-reducing conditions revealed the presence of oxidized HMGB1 in liver samples obtained after 12 h and in effluent samples after 16 h of cold preservation as well as in liver and serum samples obtained 24 h after reperfusion.These observations confirm that post-translational oxidation of HMGB1 attenuates its pro-inflammatory activity. Oxidation of HMGB1 as induced during prolonged ischemia and by reoxygenation during reperfusion in vivo might also attenuate its pro-inflammatory activity. Our findings also call for future studies to investigate the mechanism of the inhibitory effect of oxidized HMGB1 on the pro-inflammatory potential.

  7. Protective effects of lidocaine injected into the hepatoduodenal ligament on warm ischemia-reperfusion injury to the rat liver

    Institute of Scientific and Technical Information of China (English)

    陈明易; 李崇辉; 黄志强; 刘巨超; 周宁新; 黄晓强; 王燕生

    2004-01-01

    Background Ischemia-reperfusion (IR) injury to the liver is still a critical and daunting problem in the field of hepatobiliary surgery. Ischemic preconditioning (IP) of the liver serves as an effective approach against IR injury. This study was to develop a novel procedure that could mimic IP, but might be more feasible than IP during surgery. Methods Eighty-two SD rats were randomly divided into 5 groups. L group (n=21): 0.4% lidocaine (10 mg/kg) was injected into the hepatoduodenal ligament 10 minutes before a 40-minute hepatic IR. IP group (n=16): a 5-minute ischemia was followed by a 10-minute reperfusion prior to a 40-minute hepatic IR. ILR group (n=15): after a 40-minute ischemia of the liver, 0.4% lidocaine ( 10 mg/kg) was injected into the hepatoduodenal ligament 10 minutes prior to a 40-minute reperfusion of the liver. IR group (n =15): the liver of the rat was subjected to a 40-minute IR. Control group (n = 15) 0.9% sodium chloride was injected into the hepatoduodenal ligament without other treatments. The levels of plasma alanine transaminase (ALT) and aspartate transaminase (AST) were determined for each group after treatment. Results The mean concentrations of ALT and AST were (379. 80 + 141.69) U/L and (606.05± 220.26) U/L for the L group, (334.64 ±141.94) U/L and (625.68 ±267.06) U/L for the IP group,(523. 36 ±170. 35) U/L and (765.47 ±238. 45) U/L for the lLP group, (524. 29 ±163. 59) U/L and (764. 63 ±246.79) U/L for the IR group, and (150.90 ±27.05) U/L and (298. 15 ±47.68) U/L for the control group (standard error of the mean). Conclusion A significant decrease in ALT and AST levels was observed in the L and IP groups when compared to the ILR and IR groups ( P<0.05), but no significant difference in ALT and AST levels was observed in the L group when compared to the IP group (P>0. 05). These results suggest that pretreatment with lidocaine injected into the hepatoduodenal ligament prior to IR provides effective protection against

  8. Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy

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    Goel, Utsav O.; Maddox, Michael M.; Elfer, Katherine N.; Dorsey, Philip J.; Wang, Mei; McCaslin, Ian Ross; Brown, J. Quincy; Lee, Benjamin R.

    2014-10-01

    Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

  9. Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1.

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    Fang Xie

    Full Text Available To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1.The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs were cultured at the circumstances of hypoxia/reoxygenation (H/R and low temperature. The rabbit liver IRI model (I/R group was established using the Pringle's maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated.The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6-7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group.The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level.

  10. Intraportal versus Systemic Pentoxifylline Infusion after Normothermic Liver Ischemia: Effects on Regional Blood Flow Redistribution and Hepatic Ischemia-Reperfusion Injury

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    Edson A. Ribeiro

    2013-01-01

    Full Text Available Pentoxifylline (PTX has been shown to have beneficial effects on microcirculatory blood flow. In this study we evaluate the potential hemodynamic and metabolic benefits of PTX during hepatic ischemia. We also test the hypothesis that portal PTX infusion can minimize the I/R injury when compared to systemic infusion. Methods. Twenty-four dogs ( kg were subjected to portal triad occlusion (PTO for 45 min. The animals were assigned to 3 groups: CT (control, PTO, , PTX-syst (PTO + 25 mg/Kg of PTX IV, , and PTX-pv (PTO + 25 mg/Kg of PTX in the portal vein, . Animals were followed for 120 min. Systemic hemodynamics, gastrointestinal tract perfusion, oxygen-derived variables, and liver enzymes were evaluated throughout the experiment. Results. Animals treated with PTX presented significantly higher CO in the first hour after reperfusion, when compared to the CT (~3.7 vs. 2.1 L/min, . Alanine aminotransferase (ALT was similar in the PTX groups two hours after reperfusion but significantly higher in the CT (227 vs. ~64 U/L, . Conclusion. PTX infusion was associated with hemodynamic benefits and was able to minimize liver injury during normothermic hepatic I/R. However, local PTX infusion was not associated with any significant advantage over systemic route.

  11. TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion.

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    Pieter J Bakker

    Full Text Available Ischemia reperfusion injury is a common cause of acute kidney injury and is characterized by tubular damage. Mitochondrial DNA is released upon severe tissue injury and can act as a damage-associated molecular pattern via the innate immune receptor TLR9. Here, we investigated the role of TLR9 in the context of moderate or severe renal ischemia reperfusion injury using wild-type C57BL/6 mice or TLR9KO mice. Moderate renal ischemia induced renal dysfunction but did not decrease animal well-being and was not regulated by TLR9. In contrast, severe renal ischemia decreased animal well-being and survival in wild-type mice after respectively one or five days of reperfusion. TLR9 deficiency improved animal well-being and survival. TLR9 deficiency did not reduce renal inflammation or tubular necrosis. Rather, severe renal ischemia induced hepatic injury as seen by increased plasma ALAT and ASAT levels and focal hepatic necrosis which was prevented by TLR9 deficiency and correlated with reduced circulating mitochondrial DNA levels and plasma LDH. We conclude that TLR9 does not mediate renal dysfunction following either moderate or severe renal ischemia. In contrast, our data indicates that TLR9 is an important mediator of hepatic injury secondary to ischemic acute kidney injury.

  12. Effects of anti-histamine treatment on liver injury triggered by small intestinal ischemia reperfusion in rats.

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    Huang, Pin-Jie; Gan, Xiao-Liang; Liu, Jian-Pei; Liu, De-Zhao; Wang, Yan-Ling; Hei, Zi-Qing

    2014-10-31

    Mast cell (MC) degranulation has been implicated in small intestinal ischemia reperfusion (IIR) injury, therein, inhibiting overproduction of histamine released from activated MC may provide promising strategies against IIR-mediated liver injuries. The aim of the present study was to explore whether anti-histamine treatment contribute to attenuating IIR-mediated liver injury. Adult SD rats were randomized into sham-operated group (S group), sole IIR group (IIR group), and IIR treated with Ketotifen, a histamine antagonist (IIR+K group), Cromolyn Sodium, a MC stabilizer (IIR+C group), and Compound 48/80, a MC degranulator (IIR+CP group), respectively. IIR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were intravenously administrated 5 min before reperfusion to induce different levels of histamine. Subsequently, serum concentrations of ALT, AST and histamine; levels of LDH,TNF-α, IL-8 and MDA as well as SOD activities in the liver were assessed. Histopathologic changes were also evaluated. IIR resulted in severe liver injury as demonstrated by significant increases in injury scores, with concomitant significant increases in serum ALT, AST and histamine levels, as well as LDH, TNF-α, IL-8, and MDA levels in the liver, accompanied by reduction in SOD activities (all P IIR vs. S). Treatments by Ketotifen and Cromolyn Sodium similarly markedly alleviated IIR-mediated liver injury as confirmed by significant reduction of the above biomedical changes whereas Compound 48/80 further aggravated IIR-mediated liver injury by dramatically enhancing the above biomedical changes. Data of our study suggest that anti-histamine treatments may provide promising benefits in alleviating liver injury triggered by IIR.

  13. Protective effect of gadolinium chloride on early warm ischemia/reperfusion injury in rat bile duct during liver transplantation.

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    Biao Wang

    Full Text Available BACKGROUND: Activation of Kupffer cell (KC is acknowledged as a key event in the initiation and perpetuation of bile duct warm ischemia/reperfusion injury. The inhibitory effect of gadolinium chloride (GdCl(3 on KC activation shows potential as a protective intervention in liver injury, but there is less research with regard to bile duct injury. METHODS: Sixty-five male Sprague-Dawley rats (200-250 g were randomly divided into three experimental groups: a sham group (n = 15, a control group (n = 25, and a GdCl(3 group (n = 25. Specimen was collected at 0.5, 2, 6, 12 and 24 h after operation. Alanine aminotransferase (ALT, alkaline phosphatase (ALP and total bilirubin (TBIL of serum were measured. Tumor necrosis factor-α (TNF-α, Capase-3 activity and soluble Fas (sFas were detected. The pathologic changes of bile duct were observed. Immunochemistry for bile duct Fas was performed. Apoptosis of bile duct cells was evaluated by the terminal UDP nick end labeling assay. RESULTS: GdCl(3 significantly decreased the levels of ALT, ALP and TBIL at 2, 6, 12, and 24 h, and increased serum sFas at 2, 6 and 12 h (P<0.05. TNF-α was lower in the GdCl(3 group than in the control group at 2, 6, 12 and 24 h (P<0.05. Preadministration of GdCl(3 significantly reduced the Caspase-3 activity and bile duct cell apoptosis at 2, 6, 12 and 24 h. After operation for 2, 6 and 12 h, the expression of Fas protein was lower in the GdCl(3 group than in the control group (P<0.05. CONCLUSIONS: GdCl(3 plays an important role in suppressing bile duct cell apoptosis, including decreasing ALT, ALP, TBIL and TNF-α; suppressing Fas-FasL-Caspase signal transduction during transplantation.

  14. Protection of Veratrum nigrum L. var. ussuriense Nakai alkaloids against ischemia-reperfusion injury of the rat liver

    Institute of Scientific and Technical Information of China (English)

    Zhen-Zhen Wang; Ji-Hong Yao; Wei-Jie Zhao; Xue-Song Zhang; Xiao-Feng Tian; Yu-Zhu Wang; Feng Zhang; Jin-Chan Yuan; Guo-Zhu Han; Ke-Xin Liu

    2007-01-01

    AIM: To investigate the protective effects and possible mechanisms of Veratrum nigrum L. Var. Ussuriense Nakai alkaloids (VnA) on hepatic ischemia/reperfusion (I/R) injury in rats.METHODS: Forty male Wistar rats were randomly divided into four experimental groups (n = 10 in each):(A) Control group (the sham operation group); (B) I/R group (pretreated with normal saline); (C) Small-dose (10 μg/kg) VnA pretreatment group; (D) Large-dose (20 μg/kg) VnA pretreatment group. Hepatic ischemia/reperfusion (Hepatic I/R) was induced by occlusion of the portal vein and the hepatic artery for 90 min, followed by reperfusion for 240 min. The pretreatment groups were administered with VnA intraperitoneally, 30 min before surgery, while the control group and I/R group were given equal volumes of normal saline. Superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity and nitric oxide (NO) content in the liver tissue at the end of reperfusion were determined and liver function was measured. The expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin (ES) were detected by immunohistochemical examinations and Western blot analyses.RESULTS: The results showed that hepatic I/R elicited a significant increase in the plasma levels of alanine aminotransferase (ALT: 74.53 ± 2.58 IU/L vs 1512.54 ± 200.76 IU/L, P < 0.01) and lactic dehydrogenase (LDH: 473.48 ± 52.17 IU/L vs 5821.53 ± 163.69 IU/L,P < 0.01), as well as the levels of MPO (1.97 ± 0.11U/g vs 2.57 ± 0.13 U/g, P < 0.01) and NO (69.37 ± 1.52 μmol/g protein vs 78.39 ± 2.28 μmol/g protein, P < 0.01) in the liver tissue, all of which were reduced by pretreatment with VnA, respectively (ALT: 1512.54 ± 200.76 IU/L vs 977.93 ± 89.62 IU/L, 909.81 ± 132.76 IU/L, P < 0.01, P < 0.01; LDH: 5821.53 ± 163.69 IU/L vs 3015.44 ± 253.01 IU/L, 2448.75 ± 169.4 IU/L, P < 0.01, P < 0.01; MPO: 2.57 ± 0.13 U/g vs 2.13 ± 0.13 U/g,2.07 ± 0.05 U/g, P < 0.01, P < 0.01; NO: 78.39 ± 2.28

  15. Japanese herbal medicine, Saiko-keishi-to, prevents gut ischemia/reperfusion-induced liver injury in rats via nitric oxide

    Institute of Scientific and Technical Information of China (English)

    Yoshinori Horie; Mikio Kajihara; Shuka Mori; Yoshiyuki Yamagishi; Hiroyuki Kimura; Hironao Tamai; Shinzo Kato; Hiromasa Jshii

    2004-01-01

    AIM: To determine whether Saiko-keishi-to (TJ-10), a Japanese herbal medicine, could protect liver injury induced by gut ischemia/reperfusion (I/R), and to investigate the role of NO.METHODS: Male Wistar rats were exposed to 30-min gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor leukocyte recruitment. Plasma tumor necrosis factor (TNF) levels and alanine aminotransferase intragastrically administered to rats for 7 d. A NO synthase inhibitor was administered.RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF levels and ALT activities were mitigated by pretreatment with TJ-10. Pretreatment with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver, and the increase of plasma TNF levels and ALT activities. Pretreatment with TJ-10 increased plasma nitrite/nitrate levels.CONCLUSION: TJ-10 attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.

  16. Age-related differences in hepatic ischemia/reperfusion: gene activation, liver injury, and protective effect of melatonin.

    Science.gov (United States)

    Kireev, Roman A; Cuesta, Sara; Ibarrola, Carolina; Bela, Teresa; Moreno Gonzalez, Enrique; Vara, Elena; Tresguerres, Jesus A F

    2012-12-01

    Ischemia/reperfusion (I/R) causes functional and structural damage to liver cells, this being more pronounced with increasing age of the tissue. Melatonin is a pineal indole that has been shown to play an important role as a free radical scavenger and anti-inflammatory molecule. The age-dependent responses to I/R were compared in 2-mo-old and 14-mo-old male Wistar rats. After 35 min of hepatic ischemia followed by 36 h of reperfusion, rats were sacrificed. Sham-operated control rats underwent the same protocol without real vascular occlusion. Animals were intraperitoneally injected with 10 mg/kg melatonin 24 h before the operation, at the time of surgery, and 12 and 24 h after it. The tissues were submitted to histopathologic evaluation. The levels of ALT and AST were analyzed in plasma. The expression of TNF-α, IL-1β, IL-10, MCP-1, IFN-γ, iNOS, eNOS, Bad, Bax, Bcl2, AIF, PCNA, and NFKB1 genes were detected by RT-PCR in hepatic tissue. I/R was associated with significant increases in the expression of pro-inflammatory and pro-apoptotic genes in liver. Older rats submitted to I/R were found to respond with increased liver damage as compared with young rats, with serum ALT and AST levels significantly higher than in young animals. Mature rats also showed more evident increases in expression of pro-inflammatory cytokines (IL-1β, MCP-1, and IFN-γ) as well as a decrease in the mRNA expression of IL-10 as compared with young animals. Pro-apoptotic genes (Bax, Bad, and AIF) were significantly enhanced in liver after I/R, without differences between young and mature animals. However, the expression of Bcl2 gene did not show any change. Melatonin treatment was able to lower the expression of pro-inflammatory cytokines and pro-apoptotic genes and to improve liver function, as indicated by normalization of plasma AST and ALT levels and by reduction of necrosis and microsteatosis areas. Melatonin treatment was able to reduce the I/R-stimulated pro-inflammatory and pro

  17. Rapamycin Induces Heme Oxygenase-1 in Liver but Inhibits Bile Flow Recovery after Ischemia

    NARCIS (Netherlands)

    Kist, Alwine; Wakkie, Joris; Madu, Max; Versteeg, Ruth; ten Berge, Judith; Nikolic, Andrej; Nieuwenhuijs, Vincent B.; Porte, Robert J.; Padbury, Robert T. A.; Barritt, Greg J.

    2012-01-01

    Background/Aims. Rapamycin, which is employed in the management of patients undergoing liver surgery, induces the synthesis of heme oxygenase-1 (HO-1) in some non-liver cell types. The aim was to investigate whether rapamycin can induce HO-1 expression in the liver, and to test the effects of rapamy

  18. Gaseous persufflation with carbon monoxide during ischemia protects the isolated liver and enhances energetic recovery

    NARCIS (Netherlands)

    Koetting, Martina; Leuvenink, Henri; Dombrowski, Frank; Minor, Thomas

    2010-01-01

    Background: The benefit of carbon monoxide as applied by controlled, continuous gaseous persufflation during liver preservation on postischemic graft recovery was investigated in an isolated rat liver model. Methods: Livers from male Wistar rats were retrieved 30 min after cardiac arrest of the dono

  19. Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats

    Science.gov (United States)

    Copper deficiency can lead to an augmented inflammatory response through effects on both neutrophils and the microvascular endothelium. In the present study, we evaluated the effect of marginal copper deficiency on the inflammatory injury response to hepatic ischemia/reperfusion injury. Male weanlin...

  20. Increased expression of peroxiredoxin 1 and identification of a novel lipid-metabolizing enzyme in the early phase of liver ischemia reperfusion injury

    NARCIS (Netherlands)

    Wilson, Claire H.; Zeile, Susanne; Chataway, Tim; Nieuwenhuijs, Vincent B.; Padbury, Robert T. A.; Barritt, Greg J.

    2011-01-01

    Warm ischemia reperfusion (IR) injury of the liver is associated with changes in the expression and/or post-translational modification of numerous proteins. Only a few of these have been identified. We used 2-D DIGE to identify cytosolic proteins altered in the early stage of IR in an established ra

  1. Chinese Herbal Preparation Xuebijing Potently Inhibits Inflammasome Activation in Hepatocytes and Ameliorates Mouse Liver Ischemia-Reperfusion Injury.

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    Xiqiang Liu

    Full Text Available The Chinese herb preparation Xuebijing injection (XBJ has been widely used in the management of various septic disorders or inflammation-related conditions, however the molecular mechanism of its anti-inflammatory effect remains largely elusive. In the current study, we found that XBJ treatment potently ameliorated mouse hepatic ischemia-reperfusion (IR injury, manifested as decreased liver function tests (LDH, ALT, AST, improved inflammation and less hepatocyte apoptosis. Notably, XBJ markedly inhibited inflammasome activation and IL-1 production in mouse livers subjected to IRI, even in the absence of Kupffer cells, suggesting Kupffer cells are not necessary for hepatic inflammasome activation upon Redox-induced sterile inflammation. This finding led us to investigate the role of XBJ on hepatocyte apoptosis and inflammasome activation using an in vitro hydrogen peroxide (H2O2-triggered hepatocyte injury model. Our data clearly demonstrated that XBJ potently inhibited apoptosis, as well as caspase-1 cleavage and IL-1β production in a time- and dose-dependent manner in isolated hepatocytes, suggesting that in addition to its known modulatory effect on NF-κB-dependent inflammatory gene expression, it also has a direct impact on hepatocyte inflammasome activation. The current study not only deepens our understanding of how XBJ ameliorates inflammation and apoptosis, but also has immediate practical significance in many clinical situations such as partial hepatectomy, liver transplantation, etc.

  2. Arterial ischemia in the deportalized liver following associating liver partition and portal vein ligation for staged hepatectomy

    Institute of Scientific and Technical Information of China (English)

    Srinivas; Sanjeevi; Ernesto; Sparrelid; Stefan; Gilg; Eduard; Jonas; Bengt; Isaksson

    2015-01-01

    Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) is a novel 2-stage technique intended to induce rapid growth of the future liver remnant(FLR). Initial reports of a 12% mortality rate have sparked debate regarding the safety of the procedure. A 64 years old male was planned for a rightsided hemi-hepatectomy due to colorectal cancer liver metastases. Intra-operatively it was decided to convert to an ALPPS due to unexpectedly small segments 2-4. Post-operative serum laboratory tests indicated an acute liver failure and radiological imaging showed no sign of arterial blood flow to the right hemi-liver. A computed tomography examination on post-operative day 3 revealed that the FLR had increased from 290 to 690 m L in 3 d(138% growth). In the following days serum values gradually improved and stage 2 was carried out on post-operative day 7. The rest of the hospital stay was uneventful and the patient made a full recovery. ALPPS is a fascinating advancement in liver surgery. Despite severe post-operative complications, in properly selected cases it provides successful outcomes that other modalities of treatment cannot offer.

  3. Remote ischemic perconditioning prevents liver transplantation-induced ischemia/reperfusion injury in rats: Role of ROS/RNS and eNOS

    Science.gov (United States)

    He, Ning; Jia, Jun-Jun; Li, Jian-Hui; Zhou, Yan-Fei; Lin, Bing-Yi; Peng, Yi-Fan; Chen, Jun-Jie; Chen, Tian-Chi; Tong, Rong-Liang; Jiang, Li; Xie, Hai-Yang; Zhou, Lin; Zheng, Shu-Sen

    2017-01-01

    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). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, and peroxynitrite was semi-quantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of ΔΨm induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up

  4. Evaluation of light scattering and absorption properties ofin vivorat liver using a single-reflectance fiber probe during preischemia, ischemia-reperfusion, and postmortem

    Science.gov (United States)

    Akter, Sharmin; Maejima, Satoshi; Kawauchi, Satoko; Sato, Shunichi; Hinoki, Akinari; Aosasa, Suefumi; Yamamoto, Junji; Nishidate, Izumi

    2015-07-01

    Diffuse reflectance spectroscopy (DRS) has been extensively used for characterization of biological tissues as a noninvasive optical technique to evaluate the optical properties of tissue. We investigated a method for evaluating the reduced scattering coefficient , the absorption coefficient μa, the tissue oxygen saturation StO2, and the reduction of heme aa3 in cytochrome c oxidase CcO of in vivo liver tissue using a single-reflectance fiber probe with two source-collector geometries. We performed in vivo recordings of diffuse reflectance spectra for exposed rat liver during the ischemia-reperfusion induced by the hepatic portal (hepatic artery, portal vein, and bile duct) occlusion. The time courses of μa at 500, 530, 570, and 584 nm indicated the hemodynamic change in liver tissue as well as StO2. Significant increase in μa(605)/μa(620) during ischemia and after euthanasia induced by nitrogen breathing was observed, which indicates the reduction of heme aa3, representing a sign of mitochondrial energy failure. The time courses of at 500, 530, 570, and 584 nm were well correlated with those of μa, which also reflect the scattering by red blood cells. On the other hand, at 700 and 800 nm, a temporary increase in and an irreversible decrease in were observed during ischemia-reperfusion and after euthanasia induced by nitrogen breathing, respectively. The change in in the near-infrared wavelength region during ischemia is indicative of the morphological changes in the cellular and subcellular structures induced by the ischemia, whereas that after euthanasia implies the hepatocyte vacuolation. The results of the present study indicate the potential application of the current DRS system for evaluating the pathophysiological conditions of in vivo liver tissue.

  5. Hypothermic machine preservation reduces molecular markers of ischemia/reperfusion injury in human liver transplantation.

    Science.gov (United States)

    Henry, S D; Nachber, E; Tulipan, J; Stone, J; Bae, C; Reznik, L; Kato, T; Samstein, B; Emond, J C; Guarrera, J V

    2012-09-01

    Hypothermic machine perfusion (HMP) is in its infancy in clinical liver transplantation. Potential benefits include diminished preservation injury (PI) and improved graft function. Molecular data to date has been limited to extrapolation of animal studies. We analyzed liver tissue and serum collected during our Phase 1 trial of liver HMP. Grafts preserved with HMP were compared to static cold stored (SCS) transplant controls. Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and transmission electron microscopy (TEM) were performed on liver biopsies. Expression of inflammatory cytokines, adhesion molecules and chemokines, oxidation markers, apoptosis and acute phase proteins and the levels of CD68 positive macrophages in tissue sections were evaluated. RT-PCR of reperfusion biopsy samples in the SCS group showed high expression of inflammatory cytokines, adhesion molecules and chemokines, oxidative markers and acute phase proteins. This upregulation was significantly attenuated in livers that were preserved by HMP. Immunofluorescence showed larger numbers of CD68 positive macrophages in the SCS group when compared to the HMP group. TEM samples also revealed ultrastructural damage in the SCS group that was not seen in the HMP group. HMP significantly reduced proinflammatory cytokine expression, relieving the downstream activation of adhesion molecules and migration of leukocytes, including neutrophils and macrophages when compared to SCS controls.

  6. Hepatic ischemic preconditioning increases portal vein lfow in experimental liver ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Estela RR Figueira; Joel A Rocha-Filho; Mauro Nakatani; Marcelo FS Buto; Eduardo R Tatebe; Vitor O Andre

    2014-01-01

    BACKGROUND: Ischemic preconditioning (IPC) has been shown to decrease liver injury and to increase hepatic microvascular perfusion after liver ischemia reperfusion. This study aimed to evaluate the effects of IPC on hemodynamics of the portal venous system. METHODS: Thirty-two  rats  were  randomized  into  two groups: IPC group and control group. The rats of the IPC group underwent IPC by 10 minutes of liver ischemia followed by 10 minutes of reperfusion before liver ischemia, and the rats of the control group were subjected to 60 minutes of partial liver ischemia. Non-ischemic lobes were resected immediately after reperfusion. The animals were studied at 4 hours and 12 hours after reperfusion. Mean arterial pressure, heart rate, portal vein lfow and pressure were analyzed. Blood was collected for the determination of the levels of aspartate aminotransferase, alanine aminotransferase, calcium, lactate, pH, bicarbonate, and base excess. RESULTS: IPC increased the mean portal vein lfow at 4 hours and 12 hours after reperfusion. IPC recovered 78% of the mean portal vein lfow at 12 hours after reperfusion. IPC decreased the levels of aspartate aminotransferase, alanine aminotransferase and  lactate,  and  increased  the  levels  of  ionized  calcium, bicarbonate and base excess at 12 hours after reperfusion. CONCLUSIONS: This study demonstrated that IPC increases portal  vein  lfow  and  enhances  hepatoprotective  effects  in liver  ischemia  reperfusion.  The  better  recovery  of  portal vein lfow after IPC may be correlated

  7. Hemoperfusion with polymyxin B-immobilized fiber column improves liver function after ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hiroaki Sato; Kiyohiro Oshima; Katsumi Kobayashi; Hodaka Yamazaki; Yujin Suto; Izumi Takeyoshi

    2009-01-01

    AIM: To investigate the usefulness of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) for warm hepatic ischemia-reperfusion (I/R) injury after total hepatic vascular exclusion (THVE) using a porcine model.METHODS: Eleven Mexican hairless pigs weighing 22-38 kg were subjected to THVE for 120 min and then observed for 360 min. The animals were divided into two groups randomly: the DHP-PMX group (n = 5) underwent DHP-PMX at a flow rate of 80 mL/min for 120 min (beginning 10 min before reperfusion), while the control group did not (n = 6). The rate pressure product (RPP): heart rate × end-systolic arterial blood pressure,hepatic tissue blood flow (HTBF), portal vein blood flow (PVBF), and serum aspartate aminotransferase (AST) levels were compared between the two groups. RESULTS: RPP and HTBF were significantly (P < 0.05) higher in the DHP-PMX group than in the control group 240 and 360 min after reperfusion. PVBF in the DHP-PMX group was maintained at about 70% of the flow before ischemia and differed significantly (P < 0.05) compared to the control group 360 min after reperfusion. The serum AST increased gradually after reperfusion in both groups, but the AST was significantly (P < 0.05) lower in the DHP-PMX group 360 min after reperfusion. CONCLUSION: DHP-PMX therapy reduced the hepatic warm I/R injury caused by THVE in a porcine model.

  8. N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reper fusion injur y in mice

    Institute of Scientific and Technical Information of China (English)

    Xin Jin; Lin Wang; He-Shui Wu; Lei Zhang; Chun-You Wang; Yuan Tian; Jing-Hui Zhang

    2007-01-01

    BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R injury. This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS:BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-α in the portal vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours after reperfusion. The lung wet-to-dry ratio was measured, and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS: Compared with the I/R group, the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P CONCLUSIONS:TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury. NAC inhibited the activation of TLR2/4 and the induction of TNF-αresulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.

  9. The effects of sulforaphane on the liver and remote organ damage in hepatic ischemia-reperfusion model formed with pringle maneuver in rats.

    Science.gov (United States)

    Oguz, Abdullah; Kapan, Murat; Kaplan, Ibrahim; Alabalik, Ulas; Ulger, Burak Veli; Uslukaya, Omer; Turkoglu, Ahmet; Polat, Yilmaz

    2015-06-01

    The purpose of this study was to investigate the effect of Sulforaphane on ischemia/ reperfusion (IR) injury of the liver and distant organs resulting from liver blood flow arrest. Fourty Wistar rats were assigned into four groups, each included 10 rats were used. Group I as only laparatomy, Group II laparatomy and Sulforaphane application, Group III hepatic IR; and Group IV as hepatic IR and Sulforaphane application group. Animals were subjected to liver ischemia for 30 min and then reperfusion is started. 5 mg/kg Sulforaphane was applied via oral lavage 15 minutes before initiating the experimental study. Blood samples were taken from the animals for biochemical analysis at 60th minutes of the experiment in the first and second groups; 30 minutes after beginning reperfusion in the third and forth groups. Simultaneously, liver, lung and kidney tissues were sampled for biochemical and histopathological examinations. The administration of sulforaphane significantly reduced the serum TOA and liver TOA levels, increased the serum TAC and liver TAC levels and also decreased The OSI and liver OSI levels. In the histopathologic examination, the injury was reduced by the administration of sulforaphane. Administration of sulforaphane did not lead to any significant changes in any parameter including histopathological parameters in both the kidney and the lung. Sulforaphane reduced the liver oxidative stress from I/R injury. A histological injury in liver was reduced by sulforaphane administration. However, there were no significant effects of sulforaphane on the remote organ injuries induced by IR. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  10. Inhibition of NADPH-cytochrome P450 reductase by tannic acid in rat liver microsomes and primary hepatocytes: methodological artifacts and application to ischemia-reperfusion injury.

    Science.gov (United States)

    Pillai, Venkateswaran C; Mehvar, Reza

    2011-08-01

    Tannic acid (TA) inhibits nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase (CPR) activity, which is measured by reduction of cytochrome c, in rat liver microsomes (RLMs). In the current study, we noticed that TA directly reduces cytochrome c in the absence of microsomes, thus confounding the CPR activity assay. A method is presented that measures CPR activity in the presence of TA by subtracting the cytochrome c reduction in the absence of NADPH (TA effect) from that in the presence of NADPH (TA plus CPR effect). The method was used to determine the inhibitory effect of TA in RLMs, recombinant CPR enzyme, and primary hepatocytes. Additionally, application of TA in a study of role of CPR in a primary rat hepatocyte model of ischemia-reperfusion (IR) was investigated. TA showed concentration-dependent, complete inhibition of CPR with half maximal inhibitory concentration (IC(50) ) values of 58.2 μM in RLMs and 54.6 and 275 μM in primary rat hepatocytes in the absence and presence of serum in the medium, respectively. Additionally, inhibition of CPR by TA was associated with a significant reduction in reactive oxygen species and cell death after IR injury. These data may be useful in future studies using TA as an inhibitor of CPR in microsomes and primary hepatocytes.

  11. Estrogen Sulfotransferase Is an Oxidative Stress-responsive Gene That Gender-specifically Affects Liver Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Guo, Yan; Hu, Bingfang; Huang, Hai; Tsung, Allan; Gaikwad, Nilesh W; Xu, Meishu; Jiang, Mengxi; Ren, Songrong; Fan, Jie; Billiar, Timothy R; Huang, Min; Xie, Wen

    2015-06-05

    Estrogen sulfotransferase (EST) regulates estrogen homeostasis by sulfonating and deactivating estrogens. Liver ischemia and reperfusion (I/R) involves both hypoxia during the ischemic phase and oxidative damage during the reperfusion phase. In this report, we showed that the expression of EST was markedly induced by I/R. Mechanistically, oxidative stress-induced activation of Nrf2 was responsible for the EST induction, which was abolished in Nrf2(-/-) mice. EST is a direct transcriptional target of Nrf2. In female mice, the I/R-responsive induction of EST compromised estrogen activity. EST ablation attenuated I/R injury as a result of decreased estrogen deprivation, whereas this benefit was abolished upon ovariectomy. The effect of EST ablation was sex-specific because the EST(-/-) males showed heightened I/R injury. Reciprocally, both estrogens and EST regulate the expression and activity of Nrf2. Estrogen deprivation by ovariectomy abolished the I/R-responsive Nrf2 accumulation, whereas the compromised estrogen deprivation in EST(-/-) mice was associated with increased Nrf2 accumulation. Our results suggested a novel I/R-responsive feedback mechanism to limit the activity of Nrf2 in which Nrf2 induces the expression of EST, which subsequently increases estrogen deactivation and limits the estrogen-responsive activation of Nrf2. Inhibition of EST, at least in females, may represent an effective approach to manage hepatic I/R injury.

  12. Annexin V assay-proven anti-apoptotic effect of ascorbic acid 2-glucoside after cold ischemia/reperfusion injury in rat liver transplantation.

    Directory of Open Access Journals (Sweden)

    Liu J

    2003-10-01

    Full Text Available Controversy exists over whether the predominant cell death of hepatocytes is due to apoptosis or necrosis after ischemia/reperfusion injury. In this study we investigated the predominant cell death of hepatocytes after cold ischemia/reperfusion injury using the Annexin V-based assay, and evaluated the anti-apoptotic effect of ascorbic acid 2-glucoside (AA-2G added to the University of Wisconsin solution (UW solution in rat liver transplantation. The retrieved liver was preserved in 4 UW solution for 24 h, and then transplanted orthotopically to the syngeneic Wistar recipient. The animals were divided into 2 groups, a control group (n=10, in which liver grafts were preserved in UW solution (4, and an AA-2G group (n=10, in which liver grafts were preserved in UW solution (4 with AA-2G (100 ug/ml. The serum AST level 4 h after reperfusion in the control group was significantly suppressed in the AA-2G group, and the bile production of the liver graft in the AA-2G group was well recovered. The mean survival time in the AA-2G group was significantly improved compared with that in the control group. Annexin-V and Propidium iodide staining 4 h after reperfusion showed a significantly higher percentage of viable hepatocytes in the AA-2G group compared with the control group (93.4 +/- 2.0 vs. 80.3 +- 2.1%, P<0.05. In the control group, the main cell death of hepatocytes was apoptosis (early apoptosis: 10.0 +- 4.7%, late apoptosis: 6.4 +/- 1.7%. The addition of AA-2G to the UW solution significantly inhibited both early and late apoptotic cell death 4 h after reperfusion (early apoptosis: 0.98 +/- 0.88%, late apoptosis: 2.2 +/- 1.1%. The expression of caspase 9 in the immunostaining of the liver graft was suppressed in the AA-2G group compared with in the control group. Our study using the Annexin V-based assay provided evidence that the predominant cell death of hepatocytes was apoptosis after 24 h cold ischemia/reperfusion injury in rat liver

  13. Mangafodipir protects against hepatic ischemia-reperfusion injury in mice.

    Directory of Open Access Journals (Sweden)

    Romain Coriat

    Full Text Available INTRODUCTION AND AIM: Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. METHODS: Mice were subjected to 70% hepatic ischemia (continuous ischemia for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity. The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. RESULTS: Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01, in liver tissue damages, in markers of apoptosis (P<0.01, and by higher rates of survival in treated than in untreated animals (P<0.001. The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. CONCLUSIONS: Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.

  14. Suppression of graft regeneration, not ischemia/reperfusion injury, is the primary cause of small-for-size syndrome after partial liver transplantation in mice.

    Directory of Open Access Journals (Sweden)

    Ning Pan

    Full Text Available BACKGROUND: Ischemia/reperfusion injury (IRI is commonly considered to play a crucial role in the pathogenesis of small-for-size syndrome (SFSS after liver transplantation. Rapid regeneration is also considered essential for the survival of SFS grafts. METHODS: Mouse models of full-size orthotopic liver transplantation, 50% partial liver transplantation and 30% partial liver transplantation were established. Survival rate and serum alanine aminotransferase were observed. IRI was assessed by hepatic pathologic alterations, apoptosis and necrosis. Regeneration response was detected by mitotic index, BrdU incorporation and PCNA, Cyclin D1 and Cyclin E expression. The expression of mTOR, AKT, ERK, JNK2 and p70S6K, also involved in regeneration signaling pathways, were analyzed as well. RESULTS: 30% partial liver graft resulted in a significantly low 7-day survival rate (P = 0.002 with no marked difference in tissue injury compared with the 50% partial graft group. Serum alanine aminotransferase levels were not significantly different between partial transplantation and full-size transplantation. Western blot analysis of caspase-3 and TUNEL staining also indicated no significant difference in apoptosis response between 30% partial transplantation and half-size or full-size transplantation (P = 0.436, P = 0.113, respectively. However, liver regeneration response indicators, mitotic index (P<0.0001 and BrdU (P = 0.0022, were markedly lower in 30% LTx compared with 50% LTx. Suppressed expression of PCNA, cyclin D1, cyclin E, mTOR, JNK2, AKT, ERK and p70S6K was also detected by western blot. CONCLUSIONS: Liver regeneration is markedly suppressed in SFSS, and is more likely the primary cause of SFSS, rather than ischemia/reperfusion injury. Therapy for recovering graft regeneration could be a potentially important strategy to reduce the incidence of SFSS.

  15. Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury

    NARCIS (Netherlands)

    S.M.G. Fouraschen (Suomi M. G.); J.H. Wolf (Joshua H.); L.J.W. van der Laan (Luc); P.E. de Ruiter (Petra E.); W. Hancock; J.P. Van Kooten (Job P.); M.M.A. Verstegen (Monique); K.M. Olthoff (Kim); J. de Jonge (Jeroen)

    2015-01-01

    textabstractLoss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell-(MSC-) secreted factors are described to stimulate regeneration after partial hepatectomy. This study investigates if liv

  16. Intestinal Ischemia

    Science.gov (United States)

    ... some generally recognized patterns. Symptoms of acute intestinal ischemia Signs and symptoms of acute intestinal ischemia typically ... confusion in older adults Symptoms of chronic intestinal ischemia Signs and symptoms of chronic intestinal ischemia can ...

  17. Adoptive transfer of heme oxygenase-1 (HO-1)-modified macrophages rescues the nuclear factor erythroid 2-related factor (Nrf2) antiinflammatory phenotype in liver ischemia/reperfusion injury.

    Science.gov (United States)

    Huang, Jing; Shen, Xiu-Da; Yue, Shi; Zhu, Jianjun; Gao, Feng; Zhai, Yuan; Busuttil, Ronald W; Ke, Bibo; Kupiec-Weglinski, Jerzy W

    2014-10-14

    Macrophages are instrumental in the pathophysiology of liver ischemia/reperfusion injury (IRI). Although Nrf2 regulates macrophage-specific heme oxygenase-1 (HO-1) antioxidant defense, it remains unknown whether HO-1 induction might rescue macrophage Nrf2-dependent antiinflammatory functions. This study explores the mechanisms by which the Nrf2-HO-1 axis regulates sterile hepatic inflammation responses after adoptive transfer of ex vivo modified HO-1 overexpressing bone marrow-derived macrophages (BMMs). Livers in Nrf2-deficient mice preconditioned with Ad-HO-1 BMMs, but not Ad-β-Gal-BMMs, ameliorated liver IRI (at 6 h of reperfusion after 90 min of warm ischemia), evidenced by improved hepatocellular function (serum alanine aminotransferase [sALT] levels) and preserved hepatic architecture (Suzuki histological score). Treatment with Ad-HO-1 BMMs decreased neutrophil accumulation, proinflammatory mediators and hepatocellular necrosis/apoptosis in ischemic livers. Moreover, Ad-HO-1 transfection of Nrf2-deficient BMMs suppressed M1 (Nos2(+)) while promoting the M2 (Mrc-1/Arg-1(+)) phenotype. Unlike in controls, Ad-HO-1 BMMs increased the expression of Notch1, Hes1, phosphorylation of Stat3 and Akt in IR-stressed Nrf2-deficient livers as well as in lipopolysaccharide (LPS)-stimulated BMMs. Thus, adoptive transfer of ex vivo generated Ad-HO-1 BMMs rescued Nrf2-dependent antiinflammatory phenotype by promoting Notch1/Hes1/Stat3 signaling and reprogramming macrophages toward the M2 phenotype. These findings provide the rationale for a novel clinically attractive strategy to manage IR liver inflammation/damage.

  18. Silymarin preconditioning protected insulin resistant rats from liver ischemia-reperfusion injury: role of endogenous H2S.

    Science.gov (United States)

    Younis, Nahla N; Shaheen, Mohamed A; Mahmoud, Mona F

    2016-08-01

    Hydrogen sulfide (H2S) can protect against hepatic ischemia-reperfusion injury (HIR). However, it is unknown whether it can protect against HIR in insulin resistance. This study investigated the protective effects of silymarin against HIR in a rat model of insulin resistance and the possible involvement of endogenous H2S. Insulin resistance was first established using 10% fructose in drinking water for 10 weeks. HIR was conducted in fructose-fed rats treated with saline or silymarin (100 mg/kg), 15 min before HIR (30 min ischemia, followed by 1 h reperfusion). Insulin resistance and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), total nitrites (NO2(-)), and H2S were measured. Hepatic malondialdehyde (MDA), reduced glutathione (GSH), hydroxyproline, H2S synthesizing activity, and mRNA expression of cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) were determined. Additionally, histopathological examination involved H&E, Sirius red, and caspase-3 immunostaining. Fructose-induced insulin resistance increased serum ALT, TNF-α, H2S and H2S synthesizing activity, and hepatic MDA, hydroxyproline, and CSE mRNA and decreased NO2(-) and GSH. These changes exacerbated the HIR injury in which endogenous H2S production was auxiliary increased. Silymarin preconditioning decreased ALT, AST, MDA, NO2(-), TNF-α, and TNF-α/IL-10 ratio, increased GSH, IL-10, improved hepatic architecture, and lowered caspase-3 immunostaining. Serum H2S, its hepatic synthesizing activity, and CSE and CBS mRNA expressions were all suppressed by silymarin pretreatment. The increases in endogenous H2S exacerbate HIR injury, whereas silymarin preconditioning protected against HIR in insulin resistant rats via powerful antioxidant, anti-inflammatory, and antiapoptotic effects along with suppressing H2S production. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Dexmedetomidine Protects Rat Liver against Ischemia-Reperfusion Injury Partly by the α2A-Adrenoceptor Subtype and the Mechanism Is Associated with the TLR4/NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Yiheng Wang

    2016-06-01

    Full Text Available Toll-like receptor 4 (TLR4/nuclear factor kappa B (NF-κB signaling plays a dominant role in the pathogenesis of liver ischemia-reperfusion (IR injury. Dexmedetomidine (Dex protects the liver against IR injury via α2-adrenoceptor activation, but the contribution of TLR4 signaling remains unknown. The authors aimed to examine whether pretreatment with Dex produces hepatic protection and investigate the influence of Dex on TLR4/NF-κB signaling. Dex was given via intraperitoneal injection 30 min prior to orthotopic autologous liver transplantation (OALT in rats, and three α2-adrenoceptor antagonists including atipamezole (a nonselective α2 receptor blocker, ARC-239 (a specific α2B/C blocker and BRL-44408 (a specific α2A blocker were injected intraperitoneally 10 min before Dex administration. Histopathologic evaluation of the liver and the measurement of serum alanine aminotransferase activity, TLR4/NF-κB expression in the liver, and pro-inflammatory factors (serum tumor necrosis factor-α, interleukin-1β and hepatic myeloperoxidase concentrations were performed 8 h after OALT. Dex ameliorated liver injury after OALT probably by suppressing the TLR4/NF-κB pathway and decreasing inflammatory mediator levels. The protective effects of Dex were reversed by atipamezole and BRL-44408, but not by ARC-239, suggesting that these effects were mediated in part by the α2A subtype. In conclusion, Dex attenuates liver injury partly via the α2A-adrenoceptor subtype, and the mechanism is due to the suppression of the TLR4/NF-κB pathway.

  20. Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Justin; Holmuhamedov, Ekhson; Zhang, Xun; Lovelace, Gregory L.; Smith, Charles D. [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC (United States); Lemasters, John J., E-mail: JJLemasters@musc.edu [Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC (United States); Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC (United States)

    2013-11-15

    Minocycline, a tetracycline-derived compound, mitigates damage caused by ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were screened in comparison to minocycline for their ability to protect hepatocytes against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes were incubated with 50 μM of each tetracycline-derived compound 20 min prior to exposure to 500 μM iodoacetic acid plus 1 mM KCN (chemical hypoxia). In other experiments, hepatocytes were incubated in anoxic Krebs–Ringer–HEPES buffer at pH 6.2 for 4 h prior to reoxygenation at pH 7.4 (simulated I/R). Tetracycline-derived compounds were added 20 min prior to reperfusion. Ca{sup 2+} uptake was measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry was 87%, which decreased to 28% and 42% with minocycline and doxycycline, respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle to 43% and 49% with minocycline and doxycycline. No other tested compound decreased killing. Minocycline and doxycycline also inhibited mitochondrial Ca{sup 2+} uptake and suppressed the Ca{sup 2+}-induced mitochondrial permeability transition (MPT), the penultimate cause of cell death in reperfusion injury. Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca{sup 2+} uptake and the MPT. Other proposed mechanisms, including mitochondrial depolarization and matrix metalloprotease inhibition, could not account for cytoprotection. Taken together, these results indicate that minocycline and doxycycline are cytoprotective by way of inhibition of MCU. - Highlights: • Minocycline and doxycycline are the only cytoprotective tetracyclines of those tested • Cytoprotective tetracyclines inhibit the MPT and mitochondrial calcium and iron uptake. • Cytoprotective

  1. An experimental pilot study on controlled portal vein arterialization with an extracorporeal device in the swine model of partial liver resection and ischemia.

    Science.gov (United States)

    Nardo, B; Montalti, R; Puviani, L; Pacilè, V; Beltempo, P; Bertelli, R; Licursi, M; Pariali, M; Cianciavicchia, D

    2006-09-01

    To determine whether the physiologically oxygenated arterial blood reversed in the portal system by means of portal vein arterialization (PVA) through an extracorporeal device which we have called L.E.O2.NARDO (Liver Extracorporeal Oxygen. NARDO) is effective in treating swine with subtotal hepatectomy leading to acute liver failure (ALF). Ten swine with ALF induced by 85-90% liver resection and five minutes of ischemia-reperfusion injury were randomly divided into two groups: five animals received PVA extracorporeal treatment and five swine were not-treated (control group). Blood was withdrawn from the iliac artery and reversed in the portal venous system. An extracorporeal device was interposed between the outflow and the inflow in order to monitoring the hemodynamic parameters. Each treatment lasted 6 hours. Serum and liver samples were collected in both groups. The survival was assessed at 1 week. The PVA-extracorporeal treatment yielded beneficial effects for subtotal hepatectomy-induced ALF swine with decreased serum ammonia, transaminases and total bilirubin as compared with the untreated group. INR recovered rapidly in the PVA-extracorporeal group remaining significantly lower than in untreated animals. The 7-day survival of PVA-extracorporeal group swine was significantly higher than that of untreated animals, with a statistically significant difference (pportal system through the extracorporeal device is easily applicable, efficacious, safe and may represent a novel approach for ALF swine induced by subtotal liver resection.

  2. Protective effects of branched-chain amino acids on hepatic ischemia-reperfusion-induced liver injury in rats: a direct attenuation of Kupffer cell activation.

    Science.gov (United States)

    Kitagawa, Tomomi; Yokoyama, Yukihiro; Kokuryo, Toshio; Nagino, Masato

    2013-02-15

    We determined whether there is a protective effect of branched-chain amino acid (BCAA) on hepatic ischemia-reperfusion (I/R)-induced acute liver injury. Wister rats were divided into the following four groups: simple laparotomy with vehicle; simple laparotomy with BCAA (1 g/kg body wt orally); I/R (30 min clamp) with vehicle; and I/R with BCAA. Serum liver function tests and the gene expression of adhesion molecules (intercellular adhesion molecule and vascular cell adhesion molecule) and vasoconstrictor-related genes (endothelin-1) in the liver were examined. In the in vivo study, portal venous pressure, leukocyte adhesion, and hepatic microcirculation were evaluated. Furthermore, Kupffer cells were isolated and cultured with various concentrations of BCAA in the presence or absence of lipopolysaccharide (LPS). Increased levels of liver function tests following I/R were significantly attenuated by BCAA treatment. The increased expression of adhesion molecules and endothelin-1 was also significantly attenuated by BCAA treatment. Moreover, increased portal venous pressure, enhanced leukocyte adhesion, and deteriorated hepatic microcirculation following I/R were all improved by BCAA treatment. In the experiment using isolated Kupffer cells, the expression of interleukin-6, interleukin-1β, and endothelin-1 in response to LPS stimulation was attenuated by BCAA in a dose-dependent fashion. These results indicate that perioperative oral administration of BCAA has excellent therapeutic potential to reduce I/R-induced liver injury. These beneficial effects may result from the direct attenuation of Kupffer cell activation under stressful conditions.

  3. Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats.

    Science.gov (United States)

    Kawai, Miho; Harada, Naoaki; Takeyama, Hiromitsu; Okajima, Kenji

    2010-06-01

    Neutrophil elastase (NE) decreases the endothelial production of prostacyclin (PGI(2)) through the inhibition of endothelial nitric oxide synthase (NOS) activation and thereby contributes to the development of ischemia/reperfusion (I/R)-induced liver injury. We previously demonstrated that calcitonin gene-related peptide (CGRP) released from sensory neurons increases the insulin-like growth factor- I (IGF-I) production and thereby reduces I/R-induced liver injury. Because PGI(2) is capable of stimulating sensory neurons, we hypothesized that NE contributes to the development of I/R-induced liver injury by decreasing IGF-I production. In the present study, we examined this hypothesis in rats subjected to hepatic I/R. Ischemia/reperfusion-induced decreases of hepatic tissue levels of CGRP and IGF-I were prevented significantly by NE inhibitors, sivelestat, and L-658, 758, and these effects of NE inhibitors were reversed completely by the nonselective cyclooxygenase inhibitor indomethacin (IM) and the nonselective NOS inhibitor L-NAME but not by the selective inducible NOS inhibitor 1400W. I/R-induced increases of hepatic tissue levels of caspase-3, myeloperoxidase and the number of apoptotic cells were inhibited by NE inhibitors, and these effects of NE inhibitors were reversed by IM and L-NAME but not by 1400W. Administration of iloprost, a stable PGI(2) analog, produced effects similar to those induced by NE inhibitors. Taken together, these observations strongly suggest that NE may play a critical role in the development of I/R-induced liver injury by decreasing the IGF-I production through the inhibition of sensory neuron stimulation, which may lead to an increase of neutrophil accumulation and hepatic apoptosis through activation of caspase-3 in rats.

  4. Hydrogen sulfide preconditioning protects rat liver against ischemia/reperfusion injury by activating Akt-GSK-3β signaling and inhibiting mitochondrial permeability transition.

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    Qingqing Zhang

    Full Text Available Hydrogen sulfide (H2S is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC or sodium hydrosulfide (NaHS, an H2S donor preconditioning groups. To establish a model of segmental (70% warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 μmol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT and aspartate aminotransferase (AST levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 μmol/kg did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt, phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β and B-cell lymphoma-2 (Bcl-2 and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3β signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury.

  5. Impact of venous systemic oxygen persufflation supplemented with nitric oxide gas on cold-stored, warm ischemia-damaged experimental liver grafts.

    Science.gov (United States)

    Srinivasan, Pramod Kadaba; Yagi, Shintaro; Doorschodt, Benedict; Nagai, Kazuyuki; Afify, Mamdouh; Uemoto, Shinji; Tolba, Rene

    2012-02-01

    The increasing shortage of donor organs has led to the increasing use of organs from non-heart-beating donors. We aimed to assess the impact of venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the cold storage (CS) of warm ischemia (WI)-damaged experimental liver grafts. Rat livers (n = 5 per group) were retrieved after 30 minutes of WI induced by cardiac arrest (the WI group) and were thereafter preserved for 24 hours by CS in histidine tryptophan ketoglutarate solution. During CS, gaseous oxygen was insufflated via the caval vein with 40 ppm NO (the VSOP-NO group) or without NO (the VSOP group). Cold-stored livers without WI served as controls. Liver viability was assessed after the preservation period by normothermic isolated reperfusion for 45 minutes with oxygenated Krebs-Henseleit buffer. After 45 minutes of reperfusion, the VSOP-NO-treated livers showed significantly lower alanine aminotransferase values than the WI-damaged livers (10.2 ± 0.2 versus 78.2 ± 14.6 IU/L), whereas the control livers showed no differences from the VSOP-NO-treated livers. The mitochondrial enzyme release was lower in the VSOP-NO group (4.0 ± 0.7 IU/L) versus the WI group (18.2 ± 4.9 IU/L). An increased portal vein pressure was observed throughout reperfusion (45 minutes) in the WI group (21.7 ± 0.2 mm Hg) versus the VSOP-NO group (12.2 ± 0.8 mm Hg) and the control group (19.9 ± 0.4 mm Hg). Furthermore, the NO concentration in the perfusate after 5 minutes of reperfusion was highest in the VSOP-NO group. The release of malondialdehyde into the perfusate was significantly reduced in the VSOP-NO group (0.9 ± 0.1 nmol/mL) versus the WI group (31.3 ± 5.3 nmol/mL). In conclusion, the resuscitation of livers after 30 minutes of WI to a level comparable to that of nonischemically damaged livers is possible with VSOP supplemented with NO gas. Moreover, the application of VSOP with NO minimizes the extent of injuries caused by oxygen free

  6. Protective effects of L-arginine against ischemia-reper fusion injur y in non-heart beating rat liver graft

    Institute of Scientific and Technical Information of China (English)

    Jin Gong; Xue-Jun Lao; Shui-Jun Zhang; Shi Chen

    2008-01-01

    BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will beneift the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8), controls 1, 2 and 3 (C1, C2, C3, n=16), and experimental 1, 2 and 3 (E1, E2, E3, n=16). For groups C1 and E1, C2 and E2, and C3 and E3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were lfushed with and preserved in 4 ℃ Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were ifxed in 2.5%glutaraldehyde for electron microscopic observation. RESULTS: At 1 hour after portal vein reperfusion, the levels of NO in groups E1, E2, E3 and C1, C2, C3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.

  7. The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors.

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    Jin Xu

    Full Text Available The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD. The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD, we aimed to understand how ischemia/reperfusion (I/R injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration.Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13 and DBD (n = 10 livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22 and DBD (n = 13 livers.When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05 and C22 ceramide (p<0.05 were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST of DCD allografts had significantly increased.These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation.

  8. N-3 PUFA supplementation triggers PPAR-α activation and PPAR-α/NF-κB interaction: anti-inflammatory implications in liver ischemia-reperfusion injury.

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    Jessica Zúñiga

    Full Text Available Dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFA eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA to rats preconditions the liver against ischemia-reperfusion (IR injury, with reduction of the enhanced nuclear factor-κB (NF-κB functionality occurring in the early phase of IR injury, and recovery of IR-induced pro-inflammatory cytokine response. The aim of the present study was to test the hypothesis that liver preconditioning by n-3 PUFA is exerted through peroxisone proliferator-activated receptor α (PPAR-α activation and interference with NF-κB activation. For this purpose we evaluated the formation of PPAR-α/NF-κBp65 complexes in relation to changes in PPAR-α activation, IκB-α phosphorylation and serum levels and expression of interleukin (IL-1β and tumor necrosis factor (TNF-α in a model of hepatic IR-injury (1 h of ischemia and 20 h of reperfusion or sham laparotomy (controls in male Sprague Dawley rats. Animals were previously supplemented for 7 days with encapsulated fish oil (General Nutrition Corp., Pittsburg, PA or isovolumetric amounts of saline (controls. Normalization of IR-altered parameters of liver injury (serum transaminases and liver morphology was achieved by dietary n-3 PUFA supplementation. EPA and DHA suppression of the early IR-induced NF-κB activation was paralleled by generation of PPAR-α/NF-κBp65 complexes, in concomitance with normalization of the IR-induced IκB-α phosphorylation. PPAR-α activation by n-3 PUFA was evidenced by enhancement in the expression of the PPAR-α-regulated Acyl-CoA oxidase (Acox and Carnitine-Palmitoyl-CoA transferase I (CPT-I genes. Consistent with these findings, normalization of IR-induced expression and serum levels of NF-κB-controlled cytokines IL-lβ and TNF-α was observed at 20 h of reperfusion. Taken together, these findings point to an antagonistic effect of PPAR-α on NF-κB-controlled transcription of pro-inflammatory mediators

  9. Propofol postconditioning attenuates hippocampus ischemia-reperfusion injury via modulating JAK2/STAT3 pathway in rats after autogenous orthotropic liver transplantation.

    Science.gov (United States)

    Jia, Lili; Wang, Fei; Gu, Xiangqian; Weng, Yiqi; Sheng, Mingwei; Wang, Gang; Li, Shipeng; Du, Hongyin; Yu, Wenli

    2017-02-15

    Liver transplantation has been a routine treatment for the end stage liver diseases. Severe changes in circulation system and internal environment may occur during transplant surgery and cause injury to many organs including brain. Specific mechanisms of brain injury associated with liver transplantation are not yet elucidated. Previous studies have shown that the JAK/STAT signal transduction pathways are involved in the development of the central nervous system, such as nerve cell proliferation, survival, differentiation, and it also have a role in the disease processes, including brain tumor, brain ischemia and other diseases of the central nervous system. In this study we investigate whether propofol plays an important role in protecting the hippocampus through JAK2/STAT3 pathway. Thirty-two healthy male Sprague-Dawley rats, were randomly divided into four groups (n=8). Sham operation group (group S), autogenous orthotropic liver transplantation group (group I), autogenous orthotropic liver transplantation+propofol treatment group (group P) and autogenous orthotropic liver transplantation+propofol+AG490 treatment group (group A). We evaluated histological damage, inflammation, oxidative stress and apoptosis in hippocampus using HE staining, light microscope, real-time PCR and western blot. The results showed that there was a significant damage of hippocampus in group I compared to the sham group as demonstrated by increased serum levels of S100β, NSE and the histological changes. However, an induction of propofol reduced the levels of MDA, TNFα, S100β, NSE and increased activity of SOD, IL-10, and attenuated the expression of JAK2 and STAT3, meanwhile. Consistently, pretreatment with JAK2/STAT3 pathway inhibitor AG490, decreased the levels of MDA, TNFα, S100β, NSE and increased activity of SOD, IL-10, and attenuated the expression of JAK2 and STAT3. These results reveal that autogenous orthotropic liver transplantation induces the activation of JAK2/STAT3

  10. Using multiphoton fluorescence lifetime imaging to characterize liver damage and fluorescein disposition in liver in vivo

    Science.gov (United States)

    Thorling, Camilla A.; Studier, Hauke; Crawford, Darrell; Roberts, Michael S.

    2016-03-01

    Liver disease is the fifth most common cause of death and unlike many other major causes of mortality, liver disease rates are increasing rather than decreasing. There is no ideal measurement of liver disease and although biopsies are the gold standard, this only allows for a spot examination and cannot follow dynamic processes of the liver. Intravital imaging has the potential to extract detailed information over a larger sampling area continuously. The aim of this project was to investigate whether multiphoton and fluorescence lifetime imaging microscopy could detect early liver damage and to assess whether it could detect changes in metabolism of fluorescein in normal and diseased livers. Four experimental groups were used in this study: 1) control; 2) ischemia reperfusion injury; 3) steatosis and 4) steatosis with ischemia reperfusion injury. Results showed that multiphoton microscopy could visualize morphological changes such as decreased fluorescence of endogenous fluorophores and the presence of lipid droplets, characteristic of steatosis. Fluorescence lifetime imaging microscopy showed increase in NADPH in steatosis with and without ischemia reperfusion injury and could detect changes in metabolism of fluorescein to fluorescein monoglurcuronide, which was impaired in steatosis with ischemia reperfusion injury. These results concluded that the combination of multiphoton microscopy and fluorescence lifetime imaging is a promising method of assessing early stage liver damage and that it can be used to study changes in drug metabolism in the liver as an indication of liver disease and has the potential to replace the traditional static liver biopsy currently used.

  11. The relationship between different ischemia time of non-heart beating liver graft and bile duct ischemia/reperfusion in rat liver transplantation%大鼠肝移植供肝热缺血时间与胆道损伤的关系

    Institute of Scientific and Technical Information of China (English)

    邰强; 王国栋; 何晓顺; 杨建安; 朱晓峰; 马毅; 巫林伟; 鞠卫强; 胡安斌; 王东平

    2010-01-01

    目的 探讨大鼠心源性死亡(DCD)供肝不同的热缺血时间与胆道缺血再灌注损伤的关系.方法 采用无肝素化的大鼠DCD供体肝移植模型,按供肝的热缺血时间分为0 min(WI0),10 min(WI10)、15 min(WI15)3组,每组36对大鼠.术后动态观察大鼠胆道病理改变及其并发症、肝功能指标,最后统计总体生存率.结果 供肝热缺血小于10 min时,术后胆道病理改变较轻且为可逆性改变,肝功能恢复较快;供肝热缺血时间为15 min时,术后胆道病理改变较重且为不可逆性改变,肝功能恢复延迟;3组胆道并发症的发生率差异有统计学意义(5.56%比8.33%比16.67%,P<0.05).WI0组和WI10组的大鼠术后4周生存率差异无统计学意义(83.33%比77.78%,P>0.05),而与WI15组比较4周生存率的差异有统计学意义(83.33%比58.33%,77.78%比58.33%,P<0.05).结论 无肝素化的大鼠DCD供肝热缺血时间超过15 min时,移植术后胆道损伤明显,可导致不可逆改变.%Objective To elucidate the relationship between different ischemia time of Donation after Cardiac Death (DCD) liver graft and bile duct ischemia/reperfusion in rat liver transplantation. Methods We chose improved rat liver transplantation mold for the research. The rats were divided into three groups by different warm ischemia time ( WI), such as,0 min ( WI0, n = 36), 10 min ( WI10, n = 36 ), 15 min ( WI5, n = 36). We analyzed the recipient survival rate, biliary complication, liver function and pathology after operation in the three groups. Results There were significantly differences in the WI0, WI10 and WI15 group in biliary complication (5.56% vs 8.33% vs 16.67% ,P <0.05). When ischemia time was in 10min,the pathology change is littler and the liver function recover faster than WI15 group. The change was recoverable in 10min but not above 15min. There were no difference between WI0 and WI10 group in four week's survival rate ( 83.33% vs 77.78%, P > 0.05 ). There were

  12. Simultaneous measurement of hundreds of liver proteins: application in assessment of liver function.

    Science.gov (United States)

    Anderson, N L; Taylor, J; Hofmann, J P; Esquer-Blasco, R; Swift, S; Anderson, N G

    1996-01-01

    Proteins implement most biological functions at the molecular level. As one might expect based on this fact, it appears that the altered functional states associated with toxic effects involve changes in the abundance or structure of proteins. Although numerous specific assays exist to measure changes in the abundance of individual proteins, practical limitations have prevented widespread use of multiple protein assays for the global characterization of toxicity. Recent developments in protein analytical technology are rapidly changing this picture. Two-dimensional gel electrophoresis, a technique capable of resolving and quantitating hundreds of proteins simultaneously, is becoming an automated, high-throughput tool. In parallel, techniques have been developed that allow the resulting deluge of protein measurements to be organized into a prototype Molecular Effects Database describing xenobiotic effects in rodent liver. This database can detect, classify, and characterize a broad range of liver toxicity mechanisms. It currently contains approximately 10 million protein measurements, including data on the liver effects of 43 compounds, with a further 50 compounds to be added in 1995. Observed effects range from very broad (sex steroids alter levels of 45% of all liver proteins) to very specific (e.g., hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitors). Companion 2-dimensional databases describing rodent brain and kidney have been initiated, as have linkages to the genomic sequence databases. Assimilation of this approach into research and regulatory toxicology poses an interesting challenge--one that is likely to lead to a radically more sophisticated understanding of toxicity and its biological basis.

  13. Effect of cold-ischemia time on nuclear factor-κB activation and inflammatory response in graft after orthotopic liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Gu; Yong Jiang; Fu-Tao Xu; Yu-Dong Qiu; Yi-Tao Ding

    2004-01-01

    AIM: To study the mechanism and effect of nuclear factorκB (NF-κB) activation and inflammatory response on the extended cold-preserved graft injury after orthotopic liver transplantation (OLT).METHODS: OLT was performed in rats with varying time of cold ischemia grafts (6, 18 and 24 h in University Wisconsin solution at 4 ℃). We determined the time of NF-κB activation and expression of tumor necrosisfactor-α (TNF-α), cytokineinducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1 (ICAM-1) within 6 h after reperfusion.Serum alarming aminotransferase (ALT), neutrophil sequestration, circulating neutrophil CD11b and L- selectin expression were also evaluated.RESULTS: The accumulation of neutrophils in the graft was significantly increased in the 18 h and 24 h cold-ischemia groups within 0.5 h after reperfusion, compared with the 6 h group. But the strongly activated neutrophils was slightly increased at 2 h after reperfusion and remained at high levels 4 h after reperfusion, which was synchronized with the common situation of recipients after transplantation.Prolonged cold-preservation did not affect neutrophil accumulation and activation. NF-κB activation preceded the expression of TNF-α, CINC, and ICAM-1 in the liver, which was significantly increased with prolonged cold preservation.In prolonged cold preserved grafts, prominently elevated NF-κB activation occurred at 0.5 h and 1 h, compared with that at 2 h after reperfusion, which was consistent with greatly increased intrahepatic TNF-α response.CONCLUSION: NF-κB activation is correlated with the expression of TNF-α, CINC, and ICAM-1 in vivo in OLT rats.Extended cold preservation of grafts might up-regulate TNF-α,CINC, and ICAM-1 expression in the grafts, most probably through elevated NF-κB activation, and might contribute to neutrophil infiltration in the grafts after reperfusion. Elevated NF-κB activity is harmful to inflammatory response in the grafts, and inhibited

  14. Staging of liver fibrosis or cirrhosis: The role of hepaticvenous pressure gradient measurement

    Institute of Scientific and Technical Information of China (English)

    Ki Tae Suk; Dong Joon Kim

    2015-01-01

    Liver fibrosis is a common histological change ofchronic liver injury and it is closely related with portalhypertension which is hemodynamic complication ofchronic liver disease. Currently, liver fibrosis has beenknown as a reversible dynamic process in previousliteratures. Although liver biopsy is a gold standardfor assessing the stage of liver fibrosis, it may notcompletely represent the stage of liver fibrosis becauseof sampling error or semi-quantative measurement.Recent evidences suggested that histologic, clinical,hemodynamic, and biologic features are closelyassociated in patients with chronic liver disease. Hepaticvenous pressure gradient (HVPG) measurement has beenknown as a modality to evaluate the portal pressure.The HVPG measurement has been used clinicallyfor fibrosis diagnosis, risk stratification, preoperativescreening for liver resection, monitoring the efficacy ofmedical treatments, and assessing the prognosis of liverfibrosis. Therefore, the HVPG measurement can be usedto monitor areas the chronic liver disease but also otherimportant areas of chronic liver disease.

  15. Detection of cerebral ischemia using the power spectrum of the pulse wave measured by near-infrared spectroscopy.

    Science.gov (United States)

    Ebihara, Akira; Tanaka, Yuichi; Konno, Takehiko; Kawasaki, Shingo; Fujiwara, Michiyuki; Watanabe, Eiju

    2013-10-01

    The diagnosis and medical treatment of cerebral ischemia are becoming more important due to the increase in the prevalence of cerebrovascular disease. However, conventional methods of evaluating cerebral perfusion have several drawbacks: they are invasive, require physical restraint, and the equipment is not portable, which makes repeated measurements at the bedside difficult. An alternative method is developed using near-infrared spectroscopy (NIRS). NIRS signals are measured at 44 positions (22 on each side) on the fronto-temporal areas in 20 patients with cerebral ischemia. In order to extract the pulse-wave component, the raw total hemoglobin data recorded from each position are band-pass filtered (0.8 to 2.0 Hz) and subjected to a fast Fourier transform to obtain the power spectrum of the pulse wave. The ischemic region is determined by single-photon emission computed tomography. The pulse-wave power in the ischemic region is compared with that in the symmetrical region on the contralateral side. In 17 cases (85%), the pulse-wave power on the ischemic side is significantly lower than that on the contralateral side, which indicates that the transmission of the pulse wave is attenuated in the region with reduced blood flow. Pulse-wave power might be useful as a noninvasive marker of cerebral ischemia.

  16. Nondiseased liver stiffness measured by shear wave elastography: a pilot study.

    Science.gov (United States)

    Cha, Seung Woo; Jeong, Woo Kyoung; Kim, Yongsoo; Kim, Min Yeong; Kim, Jinoo; Kim, Soo Yeon; Ryu, Jeong Ah; Kim, Tae Yeob; Sohn, Joo Hyun; Kim, Young Hwan

    2014-01-01

    The purpose of this study was to investigate the value of liver stiffness in patients without liver disease using shear wave elastography and to determine the liver stiffness threshold value for identifying patients with chronic liver diseases. A total of 150 patients who underwent liver sonography coupled with shear wave elastography were enrolled. On the basis of clinical and pathologic criteria, they were assigned to 1 of 2 groups: nondiseased liver (n = 97) and noncirrhotic chronic liver disease (n = 53). Liver stiffness was measured in the right liver, and the median value of 10 measurements was calculated. Both mean and median values in the nondiseased liver group were compared with those in the noncirrhotic chronic liver disease group. To validate this comparison, liver stiffness of the patients who underwent liver biopsy revealing either no fibrosis (fibrosis score F0; n = 5) or substantial fibrosis (F2; n = 14) was also investigated and compared. To determine the optimal threshold value for determining chronic liver disease, a receiver operating characteristic curve analysis was performed. The mean liver stiffness value in the nondiseased liver group was 5.4 kPa. In the noncirrhotic chronic liver disease group, the mean value was 8.1 kPa. Differences between the nondiseased liver and both noncirrhotic chronic liver disease groups were statistically significant (P < .001). The optimal liver stiffness threshold value for discriminating nondiseased liver from noncirrhotic chronic liver disease was 6.9 kPa. The sensitivity using this threshold was 94%. In the biopsy-proven patients, the mean liver stiffness values were 6.0 kPa in the F0 group and 9.9 kPa in the F2 group. The range of liver stiffness in patients with nondiseased liver and the optimal threshold value for discriminating these patients from those with chronic liver disease were identified.

  17. Intraoperative simulation of remnant liver function during anatomic liver resection with indocyanine green clearance (LiMON) measurements.

    Science.gov (United States)

    Thomas, Michael N; Weninger, Ernst; Angele, Martin; Bösch, Florian; Pratschke, Sebastian; Andrassy, Joachim; Rentsch, Markus; Stangl, Manfred; Hartwig, Werner; Werner, Jens; Guba, Markus

    2015-06-01

    Post-hepatectomy liver failure (PHLF) is the major cause of death following liver resection. The aim of this study was to evaluate the feasibility of an intraoperative simulation of post-resection liver function. Intraoperative liver function was measured by indocyanine green (ICG) clearance using the LiMON technology. In 20 patients undergoing anatomic liver resection, ICG plasma disappearance rate (PDR (%/min) and ICG retention at 15 min (R15 ) (%) were measured immediately after the induction of anaesthesia (t0 ), after selective arterial and portovenous inflow trial clamping (TC) of the resected liver segments (t1 ), after the completion of resection (t2 ) and before the closure of the abdominal cavity (t3 ). The median baseline (t0 ) PDR was 16.5%/min. Trial clamping of the inflow (t1 ) resulted in a significant reduction in PDR to 10.5%/min. Results under TC were similar to those obtained after resection (t2 ) (median PDR: 10.5%/min). Linear regression modelling showed that post-resection liver volume could be accurately predicted by TC of liver inflow (P < 0.0001), but not by determining the resected liver volume. Simulated post-resection liver function under TC correlated well with PHLF and length of hospital stay. Intraoperative ICG clearance measurements allow real-time monitoring of intraoperative liver function during surgery. Trial clamping of arterial and portovenous inflow accurately predicts immediate post-resection liver function. The intraoperative measurement of liver function and simulation of post-resection liver function may help to avoid PHLF. © 2015 International Hepato-Pancreato-Biliary Association.

  18. Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model.

    Science.gov (United States)

    Bezinover, Dmitri; Ramamoorthy, Saravanan; Postula, Marek; Weller, Gregory; Mahmoud, Saifeldin; Mani, Haresh; Kadry, Zakiyah; Uemura, Tadahiro; Mets, Berend; Spiess, Bruce; Brucklacher, Robert; Freeman, Willard; Janicki, Piotr K

    2014-05-15

    Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Reconstruction of cerebral hemodynamics with dynamic contrast-enhanced time-resolved near-infrared measurements before and during ischemia

    Science.gov (United States)

    Elliott, Jonathan T.; Diop, Mamadou; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith

    2013-03-01

    We present a dynamic contrast-enhanced near-infrared (DCE-NIR) technique that is capable of non-invasive quantification of cerebral hemodynamics in adults. The challenge of removing extracerebral contamination is overcome through the use of multi-distance time-resolved DCE-NIR combined with the kinetic deconvolution optical reconstruction (KDOR) analytical method. As proof-of-principle, cerebral blood flow, cerebral blood volume and mean transit time recovered with DCE-NIR are compared with CT perfusion values in an adult pig during normocapnia, hypocapnia, and ischemia. Measurements of blood flow acquired with DCE-NIR were compared against concomitant measurements using CT Perfusion.

  20. Salidroside protects rat liver against ischemia/reperfusion injury by regulating the GSK-3β/Nrf2-dependent antioxidant response and mitochondrial permeability transition.

    Science.gov (United States)

    Cai, Linlin; Li, Yonghua; Zhang, Qingqing; Sun, Haijing; Yan, Xiaodi; Hua, Tong; Zhu, Qiufeng; Xu, Haitao; Fu, Hailong

    2017-07-05

    Salidroside (Sal) is a natural antioxidant that elicits cardioprotective and neuroprotective effects in vivo and in vitro; however, its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. The purpose of this study was to investigate the hepatoprotective effects of salidroside against segmental (70%) warm hepatic I/R injury in rats. Animals were randomized into Sham, Sham+salidroside pretreatment (Sal), Sham+Sal+carboxyatractyloside (CATR), Sham+CATR, I/R, I/R+Sal, I/R+Sal+CATR and I/R+CATR groups. The hepatic artery, left portal vein and median liver lobes were occluded for 60min and then unclamped to allow reperfusion. Pretreatment with salidroside (20mg/kg/day for 7 days, intraperitoneally) significantly decreased serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST) levels after 6h and 24h of reperfusion and protected the liver against I/R-induced injury. However, this protective effect could be reversed by CATR, a mitochondrial permeability transition pore (MPTP) opener (5mg/kg 30min before I/R insult, intraperitoneally). Mechanistic studies have revealed that salidroside inhibits glycogen synthase kinase-3 beta (GSK-3β) activity and enhances the NF-E2-related factor (Nrf2)-dependent antioxidant response by activating the Akt signaling pathway, thereby reducing mitochondrial reactive oxygen species generation, increasing MPTP resistance and preventing apoptosis by suppressing cytochrome c release and caspase activation during reperfusion. Therefore, salidroside ameliorates hepatocyte death and apoptosis through activation of the GSK-3β/Nrf2-dependent antioxidant response and subsequent MPTP inhibition. These results provide experimental evidence supporting the clinical use of salidroside for hepatoprotection in surgical settings. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Consequences of cold-ischemia time on primary nonfunction and patient and graft survival in liver transplantation: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    James E Stahl

    Full Text Available INTRODUCTION: The ability to preserve organs prior to transplant is essential to the organ allocation process. OBJECTIVE: The purpose of this study is to describe the functional relationship between cold-ischemia time (CIT and primary nonfunction (PNF, patient and graft survival in liver transplant. METHODS: To identify relevant articles Medline, EMBASE and the Cochrane database, including the non-English literature identified in these databases, was searched from 1966 to April 2008. Two independent reviewers screened and extracted the data. CIT was analyzed both as a continuous variable and stratified by clinically relevant intervals. Nondichotomous variables were weighted by sample size. Percent variables were weighted by the inverse of the binomial variance. RESULTS: Twenty-six studies met criteria. Functionally, PNF% = -6.678281+0.9134701*CIT Mean+0.1250879*(CIT Mean-9.895352-0.0067663*(CIT Mean-9.895353, r2 = .625, , p<.0001. Mean patient survival: 93% (1 month, 88% (3 months, 83% (6 months and 83% (12 months. Mean graft survival: 85.9% (1 month, 80.5% (3 months, 78.1% (6 months and 76.8% (12 months. Maximum patient and graft survival occurred with CITs between 7.5-12.5 hrs at each survival interval. PNF was also significantly correlated with ICU time, % first time grafts and % immunologic mismatches. CONCLUSION: The results of this work imply that CIT may be the most important pre-transplant information needed in the decision to accept an organ.

  2. Cromoglycate, not ketotifen, ameliorated the injured effect of warm ischemia/reperfusion in rat liver: role of mast cell degranulation, oxidative stress, proinflammatory cytokine, and inducible nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    El-Shitany NA

    2015-09-01

    Full Text Available Nagla A El-Shitany,1,2 Karema El-Desoky3 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 3Department of Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt Abstract: Hepatic ischemia/reperfusion (ISCH/REP is a major clinical problem that is considered to be the most common cause of postoperative liver failure. Recently, mast cells have been proposed to play an important role in the pathophysiology of ISCH/REP in many organs. In contrast, the role played by mast cells during ISCH/REP-induced liver damage has remained an issue of debate. This study aimed to investigate the protective role of mast cells in order to search for an effective therapeutic agent that could protect against fatal ISCH/REP-induced liver damage. A model of warm ISCH/REP was induced in the liver of rats. Four groups of rats were used in this study: Group I: SHAM (normal saline, intravenously [iv]; Group II: ISCH/REP; Group III: sodium cromoglycate + ISCH/REP (CROM + ISCH/REP, and Group IV: ketotifen (KET + ISCH/REP (KET + ISCH/REP. Liver damage was assessed both histopathologically and biochemically. Mast cell degranulation was assessed histochemically. Lipid peroxidation (malondialdehyde [MDA] as well as the levels of glutathione (GSH, interleukin-6 (IL-6, and tumor necrosis factor alpha (TNF-α, the formation of nitric oxide (NO, and the expression of inducible NO synthase (iNOS were determined. The results of this study revealed increased mast cell degranulation in the liver during the acute phase of ISCH/REP. Moreover, CROM, but not KET, decreased the activity of alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase and maintained normal liver tissue histology. Both CROM and KET protected against mast cell degranulation in the liver. In addition, both CROM and KET decreased IL

  3. Optimal Timing for Venous Systemic Oxygen Persufflation Supplemented with Nitric Oxide Gas in Cold-Stored, Warm Ischemia-Damaged Experimental Liver Grafts.

    Science.gov (United States)

    Porschen, Anne; Kadaba Srinivasan, Pramod; Iwasaki, Junji; Afify, Mamdouh; Tolba, René H

    2016-01-01

    Worldwide shortage of donor organs has increased the use of donation after cardiac death (DCD). The aim of this study was to analyze the best time point for venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the 1st and 24th hour of cold storage (CS) in warm ischemia (WI)-damaged experimental liver grafts. Liver grafts (n = 5) were retrieved after 30 min of WI induced by cardiac arrest and CS in histidine-tryptophan-ketoglutarate solution at 4°C. The 1st hour group was immediately persufflated with a VSOP plus NO (VSOP+NO) mixture for 1 h followed by 23 h of static CS (DCD+NO 1st hour). The 24th hour group entailed CS for 23 h followed by 1 h of VSOP+NO persufflation (DCD+NO 24th hour). CS livers without WI but with VSOP served as controls. CS livers with WI represented the fourth group (DCD). Viability of the liver grafts was assessed by normothermic isolated reperfusion for 45 min with oxygenated Krebs-Henseleit buffer. Data are presented as mean ± SEM (control vs. DCD vs. DCD+NO 1st hour vs. DCD+NO 24th hour). After 45 min of reperfusion, the DCD+NO 1st hour group showed significantly lower aspartate aminotransferase (13.4 ± 5.3, 63.2 ± 17.3, 25.6 ± 3.9, and 82.8 ± 27.3 U/l) and lactate dehydrogenase levels (289.4 ± 41.2, 2,139.4 ± 542.7, 577.2 ± 117.2, and 2,429 ± 221.6 U/l). Malondialdehyde levels were significantly abrogated (1.0 ± 0.3, 2.7 ± 1, 1.0 ± 0, and 3.9 ± 1.2 nmol/ml). Significantly higher levels of portal venous pressure were recorded in the DCD+NO 24th hour group (12.0 ± 1, 21.2 ± 3.1, 16.1 ± 1, and 23.2 ± 3.5 mm Hg). NO levels were recorded after 5 min of reperfusion (1.42 ± 0.17, 1.8 ± 0.2, 2.7 ± 0.2, and 2.6 ± 0.1 μmol/l). Bile production levels showed no statistical significance (23.2 ± 3.8, 27.3 ± 1.8, 43.5 ± 18, and 31 ± 2.5 μl/45 min). Our results present the beneficial effects of NO combined with VSOP during the 1st hour of CS of WI-damaged experimental liver grafts.

  4. Measurement of pentane in expiratory gas during rabbit hepatic ischemia/ reperfusion by solid-phase microextraction and gas chromatography–mass spectrometry (SPME GC/MS).

    Science.gov (United States)

    Liu, Shujuan; Shi, Jinghui; Wang, Changsong; Li, Peng; Gong, Yulei; He, Ying; Xu, Guowang; Li, Jianyi; Luo, Ailin; Li, Enyou

    2012-06-01

    The aim of this study was to determine the changes in the pentane concentration of expiratory gas as well as the relationship between this pentane concentration and hepatic oxidative stress during rabbit hepatic ischemia/reperfusion using solid-phase microextraction (SPME) and gas chromatography–mass spectrometry (GC/MS). 45 white male rabbits with body weights between 2.5 and 3.0 kg were randomly assigned to the following three groups: the 10 min ischemia group (group S); the 20 min ischemia group (group M); or the 30 min ischemia group(group L). Expiratory gases were collected prior to ischemia (T0) and for 1, 10, 20, 30, 60 and 120 min (T1–T6) following reperfusion. Pentane concentrations were determined using SPME and GC/MS. In addition, arterial blood samples were collected, and serum aminotransferase(AST) and malondialdehyde (MDA) concentrations were measured. In the three groups, the pentane concentrations of the expiratory gases at points T1 and T2 were significantly increased(P pentane in expiratory gases, which can reflect the degree of oxidative stress during hepatic ischemia/reperfusion.

  5. Effects of "nourishing liver and kidney" acupuncture therapy on expression of brain derived neurotrophic factor and synaptophysin after cerebral ischemia reperfusion in rats.

    Science.gov (United States)

    Xia, Wen-Guang; Zheng, Chan-Juan; Zhang, Xuan; Wang, Juan

    2017-04-01

    The aim of the present study was to investigate the effect of "nourishing liver and kidney" acupuncture therapy on motor and cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via increasing the expression of brain derived neurotrophic factor (BDNF) and synaptophysin (SYN) in the hippocampus. Healthy adult male SD rats were randomly divided into sham operation group (n=51), model group (n=51), acupuncture group (n=51) and acupuncture control group (n=51). The middle cerebral I/R model was established. Acupunctures were performed in the acupuncture group and acupuncture control group at acupoints of Taixi (K103), Taichong (ST09) of both sides, for 30 min once daily every morning. The animals in the sham operation group and model group were conventionally fed in the cage, without any intervention therapy. The rats of each group were assessed with modified neurological severity scores (mNSS). The expression of BDNF and SYN in the hippocampus was detected by immunohistochemical SP method and the synaptic structure in hippocampus area was assessed morphologically and quantitatively at the 3rd, 7th and 14th day. The Morris water Maze (MWM) test was used to evaluate the rats' learning and memory abilities on the 15th day after acupuncture. The animals in the acupuncture control group and sham operation group presented no neurological deficit. In the acupuncture group, the nerve functional recovery was significantly better than that in the model group at the 7th and 14th day after modeling. The average MWM escape latency in the acupuncture group was shorter than that in the model group at the 3rd, 4th and 5th day. The number of crossings of the platform quadrant in the acupuncture group was significantly more than that in the model group. At the each time point, the expression levels of BDNF and SYN in the hippocampal regions increased significantly in the model group as compared with the sham operation group and the acupuncture

  6. Epicardial measurement of alterations in extracellular pH and electrolytes during ischemia and reperfusion in cardiac surgery.

    Science.gov (United States)

    Vogt, Sebastian; Troitzsch, Dirk; Moosdorf, Rainer

    2009-12-01

    Simultaneous measurements of extracellular pH, potassium (K(+)), and calcium (Ca(2+)) activity might be indicative of myocardium vitality or ischemia. Ten consecutive patients undergoing elective coronary artery bypass grafting were studied. Epicardial extracellular pH, potassium, and calcium were measured by a miniaturized disposable multi-sensor probe. Blood gases and electrolytes were derived with measurements of arterial and mixed venous blood samples at intervals during surgery. The mean epicardial baseline levels for pH in all patients were 8.04+/-0.22 arbitrary units (AU) for the right ventricle (RV) and 8.03+/-0.21 AU for the left ventricle (LV); for Ca(2+) 0.23+/-0.07 mmol/l (RV) and 0.20+/-0.10 mmol/l (LV); and for K(+) 4.54+/-1.51 mmol/l (RV) and 4.38+/-0.57 mmol/l (LV). Before ischemia, epicardial pH was moderately (ppH, venous K(+) and Ca(2+), but moderately correlated with arterial K(+) and Ca(2+) (pischemia and reperfusion with reproducible trends of extracellular pH, K(+), and Ca(2+), which results in electrolyte patterns applicable for detecting inadequate myocardial protection during cardiac surgery in patients.

  7. Correlation Between Liver Volumetric Computed Tomography Results and Measured Liver Weight: A Tool for Preoperative Planning of Liver Transplant

    NARCIS (Netherlands)

    Sonnemans, L.J.; Hol, J.C.; Monshouwer, R.; Prokop, M.; Klein, W.M.

    2016-01-01

    OBJECTIVES: Before liver transplant, it is necessary to know the size of the organ in advance of the procedure. We studied the correlation between liver volumetric computed tomography results and liver weight. MATERIALS AND METHODS: Postmortem volumetric computed tomography was conducted on cadavers

  8. The protective effect of diosmin on hepatic ischemia reperfusion injury: an experimental study

    Science.gov (United States)

    Tanrikulu, Yusuf; Şahin, Mefaret; Kismet, Kemal; Kilicoglu, Sibel Serin; Devrim, Erdinc; Tanrikulu, Ceren Sen; Erdemli, Esra; Erel, Serap; Bayraktar, Kenan; Akkus, Mehmet Ali

    2013-01-01

    Liver ischemia reperfusion injury (IRI) is an important pathologic process leading to bodily systemic effects and liver injury. Our study aimed to investigate the protective effects of diosmin, a phlebotrophic drug with antioxidant and anti-inflammatory effects, in a liver IRI model. Forty rats were divided into 4 groups. Sham group, control group (ischemia-reperfusion), intraoperative treatment group, and preoperative treatment group. Ischemia reperfusion model was formed by clamping hepatic pedicle for a 60 minute of ischemia followed by liver reperfusion for another 90 minutes. Superoxide dismutase (SOD) and catalase (CAT) were measured as antioaxidant enzymes in the liver tissues, and malondialdehyde (MDA) as oxidative stress marker, xanthine oxidase (XO) as an oxidant enzyme and glutathione peroxidase (GSH-Px) as antioaxidant enzyme were measured in the liver tissues and the plasma samples. Hepatic function tests were lower in treatment groups than control group (p<0.001 for ALT and AST). Plasma XO and MDA levels were lower in treatment groups than control group, but plasma GSH-Px levels were higher (p<0.05 for all). Tissue MDA levels were lower in treatment groups than control group, but tissue GSH-Px, SOD, CAT and XO levels were higher (p<0.05 for MDA and p<0.001 for others). Samples in control group histopathologically showed morphologic abnormalities specific to ischemia reperfusion. It has been found that both preoperative and intraoperative diosmin treatment decreases cellular damage and protects cells from toxic effects in liver IRI. As a conclusion, diosmin may be used as a protective agent against IRI in elective and emergent liver surgical operations. PMID:24289756

  9. The Protective Effects of Curcumin on Experimental Acute Liver Lesion Induced by Intestinal Ischemia-Reperfusion through Inhibiting the Pathway of NF-κB in a Rat Model

    Directory of Open Access Journals (Sweden)

    Zhe Fan

    2014-01-01

    Full Text Available Objective. In this study, we investigated the protective effect and mechanism of curcumin on a rat model of intestinal ischemia/reperfusion (I/R, which induces an acute liver lesion. Methods. Curcumin was injected into rats in the curcumin groups through left femoral vein. The same volume of vehicle (0.9% normal saline was injected into sham and I/R groups. Blood and liver tissue were gathered for serological and histopathological determination. Results. Intestinal I/R led to severe liver injury manifested as a significant increase in serum AST and ALT levels; all of those were reduced by treatment with curcumin. Simultaneously, the activity of SOD in liver decreased after intestinal I/R, which was increased by curcumin treatment. On the other hand, curcumin reduced MPO activity of liver tissue, as well as serum IL-6 and TNF-α levels observably. This is in parallel with the decreased level of liver intercellular cell adhesion molecule-1 (ICAM-1 and nuclear factor-κB (NF-κB expression. Conclusion. Our findings suggest that curcumin treatment attenuates liver lesion induced by intestinal I/R, attributable to the antioxidative and anti-inflammatory effect via inhibition of the NF-κB pathway.

  10. A Case Study of Hemochromatosis and Conflicting Point Shear Wave Measurements in the Assessment of Liver Fibrosis.

    Science.gov (United States)

    Cohen, Tal; Barr, Richard G

    2017-01-09

    There are multiple factors that affect the shear wave speed in the assessment of liver stiffness. In this case report, we present a case of hemochromatosis that has elevated liver stiffness suggestive of significant fibrosis or cirrhosis; however on liver biopsy, no fibrosis was identified. This article will discuss the possibility that liver iron deposition may affect SWE measurements of the liver, leading to inaccurate assessment of liver fibrosis. In these cases, a liver biopsy may be required for accurate liver assessment.

  11. An antioxidant Trolox restores decreased oral absorption of cyclosporine A after liver ischemia-reperfusion through distinct mechanisms between CYP3A and P-glycoprotein in the small intestine.

    Science.gov (United States)

    Ikemura, Kenji; Inoue, Koichi; Mizutani, Hideki; Oka, Hisao; Iwamoto, Takuya; Okuda, Masahiro

    2012-09-01

    Oxidative stress is a critical mediator of various injuries following ischemia-reperfusion (I/R) associated with organ transplantation. Although oral bioavailability of cyclosporine A (CsA) was decreased by increased first-pass metabolism through CYP3A and P-glycoprotein (P-gp) specifically in the upper small intestine after liver I/R, the mechanism responsible for them remained to be clarified. In the present study, the effect of Trolox (an α-tocopherol analogue) on the decreased oral absorption of CsA through elevated intestinal CYP3A and P-gp after liver I/R and their regulations were investigated. Rats were subjected to 60 min of liver ischemia followed by 12h of reperfusion. Trolox was administered intravenously 5 min before reperfusion. Trolox diminished the increased malondialdehyde and total glutathione levels in plasma by liver I/R and concomitantly prevented the decreased area under the blood concentration-time curve of orally administered CsA as well as initial absorption rate of CsA from upper small intestine. The elevated CYP3A mRNA and activity in the upper small intestine as well as expression levels of P-gp in upper, middle, and lower small intestines after liver I/R were attenuated by Trolox administration. The elevations of CYP3A levels specifically in the upper small intestine of I/R rats were correlated with the lithocholic acid levels in the bile. These results demonstrate that Trolox ameliorates the decreased oral absorption of CsA through elevated intestinal CYP3A and P-gp by preventing oxidative stress, where the biliary lithocholic acid may be responsible for the elevated transcription of CYP3A specifically in the upper small intestine after liver I/R.

  12. Silent Ischemia

    Science.gov (United States)

    ... silent ischemia: An exercise stress test can show blood flow through your coronary arteries in response to exercise. Holter monitoring records your heart rate and rhythm over a 24-hour period (or ...

  13. Extracellular ascorbic acid fluctuation during the protective process of ischemic preconditioning in rabbit renal ischemia-reperfusion model measured

    Institute of Scientific and Technical Information of China (English)

    LIU Lei; LIN Yu-qing; YAN Long-tao; HONG Kai; HOU Xiao-fei; MAO Lan-qun; MA Lu-lin

    2010-01-01

    Background Ascorbic acid has important antioxidant properties, and may play a role in the protective effects of ischemic preconditioning on later ischemia-reperfusion. Herein, we examined the role of endogenous extracellular ascorbic acid in ischemic preconditioning in the kidney.Methods We developed a solitary rabbit kidney model where animals received ischemia-reperfusion only (ischemia-reperfusion group, n=15) or ischemic preconditioning followed by ischemia-reperfusion (ischemic preconditioning group, n=15). Ischemia-reperfusion was induced by occluding and loosening of the renal pedicle. The process of ischemic preconditioning included 15-minute brief ischemia and 10-minute reperfusion. In vivo microdialysis coupled with online electrochemical detection was used to determine levels of endogenous extracellular ascorbic acid in both groups. The extent of tissue damage was determined in kidney sections stained with hematoxylin and eosin. Serum creatinine and urea nitrogen were also detected to assess renal function.Results During ischemia-reperfusion, the extracellular ascorbic acid concentration during ischemia increased rapidly to the peak level ((130.01 ±9.98)%), and then decreased slowly to near basal levels. Similar changes were observed during reperfusion (peak level, (126.78±18.24)%). In the ischemic preconditioning group there was a similar pattern of extracellular ascorbic acid concentration during ischemic preconditioning. However, the ascorbic acid level was significantly lower during the ischemia and early reperfusion stage compared to the ischemia-reperfusion group. Additionally, the extent of glomerular ischemic collapse, tubular dilation, tubular denudation, and loss of brush border were markedly attenuated in the ischemic preconditioning group. Levels of serum creatinine and urea nitrogen were also decreased significantly in the ischemic preconditioning group.Conclusions Ischemic preconditioning may protect renal tissue against ischemia

  14. Gadolinium decreases inflammation related to myocardial ischemia and reperfusion injury

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    Nicolosi Alfred C

    2009-12-01

    Full Text Available Abstract Background The lanthanide cation, gadolinium (GdCl3 protects the myocardium against infarction following ischemia and reperfusion. Neutrophils and macrophages are the main leukocytes responsible for infarct expansion after reperfusion. GdCl3 interferes with macrophage and neutrophil function in the liver by decreasing macrophage secretion of inflammatory cytokines and neutrophil infiltration. We hypothesized that GdCl3 protects against ischemia and reperfusion injury by decreasing inflammation. We determined the impact of GdCl3 treatment for reperfusion injury on 1 circulating monoctye and neutrophil counts, 2 secretion of inflammatory cytokines, and 3 influx of monocytes and neutrophils into the myocardium. Methods Rats (n = 3-6/gp were treated with saline or GdCl3 (20 μmol/kg 15 min prior to a 30 min period of regional ischemia and 120 min reperfusion. Sham rats were not subject to ischemia. Blood was collected either after 30 min ischemia or 120 min reperfusion and hearts were harvested at 120 min reperfusion for tissue analysis. Blood was analyzed for leukocytes counts and cytokines. Tissue was analyzed for cytokines and markers of neutrophil and monocyte infiltration by measuring myeloperoxidase (MPO and α-naphthyl acetate esterase (ANAE. Results GdCl3 did not affect the number of circulating neutrophils prior to ischemia. Two hours reperfusion resulted in a 2- and 3- fold increase in circulating monocytes and neutrophils, respectively. GdCl3 decreased the number of circulating monocytes and neutrophils during reperfusion to levels below those present prior to ischemia. Furthermore, after 120 min of reperfusion, GdCl3 decreased ANAE and MPO activity in the myocardium by 1.9-fold and 6.5-fold respectively. GdCl3 decreased MPO activity to levels below those measured in the Sham group. Serum levels of the major neutrophil chemoattractant cytokine, IL-8 were increased from pre-ischemic levels during ischemia and reperfusion in both

  15. Cromoglycate, not ketotifen, ameliorated the injured effect of warm ischemia/reperfusion in rat liver: role of mast cell degranulation, oxidative stress, proinflammatory cytokine, and inducible nitric oxide synthase

    Science.gov (United States)

    El-Shitany, Nagla A; El-Desoky, Karema

    2015-01-01

    Hepatic ischemia/reperfusion (ISCH/REP) is a major clinical problem that is considered to be the most common cause of postoperative liver failure. Recently, mast cells have been proposed to play an important role in the pathophysiology of ISCH/REP in many organs. In contrast, the role played by mast cells during ISCH/REP-induced liver damage has remained an issue of debate. This study aimed to investigate the protective role of mast cells in order to search for an effective therapeutic agent that could protect against fatal ISCH/REP-induced liver damage. A model of warm ISCH/REP was induced in the liver of rats. Four groups of rats were used in this study: Group I: SHAM (normal saline, intravenously [iv]); Group II: ISCH/REP; Group III: sodium cromoglycate + ISCH/REP (CROM + ISCH/REP), and Group IV: ketotifen (KET) + ISCH/REP (KET + ISCH/REP). Liver damage was assessed both histopathologically and biochemically. Mast cell degranulation was assessed histochemically. Lipid peroxidation (malondialdehyde [MDA]) as well as the levels of glutathione (GSH), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), the formation of nitric oxide (NO), and the expression of inducible NO synthase (iNOS) were determined. The results of this study revealed increased mast cell degranulation in the liver during the acute phase of ISCH/REP. Moreover, CROM, but not KET, decreased the activity of alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase and maintained normal liver tissue histology. Both CROM and KET protected against mast cell degranulation in the liver. In addition, both CROM and KET decreased IL-6 and TNF-α. However, CROM, but not KET, decreased MDA formation and increased GSH. Furthermore, KET, but not CROM, increased both NO formation and iNOS expression. In conclusion, this study clearly demonstrated mast cell degranulation in warm ISCH/REP in the liver of rats. More importantly, CROM, but not KET, ameliorated the effect of ISCH

  16. Cromoglycate, not ketotifen, ameliorated the injured effect of warm ischemia/reperfusion in rat liver: role of mast cell degranulation, oxidative stress, proinflammatory cytokine, and inducible nitric oxide synthase.

    Science.gov (United States)

    El-Shitany, Nagla A; El-Desoky, Karema

    2015-01-01

    Hepatic ischemia/reperfusion (ISCH/REP) is a major clinical problem that is considered to be the most common cause of postoperative liver failure. Recently, mast cells have been proposed to play an important role in the pathophysiology of ISCH/REP in many organs. In contrast, the role played by mast cells during ISCH/REP-induced liver damage has remained an issue of debate. This study aimed to investigate the protective role of mast cells in order to search for an effective therapeutic agent that could protect against fatal ISCH/REP-induced liver damage. A model of warm ISCH/REP was induced in the liver of rats. Four groups of rats were used in this study: Group I: SHAM (normal saline, intravenously [iv]); Group II: ISCH/REP; Group III: sodium cromoglycate + ISCH/REP (CROM + ISCH/REP), and Group IV: ketotifen (KET) + ISCH/REP (KET + ISCH/REP). Liver damage was assessed both histopathologically and biochemically. Mast cell degranulation was assessed histochemically. Lipid peroxidation (malondialdehyde [MDA]) as well as the levels of glutathione (GSH), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), the formation of nitric oxide (NO), and the expression of inducible NO synthase (iNOS) were determined. The results of this study revealed increased mast cell degranulation in the liver during the acute phase of ISCH/REP. Moreover, CROM, but not KET, decreased the activity of alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase and maintained normal liver tissue histology. Both CROM and KET protected against mast cell degranulation in the liver. In addition, both CROM and KET decreased IL-6 and TNF-α. However, CROM, but not KET, decreased MDA formation and increased GSH. Furthermore, KET, but not CROM, increased both NO formation and iNOS expression. In conclusion, this study clearly demonstrated mast cell degranulation in warm ISCH/REP in the liver of rats. More importantly, CROM, but not KET, ameliorated the effect of ISCH

  17. 阿托伐他汀对老年大鼠心肌缺血再灌注损伤及多器官功能的保护作用%Protective effect of atrovastatin against myocardial ischemia-reperfusion injury and on liver and kidney functions in aged rats

    Institute of Scientific and Technical Information of China (English)

    张今尧; 王浩; 叶平

    2012-01-01

    目的 观察阿托伐他汀对老年大鼠心肌缺血再灌注过程中心脏的影响,并进一步关注此过程中肝、肾功能的变化.方法 10月龄Wistar大鼠饲养至20月龄,阿托伐他汀灌胃至24月龄,分为大剂量他汀组、小剂量他汀组、老年对照组,并设立青年对照组.采用结扎冠状动脉方法建立心肌缺血再灌注模型,纪录缺血再灌注过程中大鼠死亡率、血流动力学变化、心肌梗塞面积变化,及肝肾功能指标.结果 与老年对照组相比,青年对照组及大剂量他汀组在缺血再灌注过程中死亡率明显降低(P<0.05)、血流动力学紊乱减少、心梗面积减小(P<0.05);青年对照组及大剂量他汀组在缺血再灌注后,肝肾功能无明显恶化,小剂量他汀组肝脏功能显著恶化(P<0.05),老年对照组肝肾功能均出现显著恶化(P<0.05).结论 阿托伐他汀对老年大鼠心肌缺血再灌注过程中的心、肝、肾多器官产生保护作用.%Objuctive To observe the effect of atorvastatin against myocardial ischemia-reperfusion injury and its protective effect on liver and kidney functions. Methods Ten-month-old Wistar rats were fed to the age of 20 months, and atorvastatin statins gavage was administered till 24 months. The rats were divided into high-dose statin group, small-dose statin group, aged control group and young control group. The myocardial ischemia-reperfusion model was established by ligating the coronary artery. The mortality, hemodynamic changes, infarct size and liver and kidney functions of the rats were recorded or measured. Results Compared with the aged control group, the young control group and high-dose statin group showed significantly lower mortality rate, reduced hemodynamic abnormalities, and smaller myocardial infarct size following myocardial ischemia-reperfusion (P<0.05). The liver and kidney functions of the young control group and high-dose statin group underwent no significant deterioration

  18. 移植肝再灌注损伤的发生机制%Mechnisms of ischemia/reperfusion injury in transplanted liver

    Institute of Scientific and Technical Information of China (English)

    邵堂雷; 蔡伟耀; 李宏为

    2001-01-01

    目的介绍有关移植肝再灌注损伤发生机制的研究动向。方法复习有关文献并进行综述性报告。结果移植肝冷保存后的再灌注损伤的发生机制主要有:(1)内皮细胞损伤和Kupffer细胞激活,导致一系列细胞因子的产生,引起移植肝损伤,并引发全身炎症反应综合征;(2)白细胞、血小板与肝血窦壁的粘附而损害肝细胞,并可阻塞肝血窦造成“无复流”现象;(3)pH值的变化。再灌注后移植肝的代谢恢复正常后,组织内pH值的改变可引起肝细胞损伤;并可造成线粒体的肿胀,使肝细胞的功能降低;(4)复氧损伤。主要与白细胞释放活性氧(ROS)有关。结论移植肝再灌注损伤是多种因素综合作用的结果,在再灌注前后提高肝细胞和内皮细胞的活性,抑制kupffer细胞的激活,减少ROS及肿瘤坏死因子(TNF)的产生将是今后预防移植肝再灌注损伤研究的关键。%Objective To introduce the research trence of the medchnisims of ischemia/reperfusion(I/R) injury in transplanted liver(TL). Methods Making a literature summarization based on papers review.Results The main mechnisms of I/R injury in TL as the followings: (1) Production of various cytokines resulted from endothelial cell injury with activation of kupffer cells, which can result in TL injury and induce systemic inflammation syndrom. (2) White blood cells and platelets adhere to the liver sinusoid (LS), which can cause TL injury and obstruct the LS causing “no reperfusion" of TL. (3) Alteration of pH in the cells of TL. After recovery of normal metabolism of the reperfused TL, alteration of pH in the TL can cause damage to TL cells, and cause edema of mitochrondria resulting in decresing of TL function. (4) Reoxygenation injury mainly caused by activated oxygen relsased by white blood cell. Conclusions I/R injury of TL is caused by combination of muttiple foctors. Improving the activity of hepatocytes

  19. Protective effects of alprostadil on hepatocyte apoptosis by Liver Ischemia-Reperfusion Injury in rabbits%前列地尔对兔肝缺血再灌注时肝细胞凋亡的保护作用

    Institute of Scientific and Technical Information of China (English)

    郭凌燕; 赵刚

    2011-01-01

    Objective To study the protective the positive effects of alprostadil Hepatocyte Apoptosis by Liver Ischemia-Reperfusion Injury in rabbits. Methods Thirty-six rabbits were made the model of liver ischemia-reperfusion injury, and randourly divided into three groups:Control group, Ischemia-Reperfusion Injury group and Alprostadil intervention group. The alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , lactate dehydrogenase (LDH) were determined; Each group inducible nitric oxide synthase (iNOS) , myeloperoxidase (MPO) and bcl-2, bax, Caspase-3 and apoptosis of the hepatocyte by TUNEL were assayed at 60 and 90 min after reperfusion. Results The ALT, AST, LDH concentration in plasma in Ischemia-Reperfusion Injury group and Alprostadil intervention group were increased obviously at 60, 90 min after reperfusion and it was significantly higher than that in the Control group in the same time point (P<0.05). And the ALT, AST, LDH concentration in plasma in Alprostadil intervention group was significantly lower than that in the in Ischemia-Reperfusion Injury group in the same time point (P<0.05). The level of bcl-2, bax, Caspase-3 in the liver tissue in the Control group was smaller, but the obvious increase of the expression those was found in the Ischemia-Reperfusion Injury group and Alprostadil intervention group. Compared with those in the Ischemia-Reperfusion Injury group group, the expression of bcl-2, bax, Caspase-3 in the Alprostadil intervention group werw obviously smaller (P<0.05). The contents of iNOS and MPO in liver tissue in the Ischemia-Reperfusion Injury group and Alprostadil intervention group were significantly higher than that in the Control group (P<0.05). Conclusion Alprostadil could be used to protect liver ischemia-reperfusion injury, it could decrease oxygen free radicals generation, inhibit neutrophils aggregating and activating in the liver, thereby inhibiting expression of bcl-2, bax, Caspase-3.%目的 探讨前列地尔对兔

  20. L-arginine in the ischemic phase protects against liver ischemia-reperfusion injury A L-arginina durante a fase isquêmica protege o fígado das lesões de isquemia e reperfusão

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    Murched Omar Taha

    2012-09-01

    Full Text Available PURPOSE: To investigate the effects of intravenous L-arginine (LG infusion on liver morphology, function and proinflammatory response of cytokines during the early phase of ischemia-reperfusion injury (IRI. METHODS: Thirty rabbits were subjected to 60 minutes of hepatic ischemia and 120 minutes of reperfusion. An intravenous injection of saline or L-arginine was administered five minutes before the ischemia and five minutes before initiating the reperfusion and at the 55th and 115th minutes after the ischemia. Samples were collected for histological analysis of the liver and measurements of the serum AST, ALT and LDH and the cytokines IL-6 and TNF-alpha. RESULTS: It was observed a significant reduction of sinusoidal congestion, cytoplasmic vacuolization, infiltration of polymorphonuclear leukocyte, nuclear pyknosis, necrosis and steatosis in liver tissue, as well as AST, ALT and LDH after injection of LG in the ischemia (p OBJETIVO: Investigar os efeitos da infusão endovenosa da L-arginina (LG na morfologia, função e resposta de citocinas pró-inflamatórias do fígado durante a fase precoce da lesão de isquemia e reperfusão (IRI. MÉTODOS: Trinta coelhos foram submetidos a 60 minutos de isquemia hepática e 120 minutos de reperfusão. Foi administrada injecção intravenosa de solução salina ou L-arginina aos cinco minutos antes de iniciar a isquemia e cinco minutos antes de iniciar a reperfusão e aos 55 e 115 minutos após o início da isquemia. Realizou-se análise histológica do fígado e dosagens séricas de AST, ALT, LDH, citocinas IL-6 e TNF-alfa. RESULTADOS: Ocorreu redução significante da congestão sinusoidal, vacuolização citoplasmática, infiltração de leucócitos polimorfonucleares, picnose nuclear, necrose e esteatose no tecido hepático, assim como nos níveis de AST, ALT e LDH após a injeção da LG na isquemia (p<0,001. Níveis mais baixos de IL-6 e TNF-alfa foram associados com a infusão LG durante a isquemia

  1. Effect of tumor necrosis factor-alpha in rats with hepatic ischemia-reper fusion injur y

    Institute of Scientific and Technical Information of China (English)

    Mao Ma; Zhen-Hua Ma

    2008-01-01

    BACKGROUND:With the development of hepatic surgery, especially liver transplantation, the pathophysiological processes of hepatic ischemia-reperfusion (I/R) injury have gained special attention. Controlling I/R injury has become one of the most important factors for successful liver transplantation. This study aimed to investigate the effects of tumor necrosis factor-alpha (TNF-α) in rats with hepatic I/R injury and promote the recognition of I/R injury in the liver. METHODS:Thirty-two Sprague-Dawley rats were randomly divided into 2 groups. Rats in the sham-operated (SO) group served as controls. Rats in the hepatic ischemia-reperfusion (I/R) group underwent reperfusion after 30 minutes of liver ischemia. Rats were sacriifced at 1, 6 and 12 hours. The expression of TNF-αmRNA in the liver was measured by RT-PCR. Histological changes in the liver were assessed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were measured. RESULTS:The expression of TNF-αmRNA in the SO group was decreased compared with that in the I/R group (P CONCLUSION:ALT and AST in serum are closely related to hepatic I/R injury and inlfammatory reaction. TNF-αproduction in the liver triggers hepatic I/R injury through a cascade.

  2. Isquemia e reperfusão hepática total associada ao estado de choque hemorrágico controlado: efeitos no seqüestro de neutrófilos no fígado do rato Total hepatic warm ischemia and reperfusion associated with controlled hemorrhagic shock: effects of neutrophil sequestration in rat liver

    Directory of Open Access Journals (Sweden)

    Mario Mantovani

    2003-08-01

    60 min of observation; Shock group, was submitted to controlled hemorrhagic shock (mean arterial blood pressure = 40 mmHg, 20 min followed by volume resuscitation (lactated Ringer's solution + blood, 3:1 and reperfusion for 60 min; Pringle group, was submitted to total hepatic ischemia for 15 min and reperfusion for 60 min; The Total group, was submitted to controlled hemorrhagic shock for 15 min followed by volume resuscitation (lactated Ringer's solution + blood, 3:1, total hepatic ischemia for 15 min and reperfusion for 60 min. Measurements of serum lactate and base excess were used to characterize the hemorrhagic shock state with low tissue perfusion. The counting of neutrophils on the liver tissue was performed after the euthanasia of animals. RESULTS: Values for the counting of neutrophils on the liver indicate that, the animals from Pringle group differed from Shock and Total groups (Control 10.30±3.20, Shock 13.94±2.84, Pringle 7.00±3.40, Total 12.45±3.65 but did not differ from Control group. CONCLUSIONS: Rats submitted to controlled hemorrhagic shock state associated to total hepatic ischemia for 15 minutes, followed by 60 minutes of reperfusion, did not present significant neutrophils accumulation on liver tissue.

  3. High-frequency ultrasound for monitoring changes in liver tissue during preservation

    Energy Technology Data Exchange (ETDEWEB)

    Vlad, Roxana M [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Czarnota, Gregory J [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Giles, Anoja [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Sherar, Michael D [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Hunt, John W [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Kolios, Michael C [Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada)

    2005-01-21

    Currently the only method to assess liver preservation injury is based on liver appearance and donor medical history. Previous work has shown that high-frequency ultrasound could detect ischemic cell death due to changes in cell morphology. In this study, we use high-frequency ultrasound integrated backscatter to assess liver damage in experimental models of liver ischemia. Ultimately, our goal is to predict organ suitability for transplantation using high-frequency imaging and spectral analysis techniques. To examine the effects of liver ischemia at different temperatures, livers from Wistar rats were surgically excised, immersed in phosphate buffer saline and stored at 4 and 20 deg. C for 24 h. To mimic organ preservation, livers were excised, flushed with University of Wisconsin (UW) solution and stored at 4 deg. C for 24 h. Preservation injury was simulated by either not flushing livers with UW solution or, before scanning, allowing livers to reach room temperature. Ultrasound images and corresponding radiofrequency data were collected over the ischemic period. No significant increase in integrated backscatter ({approx}2.5 dBr) was measured for the livers prepared using standard preservation conditions. For all other ischemia models, the integrated backscatter increased by 4-9 dBr demonstrating kinetics dependent on storage conditions. The results provide a possible framework for using high-frequency imaging to non-invasively assess liver preservation injury.

  4. Quantitative dual energy CT measurements in rabbit VX2 liver tumors: Comparison to perfusion CT measurements and histopathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Long Jiang, E-mail: kevinzhanglongjiang@yahoo.com.cn [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Wu, Shengyong, E-mail: cjr.wushengyong@vip.163.com [Institute of Tianjin Medical Imaging, Tianjin 300192 (China); Wang, Mei, E-mail: 281406196@qq.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Lu, Li, E-mail: xuzhoululi@163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Chen, Bo, E-mail: chenbo1985@yahoo.com.cn [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China); Jin, Lixin, E-mail: lixin.jin@siemens.com [Siemens Healthcare, MR Collaboration NE Asia, Shanghai (China); Wang, Jiandong, E-mail: jdwang1216@163.com [Department of Pathology, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 200012 (China); Larson, Andrew C., E-mail: a-larson@northwestern.edu [Department of Radiology, Northwestern University, Chicago, IL (United States); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province 210002 (China)

    2012-08-15

    Purpose: To evaluate the correlation between quantitative dual energy CT and perfusion CT measurements in rabbit VX2 liver tumors. Materials and methods: This study was approved by the institutional animal care and use committee at our institution. Nine rabbits with VX2 liver tumors underwent contrast-enhanced dual energy CT and perfusion CT. CT attenuation for the tumors and normal liver parenchyma and tumor-to-liver ratio were obtained at the 140 kVp, 80 kVp, average weighted images and dual energy CT iodine maps. Quantitative parameters for the viable tumor and adjacent liver were measured with perfusion CT. The correlation between the enhancement values of the tumor in iodine maps and perfusion CT parameters of each tumor was analyzed. Radiation dose from dual energy CT and perfusion CT was measured. Results: Enhancement values for the tumor were higher than that for normal liver parenchyma at the hepatic arterial phase (P < 0.05). The highest tumor-to-liver ratio was obtained in hepatic arterial phase iodine map. Hepatic blood flow of the tumor was higher than that for adjacent liver (P < 0.05). Enhancement values of hepatic tumors in the iodine maps positively correlated with permeability of capillary vessel surface (r = 0.913, P < 0.001), hepatic blood flow (r = 0.512, P = 0.010), and hepatic blood volume (r = 0.464, P = 0.022) at the hepatic arterial phases. The effective radiation dose from perfusion CT was higher than that from DECT (P < 0.001). Conclusions: The enhancement values for viable tumor tissues measured in iodine maps were well correlated to perfusion CT measurements in rabbit VX2 liver tumors. Compared with perfusion CT, dual energy CT of the liver required a lower radiation dose.

  5. Measurement of Liver Iron Concentration by MRI Is Reproducible

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    José María Alústiza

    2015-01-01

    Full Text Available Purpose. The objectives were (i construction of a phantom to reproduce the behavior of iron overload in the liver by MRI and (ii assessment of the variability of a previously validated method to quantify liver iron concentration between different MRI devices using the phantom and patients. Materials and Methods. A phantom reproducing the liver/muscle ratios of two patients with intermediate and high iron overload. Nine patients with different levels of iron overload were studied in 4 multivendor devices and 8 of them were studied twice in the machine where the model was developed. The phantom was analysed in the same equipment and 14 times in the reference machine. Results. FeCl3 solutions containing 0.3, 0.5, 0.6, and 1.2 mg Fe/mL were chosen to generate the phantom. The average of the intramachine variability for patients was 10% and for the intermachines 8%. For the phantom the intramachine coefficient of variation was always below 0.1 and the average of intermachine variability was 10% for moderate and 5% for high iron overload. Conclusion. The phantom reproduces the behavior of patients with moderate or high iron overload. The proposed method of calculating liver iron concentration is reproducible in several different 1.5 T systems.

  6. Relaxin as a protective substance in the preserving solution for liver transplantation: spectrophotometric in vivo imaging of local oxygen supply in an isolated perfused rat liver model.

    Science.gov (United States)

    Boehnert, Markus U; Armbruster, Franz Paul; Hilbig, Heidegard

    2009-04-01

    Ischemia reperfusion injury (IRI) is a problem in organ transplantation. Relaxin is known to have a protective effect against liver injury caused by IRI. Using a model of isolated perfused rat liver, the local oxygen supply in liver tissue was investigated by spectrophotometric in vivo imaging and compared to the protective effect of relaxin shown by immunohistochemical measurement of myeloperoxidase and malonyldialdehyde activities as determinants of oxidative stress. In relaxin-treated liver tissue, spectrophotometry showed a better oxygen supply and decreased myeloperoxidase and malonyldialdehyde activities. Our data suggest that relaxin can influence the oxygen distribution in liver tissue and reduce cell damage caused by IRI.

  7. Evaluation of liver functional reserve by combining D-sorbitol clearance rate and CT measured liver volume

    Institute of Scientific and Technical Information of China (English)

    Yi-Ming Li; Fan Lv; Xin Xu; Hong Ji; Wen-Tao Gao; Tuan-Jie Lei; Gui-Bing Ren; Zhi-Lan Bai; Qiang Li

    2003-01-01

    AIM: Our research attempted to evaluate the overall functional reserve of cirrhotic liver by combination of hepatic functional blood flow, liver volume, and ChildPugh′s classification, and to discuss its value of clinical application.METHODS: Ninety two patients with portal hypertension due to hepatic cirrhosis were investigated. All had a historyof haematemesis and hematochezia, esophageal and gastric fundus varices, splenomegaly and hypersplenia.A 2-year follow-up was routinely performed and no one was lost. Twenty two healthy volunteers were used as control group. Blood and urine samples were collected 4times before and after intravenous D-sorbitol infusion.The hepatic clearance (CLH) of D-sorbitol was then calculated according to enzymatic spectrophotometric method while the total blood flow (QToTAL) and intrahepatic shunt (RINs) were detected by multicolor Doppler ultrasound, and the liver volume was measured by spiral CT. Data were estimated by t-test, variance calculation and chi-squared test. The relationships between all these parameters and different groups were investigated according to Child-Pugh classification and postoperative complications respectively.RESULTS: Steady blood concentration was achieved 120 mins after D-sorbitol intravenous infusion, which was (0.358±0.064) mmoⅠ@L-1 in cirrhotic group and (0.189±0.05)mmol@L-1 in control group (P<0.01). CLH=(812.7±112.4) ml@min-1,QTOTAL=(1280.6±131.4) ml@min-1, and RINS=(36.54±10.65)%in cirrhotic group and CLH=(1248.3±210.5) ml.min-1, QTOTAL=(1362.4-±126.9) ml@min-1, and RINS=(8.37±3.32) % in control group (P<0.01). The liver volume of cirrhotic group was 1057±249 cm3, 851±148 cm3 and 663±77 cm3 in Child A, B and C group respectively with significant difference (P<0.001).The average volume of cirrhotic liver in Child B, C group was significantly reduced in comparison with that in control group (P<0.001). The patient, whose liver volume decreased by 40 % with the CLH below 600 ml

  8. Using old liver grafts for liver transplantation: where are the limits?

    Science.gov (United States)

    Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2014-08-21

    The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts.

  9. Quantitative Measurement of Cerebral Perfusion with Intravoxel Incoherent Motion in Acute Ischemia Stroke: Initial Clinical Experience

    Institute of Scientific and Technical Information of China (English)

    Li-Bao Hu; Nan Hong; Wen-Zhen Zhu

    2015-01-01

    Background:Intravoxel incoherent motion (IVIM) has the potential to provide both diffusion and perfusion information without an exogenous contrast agent,its application for the brain is promising,however,feasibility studies on this are relatively scarce.The aim of this study is to assess the feasibility of IVIM perfusion in patients with acute ischemic stroke (AIS).Methods:Patients with suspected AIS were examined by magnetic resonance imaging within 24 h of symptom onset.Fifteen patients (mean age was 68.7 ± 8.0 years) who underwent arterial spin labeling (ASL) and diffusion-weighted imaging (DWI) were identified as having AIS with ischemic penumbra were enrolled,where ischemic penumbra referred to the mismatch areas of ASL and DWI.Eleven different b-values were applied in the biexponential model.Regions of interest were selected in ischemic penumbras and contralateral normal brain regions.Fast apparent diffusion coefficients (ADCs) and ASL cerebral blood flow (CBF) were measured.The paired t-test was applied to compare ASL CBF,fast ADC,and slow ADC measurements between ischemic penumbras and contralateral normal brain regions.Linear regression and Pearson's correlation were used to evaluate the correlations among quantitative results.Results:The fast ADCs and ASL CBFs of ischemic penumbras were significantly lower than those of the contralateral normal brain regions (1.93 ± 0.78 μm2/ms vs.3.97 ± 2.49 μm2/ms,P =0.007;13.5 ± 4.5 ml· 100 g-1 ·min-1 vs.29.1 ± 12.7 ml·100 g-1 ·min-1,P < 0.001,respectively).No significant difference was observed in slow ADCs between ischemic penumbras and contralateral normal brain regions (0.203 ± 0.090 μm2/ms vs.0.198 ± 0.100 μm2/ms,P =0.451).Compared with contralateral normal brain regions,both CBFs and fast ADCs decreased in ischemic penumbras while slow ADCs remained the same.A significant correlation was detected between fast ADCs and ASL CBFs (r =0.416,P < 0.05).No statistically significant correlation was

  10. Measuring Coping Behavior in Liver Transplant Candidates: A Psychometric Analysis of the Brief COPE.

    Science.gov (United States)

    Amoyal, Nicole; Fernandez, Anne C; Ng, Reuben; Fehon, Dwain C

    2016-09-01

    Liver transplant candidates must cope with significant physiological and psychological challenges. The Brief COPE is a frequently used measure of coping behavior; however, knowledge of the scale's factor structure and construct validity is limited with regard to liver transplant candidates. This study assessed the validity of the Brief COPE in 120 liver transplant candidates using exploratory factor analysis. Results revealed a 6-factor solution, only 2 of which were consistent with the original scale assignments. Construct validity of the 6 Brief COPE scales yielded in this study was demonstrated. The results indicate that the Brief COPE is valid, reliable, and can be meaningfully interpreted in liver transplant patients. Future research should confirm this factor structure and examine its predictive validity prior to widespread use among liver transplant patients. Suggestions are presented for enhancing the care of transplant candidates by promoting the use of adaptive coping mechanisms to manage distress.

  11. Validating new software for semiautomated liver volumetry. Better than manual measurement?

    Energy Technology Data Exchange (ETDEWEB)

    Noschinski, L.E.; Maiwald, B.; Voigt, P.; Kahn, T.; Stumpp, P. [University Hospital Leipzig (Germany). Dept. of Diagnostic and Interventional Radiology; Wiltberger, G. [University Hospital Leipzig (Germany). Dept. of Visceral, Transplantation, Thoracic and Vascular Surgery

    2015-09-15

    This prospective study compared a manual program for liver volumetry with semiautomated software. The hypothesis was that the semiautomated software would be faster, more accurate and less dependent on the evaluator's experience. Ten patients undergoing hemihepatectomy were included in this IRB approved study after written informed consent. All patients underwent a preoperative abdominal 3-phase CT scan, which was used for whole liver volumetry and volume prediction for the liver part to be resected. Two different types of software were used: 1) manual method: borders of the liver had to be defined per slice by the user; 2) semiautomated software: automatic identification of liver volume with manual assistance for definition of Couinaud segments. Measurements were done by six observers with different experience levels. Water displacement volumetry immediately after partial liver resection served as the gold standard. The resected part was examined with a CT scan after displacement volumetry. Volumetry of the resected liver scan showed excellent correlation to water displacement volumetry (manual: ρ = 0.997; semiautomated software: ρ = 0.995). The difference between the predicted volume and the real volume was significantly smaller with the semiautomated software than with the manual method (33 % vs. 57 %, p = 0.002). The semiautomated software was almost four times faster for volumetry of the whole liver (manual: 6:59 ± 3:04min; semiautomated: 1:47 ± 1:11 min). Both methods for liver volumetry give an estimated liver volume close to the real one. The tested semiautomated software is faster, more accurate in predicting the volume of the resected liver part, gives more reproducible results and is less dependent on the user's experience.

  12. Non-invasive measurement of hepatic oxygenation by an oxygen electrode in human orthotopic liver transplantation.

    Science.gov (United States)

    Seifalian, A M; Mallett, S; Piasecki, C; Rolles, K; Davidson, B R

    2000-06-01

    Precise evaluation of graft reperfusion is difficult in clinical liver transplantation. The oxygen electrode (OE) is a novel technique to detect blood flow indirectly by measuring the quantity of oxygen which can diffuse from the hepatic tissue to the surface electrode. Application of the surface OE does not influence the liver blood flow or parenchymal perfusion. Adequate graft oxygenation is essential to the outcome of organ transplantation and has not previously been analysed intra-operatively in liver transplant recipients. The OE was applied to the surface of the graft intra-operatively in 22 human liver grafts after restoring portal vein and hepatic artery inflow. OE readings were compared with liver blood flow using an electromagnetic flowmeter (EMF). Intra-operative haemodynamics and donor organ parameters known to influence graft function were correlated with the OE readings. There was a significant correlation (r=0.89; poxygenation using the OE and total liver blood flow measured by EMF. The tissue oxygenation measurements were reproducible with a coefficient of variation of 5%. The hepatic tissue oxygenation increased significantly from baseline following venous reperfusion of the graft (282+/-23 vs 3107+/-288 (+/-SE) nA, poxygen perfusion. There was significant negative correlation (r=0.80, poxygenation. The OE provides a reliable, cheap and non-invasive method of monitoring liver graft oxygenation and perfusion during transplantation.

  13. Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats

    Science.gov (United States)

    Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

    2015-01-01

    This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use. PMID:26885068

  14. Liver Stiffness Measurement-Based Scoring System for Significant Inflammation Related to Chronic Hepatitis B

    Science.gov (United States)

    Hong, Mei-Zhu; Zhang, Ru-Mian; Chen, Guo-Liang; Huang, Wen-Qi; Min, Feng; Chen, Tian; Xu, Jin-Chao; Pan, Jin-Shui

    2014-01-01

    Objectives Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers. Methods The training set included chronic hepatitis B patients (n = 327), and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement. Results An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+) patients and 0.978, 85.0%, and 94.0% in the HBeAg(−) patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+) patients and 0.977, 95.2%, and 95.8% in the HBeAg(−) patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+) and HBeAg(−) patients for recognizing significant inflammation (G ≥3). Conclusions Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation. PMID:25360742

  15. Liver stiffness measurement-based scoring system for significant inflammation related to chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Mei-Zhu Hong

    Full Text Available Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers.The training set included chronic hepatitis B patients (n = 327, and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement.An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+ patients and 0.978, 85.0%, and 94.0% in the HBeAg(- patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+ patients and 0.977, 95.2%, and 95.8% in the HBeAg(- patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+ and HBeAg(- patients for recognizing significant inflammation (G ≥3.Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation.

  16. In vitro measurements of temperature-dependent specific heat of liver tissue.

    Science.gov (United States)

    Haemmerich, Dieter; dos Santos, Icaro; Schutt, David J; Webster, John G; Mahvi, David M

    2006-03-01

    We measured the specific heat of liver tissue in vitro by uniformly heating liver samples between two electrodes. We insulated the samples by expanded polystyrene, and corrected for heat loss and water loss. The specific heat of the liver is temperature-dependent, and increases by 17% at 83.5 degrees C (p specific heat was 3411 J kg(-1)K(-1) at 25 degrees C, and 4187 J kg(-1)K(-1) at 83.5 degrees C. Water loss from the samples was significant above 70 degrees C, with approximately 20% of reduction in sample mass at 90 degrees C.

  17. Improved noninvasive prediction of liver fibrosis by liver stiffness measurement in patients with nonalcoholic fatty liver disease accounting for controlled attenuation parameter values.

    Science.gov (United States)

    Petta, Salvatore; Wong, Vincent Wai-Sun; Cammà, Calogero; Hiriart, Jean-Baptiste; Wong, Grace Lai-Hung; Marra, Fabio; Vergniol, Julien; Chan, Anthony Wing-Hung; Di Marco, Vito; Merrouche, Wassil; Chan, Henry Lik-Yuen; Barbara, Marco; Le-Bail, Brigitte; Arena, Umberto; Craxì, Antonio; de Ledinghen, Victor

    2017-04-01

    Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis in nonalcoholic fatty liver disease (NAFLD). Controlled attenuation parameter (CAP) is a new parameter provided by the same machine used for LSM and associated with both steatosis and body mass index, the two factors mostly affecting LSM performance in NAFLD. We aimed to determine whether prediction of liver fibrosis by LSM in NAFLD patients is affected by CAP values. Patients (n = 324) were assessed by clinical and histological (Kleiner score) features. LSM and CAP were performed using the M probe. CAP values were grouped by tertiles (lower 132-298, middle 299-338, higher 339-400 dB/m). Among patients with F0-F2 fibrosis, mean LSM values, expressed in kilopascals, increased according to CAP tertiles (6.8 versus 8.6 versus 9.4, P = 0.001), and along this line the area under the curve of LSM for the diagnosis of F3-F4 fibrosis was progressively reduced from lower to middle and further to higher CAP tertiles (0.915, 0.848-0.982; 0.830, 0.753-0.908; 0.806, 0.723-0.890). As a consequence, in subjects with F0-F2 fibrosis, the rates of false-positive LSM results for F3-F4 fibrosis increased according to CAP tertiles (7.2% in lower versus 16.6% in middle versus 18.1% in higher). Consistent with this, a decisional flowchart for predicting fibrosis was suggested by combining both LSM and CAP values.

  18. Effect of liver ischemic preconditioning in cirrhotic rats submitted to hepatic ischemia/reperfusion injury Efeito do pré-condicionamento isquêmico hepático submetidos a lesão de isquemia/reperfusão do fígado

    Directory of Open Access Journals (Sweden)

    Eduardo Garcia Pacheco

    2006-01-01

    Full Text Available PURPOSE: The main aim of this study was to determine the influence of ischemic preconditioning (IPC on rat liver cirrhosis. METHODS: Cirrhosis was induced in Wistar rats by occlusion of the hepatic duct. The animals were divided into four groups of six animals each: non-cirrhotic group (simulated operation only, cirrhotic control group (simulated operation in cirrhotic rats, I/R group (40-minute ischemia without IPC, and IPC group (cirrhotic rats with ischemia, previously submitted to IPC. The IPC procedure consisted of partial hepatic ischemia for five minutes, followed by 10 minutes of reperfusion. In the case of the IPC group, the animals were submitted to liver ischemia for 40 minutes after the preconditioning procedure, followed by 2 hours of reperfusion. Blood samples were collected for measurement of serum aminotransferases (ALT and AST. The respiratory control ratio (RCR, the mitochondrial membrane potential (MMP, and malondialdehyde (MDA values in the hepatic tissue were analyzed. Nonparametric statistical analysis was used and a value of pOBJETIVO: O objetivo deste estudo foi determinar a influência do pré-condicionamento isquêmico (IPC em fígados de ratos cirróticos. MÉTODOS: A cirrose hepática foi induzida em ratos Wistar machos (250 a 300g por oclusão, durante 30 dias, do ducto hepático comum.A seguir, os animais cirróticos foram divididos em três grupos de seis; Grupo controle cirrótico (operação simulada para isquemia/reperfusão/pré-condicionamento, Grupo I/R, isquemia de 40 minutos sem pré-condicionamento (IPC e grupo IPC com isquemia precedida por IPC. O IPC consistiu de uma isquemia parcial por cinco minutos, seguida por 10 minutos de reperfusão. No grupo IPC, após o pré-condicionamento, os animais foram submetidos à isquemia hepática de 40 minutos seguida de 2 horas de reperfusão. Foram colhidas amostras de sangue para dosagem sérica de aminotransferases (ALT e AST. Razão de controle respiratório (RCR

  19. N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.

    Directory of Open Access Journals (Sweden)

    Chengfen Wang

    Full Text Available BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI remains a pivotal clinical problem after hemorrhagic shock, transplantation, and some types of toxic hepatic injury. Apoptosis and autophagy play important roles in cell death during HIRI. It is also known that N-acetylcysteine (NAC has significant pharmacologic effects on HIRI including elimination of reactive oxygen species (ROS and attenuation of hepatic apoptosis. However, the effects of NAC on HIRI-induced autophagy have not been reported. In this study, we evaluated the effects of NAC on autophagy and apoptosis in HIRI, and explored the possible mechanism involved. METHODS: A mouse model of segmental (70% hepatic warm ischemia was adopted to determine hepatic injury. NAC (150 mg/kg, a hepatoprotection agent, was administered before surgery. We hypothesized that the mechanism of NAC may involve the ROS/JNK/Bcl-2 pathway. We evaluated the expression of JNK, P-JNK, Bcl-2, Beclin 1 and LC3 by western blotting and immunohistochemical staining. Autophagosomes were evaluated by transmission electron microscopy (TEM. RESULTS: We found that ALT, AST and pathological changes were significantly improved in the NAC group. Western blotting analysis showed that the expression levels of Beclin 1 and LC3 were significantly decreased in NAC-treated mice. In addition, JNK, p-JNK, Bax, TNF-α, NF-κB, IL2, IL6 and levels were also decreased in NAC-treated mice. CONCLUSION: NAC can prevent HIRI-induced autophagy and apoptosis by influencing the JNK signal pathway. The mechanism is likely to involve attenuation of JNK and p-JNK via scavenged ROS, an indirect increase in Bcl-2 level, and finally an alteration in the balance of Beclin 1 and Bcl-2.

  20. Metrically measuring liver biopsy:A chronic hepatitis B and C computer-aided morphologic description

    Institute of Scientific and Technical Information of China (English)

    Nicola Dioguardi; Fabio Grizzi; Barbara Fiamengo; Carlo Russo

    2008-01-01

    AIM:To describe a quantitative analysis method for liver biopsy sections with a machine that we have named "Dioguardi Histological Metriser" which automatically measures the residual hepatocyte mass (including hepatocytes vacuolization),inflammation,fibrosis and the loss of liver tissue tectonics.METHODS:We analysed digitised images of liver biopsy sections taken from 398 patients.The analysis with Dioguardi Histological Metriser was validated by comparison with semi-quantitative scoring system.RESULTS:The method provides:(1) the metrical extension in two-dimensions (the plane) of the residual hepatocellular set,including the area of vacuoles pertinent to abnormal lipid accumulation;(2) the geometric measure of the inflammation basin,which distinguishes intra-basin space and extra-basin dispersed parenchymal leukocytes;(3) the magnitude of collagen islets,(which were considered truncated fractals and classified into three degrees of magnitude);and (4)the tectonic index that quantifies alterations (disorders)in the organization of liver tissue.Dioguardi Histological Metriser machine allows to work at a speed of 0.1 mm2/s,scanning a whole section in 6-8 min.CONCLUSION:The results are the first standardized metrical evaluation of the geometric properties of the parenchyma,inflammation,fibrosis,and alterations in liver tissue tectonics of the biopsy sections.The present study confirms that biopsies are still valuable,not only for diagnosing chronic hepatitis,but also for quantifying changes in the organization and order of liver tissue structure.

  1. Acute mesenteric ischemia in young adults.

    Science.gov (United States)

    Ozturk, Gurkan; Aydinli, Bulent; Atamanalp, S Selcuk; Yildirgan, M Ilhan; Ozoğul, Bünyami; Kısaoğlu, Abdullah

    2012-08-01

    Acute mesenteric ischemia is commonly seen in old patients. This study was undertaken to show that mesenteric ischemia might be seen in individuals under 40 years of age and that its diagnosis is challenging. Twenty-six patients with acute mesenteric ischemia under the age of 40 were studied. The main symptom on admission was abdominal pain. Symptom duration varied between 12 h and 5 days. The medical history of the patients revealed that 9 had no previous diseases. Other 17 had predisposing factors in the first evaluation. None of the patients had any history of narcotic or drug abuse. Ten patients presented with signs and symptoms of sepsis and septic shock. Preoperative diagnosis was acute intestinal ischemia only in 6 patients. Preoperatively, all the patients had intestinal or colonic ischemia and necrosis; one had additional ischemia of the liver, stomach, duodenum, and pancreas. Six patients had massive intestinal necrosis. The overall postoperative complication and overall mortality rates were 61.5 and 26.9 %, respectively. Complications and mortality were determined to be associated with previous pulmonary disease, acidosis, presence of septic shock, acute renal failure, extent of the ischemia and extent of resection, second look operations, previous cardiac events, and the kind of affected bowel (colon involvement).

  2. Effects of intermittent hypoxic preconditioning on apoptosis-related Bcl-2 and Bax protein expression in rat liver after partial hepatectomy under ischemia-reperfusion%间断低氧预适应对大鼠肝切除缺血再灌注肝脏凋亡相关蛋白Bcl-2、Bax表达的影响

    Institute of Scientific and Technical Information of China (English)

    王健; 李鹏飞; 韩效帆; 朱世春; 李广; 李俊; 张培建

    2014-01-01

    oxygen for 1 h/d.After 7 consecutive days,the left and middle lobes of liver were resected under the portal triad clamping.At 12,24 and 48 hours after the operation,the rats were killed and detected.The serum levels of ALT and AST were determined by automatic biochemical analyzer.The expression of Bcl-2 and Bax protein in liver tissue were measured by immunohistochemistry.Results At each time point after surgery,the serum levels of ALT and AST in IR group and IHP group were higher than that of PH group,and IHP group were lower than in IR group.Compared with IR group,the expression of Bcl2 protein significantly increased and Bax protein expression significantly decreased in IHP group.All these differences were statistically significant (P < 0.05).Conclusions Intermittent hypoxic preconditioning might protect residual liver against ischemia reperfusion injury,through increasing the expression of Bcl-2 protein and reducing the expression of Bcl-2 protein to decrease liver cell apoptosis.

  3. 心脏死亡捐献供肝热缺血再灌注损伤及MRI评价的研究进展%Study progress of hepatic warm ischemia-reperfusion injury in donation after cardiac death liver graft and its MRI evaluation

    Institute of Scientific and Technical Information of China (English)

    季倩; 沈文

    2016-01-01

    供体严重短缺是制约我国肝移植事业发展的瓶颈,而心脏死亡捐献(DCD)将有效扩大供体来源,但肝脏热缺血再灌注损伤一直困扰着DCD供肝的利用效果。功能MR成像能够无创、准确评价活体肝组织的微观信息变化,并获得动态的定量资料,对进一步认识肝脏热缺血再灌注损伤的机制及其预后评估提供有价值的信息。现就我国DCD供肝现状、肝脏热缺血再灌注损伤及MRI评价予以综述。%Donor shortage has hampered the development of liver transplantation in China. Donation after Cardiac Death (DCD) will effectively expand the donor source, while hepatic warm ischemia-reperfusion injury has severe influence on the prognosis of DCD liver graft. Functional MR imaging can evaluate microscopic information changes of liver tissue in vivo non-invasively, accurately and quantitatively, the results are expected to provide valuable information on further understanding the mechanism and prognosis of hepatic warm ischemia-reperfusion injury. The aims of the present review were as follows: (a) to present the state of DCD donor liver in China, (b) to present the hepatic warm ischemia-reperfusion injury, and (c) to review the MRI evaluation of hepatic warm ischemia-reperfusion injury.

  4. Measurement of trace elements in liver biopsy samples from cattle

    NARCIS (Netherlands)

    Ouweltjes, W.; Zeeuw, de A.C.; Moen, A.; Counotte, G.H.M.

    2007-01-01

    Serum, plasma, or urine samples are usually used for the measurement of the trace elements copper, zinc, iron, selenium, because these samples are easy to obtain; however, these samples are not always appropriate. For example, it is not possible to measure molybdenum, the major antagonist of copper,

  5. Rosmarinic acid attenuates hepatic ischemia and reperfusion injury in rats.

    Science.gov (United States)

    Ramalho, Leandra Naira Z; Pasta, Ângelo Augusto C; Terra, Vânia Aparecida; Augusto, Marlei Josiele; Sanches, Sheila Cristina; Souza-Neto, Fernando P; Cecchini, Rubens; Gulin, Francine; Ramalho, Fernando Silva

    2014-12-01

    Rosmarinic acid (RosmA) demonstrates antioxidant and anti-inflammatory properties. We investigated the effect of RosmA on liver ischemia/reperfusion injury. Rats were submitted to 60 min of ischemia plus saline or RosmA treatment (150 mg/kg BW intraperitoneally) followed by 6 h of reperfusion. Hepatocellular injury was evaluated according to aminotransferase activity and histological damage. Hepatic neutrophil accumulation was also evaluated. Oxidative/nitrosative stress was estimated by measuring the reduced glutathione, lipid hydroperoxide and nitrotyrosine levels. Endothelial and inducible nitric oxide synthase (eNOS/iNOS) and nitric oxide (NO) were assessed with immunoblotting and chemiluminescence assays. Hepatic tumor necrosis factor-alpha (TNF-α) and interleukin-1beta mRNA were assessed using real-time PCR, and nuclear factor-kappaB (NF-κB) activation was estimated by immunostaining. RosmA treatment reduced hepatocellular damage, neutrophil infiltration and all oxidative/nitrosative stress parameters. RosmA decreased the liver content of eNOS/iNOS and NO, attenuated NF-κB activation, and down-regulated TNF-α and interleukin-1beta gene expression. These data indicate that RosmA exerts anti-inflammatory and antioxidant effects in the ischemic liver, thereby protecting hepatocytes against ischemia/reperfusion injury. The mechanisms underlying these effects may be related to the inhibitory potential of RosmA on the NF-κB signaling pathway and the reduction of iNOS and eNOS expressions and NO levels, in addition to its natural antioxidant capability.

  6. Protection Against Hepatic Ischemia-reperfusion Injury in Rats by Oral Pretreatment With Quercetin

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats. Methods The quercetin (0.13 mmol/kg) was orally administrated in 50 min prior to hepatic ischemia-reperfusion injury. Ascorbic acid was also similarly administered. The hepatic content of quercetin was assayed by high performance liquid chromatography (HPLC). Plasma glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) activities and malondialdehyde (MDA) concentration were measured as markers of hepatic ischemia-reperfusion injury. Meanwhile, hepatic content of glutathione (GSH), activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO), total antioxidant capacity (TAOC), contents of reactive oxygen species (ROS) and MDA, DNA fragmentation were also determined. Results Hepatic content of quercetin after intragastric administration of quercetin was increased significantly. The increases in plasma GPT, GOT activities and MDA concentration after hepatic ischemia-reperfusion injury were reduced significantly by pretreatment with quercetin. Hepatic content of GSH and activities of SOD, GSH-Px and TAOC were restored remarkably while the ROS and MDA contents were significantly diminished by quercetin pretreatment after ischemia-reperfusion injury. However, quercetin pretreatment did not reduce significantly hepatic XO activity and DNA fragmentation. Ascorbic acid pretreatment had also protective effects against hepatic ischemia-reperfusion injury by restoring hepatic content of GSH, TAOC and diminishing ROS and MDA formation and DNA fragmentation. Conclusion It is indicated that quercetin can protect the liver against ischemia-reperfusion injury after oral pretreatment and the underlying mechanism is associated with improved hepatic antioxidant capacity.

  7. Measurement of the QT Dispersion in Patients with Cardiac Syndrome X for the Investigation of Ischemia as an Etiological Factor

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    Ali Metin Esen

    2011-04-01

    Full Text Available Clinical and demographic characteristics of the groups such as age, gender bodymass index, systolic and diastolic blood pressure showed no statistically significant differences between both groups. Although there was no difference in QTd values between groups at baseline (43,28 ± 12,55 msec in the positive ETT group, and 40,28± 11,08 msec in the control group, p=NS, peak exercise QTd was much higher in the positive ETT group than the control group (57,40 ± 13,70 msec and 28,23 ± 5,05 msec, respectively, p< 0.01. Since QTd greater than 60 msec related to ischemia has been previously reported, ETT positive patients were reevaluated in two different subgroups with QTd ≥ 60 msec (34 patients, and QTd < 60 msec(32 patients. The sum of ST depression were much more in the QTd ≥ 60 msec group (7,22 ± 0,74 vs 4,40± 1,78; t: -8,458, p<0.001. Conclusions: As a result, peak exercise QTd have been found to be higher in the group of patients with CSX than the control group, and especially when peak exercise QTd ≥ 60 msec, ischemia due to microvascular dysfunction or spasm must be considered as one of the leading causes of chest pain.

  8. In vivo liver visualizations with magnetic particle imaging based on the calibration measurement approach

    Science.gov (United States)

    Dieckhoff, J.; Kaul, M. G.; Mummert, T.; Jung, C.; Salamon, J.; Adam, G.; Knopp, T.; Ludwig, F.; Balceris, C.; Ittrich, H.

    2017-05-01

    Magnetic particle imaging (MPI) facilitates the rapid determination of 3D in vivo magnetic nanoparticle distributions. In this work, liver MPI following intravenous injections of ferucarbotran (Resovist®) was studied. The image reconstruction was based on a calibration measurement, the so called system function. The application of an enhanced system function sample reflecting the particle mobility and aggregation status of ferucarbotran resulted in significantly improved image reconstructions. The finding was supported by characterizations of different ferucarbotran compositions with the magnetorelaxometry and magnetic particle spectroscopy technique. For instance, similar results were obtained between ferucarbotran embedded in freeze-dried mannitol sugar and liver tissue harvested after a ferucarbotran injection. In addition, the combination of multiple shifted measurement patches for a joint reconstruction of the MPI data enlarged the field of view and increased the covering of liver MPI on magnetic resonance images noticeably.

  9. Measurement of peroxisomal enzyme activities in the liver of brown trout (Salmo trutta, using spectrophotometric methods

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    Resende Albina D

    2003-03-01

    Full Text Available Abstract Background This study was aimed primarily at testing in the liver of brown trout (Salmo trutta spectrophotometric methods previously used to measure the activities of catalase and hydrogen peroxide producing oxidases in mammals. To evaluate the influence of temperature on the activities of those peroxisomal enzymes was the second objective. A third goal of this work was the study of enzyme distribution in crude cell fractions of brown trout liver. Results The assays revealed a linear increase in the activity of all peroxisomal enzymes as the temperature rose from 10° to 37°C. However, while the activities of hydrogen peroxide producing oxidases were strongly influenced by temperature, catalase activity was only slightly affected. A crude fraction enriched with peroxisomes was obtained by differential centrifugation of liver homogenates, and the contamination by other organelles was evaluated by the activities of marker enzymes for mitochondria (succinate dehydrogenase, lysosomes (aryl sulphatase and microsomes (NADPH cytochrome c reductase. For peroxisomal enzymes, the activities per mg of protein (specific activity in liver homogenates were strongly correlated with the activities per g of liver and with the total activities per liver. These correlations were not obtained with crude peroxisomal fractions. Conclusions The spectrophotometric protocols originally used to quantify the activity of mammalian peroxisomal enzymes can be successfully applied to the study of those enzymes in brown trout. Because the activity of all studied peroxisomal enzymes rose in a linear mode with temperature, their activities can be correctly measured between 10° and 37°C. Probably due to contamination by other organelles and losses of soluble matrix enzymes during homogenisation, enzyme activities in crude peroxisomal fractions do not correlate with the activities in liver homogenates. Thus, total homogenates will be used in future seasonal and

  10. Indications for portal pressure measurement in chronic liver disease

    DEFF Research Database (Denmark)

    Hobolth, Lise; Bendtsen, Flemming; Møller, Søren

    2012-01-01

    Portal hypertension leads to development of serious complications such as esophageal varices, ascites, renal and cardiovascular dysfunction. The importance of the degree of portal hypertension has been substantiated within recent years. Measurement of the portal pressure is simple and safe...... of HVPG should therefore be considered as a part of the general characterization of patients with portal hypertension in departments assessing and treating this condition....

  11. Ischemia causes muscle fatigue

    Science.gov (United States)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  12. Ischemia causes muscle fatigue

    Science.gov (United States)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P < 0.05) than baseline value. Reduced twitch force was correlated in a dose-dependent manner with reduced muscle oxygenation (r = 0.78, P < 0.001). Although the correlation does not prove causation, the results indicate that ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  13. Acute Mesenteric Ischemia

    Science.gov (United States)

    ... Side Effects Additional Content Medical News Acute Mesenteric Ischemia By Parswa Ansari, MD, Department of Surgery, Lenox ... Abscesses Abdominal Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of ...

  14. Mesenteric artery ischemia

    Science.gov (United States)

    ... medlineplus.gov/ency/article/001156.htm Mesenteric artery ischemia To use the sharing features on this page, please enable JavaScript. Mesenteric artery ischemia occurs when there is a narrowing or blockage ...

  15. Intestinal ischemia and infarction

    Science.gov (United States)

    ... medlineplus.gov/ency/article/001151.htm Small intestinal ischemia and infarction To use the sharing features on this page, please enable JavaScript. Intestinal ischemia and infarction occurs when there is a narrowing ...

  16. Measurement of serum paraoxonase-1 activity in the evaluation of liver function

    Institute of Scientific and Technical Information of China (English)

    Jordi Camps; Judit Marsillach; Jorge Joven

    2009-01-01

    Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement,paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function,its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation.

  17. Liver stiffness measurements in patients with HBV vs HCV chronic hepatitis:A comparative study

    Institute of Scientific and Technical Information of China (English)

    Ioan; Sporea; Roxana; Sirli; Alexandra; Deleanu; Adriana; Tudora; Alina; Popescu; Manuela; Curescu; Simona; Bota

    2010-01-01

    AIM:To assess the values of liver stiffness (LS) in pa-tients with hepatitis B virus (HBV) chronic hepatitis and to compare them with those in patients with hepatitis C virus (HCV) chronic hepatitis. METHODS: The study included 140 patients with HBV chronic hepatitis, and 317 patients with HCV chronic hepatitis, in which LS was measured (FibroScan-Echo-sens) and liver biopsy was performed in the same session (assessed according to the Metavir score). RESULTS:According to the Metavir score of the 140 HBV p...

  18. In vivo measurements of relaxation process in the human liver by MRI. The role of respiratory gating/triggering

    DEFF Research Database (Denmark)

    Thomsen, C; Henriksen, O; Ring, P

    1988-01-01

    In vivo estimation of relaxation processes in the liver by magnetic resonance imaging (MRI) may be helpful for characterization of various pathological conditions in the liver. However, such measurements may be significantly hampered by movement of the liver with the respiration. The effect...... of synchronization of data acquisition to the respiratory cycle on measured T1- and T2-relaxation curves was studied in normal subjects, patients with diffuse liver disease, and patients with focal liver pathology. Multi spin echo sequences with five different repetition times were used. The measurements were...... different, when respiratory synchronization was employed. The results indicate that respiratory synchronization is only necessary for estimation of relaxation processes in the liver with focal pathology....

  19. Effect of controlled hypotension at the beginning of reperfusion on ischemia-reperfusion injury of liver in patients undergoing hepatectomy%再灌注初期控制性降压对肝叶切除术病人肝缺血再灌注损伤的影响

    Institute of Scientific and Technical Information of China (English)

    牛新环; 张孟元; 徐艳冰

    2014-01-01

    Objective To evaluate the effect of controlled hypotension at the beginning of reperfusion on ischemia-reperfusion (I/R) injury of the liver in patients undergoing hepatectomy.Methods Forty ASA Ⅱ or Ⅲ patients (aged 30-60 years and weighing 40-70 kg) undergoing elective partial hepatectomy for liver cancer were randomly divided into two groups (n =20 each):normal blood pressure group (control group,group C) and controlled hypotension group (group H).In group C,normal blood pressure was maintained during reperfusion,while in group H,controlled hypotension (the mean arterial blood pressure (MAP) was maintained at 60-70 mm Hg) was performed for 10 minutes since the beginning of reperfusion.Hepatic portal was occluded during operation.Venous blood samples were taken before hepatic ischemia (T0,baseline) and after 15 minutes of ischemia (T1) and after 25 minutes of reperfusion (T2) for determination of plasma levels of endothelin (ET),nitric oxide (NO),tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1).Results I/R of the liver led to significant increases in plasma levels of ET,TNF-α and IL-1 and a decrease in plasma level of NO at T1,2 as compared with the baseline values at T0 in both groups.Plasma levels of ET,TNF-α and IL-1 were significantly lower while plasma level of NO was significantly higher at T2 in group H than in group C.Conclusion Controlled hypotension for 10 minutes in the initial stage of reperfusion can attenuate I/R-induced injury to the liver in patients undergoing hepatectomy through balancing ET with NO and inhibiting inflammation responses.

  20. Stereological Analysis of Liver Biopsy Histology Sections as a Reference Standard for Validating Non-Invasive Liver Fat Fraction Measurements by MRI

    Science.gov (United States)

    St. Pierre, Tim G.; House, Michael J.; Bangma, Sander J.; Pang, Wenjie; Bathgate, Andrew; Gan, Eng K.; Ayonrinde, Oyekoya T.; Bhathal, Prithi S.; Clouston, Andrew; Olynyk, John K.; Adams, Leon A.

    2016-01-01

    Background and Aims Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7–8.8)% and 2.4 (95% CI 2.2–2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69–0.93) and 0.990 (95% CI 0.985–0.994) respectively. Small biases (≤3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using HepaFat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF. PMID:27501242

  1. Characterization of microparticles after hepatic ischemia-reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Christopher M Freeman

    Full Text Available BACKGROUND: Hepatic ischemia-reperfusion (I/R is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins-platelets, neutrophils, and endolethial cells-following hepatic ischemia-reperfusion injury. METHODS: A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. RESULTS: MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. CONCLUSION: This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver.

  2. Pretreatment with erythropoietin reduces hepatic ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Yu-Hong Luo; Zheng-Dong Li; Li-Xin Liu; Gao-Hong Dong

    2009-01-01

    BACKGROUND: During hepatectomy, a period of ischemia and restoration of the blood supply can result in hepatic ischemia-reperfusion injury (IRI). Current research indicates that erythropoietin (EPO) has a protective effect in animal models of cerebral ischemia, myocardial infarction, and renal IRI. However there is lack of research into the role of EPO in hepatic IRI. This study aimed to explore the role of EPO in hepatic IRI and its possible mechanism of action. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: (1) ten rats in the experimental group were given 1000 IU/kg EPO one day before the operation; (2) ten rats in a control group were given normal saline preoperatively as a placebo; and (3) ten rats served as a sham-operated group. Hepatic IRI was induced by occluding the hepatic arteries of the three cephalad hepatic segments and the portal vein for about 45 minutes, while in the sham-operated group only laparotomy was performed. The levels of ALT and AST were tested 24 hours pre- and post-operation. All rats were sacriifced 24 hours after the operation to assess the pathologic changes in the liver and measure the expression of heme oxygenase-1 (HO-1) through Western blotting and RT-PCR. RESULTS: Hepatic IRI was markedly mitigated in the experimental group as compared with the control group. Moreover, the expression of HO-1 at the level of both transcription and protein increased prominently (P<0.05) in the experimental group. CONCLUSION: These results demonstrate that EPO can up-regulate HO-1 in liver tissues and accordingly decrease hepatic injury through its anti-inlfammatory property.

  3. Attenuation measuring ultrasound shearwave elastography and in vivo application in post-transplant liver patients

    Science.gov (United States)

    Nenadic, Ivan Z.; Qiang, Bo; Urban, Matthew W.; Zhao, Heng; Sanchez, William; Greenleaf, James F.; Chen, Shigao

    2017-01-01

    Ultrasound and magnetic resonance elastography techniques are used to assess mechanical properties of soft tissues. Tissue stiffness is related to various pathologies such as fibrosis, loss of compliance, and cancer. One way to perform elastography is measuring shear wave velocity of propagating waves in tissue induced by intrinsic motion or an external source of vibration, and relating the shear wave velocity to tissue elasticity. All tissues are inherently viscoelastic and ignoring viscosity biases the velocity-based estimates of elasticity and ignores a potentially important parameter of tissue health. We present attenuation measuring ultrasound shearwave elastography (AMUSE), a technique that independently measures both shear wave velocity and attenuation in tissue and therefore allows characterization of viscoelasticity without using a rheological model. The theoretical basis for AMUSE is first derived and validated in finite element simulations. AMUSE is validated against the traditional methods for assessing shear wave velocity (phase gradient) and attenuation (amplitude decay) in tissue mimicking phantoms and excised tissue. The results agreed within one standard deviation. AMUSE was used to measure shear wave velocity and attenuation in 15 transplanted livers in patients with potential acute rejection, and the results were compared with the biopsy findings in a preliminary study. The comparison showed excellent agreement and suggests that AMUSE can be used to separate transplanted livers with acute rejection from livers with no rejection.

  4. Fatty Liver

    Science.gov (United States)

    ... Abbreviations Weights & Measures ENGLISH View Professional English Deutsch Japanese Espaniol Find information on medical topics, symptoms, drugs, ... inside liver cells. Just consuming a high-fat diet does not result in fatty liver. Rarely, fat ...

  5. Noninvasive measurement of liver iron concentration at MRI in children with acute leukemia: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Vag, Tibor; Krumbein, Ines; Reichenbach, Juergen R.; Lopatta, Eric; Stenzel, Martin; Kaiser, Werner A.; Mentzel, Hans-Joachim [Friedrich Schiller University Jena, Institute of Diagnostic and Interventional Radiology, Jena (Germany); Kentouche, Karim; Beck, James [Friedrich Schiller University Jena, Department of Pediatrics, Jena (Germany); Renz, Diane M. [Charite University Medicine Berlin, Department of Radiology, Campus Virchow Clinic, Berlin (Germany)

    2011-08-15

    Routine assessment of body iron load in patients with acute leukemia is usually done by serum ferritin (SF) assay; however, its sensitivity is impaired by different conditions including inflammation and malignancy. To estimate, using MRI, the extent of liver iron overload in children with acute leukemia and receiving blood transfusions, and to examine the association between the degree of hepatic iron overload and clinical parameters including SF and the transfusion iron load (TIL). A total of 25 MRI measurements of the liver were performed in 15 children with acute leukemia (mean age 9.75 years) using gradient-echo sequences. Signal intensity ratios between the liver and the vertebral muscle (L/M ratio) were calculated and compared with SF-levels. TIL was estimated from the cumulative blood volume received, assuming an amount of 200 mg iron per transfused red blood cell unit. Statistical analysis revealed good correlation between the L/M SI ratio and TIL (r = -0.67, P = 0.002, 95% confidence interval CI = -0.83 to -0.34) in patients with acute leukemia as well as between L/M SI ratio and SF (r = -0.76, P = 0.0003, 95% CI = -0.89 to -0.52). SF may reliably reflect liver iron stores as a routine marker in patients suffering from acute leukemia. (orig.)

  6. Validity of diagnostic codes and laboratory measurements to identify patients with idiopathic acute liver injury in a hospital database

    DEFF Research Database (Denmark)

    Udo, Renate; Maitland-van der Zee, Anke H; Egberts, Toine C G;

    2016-01-01

    of liver enzyme values (ALT > 2× upper limit of normal (ULN); AST > 1ULN + AP > 1ULN + bilirubin > 1ULN; ALT > 3ULN; ALT > 3ULN + bilirubin > 2ULN; ALT > 10ULN) and (II) algorithms based on solely liver enzyme values (ALT > 3ULN + bilirubin > 2ULN; ALT > 10ULN). Hospital medical records were reviewed......PURPOSE: The development and validation of algorithms to identify cases of idiopathic acute liver injury (ALI) are essential to facilitate epidemiologic studies on drug-induced liver injury. The aim of this study is to determine the ability of diagnostic codes and laboratory measurements...... 32% (13/41) to 48% (43/90) with the highest PPV found with ALT > 2ULN. The PPV for (II) algorithms with liver test abnormalities was maximally 26% (150/571). CONCLUSIONS: The algorithm based on ICD-9-CM codes indicative of ALI combined with abnormal liver-related laboratory tests is the most...

  7. Acute changes in liver tumour perfusion measured non-invasively with arterial spin labelling

    Science.gov (United States)

    Johnson, S Peter; Ramasawmy, Rajiv; Campbell-Washburn, Adrienne E; Wells, Jack A; Robson, Mathew; Rajkumar, Vineeth; Lythgoe, Mark F; Pedley, R Barbara; Walker-Samuel, Simon

    2016-01-01

    Background: Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503. Methods: SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R2* MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg−1 OXi4503. Results: A significant decrease in SW1222 tumour perfusion was observed (−43±33%, Pchange in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits. Conclusions: Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting. PMID:27031853

  8. Cornel iridoid glycoside reduces infarct size measured by magnetic resonance imaging and improves neurological function after focal cerebral ischemia in rats.

    Science.gov (United States)

    Yang, Cui-Cui; Li, Lin; Zheng, Sha-Sha; Lu, Jie; Zhang, Li; Li, Ya-Li; Zhang, Lan

    2015-08-11

    To investigate the effect of cornel iridoid glycoside (CIG), an ingredient extracted from traditional Chinese herb Cornus offificinalis, on neurological function and infarct size in rats as measured by magnetic resonance imaging (MRI) after ischemic stroke. Sprague-Dawley rats were divided into three group: control (n=11), model (n=20) and CIG (n=16) groups. Rats in the model and CIG groups underwent 90-min middle cerebral artery occlusion (MCAO) followed by reperfusion. Their neurological defect was measured by using a modified neurological severity score (mNSS). T2-weighted MRI (T2-MRI) of the brain was performed in vivo from 2 to 28 days after MCAO. The infarct volume in the brain was also measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining 28 days after stroke. CIG, 60 mg/(kg day), administered by oral gavage starting from 6 h after the onset of MCAO improved neurological function at 7, 14, 21, and 28 days post occlusion (PCIG-treated group compared with the model group at 7, 14 and 28 days after MCAO (PCIG-treated group than that in the model group (PCIG treatment, starting from 6 h after MCAO, reduced infarct size in the brain as measured by MRI and improved neurological function 2-28 days after focal cerebral ischemia in rats, suggesting that CIG could be a clinical application in improving stroke treatment.

  9. Measures for increasing the safety of donors in living donor liver transplantation using right lobe grafts

    Institute of Scientific and Technical Information of China (English)

    Tian-Fu Wen; Ming-Qing Xu; Jiang-Wen Liu; Zhi-Gang Deng; Hong Wu; Zhe-Yu Chen; Lu-Nan Yan; Bo Li; Yong Zeng; Ji-Chun Zhao; Wen-Tao Wang; Jia-Yin Yang; Yu-Kui Ma

    2007-01-01

    BACKGROUND:The safety of donors in living donor liver transplantation (LDLT) should be the primary consideration. The aim of this study was to report our experience in increasing the safety of donors in LDLTs using right lobe grafts. METHODS:We retrospectively studied 37 living donors of right lobe grafts from January 2002 to March 2006. The measures for increasing the safety of donors in LDLT included carefully selected donors, preoperative evaluation by ultrasonography, angiography and computed tomography; and necessary intraoperative cholangiography and ultrasonography. Right lobe grafts were obtained using an ultrasonic dissector without inlfow vascular occlusion on the right side of the middle hepatic vein. The standard liver volume and the ratio of left lobe volume to standard liver volume were calculated. RESULTS:There was no donor mortality in our group. Postoperative complications only included bile leakage (1 donor), biliary stricture (1) and portal vein thrombosis (1). All donors recovered well and resumed their previous occupations. In recipients, complications included acute rejection (2 patients), hepatic artery thrombosis (1), bile leakage (1), intestinal bleeding (1), left subphrenic abscess (1) and pulmonary infection (1). The mortality rate of recipients was 5.4% (2/37); one recipient with pulmonary infection died from multiple organ failure and another from occurrence of primary disease. CONCLUSIONS:The ifrst consideration in adult-to-adult LDLT is the safety of donors. The donation of a right lobe graft is safe for adults if the remnant hepatic vasculature and bile duct are ensured, and the volume of the remnant liver exceeds 35% of the total liver volume.

  10. Thymoquinone protects end organs from abdominal aorta ischemia/reperfusion injury in a rat model

    Directory of Open Access Journals (Sweden)

    Mehmet Salih Aydin

    2015-02-01

    Full Text Available Introduction: Previous studies have demonstrated that thymoquinone has protective effects against ischemia reperfusion injury to various organs like lungs, kidneys and liver in different experimental models. Objective: We aimed to determine whether thymoquinone has favorable effects on lung, renal, heart tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Methods: Thirty rats were divided into three groups as sham (n=10, control (n=10 and thymoquinone (TQ treatment group (n=10. Control and TQ-treatment groups underwent abdominal aorta ischemia for 45 minutes followed by a 120-min period of reperfusion. In the TQ-treatment group, thymoquinone was given 5 minutes. before reperfusion at a dose of 20 mg/kg via an intraperitoneal route. Total antioxidant capacity, total oxidative status (TOS, and oxidative stress index (OSI in blood serum were measured and lung, kidney, and heart tissue histopathology were evaluated with light microscopy. Results: Total oxidative status and oxidative stress index activity in blood samples were statistically higher in the control group compared to the sham and TQ-treatment groups (P<0.001 for TOS and OSI. Control group injury scores were statistically higher compared to sham and TQ-treatment groups (P<0.001 for all comparisons. Conclusion: Thymoquinone administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta ischemia-reperfusion rat model.

  11. Influence of relative warm ischemia on bile component in rats self-liver transplantation%胆道相对热缺血对大鼠自体肝移植早期胆汁成分的影响

    Institute of Scientific and Technical Information of China (English)

    任旋磊; 赵宏峰; 周杰

    2014-01-01

    目的 研究胆道相对热缺血(RWI)对肝移植术后所产生的胆汁性质及胆盐构成的影响.方法 将32只SD大鼠按随机数字表法分为第Ⅰ~Ⅳ组(分别为对照组、RWI 0 min、30 min和60 min组).测定自体原位肝移植术后早期所产生的胆汁中磷脂(PL)、总胆汁酸盐(TBA)水平及PL/TBA值,并检测各亲水性和疏水性胆汁酸盐的变化.结果与Ⅰ组相比,Ⅱ组PL浓度略降低,但差异无统计学意义(P>0.05);Ⅲ组的PL及TBA浓度比Ⅱ组明显降低(P<0.05),Ⅲ组的PL/TBA值略低于Ⅱ组,但差异不具有统计学意义(P>0.05).Ⅱ组与Ⅲ组的亲水性胆盐浓度、疏水性胆盐浓度差异均无统计学意义(P>0.05).与其他三组相比,Ⅳ组PL浓度、TBA浓度、PL/TBA值、亲水性胆盐牛磺-β-鼠胆酸(T-3-MC)的摩尔分数均下降(P<0.05),疏水性胆盐牛磺胆酸(TC)的摩尔分数升高(P<0.05).结论胆道相对热缺血会导致肝移植术后胆汁中磷脂/胆盐比例及胆汁中疏水/亲水性质发生改变,这种变化随着RWI时间的延长而加重.当RWI时间达60 min时,胆汁成分变化明显,“去垢”作用增强.肝移植时应尽快完成肝动脉吻合,最好能将相对热缺血时间控制在30 min以内.%Objective To explore the effect of relative warm ischemia (RWI) on bile nature and component in rats self-liver transplantation.Methods Thirty two rats were randomly divided into group Ⅰ (control group),group Ⅱ (RWI 0 min),group Ⅲ (RWI 30 min),and group Ⅳ (RWI 60 min).The levels of bile phospholipids (PL),total bile acids (TBA),and PL/TBA ratio were detected early after self-liver transplantation.The concentration changes of hydrophilic and hydrophobic bile acids were examined.Results Only PL concentration of group Ⅱ seemed to be lower than that of group Ⅰ (P < 0.05),without any change for other indexes.Compared with group Ⅱ,only the PL and TBA concentrations of the group Ⅲ were decreased significantly (P < 0

  12. Applicability and variability of liver stiffness measurements according to probe position

    Institute of Scientific and Technical Information of China (English)

    Patrick Ingiliz; Kim Pav Chhay; Mona Munteanu; Pascal Lebray; Yen Ngo; Dominique Roulot; Yves Benhamou; Dominique Thabut; Vlad Ratziu; Thierry Poynard

    2009-01-01

    AIM: To investigate the liver stiffness measurement (LSM) applicability and variability with reference to three probe positions according to the region of liver biopsy. METHODS: The applicability for LSM was defined as at least 10 valid measurements with a success rate greater than 60% and an interquartile range/median LSM <30%. The LSM variability compared the inter-position concordance and the concordance with FibroTest. RESULTS: Four hundred and forty two consecutive patients were included. The applicability of the anterior position (81%) was significantly higher than that of the reference (69%) and lower positions (68%),(both P = 0.0001). There was a significant difference (0.5 kPa, 95% CI 0.13-0.89; P < 0.0001) between mean LSM estimated at the reference position (9.3 kPa) vs the anterior position (8.8 kPa). Discordance between positions was associated with thoracic fold ( P = 0.008). The discordance rate between the reference position result and FibroTest was higher when the 7.1 kPa cutoff was used to define advanced fibrosis instead of 8.8 kPa (33.6% vs 23.5%, P = 0.03).CONCLUSION: The anterior position of the probe should be the first choice for LSM using Fibroscan, as it has a higher applicability without higher variability compared to the usual liver biopsy position.

  13. Measurement of the coagulation dynamics of bovine liver using the modified microscopic Beer-Lambert law.

    Science.gov (United States)

    Terenji, Albert; Willmann, Stefan; Osterholz, Jens; Hering, Peter; Schwarzmaier, Hans-Joachim

    2005-06-01

    During heating, the optical properties of biological tissues change with the coagulation state. In this study, we propose a technique, which uses these changes to monitor the coagulation process during laser-induced interstitial thermotherapy (LITT). Untreated and coagulated (water bath, temperatures between 35 degrees C and 90 degrees C for 20 minutes.) samples of bovine liver tissue were examined using a Nd:YAG (lambda = 1064 nm) frequency-domain reflectance spectrometer. We determined the time integrated intensities (I(DC)) and the phase shifts (Phi) of the photon density waves after migration through the tissue. From these measured quantities, the time of flight (TOF) of the photons and the absorption coefficients of the samples were derived using the modified microscopic Beer-Lambert law. The absorption coefficients of the liver samples decreased significantly with the temperature in the range between 50 degrees C and 70 degrees C. At the same time, the TOF of the investigated photos was found increased indicating an increased scattering. The coagulation dynamics could be well described using the Arrhenius formalism with the activation energy of 106 kJ/mol and the frequency factor of 1.59 x 10(13)/second. Frequency-domain reflectance spectroscopy in combination with the modified microscopic Beer-Lambert (MBL) is suitable to measure heat induced changes in the absorption and scattering properties of bovine liver in vitro. The technique may be used to monitor the coagulation dynamics during local thermo-coagulation in vivo. Copyright 2005 Wiley-Liss, Inc.

  14. Cytometric measurement of cell proliferation in echo-guided biopsies from focal lesions of the liver.

    Science.gov (United States)

    Faccioli, S; Chieco, P; Gramantieri, L; Stecca, B A; Bolondi, L

    1996-02-01

    Increased proliferative activity determined in surgical specimens of hepatocellular carcinoma (HCC) has been associated with tumor grade and patient survival. The measurement of cell proliferation in echo-guided biopsies of small focal liver lesions might provide useful information for the early recognition of malignancy and for predicting the aggressiveness of small HCCs. We assessed the diagnostic and prognostic value of cell proliferation in 91 echo-guided needle biopsies of focal liver lesions using the monoclonal antibody Ki-67, which detects a human nuclear antigen that is present in proliferating cells. Measurements were performed by image cytometry as the percentage of Ki-67 positive hepatocytes nuclei over total hepatocyte nuclei in the biopsy. At the histological examination, 27 lesions were diagnosed as chronic hepatitis, 10 as cirrhosis, 11 as macroregenerative nodule, and 43 as HCC in cirrhotic liver. Although the highest Ki-67 values (> 20%) were found in less-differentiated HCCs, most well-differentiated HCCs and nine borderline nodules were completely devoid of Ki-67-positive hepatocytes. A sustained Ki-67 labeling (up to 16%) was found in hepatitis and cirrhosis, similar to that found in several malignant tumors. In the HCC subset, Ki-67 labeling was strongly correlated to the Edmondson-Steiner histological grade. However, survival analysis did not indicate a better outcome for those patients with low-proliferating tumors.

  15. Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst's exponent

    Institute of Scientific and Technical Information of China (English)

    Nicola Dioguardi; Fabio Grizzi; Barbara Franceschini; Paola Bossi; Carlo Russo

    2006-01-01

    AIM: To provide the accurate alternative metrical means of monitoring the effects of new antiviral drugs on the reversal of newly formed collagen.METHODS: Digitized histological biopsy sections taken from 209 patients with chronic C virus hepatitis with different grade of fibrosis or cirrhosis, were measured by means of a new, rapid, user-friendly, fully computeraided method based on the international system meter rectified using fractal principles.RESULTS: The following were described: geometric perimeter, area and wrinkledness of fibrosis; the collation of the Knodell, Sheuer, Ishak and METAVIR scores with fractal-rectified metric measurements; the meaning of the physical composition of fibrosis in relation to the magnitude of collagen islets; the intra- and inter-biopsy sample variability of these parameters; the "staging"of biopsy sections indicating the pathway covered by fibrosis formation towards its maximum known value;the quantitative liver tissue architectural changes with the Hurst exponent.CONCLUSION: Our model provides the first metrical evaluations of the geometric properties of fibrosis and the quantitative architectural changes of the liver tissue.The representativeness of histological sections of the whole liver is also discussed in the light of the results obtained with the Hurst coefficient.

  16. The error analysis of Lobular and segmental division of right liver by volume measurement.

    Science.gov (United States)

    Zhang, Jianfei; Lin, Weigang; Chi, Yanyan; Zheng, Nan; Xu, Qiang; Zhang, Guowei; Yu, Shengbo; Li, Chan; Wang, Bin; Sui, Hongjin

    2017-07-01

    The aim of this study is to explore the inconsistencies between right liver volume as measured by imaging and the actual anatomical appearance of the right lobe. Five healthy donated livers were studied. The liver slices were obtained with hepatic segments multicolor-infused through the portal vein. In the slices, the lobes were divided by two methods: radiological landmarks and real anatomical boundaries. The areas of the right anterior lobe (RAL) and right posterior lobe (RPL) on each slice were measured using Photoshop CS5 and AutoCAD, and the volumes of the two lobes were calculated. There was no statistically significant difference between the volumes of the RAL or RPL as measured by the radiological landmarks (RL) and anatomical boundaries (AB) methods. However, the curves of the square error value of the RAL and RPL measured using CT showed that the three lowest points were at the cranial, intermediate, and caudal levels. The U- or V-shaped curves of the square error rate of the RAL and RPL revealed that the lowest value is at the intermediate level and the highest at the cranial and caudal levels. On CT images, less accurate landmarks were used to divide the RAL and RPL at the cranial and caudal layers. The measured volumes of hepatic segments VIII and VI would be less than their true values, and the measured volumes of hepatic segments VII and V would be greater than their true values, according to radiological landmarks. Clin. Anat. 30:585-590, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Rosiglitazone-enriched diet did not protect liver ischemia-reperfusion injury in a rat model Dieta enriquecida com rosiglitazona não protege a lesão de isquemia e reperfusão hepática em modelo experimental no rato

    Directory of Open Access Journals (Sweden)

    Antonio Roberto Franchi Teixeira

    2008-08-01

    Full Text Available PURPOSE: To determine whether rosiglitazone-enriched diet offer protection in a classical model of liver ischemia-reperfusion injury in rats. METHODS: Two days before the experiment, rats were divided into 2 groups: Control Group (n=13 rats fed with standard diet; Rosi Group (n=13: rats fed with a powdered standard diet supplemented with rosiglitazone. The animals were submitted to liver ischemia-reperfusion by clamping the pedicle of median and left anterolateral lobes. After 1 hour of partial hepatic ischemia, the clamp was removed for reperfusion. After 2 or 24 hours (Control and Rosi Groups, blood was collected for enzymes and cytokines analysis. Ischemic and non-ischemic liver were collected for malondialdehyde analysis and histological assessment. Lungs were removed for tissue myeloperoxidase quantification. RESULTS: There were no statistical differences between groups for all analysed parameters. CONCLUSION: In this model, rosiglitazone-enriched diet did not protect liver against ischemia-reperfusion injury.OBJETIVO: Determinar se a dieta enriquecida com rosiglitazona oferece proteção em um modelo clássico de lesão de isquemia e reperfusão hepática em ratos. MÉTODOS: Dois dias antes do experimento, os ratos foram divididos em 2 grupos: Grupo Controle (n=13: ratos alimentados com dieta padrão; Grupo Rosi (n=13: ratos alimentados com dieta em pó padrão enriquecida com rosiglitazona. Os animais foram submetidos à isquemia e reperfusão hepática por clampeamento do pedículo dos lobos médio e anterolateral esquerdo. Após 1 hora de isquemia, o clampe foi removido para a reperfusão. Após 2 ou 24 horas (Grupos Controle e Rosi, o sangue foi coletado para análise de enzimas e citocinas. Os fígados isquêmico e não isquêmico foram coletados para análise de malondialdeído e avaliação histológica. Pulmões foram removidos para quantificação da mieloperoxidase tecidual. RESULTADOS: Não houve diferenças estatísticas entre

  18. The role of amputation as an outcome measure in cellular therapy for critical limb ischemia: implications for clinical trial design

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    Pearl Gregory J

    2011-09-01

    Full Text Available Abstract Background Autologous bone marrow-derived stem cells have been ascribed an important therapeutic role in No-Option Critical limb Ischemia (NO-CLI. One primary endpoint for evaluating NO-CLI therapy is major amputation (AMP, which is usually combined with mortality for AMP-free survival (AFS. Only a trial which is double blinded can eliminate physician and patient bias as to the timing and reason for AMP. We examined factors influencing AMP in a prospective double-blinded pilot RCT (2:1 therapy to control of 48 patients treated with site of service obtained bone marrow cells (BMAC as well as a systematic review of the literature. Methods Cells were injected intramuscularly in the CLI limbs as either BMAC or placebo (peripheral blood. Six month AMP rates were compared between the two arms. Both patient and treating team were blinded of the assignment in follow-up examinations. A search of the literature identified 9 NO-CLI trials, the control arms of which were used to determine 6 month AMP rates and the influence of tissue loss. Results Fifteen amputations occurred during the 6 month period, 86.7% of these during the first 4 months. One amputation occurred in a Rutherford 4 patient. The difference in amputation rate between patients with rest pain (5.6% and those with tissue loss (46.7%, irrespective of treatment group, was significant (p = 0.0029. In patients with tissue loss, treatment with BMAC demonstrated a lower amputation rate than placebo (39.1% vs. 71.4%, p = 0.1337. The Kaplan-Meier time to amputation was longer in the BMAC group than in the placebo group (p = 0.067. Projecting these results to a pivotal trial, a bootstrap simulation model showed significant difference in AFS between BMAC and placebo with a power of 95% for a sample size of 210 patients. Meta-analysis of the literature confirmed a difference in amputation rate between patients with tissue loss and rest pain. Conclusions BMAC shows promise in improving AMP

  19. The role of amputation as an outcome measure in cellular therapy for critical limb ischemia: implications for clinical trial design

    Science.gov (United States)

    2011-01-01

    Background Autologous bone marrow-derived stem cells have been ascribed an important therapeutic role in No-Option Critical limb Ischemia (NO-CLI). One primary endpoint for evaluating NO-CLI therapy is major amputation (AMP), which is usually combined with mortality for AMP-free survival (AFS). Only a trial which is double blinded can eliminate physician and patient bias as to the timing and reason for AMP. We examined factors influencing AMP in a prospective double-blinded pilot RCT (2:1 therapy to control) of 48 patients treated with site of service obtained bone marrow cells (BMAC) as well as a systematic review of the literature. Methods Cells were injected intramuscularly in the CLI limbs as either BMAC or placebo (peripheral blood). Six month AMP rates were compared between the two arms. Both patient and treating team were blinded of the assignment in follow-up examinations. A search of the literature identified 9 NO-CLI trials, the control arms of which were used to determine 6 month AMP rates and the influence of tissue loss. Results Fifteen amputations occurred during the 6 month period, 86.7% of these during the first 4 months. One amputation occurred in a Rutherford 4 patient. The difference in amputation rate between patients with rest pain (5.6%) and those with tissue loss (46.7%), irrespective of treatment group, was significant (p = 0.0029). In patients with tissue loss, treatment with BMAC demonstrated a lower amputation rate than placebo (39.1% vs. 71.4%, p = 0.1337). The Kaplan-Meier time to amputation was longer in the BMAC group than in the placebo group (p = 0.067). Projecting these results to a pivotal trial, a bootstrap simulation model showed significant difference in AFS between BMAC and placebo with a power of 95% for a sample size of 210 patients. Meta-analysis of the literature confirmed a difference in amputation rate between patients with tissue loss and rest pain. Conclusions BMAC shows promise in improving AMP-free survival if the

  20. Forensic postmortem computed tomography: volumetric measurement of the heart and liver.

    Science.gov (United States)

    Jakobsen, Lykke Schrøder; Lundemose, Sissel; Banner, Jytte; Lynnerup, Niels; Jacobsen, Christina

    2016-12-01

    The purpose of this study was to investigate the utility of postmortem computed tomography (PMCT) images in estimating organ sizes and to examine the use of the cardiothoracic ratio (CTR). We included 45 individuals (19 females), who underwent a medico-legal autopsy. Using the computer software program Mimics(®), we determined in situ heart and liver volumes derived from linear measurements (width, height and depth) on a whole body PMCT-scan, and compared the volumes with ex vivo volumes derived by CT-scan of the eviscerated heart and liver. The ex vivo volumes were also compared with the organ weights. Further, we compared the CTR with the ex vivo heart volume and a heart weight-ratio (HWR). Intra- and inter-observer analyses were performed. We found no correlation between the in situ and ex vivo volumes of the heart and liver. However, a highly significant correlation was found between the ex vivo volumes and weights of the heart and liver. No correlations between CTR and the ex vivo heart volume nor with HWR was found. Concerning cardiomegaly, we found no agreement between the CTR and HWR. The intra- and inter-observer analyses showed no significant differences. Noninvasive in situ PMCT methods for organ measuring, as performed in this study, are not useful tools in forensic pathology. The best method to estimate organ volume is a CT-scan of the eviscerated organ. PMCT-determined CTR seems to be useless for ascertaining cardiomegaly, as it neither correlated with the ex vivo heart volume nor with the HWR.

  1. Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case-control study

    Energy Technology Data Exchange (ETDEWEB)

    Motosugi, Utaroh; Ichikawa, Tomoaki; Koshiishi, Tsuyota; Sano, Katsuhiro; Morisaka, Hiroyuki; Ichikawa, Shintaro; Araki, Tsutomu [University of Yamanashi, Department of Radiology, Yamanashi-ken (Japan); Enomoto, Nobuyuki [University of Yamanashi, 1st Department of Internal Medicine, Yamanashi (Japan); Matsuda, Masanori; Fujii, Hideki [University of Yamanashi, 1st Department of Surgery, Yamanashi (Japan)

    2013-01-15

    To examine if liver stiffness measured by magnetic resonance elastography (MRE) is a risk factor for hepatocellular carcinoma (HCC) in patients with chronic liver disease. By reviewing the records of magnetic resonance (MR) examinations performed at our institution, we selected 301 patients with chronic liver disease who did not have a previous medical history of HCC. All patients underwent MRE and gadoxetic acid-enhanced MR imaging. HCC was identified on MR images in 66 of the 301 patients, who were matched to controls from the remaining patients without HCC according to age. MRE images were obtained by visualising elastic waves generated in the liver by pneumatic vibration transferred via a cylindrical passive driver. Risk factors of HCC development were determined by the odds ratio with logistic regression analysis; gender and liver stiffness by MRE and serum levels of aspartate transferase, alanine transferase, alpha-fetoprotein, and protein induced by vitamin K absence-II. Multivariate analysis revealed that only liver stiffness by MRE was a significant risk factor for HCC with an odds ratio (95 % confidence interval) of 1.38 (1.05-1.84). Liver stiffness measured by MRE is an independent risk factor for HCC in patients with chronic liver disease. (orig.)

  2. Beneficial effect of hyperbaric oxygenation on liver regeneration in cirrhosis.

    Science.gov (United States)

    Ozdogan, Mehmet; Ersoy, Eren; Dundar, Kadir; Albayrak, Levent; Devay, Seda; Gundogdu, Haldun

    2005-12-01

    Underlying hepatic injury and cirrhosis are leading factors that interfere with the post-operative liver regeneration and function. Hyperbaric oxygenation (HBO) has been reported to ameliorate the ischemia-reperfusion injury of the liver, to induce compensatory hypertrophy of the predicted remnant liver in rats after portal vein ligation and to augment liver regeneration after hepatectomy in non-cirrhotic rats. Our aim was to determine the effect of HBO treatment on liver regeneration after partial hepatectomy in normal and cirrhotic mice in this experimental study. The effect of HBO on liver regeneration was studied in a mice model combining carbon tetrachloride induced cirrhosis and partial hepatectomy. Mice were divided into four groups: Control, cirrhotic, non-cirrhotic HBO-treated, and cirrhotic HBO-treated. All animals underwent 40% hepatectomy. Liver regeneration was evaluated by the proliferating cell nuclear antigen-labeling index. Serum aspartate aminotransferase and alanine aminotransferase levels were measured to evaluate liver injury. Serum alanine aminotransferase and aspartate aminotransferase levels were significantly decreased in HBO-treated cirrhotic group compared to cirrhosis group after hepatectomy (P = 0.001 and P = 0.014, respectively). The proliferating cell nuclear antigen labeling index was significantly higher in HBO treated cirrhotic group than in cirrhotic group after hepatectomy (P = 0.022). Our results suggest that HBO treatment improves liver functions and augments hepatocyte regeneration in cirrhotic mice after hepatectomy. Post-operative HBO treatment may have a beneficial effect on post-operative liver function and regeneration in cirrhotic patients.

  3. Migraine and ischemia

    NARCIS (Netherlands)

    van der Wammes-van der Heijden, E.A.

    2009-01-01

    An association between migraine and ischemic events, especially ischemic stroke, has been debated for many years. Whether migraine is a risk factor for ischemic events or ischemia triggers migraine, or both, is still unclear. This thesis explores different relationships between migraine and ischemia

  4. Treatment response classification of liver metastatic disease evaluated on imaging. Are RECIST unidimensional measurements accurate?

    Science.gov (United States)

    Mantatzis, Michael; Kakolyris, Stylianos; Amarantidis, Kyriakos; Karayiannakis, Anastasios; Prassopoulos, Panos

    2009-07-01

    The purpose of this study was to evaluate the accuracy of unidimensional measurements (response evaluation criteria in solid tumors, RECIST) compared with volumetric measurements in patients with liver metastases undergoing chemotherapy. Forty-four patients with newly diagnosed liver lesions underwent three MRI examinations at treatment initiation, during chemotherapy, and immediately post-treatment. Measurements based on RECIST guidelines and volume calculations were performed on the "target" lesions (TLs). The two methods were in agreement in 64/77 of patients and 253/301 of individual lesions classification in response categories ("good" agreement, Cohen kappa = 0.735 and 0.741, respectively). In 16.88% of the comparisons the two methods stratified patients to a different response category; 27.6% of TLs did not follow the response category of the patient in whom lesions were located. The actual volume of TLs differs from the calculated volume of a sphere with the same diameter. Our study supports the use of volumetric techniques that may overcome certain disadvantages of unidimensional measurements.

  5. Behavior of cholinesterase and liver mitochondrial function in dogs submitted to normothermic ischemia and reperfusion Colinesterase e função mitocondrial hepática em cães submetidos a isquemia normotérmica e reperfusão do fígado

    Directory of Open Access Journals (Sweden)

    Luis Pinto Fernandes

    2003-01-01

    Full Text Available PURPOSE: The plasmatic activity of the cholinesterase (CHE and the liver mitochondrial function, expressed by the ratio of respiratory control (RCR, were studied during normothermic ischemia. METHODS: Sixteen adult mongrels, eight females and eight males were submitted to ischemia by clamping of the hepatic artery, portal vein and infrahepatic inferior vena cava, infra-hepatic, for two h, follwed by reperfusion for 1 h. The CHE and the mitochondrial function were evaluated at 60 and 120 min. of ischemia and at 15 and 60 minutes of reperfusion. RESULTS: The CHE decreased, significantly, during ischemia and in reperfusion. The RCR was decreased at 120 min. of ischemia, returning to the initial values on reperfusion. CONCLUSION: In this study, the CHE was a sensitive indicator of ischemic injury , suggesting irreversibility of ischemia injury. The RCR, by other side, showed a greater sensibility than the CHE in detection sense, during the studied period, the reversibility of the hepatic ischemic injury.OBJETIVO: A atividade plasmática da colinesterase (CHE e a função mitocondrial do fígado expressa pela RCR- razão de controle respiratório mitocondrial foram estudadas durante a isquemia/reperfusão hepáticas. MÉTODOS: Dezesseis cães adultos sem raça definida (oito machos e oito fêmeas foram submetidos a isquemia normotérmica por pinçamento do pedículo hepático e da veia cava inferior infra-hepática por 2 horas, seguida de 15 e 60 minutos de reperfusão.A CHE e a RCR foram avaliadas após 60 e 120 minutos de isquemia e após 15 e 60 minutos de reperfusão. RESULTADOS: Os níveis de CHE diminuíram significativamente na isquemia e reperfusão.A RCR diminuiu após 120 minutos de isquemia retornando a níveis semelhantes ao controle após a reperfusão. CONCLUSÃO: A CHE foi sensível para indicar a lesão isquêmica, sugerindo irreversibilidade da lesão. Já a RCR foi mais sensível no sentido de detectar a reversibilidade da les

  6. Efeito protetor de antagonista das gliproteínas IIb/IIa nas alterações hepáticas e pulmonares secundárias à isquemia e reperfusão do fígado em ratos Protective effects of an inhibitor of glycoprotein IIb/IIIa in the hepatic and pulmonary disturbances secondary to ischemia and reperfusion injury of rat’s liver

    Directory of Open Access Journals (Sweden)

    Leonardo F. Canedo

    2007-09-01

    = 6, rats submitted to ischemia-reperfusion that received saline solution (n = 8, and rats submitted to ischemia-reperfusion treated with 0.7 mg/kg of tirofiban (n = 9. Serum aminotransferases (AST and ALT were also determined, and the study of hepatic tissue histology was carried out. The evaluation of the pulmonary disturbances was done using the Evans blue test and the tissular determination of myeloperoxidase. Hepatic mitochondrial oxidation and phosphorylation were also measured. RESULTS: There was an increase in the state 3 respiration, ADP/O ratio and respiration control rate in the group treated with tirofiban. This group had also lower levels of aminotransferases and the histological findings were significantly less intense. Pulmonary evaluation demonstrated decrease of the Evans blue test in the tirofiban group and an increase of its tissular determination of myeloperoxidase. CONCLUSION: The inhibition of glycoprotein IIb/IIIa receptor with tirofiban protected the hepatic disturbances and prevented the increase of pulmonary vascular permeability secondary to the ischemia-reperfusion injury of the liver.

  7. Establishment and primary clinical application of competitive inhibition for measurement of augmenter of liver regeneration.

    Science.gov (United States)

    Wang, Na; Sun, Hang; Tang, Lin; Deng, Jianchuan; Luo, Ya; Guo, Hui; Liu, Qi

    2014-01-01

    The aim of the present study was to establish a quantitative method for the measurement of serum human augmenter of liver regeneration (hALR) using competitive inhibition that is applicable in the clinic. A monoclonal antibody to hALR was used as the primary antibody and the pure hALR protein was used as a standard for competition with Eu(3+)-labeled hALR (Eu(3+)-hALR) to plot a standard curve. Serum samples from 90 patients with various liver diseases due to hepatitis B virus (HBV) infection were used for a competitive reaction with Eu(3+)-hALR. A regression analysis of the results was performed using the standard curve to calculate the serum concentration of hALR. The minimum detectable value using direct competitive measurement established by Eu(3+)-hALR was 1 ng/ml, with a positive linear correlation within the range of 200 ng/ml. In the sera of the 90 patients, the hALR level in the severe hepatitis group was the highest, followed by that in the acute hepatitis group. The serum hALR levels in the cirrhosis and chronic hepatitis groups were significantly higher compared with those in the normal control groups (Pcompetitive measurement method of serum hALR established in the present study has high sensitivity, specificity, stability and reliability, meets clinical requirements and may be used as potential index in clinical tests.

  8. Measurement of mouse liver glutathione S-transferase activity by the integrated method

    Institute of Scientific and Technical Information of China (English)

    廖飞; 李甲初; 康格非; 曾昭淳; 左渝萍

    2003-01-01

    Objective: The integrated method was investigated to measure Vm/Km of mouse liver glutathione S-transferase (GST) activity on GSH and 7-Cl-4-nitrobenzofurazozan. Methods: Presetting concentration of one substrate twenty-fold above the others and taking maximum product absorbance Am as parameter while Km as constant, Vm/Km was obtained by nonlinear fitting of GST reaction curve to the integrated Michaelis-Menten equation ln [Am/(Am-Ai)]+Ai/(ε×Km)=(Vm/Km)×ti (1). Results: Vm/Km for GST showed slight dependence on initial substrate concentration and data range, but it was resistant to background absorbance, error in reaction origin and small deviation in presetting Km. Vm/Km was proportional to the amount of GST with upper limit higher than that by initial rate. There was close correlation between Vm/Km and initial rate of the same GST. Consistent results were obtained by this integrated method and classical initial rate method for the measurement of mouse liver GST. Conclusion: With the concentration of one substrate twenty-fold above the others, this integrated method was reliable to measure the activity of enzyme on two substrates, and substrate concentration of the lower one close to its apparent Km was able to be used.

  9. Factors influencing reliability of liver stiffness measurements using transient elastography (M-probe)—Monocentric experience

    Energy Technology Data Exchange (ETDEWEB)

    Şirli, Roxana, E-mail: roxanasirli@gmail.com; Sporea, Ioan, E-mail: isporea@umft.ro; Bota, Simona, E-mail: bota_simona1982@yahoo.com; Jurchiş, Ana, E-mail: ana.jurchis@yahoo.com

    2013-08-15

    Aim: To retrospectively assess the feasibility of transient elastography (TE) and the factors associated with failed and unreliable liver stiffness measurements (LSMs), in patients with chronic liver diseases. Material and methods: Our retrospective study included 8218 consecutive adult patients with suspected chronic liver diseases. In each patient, LSMs were performed with a FibroScan{sup ®} device (Echosens, France), with the M probe. Failure of TE measurements was defined if no valid measurement was obtained after at least 10 shots and unreliable if fewer than 10 valid shots were obtained, success rate (SR) <60% and/or interquartile range interval/median value (IQR/Med) ≥30%. Results: From the 8218 patients, failed and unreliable LSMs were observed in 29.2% of cases. In univariant analysis, the following risk factors were associated with failed and unreliable measurements: age over 50 years (OR 2.04; 95%CI 1.84–2.26), female gender (OR 1.32; 95%CI 1.20–1.45), BMI > 27.7 kg/m{sup 2} (OR 2.89, 95%CI 2.62–3.19), weight > 77 kg (OR 2.17; 95%CI 1.97–2.40) and height < 162 cm (OR 1.26; 95%CI 1.14–1.40). In multivariate analysis all the factors mentioned above were independently associated with the risk of failed and unreliable measurements. If all the negative predictive factors were present (woman, older than 50 years, with BMI > 27.7 kg/m{sup 2}, heavier than 77 kg and shorter than 162 cm), the rate of failed and unreliable measurements was 58.5%. In obese patients (BMI ≥ 30 kg/m{sup 2}), the rate of failed and unreliable measurements was 49.5%. Conclusion: Failed and unreliable LSMs were observed in 29.1% of patients. Female gender, older age, higher BMI, higher weight and smaller height were significantly associated with failed and unreliable LSMs.

  10. The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Bayramoglu, Gokhan; Bayramoglu, Aysegul; Engur, Selin; Senturk, Hakan; Ozturk, Nilgun; Colak, Suat

    2014-05-01

    Little is known about the effective role of Hypericum perforatum on hepatic ischemia-reperfusion (I/R) injury in rats. Hence, albino rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. Hypericum perforatum extract (HPE) at the dose of 50 mg/kg body weight (HPE50) was intraperitonally injected as a single dose, 15 min prior to ischemia. Rats were sacrificed at the end of reperfusion period and then, biochemical investigations were made in serum and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (p < 0.05). Treatment with HPE50 significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats without treatment-control group (p < 0.05). In oxidative stress generated by hepatic ischemia-reperfusion, H. perforatum L. as an antioxidant agent contributes an alteration in the delicate balance between the scavenging capacity of antioxidant defence systems and free radicals in favour of the antioxidant defence systems in the body.

  11. Warm ischemic injury is reflected in the release of injury markers during cold preservation of the human liver.

    Directory of Open Access Journals (Sweden)

    Bote G Bruinsma

    Full Text Available Liver transplantation plays a pivotal role in the treatment of patients with end-stage liver disease. Despite excellent outcomes, the field is strained by a severe shortage of viable liver grafts. To meet high demands, attempts are made to increase the use of suboptimal livers by both pretransplant recovery and assessment of donor livers. Here we aim to assess hepatic injury in the measurement of routine markers in the post-ischemic flush effluent of discarded human liver with a wide warm ischemic range.Six human livers discarded for transplantation with variable warm and cold ischemia times were flushed at the end of preservation. The liver grafts were flushed with NaCl or Lactated Ringer's, 2 L through the portal vein and 1 L through the hepatic artery. The vena caval effluent was sampled and analyzed for biochemical markers of injury; lactate dehydrogenase (LDH, alanine transaminase (ALT, and alkaline phosphatase (ALP. Liver tissue biopsies were analyzed for ATP content and histologically (H&E examined.The duration of warm ischemia in the six livers correlated significantly to the concentration of LDH, ALT, and ALP in the effluent from the portal vein flush. No correlation was found with cold ischemia time. Tissue ATP content at the end of preservation correlated very strongly with the concentration of ALP in the arterial effluent (P<0.0007, R2 = 0.96.Biochemical injury markers released during the cold preservation period were reflective of the duration of warm ischemic injury sustained prior to release of the markers, as well as the hepatic energy status. As such, assessment of the flush effluent at the end of cold preservation may be a useful tool in evaluating suboptimal livers prior to transplantation, particularly in situations with undeterminable ischemic durations.

  12. Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation

    NARCIS (Netherlands)

    Hendriks, HGD; Meijer, K; de Wolf, JTM; Porte, RJ; Klompmaker, IJ; Lip, H; Slooff, MJH; van der Meer, J

    Besides the conventional laboratory tests, thromboelastography (TEG) is used to monitor hemostasis during liver transplantation. A previous pilot study suggested a beneficial effect of recombinant activated factor VII (rFVIIa) on transfusion requirements in liver transplantation. In the present

  13. Pharmacokinetics of ligustrazine ethosome patch in rats and anti-myocardial ischemia and anti-ischemic reperfusion injury effect

    Directory of Open Access Journals (Sweden)

    Liu X

    2011-07-01

    Full Text Available Xingyan Liu1, Hong Liu1, Zhaowu Zeng2, Weihua Zhou3, Jianqiang Liu2, Zhiwei He11China-America Cancer Research Institute, Guangdong Medical College, 2Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Dongguan, Guangdong, 3Yichun University, Yichun, Jiangxi, People's Republic of ChinaAbstract: The objective of this study was to investigate the pharmacokinetics of the ligustrazine ethosome patch and antimyocardial ischemia and anti-ischemic reperfusion injury effect. Male Sprague Dawley rats were divided randomly into 3 groups: Group A (intragastric ligustrazine, Group B (transdermal ligustrazine ethosome patch, and Group C (conventional transdermal ligustrazine patch. After treatment, samples of blood and of various tissues such as heart, liver, spleen, lung, kidney, brain, and muscle samples were taken at different time points. Drug concentration was measured with HPLC, and the drug concentration–time curve was plotted. Pharmacokinetic software 3p97 was applied to calculate pharmacokinetic parameters and the area under the drug concentration–time curve (AUC in various tissues. The rat model of acute myocardial ischemia was constructed with intravenous injection of pituitrin and the model of myocardial ischemia-perfusion injury was constructed by tying off the left anterior descending coronary artery of rats to observe the effect of ligustrazine ethosome patches on ischemic myocardium and ischemia-reperfusion injury. Results showed that AUC was highest in the transdermal drug delivery group of ligustrazine ethosome patch. There were significant differences in whole blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation index, and deformation index between ligustrazine the ethosome patch group and ischemic control group (P < 0.01. Moreover, ligustrazine ethosome patches could reduce the scope of myocardial infarction induced by long-term ischemia. Ligustrazine ethosome patches

  14. Silent myocardial ischemia.

    Science.gov (United States)

    Gutterman, David D

    2009-05-01

    Although much progress has been made in reducing mortality from ischemic cardiovascular disease, this condition remains the leading cause of death throughout the world. This might in part be due to the fact that over half of patients have a catastrophic event (heart attack or sudden death) as their initial manifestation of coronary disease. Contributing to this statistic is the observation that the majority of myocardial ischemic episodes are silent, indicating an inability or failure to sense ischemic damage or stress on the heart. This review examines the clinical characteristics of silent myocardial ischemia, and explores mechanisms involved in the generation of angina pectoris. Possible mechanisms for the more common manifestation of injurious reductions in coronary flow; namely, silent ischemia, are also explored. A new theory for the mechanism of silent ischemia is proposed. Finally, the prognostic importance of silent ischemia and potential future directions for research are discussed.

  15. Critical Limb Ischemia (CLI)

    Science.gov (United States)

    ... Buerger’s Disease Carotid Artery Disease Chronic Venous Insufficiency Congenital Vascular Malformation Critical Limb Ischemia (CLI) Deep Vein Thrombosis (DVT) Diabetes and Vascular Disease Fibromuscular Dysplasia High Blood Pressure and Vascular Disease Kidney Failure ...

  16. Evaluation of liver stiffness measurement by fibroscan as compared to liver biopsy for assessment of hepatic fibrosis in children with chronic hepatitis C.

    Science.gov (United States)

    Awad, Mohiee El-Deen Abd El-Aziz; Shiha, Gamal Elsayed; Sallam, Fersan Abdallah; Mohamed, Amany; El Tawab, Abd

    2013-12-01

    The study evaluated liver stiffness measurement (LSM) using non-invasive transient elastography (TE) in comparison with liver biopsy for assessment of hepatic fibrosis in children with chronic hepatitis C (CHC). Thirty children (mean age 10.13 +/- 3.4 years) with CHC were subjected to histopathological assessment of liver biopsy specimens using METAVIER score and LSM using TE (FibroScan) as well as appropriate laboratory investigations. The results showed a highly significant stepwise increase of the mean liver stiffness values with increasing histological severity of hepatic fibrosis with the highest level detected in patients with stage F4 "cirrhosis" and significant differences for F3 and F4 vs. other fibrosis stages. There were significant positive correlations between LSM and several parameters of activity and progression of the chronic liver disease including METAVIER fibrosis stages (r=0.774, p=0.0001), necroinflammatory activity grades, AST, ALT, total serum bilirubin, prothrombin time and Child-Pugh grades as well as biochemical serum fibrosis markers (Fibrotest, Actitest, AST-to-platelet ratio index, Forns index and hyaluronic acid). The variables significantly negatively associated with the LSM were platelets count and serum albumin. The highest predictive performance of LSM was detected for stage F4 "cirrhosis", followed by F3 "advanced fibrosis" where accuracy of(96.7%, 85.3%) and AUROC of (1.00, 0.815) were obtained for these fibrosis stages at cutoff values of 9.5 and 12.5 kPa, respectively. The negative predictive values to exclude advanced fibrosis and cirrhosis at these cutoffs were high, whereas positive predictive values were modest.

  17. Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists

    Directory of Open Access Journals (Sweden)

    Roth Robert

    2006-02-01

    Full Text Available Abstract Background Cytokine production is critical in ischemia/reperfusion (IR injury. Acetylcholine binds to macrophages and inhibits cytokine synthesis, through the cholinergic anti-inflammatory pathway. This study examined the role of the cholinergic pathway in cytokine production and hepatic IR- injury. Methods Adult male mice underwent 90-min of partial liver ischemia followed by reperfusion. The AChR agonists (1,1-dimethyl-4-phenyl-L-pioperazinium-iodide [DMPP], and nicotine or saline-vehicle were administered i.p. before ischemia. Plasma cytokine tumor necrosis factor (TNF-α, macrophage inflammatory protein-2, and Interleukin-6 were measured. Liver injury was assessed by plasma alanine transaminase (ALT and liver histopathology. Results A reperfusion time-dependent hepatocellular injury occurred as was indicated by increased plasma-ALT and histopathology. The injury was associated with marked elevation of plasma cytokines/chemokines. Pre-ischemic treatment of mice with DMPP or nicotine significantly decreased plasma-ALT and cytokines after 3 h of reperfusion. After 6 h of reperfusion, the protective effect of DMPP decreased and reached a negligible level by 24 h of reperfusion, despite significantly low levels of plasma cytokines. Histopathology showed markedly diminished hepatocellular injury in DMPP- and nicotine-pretreated mice during the early-phase of hepatic-IR, which reached a level comparable to saline-treated mice at late-phase of IR. Conclusion Pharmacological modulation of the cholinergic pathway provides a means to modulate cytokine production and to delay IR-induced heaptocellular injury.

  18. 供肝冷缺血时间延长诱发大鼠原位肝移植术后早期急性排斥反应的研究%Effect of cold ischemia on early acute rejection after orthotopic liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    施晓敏; 朱有华; 傅志仁; 丁国善; 王正昕; 倪之嘉; 傅宏; 马钧; 郭闻渊; 高晓刚

    2008-01-01

    Objective To study the mechanism and the impact of prolonged cold ischemia on early acute rejection in rat liver allografts.Methods Thirty cases of isotransplantations from BN to BN rats and 30 cases of allotransplantations from Lewis to BN rats were performed,and donor livers were subjected to 1 or 18 h cold ischemia in 4℃ University of Wisconsin solution before transplantation.Rats were randomly divided into 4 groups (n=15 each):group A:isografts with 1 h cold ischemia transplantation;group B:isografts with 18 h cold isehemia transplantation;group C:allografts with 1 h cold ischemia transplantation;group D:allografts with 18 h cold ischemia transplantation.Recipients were sacrificed at day 2,4 and 6 postoperation (n=3 animals/group/time point for isografts and allografts).Representative specimens were collected for immunohistological assay of MHC-Ⅱand NF-κB or snap frozen in liquid nitrogen for morphological observation.Serum levels of ALT and TBiL were determined.Six recipients of each group were observed for 2-week survival rate postoperatively.Results Immunohistochemical staining of postoperative liver specimens showed stronger MHC-Ⅱ expression on either vascular endothelium or bile duct epithelium in group B than in group A (P<0.05).In allografts groups,there was a significantly greater expression of MHC-Ⅱ in liver specimens.Prolonged cold ischemia not only up-regulated the expression of NF-κB,but also advanced peak value of the expression of them.There was a significant difference in 2-week survival rate between two allografts groups (P<0.05).Conclusions Cold ischemia may predispose the liver allograft to the development of acute rejection,in part,not only through the upregulation of the expression of MHC-Ⅱ,but also through the activation of NF-κB.Prolonged cold ischemia can shortern 2-week survival rate postoperatively as well.%目的 研究供肝冷缺血时间延长对大鼠原位肝移植术后早期急性排斥反应的影响.方法

  19. Anti-inflammatory effect of erythropoietin on hepatic ischemia reperfusion injury in fatty liver rats%促红细胞生成素对脂肪肝大鼠肝脏缺血再灌注损伤的抗炎作用

    Institute of Scientific and Technical Information of China (English)

    冯赞杰; 曹宇; 彭慈军; 梅永; 李伟男; 李雄雄; 谢万桃

    2016-01-01

    目的 探讨促红细胞生成素(EPO)预处理对脂肪肝大鼠肝脏缺血再灌注损伤的抗炎作用.方法 雄性SD大鼠100只,高脂饲料喂养12周.造模成功后,采用随机数字表法将脂肪肝大鼠平均分为五组:假手术(SHAM)组、缺血再灌注(IR)组、IR+低剂量EPO组(EPO-1)、IR+中剂量EPO组(EPO-2)和IR+高剂量EPO组(EPO-3,5 000 IU/kg).IR模型通过阻断中叶及左肝叶血流造成70%肝脏缺血建立,缺血时间为80 min.检测各组大鼠不同时点血清ALT、AST,血浆肿瘤坏死因子α(TNF-α)、白细胞介素1(IL-1)水平,肝组织HE染色观察并行超氧化物歧化酶(SOD)及丙二醛(MDA)含量检测.结果 与IR组比较,光镜下EPO各组肝细胞水肿及炎细胞浸润程度明显减轻,未见肝细胞坏死.EPO预处理各组ALT和AST水平明显低于同时相IR组(P<0.05).EPO预处理各组SOD活力明显高于同时相IR组(P <0.05);EPO预处理各组MDA含量明显低于同时相IR组(P<0.05).EPO预处理各组血浆TNF-α和IL-1含量明显低于同时相IR组(P<0.05).EPO预处理组血清ALT、AST以及血浆TNF-α、IL-1和肝组织MDA含量为:EPO-1组>EPO-2组>EPO-3组;肝组织SOD:EPO-1组<EPO-2组<EPO-3组,各组间差异有统计学意义(P<0.05).结论 EPO预处理对脂肪肝大鼠肝脏IR损伤具有保护作用,其作用机制可能是通过抑制炎症反应减轻肝脏IR损伤.高剂量EPO的抗炎作用效果优于中低剂量.%Objective To explore the anti-inflammatory effect of erythropoietin (EPO) on hepatic ischemia reperfusion (IR) injury in fatty liver rats.Methods A total of 100 male SD rats were fed with high-fat diet for 12 weeks.After the model was successfully established,the fatty liver rats were randomly divided into sham-operation (SHAM),the ischemia-reperfusion (IR) and EPO preconditioning group.Serum ALT and AST as well as hepatic histopathological changes were measured.Xanthine oxidase method was used to detect the liver tissue SOD

  20. Quantitative ATP synthesis in human liver measured by localized 31P spectroscopy using the magnetization transfer experiment.

    Science.gov (United States)

    Schmid, A I; Chmelík, M; Szendroedi, J; Krssák, M; Brehm, A; Moser, E; Roden, M

    2008-06-01

    The liver plays a central role in intermediate metabolism. Accumulation of liver fat (steatosis) predisposes to various liver diseases. Steatosis and abnormal muscle energy metabolism are found in insulin-resistant and type-2 diabetic states. To examine hepatic energy metabolism, we measured hepatocellular lipid content, using proton MRS, and rates of hepatic ATP synthesis in vivo, using the 31P magnetization transfer experiment. A suitable localization scheme was developed and applied to the measurements of longitudinal relaxation times (T1) in six healthy volunteers and the ATP-synthesis experiment in nine healthy volunteers. Liver 31P spectra were modelled and quantified successfully using a time domain fit and the AMARES (advanced method for accurate, robust and efficient spectral fitting of MRS data with use of prior knowledge) algorithm describing the essential components of the dataset. The measured T1 relaxation times are comparable to values reported previously at lower field strengths. All nine subjects in whom saturation transfer was measured had low hepatocellular lipid content (1.5 +/- 0.2% MR signal; mean +/- SEM). The exchange rate constant (k) obtained was 0.30 +/- 0.02 s(-1), and the rate of ATP synthesis was 29.5 +/- 1.8 mM/min. The measured rate of ATP synthesis is about three times higher than in human skeletal muscle and human visual cortex, but only about half of that measured in perfused rat liver. In conclusion, 31P MRS at 3 T provides sufficient sensitivity to detect magnetization transfer effects and can therefore be used to assess ATP synthesis in human liver.

  1. Transient micro-elastography:A novel non-invasive approach to measure liver stiffness in mice

    Institute of Scientific and Technical Information of China (English)

    Cécile Bastard; Matteo R Bosisio; Michèle Chabert; Athina D Kalopissis; Meriem Mahrouf-Yorgov; Hélène Gilgenkrantz; Sebastian Mueller; Laurent Sandrin

    2011-01-01

    AIM:To develop and validate a transient micro-elastography device to measure liver stiffness (LS) in mice. METHODS:A novel transient micro-elastography (TME) device,dedicated to LS measurements in mice with a range of measurement from 1-170 kPa,was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston.The novel probe was validated in a classical fibrosis model (CCl4) and in a transgenic murine model of systemic amyloidosis.RESULTS:TME could be successfully performed in control mice below the xiphoid cartilage,with a mean LS of 4.4 ± 1.3 kPa,a mean success rate of 88%,and an excellent intra-observer agreement (0.98).Treatment with CCl4 over seven weeks drastically increased LS as compared to controls (18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa).Moreover, fibrosis stage was highly correlated with LS (Spearman coefficient = 0.88,P 150 kPa.LS significantly correlated with the amyloidosis index (0.93,P < 0.0001) and the plasma concentration of mutant hapoA-Ⅱ (0.62,P < 0.005). CONCLUSION:Here,we have established the first non-invasive approach to measure LS in mice,and have successfully validated it in two murine models of high LS.

  2. Prognostic factors for late mortality after liver transplantation for benign end-stage liver disease

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying-cai; LU Min-qiang; YANG Yang; CHEN Gui-hua; ZHANG Qi; LI Hua; ZHANG Jian; WANG Gen-shu; XU Chi; YI Shu-hong; YI Hui-min; CAI Chang-jie

    2011-01-01

    Background There are increasing numbers of patients who survive more than one year after liver transplantation.Many studies have focused on the early mortality of these patients.However,the factors affecting long-term survival are not fully understood.This study aims to evaluate prognostic factors predicting long-term survival and to explore measures for improving the survival outcomes of patients who underwent liver transplantation for benign end-stage liver diseases.Methods The causes of late death after liver transplantation and potential prognostic factors were retrospectively analyzed for 221 consecutive patients who underwent liver transplantation from October 2003 to June 2008.Twenty-seven variables were assessed using the Kaplan-Meier method,and those variables found to be univariately significant at P <0.10 were entered into a backward step-down Cox proportional hazard regression analysis to identify the independent prognostic factors influencing the recipients' long-term survival.Results Twenty-eight recipients died one year after liver transplantation.The major causes of late mortality were infectious complications,biliary complications,and Hepatitis B virus recurrence/reinfection.After Cox analysis,the five remaining co-variables were:age,ABO blood group,cold ischemia time,post-infection region,and biliary complications.Conclusions The major causes of late mortality were infection,biliary complications and Hepatitis B virus recurrence/reinfection.Five variables (Age,ABO blood group,cold ischemia time,infection,and biliary complications) had significant impacts on patient survival.

  3. Quantitative MRI for hepatic fat fraction and T2* measurement in pediatric patients with non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Jie; Rigsby, Cynthia K.; Donaldson, James S. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Fishbein, Mark H. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Gastroenterology, Hepatology, and Nutrition, Chicago, IL (United States); Zhang, Gang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Biostatistics Research Core, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2014-11-15

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The gold standard for diagnosis is liver biopsy. MRI is a non-invasive imaging method to provide quantitative measurement of hepatic fat content. The methodology is particularly appealing for the pediatric population because of its rapidity and radiation-free imaging techniques. To develop a multi-point Dixon MRI method with multi-interference models (multi-fat-peak modeling and bi-exponential T2* correction) for accurate hepatic fat fraction (FF) and T2* measurements in pediatric patients with NAFLD. A phantom study was first performed to validate the accuracy of the MRI fat fraction measurement by comparing it with the chemical fat composition of the ex-vivo pork liver-fat homogenate. The most accurate model determined from the phantom study was used for fat fraction and T2* measurements in 52 children and young adults referred from the pediatric hepatology clinic with suspected or identified NAFLD. Separate T2* values of water (T2*{sub W}) and fat (T2*{sub F}) components derived from the bi-exponential fitting were evaluated and plotted as a function of fat fraction. In ten patients undergoing liver biopsy, we compared histological analysis of liver fat fraction with MRI fat fraction. In the phantom study the 6-point Dixon with 5-fat-peak, bi-exponential T2* modeling demonstrated the best precision and accuracy in fat fraction measurements compared with other methods. This model was further calibrated with chemical fat fraction and applied in patients, where similar patterns were observed as in the phantom study that conventional 2-point and 3-point Dixon methods underestimated fat fraction compared to the calibrated 6-point 5-fat-peak bi-exponential model (P < 0.0001). With increasing fat fraction, T2*{sub W} (27.9 ± 3.5 ms) decreased, whereas T2*{sub F} (20.3 ± 5.5 ms) increased; and T2*{sub W} and T2*{sub F} became increasingly more similar when fat

  4. Influence of Hysulfide on the Expression of TNF-αand IL-1βin Rats with Liver Cirrhosis after He-patic Ischemia Reperfusion%硫化氢对肝硬化大鼠肝脏缺血再灌注后TNF-α和IL-1β表达的影响

    Institute of Scientific and Technical Information of China (English)

    罗锋; 魏来; 陈文雁; 牟燕; 孔高茵

    2013-01-01

    [Objective]To explore the influence of sodium hydrosulfide (NaHS ,a donor of hydrogen sulfide) precondi-tioning on the changes of liver function and the expression of tissue tumor necrosis factor-alpha(TNF-α) and interleukin-1beta (IL-1β) in rats with liver cirrhosis after hepatic ischemia reperfusion .[Methods]Thirty rats with liver cirrhosis were random-ly divided into three groups including sham group ,hepatic ischemia reperfusion injury group (HIRI group) and NaHS precon-ditioning group(NaHS group) .The inferior vena cava blood were gathered at the end of reperfusion for detecting liver func-tionindexessuchasalaninetransaminase(ALT)andaspartateaminotransferase(AST).Theexpressionof TNF-αandIL-1βin partial liver tissues was examined by using enzyme-linked immunosorbent assay (ELISA) .[Results]At the end of reperfu-sion ,the levels of ALT and AST and the expression of TNF-αand IL-1βin HIRI group and NaHS group were obviously higher than those in sham group ,but those in NaHS group were lower than those in HIRI group ,and there were significant differences( P<0 .05) .[Conclusion]NaHS preconditioning can increase the ability of anti-hepatic ischemia reperfusion injury of rats with liver cirrhosis .Moreover ,the effect may be achieved by inhibiting inflammatory response .%[目的]探讨硫氢化钠(NaHS)预处理对肝硬化大鼠肝脏缺血再灌注后肝功能变化的影响及对肝组织肿瘤坏死因子α(T N F-α)和白介素-1β(IL-1β)表达的影响。[方法]30只肝硬化大鼠随机分为3组(n=10),包括假手术组(Sham组),肝脏缺血再灌注损伤组(HIRI组)和NaHS预处理组(NaHS组)。再灌注末取腔静脉血检测肝功能指标:谷丙转氨酶(ALT)和谷草转氨酶(AST)浓度。取部分肝组织酶联免疫吸附法(ELISA)检测 TNF-α和IL-1β表达情况。[结果]再灌注末,HIRI组、NaHS组 ALT、AST、TNF-α和IL-1β表达明显高于Sham组, NaHS组低于 HIRI组

  5. Phosphodiester content measured in human liver by in vivo (31) P MR spectroscopy at 7 tesla.

    Science.gov (United States)

    Purvis, Lucian A B; Clarke, William T; Valkovič, Ladislav; Levick, Christina; Pavlides, Michael; Barnes, Eleanor; Cobbold, Jeremy F; Robson, Matthew D; Rodgers, Christopher T

    2017-02-28

    Phosphorus ((31) P) metabolites are emerging liver disease biomarkers. Of particular interest are phosphomonoester and phosphodiester (PDE) "peaks" that comprise multiple overlapping resonances in (31) P spectra. This study investigates the effect of improved spectral resolution at 7 Tesla (T) on quantifying hepatic metabolites in cirrhosis. Five volunteers were scanned to determine metabolite T1 s. Ten volunteers and 11 patients with liver cirrhosis were scanned at 7T. Liver spectra were acquired in 28 min using a 16-channel (31) P array and 3D chemical shift imaging. Concentrations were calculated using γ-adenosine-triphosphate (γ-ATP) = 2.65 mmol/L wet tissue. T1 means ± standard deviations: phosphatidylcholine 1.05 ± 0.28 s, nicotinamide-adenine-dinucleotide (NAD(+) ) 2.0 ± 1.0 s, uridine-diphosphoglucose (UDPG) 3.3 ± 1.4 s. Concentrations in healthy volunteers: α-ATP 2.74 ± 0.11 mmol/L wet tissue, inorganic phosphate 2.23 ± 0.20 mmol/L wet tissue, glycerophosphocholine 2.34 ± 0.46 mmol/L wet tissue, glycerophosphoethanolamine 1.50 ± 0.28 mmol/L wet tissue, phosphocholine 1.06 ± 0.16 mmol/L wet tissue, phosphoethanolamine 0.77 ± 0.14 mmol/L wet tissue, NAD(+) 2.37 ± 0.14 mmol/L wet tissue, UDPG 2.00 ± 0.22 mmol/L wet tissue, phosphatidylcholine 1.38 ± 0.31 mmol/L wet tissue. Inorganic phosphate and phosphatidylcholine concentrations were significantly lower in patients; glycerophosphoethanolamine concentrations were significantly higher (P < 0.05). We report human in vivo hepatic T1 s for phosphatidylcholine, NAD(+) , and UDPG for the first time at 7T. Our protocol allows high signal-to-noise, repeatable measurement of metabolite concentrations in human liver. The splitting of PDE into its constituent peaks at 7T may allow more insight into changes in metabolism. Magn Reson Med, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of

  6. [Cerebral ischemia and histamine].

    Science.gov (United States)

    Adachi, Naoto

    2002-10-01

    Cerebral ischemia induces excess release of glutamate and an increase in the intracellular Ca2+ concentration, which provoke catastrophic enzymatic processes leading to irreversible neuronal injury. Histamine plays the role of neurotransmitter in the central nervous system, and histaminergic fibers are widely distributed in the brain. In cerebral ischemia, release of histamine from nerve endings has been shown to be enhanced by facilitation of its activity. An inhibition of the histaminergic activity in ischemia aggravates the histologic outcome. In contrast, intracerebroventricular administration of histamine improves the aggravation, whereas blockade of histamine H2 receptors aggravates ischemic injury. Furthermore, H2 blockade enhances ischemic release of glutamate and dopamine. These findings suggest that central histamine provides beneficial effects against ischemic neuronal damage by suppressing release of excitatory neurotransmitters. However, histaminergic H2 action facilitates the permeability of the blood-brain barrier and shows deleterious effects on cerebral edema.

  7. The relationship between HbA(1c) and fasting plasma glucose in patients with increased plasma liver enzyme measurements

    DEFF Research Database (Denmark)

    Christiansen, R; Rasmussen, L Melholt; Nybo, H;

    2012-01-01

    levels of increased liver enzyme concentrations. Methods:  Data from 10 065 patients with simultaneous measurement of HbA(1c) , venous fasting plasma glucose, alanine aminotransferase and γ-glutamyl transferase were extracted from our laboratory database. Correlations were investigated in four patient...

  8. 1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents

    DEFF Research Database (Denmark)

    Fonvig, Cilius Esmann; Chabanova, Elizaveta; Andersson, Ehm Astrid

    2015-01-01

    OBJECTIVES: This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children. METHODS: Fasting plasma...... glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8-18 years. RESULTS: In 287 overweight/obese children, the prevalences...... associated inversely to high density lipoprotein cholesterol. CONCLUSION: Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased...

  9. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  10. Sampling variability of computer-aided fractal-corrected measures of liver fibrosis in needle biopsy specimens

    Institute of Scientific and Technical Information of China (English)

    Fabio Grizzi; Carlo Russo; Barbara Franceschini; Mariagrazia Di Rocco; Valter Torri; Emanuela Morenghi; Luigi Rainiero Fassati; Nicola Dioguardi

    2006-01-01

    AIM: To assess the sampling variability of computeraided, fractal-corrected measures of fibrosis in liver biopsies.METHODS: Samples were derived from six to eight different parts of livers removed from 12 patients with clinically and histologically proven cirrhosis undergoing orthotopic liver transplantation. Sirius red-stained sections with a thickness of 2 μm were digitized using a computer-aided image analysis system that automatically measures the surface of fibrosis, as well as its outline perimeter, fractal surface and outline dimensions,wrinkledness, and Hurst coefficient.RESULTS: We found a high degree of inter-sample variability in the measurements of the surface [coefficient of variation (CV) = 43% ± 13%] and wrinkledness (CV = 28% ± 9%) of fibrosis, but the inter-sample variability of Hurst's exponent was low (CV = 14% ± 2%).CONCLUSION: This study suggests that Hurst's exponent might be used in clinical practice as the best histological estimate of fibrosis in the whole organ,and evidences the fact that biopsy sections, which are fundamental for the qualitative diagnosis of chronic hepatitis, play a key role in the quantitative estimate of architectural changes in liver tissue.

  11. The frequency and determinants of liver stiffness measurement failure: a retrospective study of "real-life" 38,464 examinations.

    Directory of Open Access Journals (Sweden)

    Dong Ji

    Full Text Available To investigate the frequency and determinants of liver stiffness measurement (LSM failure by means of FibroScan in "real-life" Chinese patients.A total of 38,464 "real-life" Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC, alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m and M probe (for adults were used. LSM failure defined as zero valid shots (unsuccessful LSM, or the ratio of the interquartile range to the median of 10 measurements (IQR/M greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM.LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464, among them, there were 958 cases (2.49% with unsuccessful LSM, and 328 patients (0.85% with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI greater than 30 kg/m(2, female sex, age greater than 50 years, intercostal spaces (IS less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P<0.0001.The principal reasons of LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC, decompensated LC, elder or female patients are higher. These results emphasize the need for adequate operator training, technological improvements and optimal criteria for specific patient subpopulations.

  12. Assessment of hepatic functional reserve by cirrhosis grading and liver volume measurement using CT

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To explore a method for quantitative assessment of hepatic functional reserve by combining computed tomography (CT) volumetry with CT grading of liver cirrhosis before liver resection in patients with hepatocellular carcinoma.METHODS: CT images of 55 patients undergoing liver resection were studied prospectively. The degree of liver cirrhosis was referred as "CT grade" and the percentage of remnant liver volume (PRLV) [PRLV = predicted RLV/predicted total liver volume (PTLV) × 100%;PTLV (mL) = 121.75 + 16.49 × body mass (kg)] were calculated by adding slice by slice of CT liver images.The postoperative RLV, pathologic stages of liver fibrosis in non-tumor area and survival time in these cases were analyzed.RESULTS: There was a significant difference in survival time between the group with PRLV ≤ 50% and the group with PRLV > 50% (χ2= 4.988, P = 0.026), and between the group with CT grade 0/1 and the group with CT grade 2/3 (χ2= 5.429, P = 0.026). With combination of the both parameters, an oblique line was identified according to the distribution of 32 survivors versus 23 deceased subjects. The mortality rate above the line was 7.1% (1/14), and that below the line was 53.7% (22/41),indicating a significant difference between the two rates (χ2 = 9.281, P = 0.002, P < 0.05).CONCLUSION: PRLV and CT grades are significantly correlated with hepatic functional reserve. The predicted line using these two parameters is useful in candidates undergoing liver resection for judging hepatic functional reserve.

  13. A pilot study estimating liver fibrosis with ultrasound shear-wave elastography: does the cause of liver disease or location of measurement affect performance?

    Science.gov (United States)

    Beland, Michael D; Brown, Sanford F; Machan, Jason T; Taliano, Ross J; Promrat, Kittichai; Cronan, John J

    2014-09-01

    The purpose of this study was to evaluate the diagnostic accuracy of real-time shear-wave elastography for assessment of liver fibrosis in an unselected patient population, comparing shear-wave elastography measurements obtained at and remote from the site of random liver biopsy. In a prospective study of 50 patients (21 with and 29 without hepatitis C) referred for clinically indicated random liver biopsy for diffuse liver disease, shear-wave elastography measurements were taken from four locations before biopsy: one at the left lobe, two at the right lobe, and one at the biopsy location. The mean, minimum, maximum, and SD of shear-wave elastography were compared with pathologic grading. Steatosis and serum markers were analyzed using multiple logistic regression. Optimized shear-wave elastography thresholds were calculated using AUC analysis. The AUC (95% CI) at the biopsy site, ipsilateral lobe, and contralateral lobe were 0.82 (0.63-1.0), 0.84 (0.67-1.0), and 0.59 (0.19-0.99) in hepatitis C patients; 0.89 (0.75-1.0), 0.88 (0.73-1.0), and 0.93 (0.80-1.0) in nonhepatitis C patients; and 0.85 (0.74-0.96), 0.89 (0.79-0.99), and 0.80 (0.67-0.93) in all patients, respectively. Optimized biopsy site shear-wave elastography values for detecting Metavir score F2 or greater were 1.87 m/s (75% sensitivity and specificity), 2.00 m/s (80% sensitivity and specificity), and 1.89 m/s (76% sensitivity and specificity) in hepatitis C, nonhepatitis C, and all patients, respectively. Steatosis and serum markers were not significant. Real-time shear-wave elastography accurately predicted significant fibrosis (stage ≥ 2) in an unselected patient population with diffuse disease, including patients with and without hepatitis C. Shear-wave elastography best predicts pathologic grading when taken at the biopsy site or ipsilateral lobe in hepatitis C patients. Percentage steatosis was not predictive of shear-wave elastography results.

  14. Direct comparison of local cerebral blood flow rates measured by MRI arterial spin-tagging and quantitative autoradiography in a rat model of experimental cerebral ischemia.

    Science.gov (United States)

    Ewing, James R; Wei, Ling; Knight, Robert A; Pawa, Swati; Nagaraja, Tavarekere N; Brusca, Thomas; Divine, George W; Fenstermacher, Joseph D

    2003-02-01

    The present study determined cerebral blood flow (CBF) in the rat using two different magnetic resonance imaging (MRI) arterial spin-tagging (AST) methods and 14C-iodoantipyrine (IAP)-quantitative autoradiography (QAR), a standard but terminal technique used for imaging and quantitating CBF, and compared the resulting data sets to assess the precision and accuracy of the different techniques. Two hours after cerebral ischemia was produced in eight rats via permanent occlusion of one middle cerebral artery (MCA) with an intraluminal suture, MRI-CBF was measured over a 2.0-mm coronal slice using single-coil AST, and tissue magnetization was assessed by either a spin-echo (SE) or a variable tip-angle gradient-echo (VTA-GE) readout. Subsequently ( approximately 2.5 hours after MCA occlusion), CBF was assayed by QAR with the blood flow indicator 14C-IAP, which produced coronal images of local flow rates every 0.4 mm along the rostral-caudal axis. The IAP-QAR images that spanned the 2-mm MRI slice were selected, and regional flow rates (i.e., local CBF [lCBF]) were measured and averaged across this set of images by both the traditional approach, which involved reader interaction and avoidance of sectioning artifacts, and a whole film-scanning technique, which approximated total radioactivity in the entire MRI slice with minimal user bias. After alignment and coregistration, the concordance of the CBF rates generated by the two QAR approaches and the two AST methods was examined for nine regions of interest in each hemisphere. The QAR-lCBF rates were higher with the traditional method of assaying tissue radioactivity than with the MRI-analog approach; although the two sets of rates were highly correlated, the scatter was broad. The flow rates obtained with the whole film-scanning technique were chosen for subsequent comparisons to MRI-CBF results because of the similarity in tissue "sampling" among these three methods. As predicted by previous modeling, "true" flow rates

  15. The Complement System in Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Xuebin Qin; Bin Gao

    2006-01-01

    The complement system plays an important role in mediating both acquired and innate responses to defend against microbial infection, and in disposing immunoglobins and apoptotic cells. The liver (mainly hepatocytes) is responsible for biosynthesis of about 80-90% of plasma complement components and expresses a variety of complement receptors.Recent evidence from several studies suggests that the complement system is also involved in the pathogenesis of a variety of liver disorders including liver injury and repair, fibrosis, viral hepatitis, alcoholic liver disease, and liver ischemia/reperfusion injury. In this review, we will discuss the potential role of the complement system in the pathogenesis of liver diseases.

  16. Protective effect of N2-mercaptopropionylglycine on rats and dogs liver during ischemia/reperfusion process Efeito protetor do N2-mercaptopropionilglicina em ratos e cães submetidos a isquemia/reperfusão normotécnica do fígado

    Directory of Open Access Journals (Sweden)

    Emilio Elias Abdo

    2003-09-01

    Full Text Available BACKGROUND: N2-mercaptopropionylglycine is a powerful super oxide synthesis inhibitor and has been tested as a preventive agent of metabolic and structural hepatic damage in the ischemia/reperfusion process. AIM: To analyze some effects of N2-mercaptopropionylglycine administration to animals of two species submitted to normothermic liver ischemia/reperfusion. MATERIAL AND METHODS: Twenty-two rats and 22 dogs were divided into four groups: group I: rats that received intravenous saline 0.9%; group II: rats that received 100 mg/kg of N2-mercaptopropionylglycine; group III: dogs that received saline intravenous 0.9% and group IV: dogs that received 100 mg/kg N2-mercaptopropionylglycine. RESULTS: Ten minutes after the saline or drug administration, each group was submitted to left lobe liver ischemia for 25 minutes followed by reperfusion. Biochemical studies 24 hours after reperfusion revealed a significantly lower elevation of transaminases in animals of groups II (AST = 271 ± 182; ALT = 261 ± 161 and IV (AST = 101 ± 45; ALT = 123 ± 89 when compared to the controls group: I (AST = 2144 ± 966; ALT = 1869 ± 1040 00 and III (AST = 182 ± 76.51; ALT = 277 ± 219, respectively. Histology study demonstrated a significantly minor aggression to animals of groups II and IV when compared to groups I and III, respectively. CONCLUSION: These results suggest a significant release of free radicals of oxygen in the process and that N2-mercaptopropionylglycine may have a significant protective effect on liver parenchyma when submitted to ischemia/reperfusion.RACIONAL: O medicamento N2-mercaptopropionilglicina é um potente inibidor da síntese de radicais superóxidos e foi testado como agente preventivo de lesão metabólica e estrutural do parênquima hepático, no processo de isquemia/reperfusão. OBJETIVOS: Analisar alguns efeitos da administração do N2-mercaptopropionilglicina a animais de duas espécies submetidas a isquemia/reperfusão normot

  17. Lipidomics comparing DCD and DBD liver allografts uncovers lysophospholipids elevated in recipients undergoing early allograft dysfunction.

    Science.gov (United States)

    Xu, Jin; Casas-Ferreira, Ana M; Ma, Yun; Sen, Arundhuti; Kim, Min; Proitsi, Petroula; Shkodra, Maltina; Tena, Maria; Srinivasan, Parthi; Heaton, Nigel; Jassem, Wayel; Legido-Quigley, Cristina

    2015-12-04

    Finding specific biomarkers of liver damage in clinical evaluations could increase the pool of available organs for transplantation. Lipids are key regulators in cell necrosis and hence this study hypothesised that lipid levels could be altered in organs suffering severe ischemia. Matched pre- and post-transplant biopsies from donation after circulatory death (DCD, n = 36, mean warm ischemia time = 2 min) and donation after brain death (DBD, n = 76, warm ischemia time = none) were collected. Lipidomic discovery and multivariate analysis (MVA) were applied. Afterwards, univariate analysis and clinical associations were conducted for selected lipids differentiating between these two groups. MVA grouped DCD vs. DBD (p = 6.20 × 10(-12)) and 12 phospholipids were selected for intact lipid measurements. Two lysophosphatidylcholines, LysoPC (16:0) and LysoPC (18:0), showed higher levels in DCD at pre-transplantation (q < 0.01). Lysophosphatidylcholines were associated with aspartate aminotransferase (AST) 14-day post-transplantation (q < 0.05) and were more abundant in recipients undergoing early allograft dysfunction (EAD) (p < 0.05). A receiver-operating characteristics (ROC) curve combining both lipid levels predicted EAD with 82% accuracy. These findings suggest that LysoPC (16:0) and LysoPC (18:0) might have a role in signalling liver tissue damage due to warm ischemia before transplantation.

  18. Ischemic preconditioning-induced hyperperfusion correlates with hepatoprotection after liver resection

    Institute of Scientific and Technical Information of China (English)

    Oleg; Heizmann; Georgios; Meimarakis; Andreas; Volk; Daniel; Matz; Daniel; Oertli; Rolf; J; Schauer

    2010-01-01

    AIM:To characterize the impact of the Pringle ma-neuver (PM) and ischemic preconditioning (IP) on total blood supply to the liver following hepatectomies. METHODS: Sixty one consecutive patients who un-derwent hepatic resection under in flow occlusion were randomized either to receive PM alone (n = 31) or IP (10 min of ischemia followed by 10 min of reperfusion) prior to PM (n = 30). Quantification of liver perfusion was measured by Doppler probes at the hepatic artery and portal vein at various time points...

  19. Computer-aided measurement of liver volumes in CT by means of geodesic active contour segmentation coupled with level-set algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kenji; Kohlbrenner, Ryan; Epstein, Mark L.; Obajuluwa, Ademola M.; Xu Jianwu; Hori, Masatoshi [Department of Radiology, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637 (United States)

    2010-05-15

    Purpose: Computerized liver extraction from hepatic CT images is challenging because the liver often abuts other organs of a similar density. The purpose of this study was to develop a computer-aided measurement of liver volumes in hepatic CT. Methods: The authors developed a computerized liver extraction scheme based on geodesic active contour segmentation coupled with level-set contour evolution. First, an anisotropic diffusion filter was applied to portal-venous-phase CT images for noise reduction while preserving the liver structure, followed by a scale-specific gradient magnitude filter to enhance the liver boundaries. Then, a nonlinear grayscale converter enhanced the contrast of the liver parenchyma. By using the liver-parenchyma-enhanced image as a speed function, a fast-marching level-set algorithm generated an initial contour that roughly estimated the liver shape. A geodesic active contour segmentation algorithm coupled with level-set contour evolution refined the initial contour to define the liver boundaries more precisely. The liver volume was then calculated using these refined boundaries. Hepatic CT scans of 15 prospective liver donors were obtained under a liver transplant protocol with a multidetector CT system. The liver volumes extracted by the computerized scheme were compared to those traced manually by a radiologist, used as ''gold standard.''Results: The mean liver volume obtained with our scheme was 1504 cc, whereas the mean gold standard manual volume was 1457 cc, resulting in a mean absolute difference of 105 cc (7.2%). The computer-estimated liver volumetrics agreed excellently with the gold-standard manual volumetrics (intraclass correlation coefficient was 0.95) with no statistically significant difference (F=0.77; p(F{<=}f)=0.32). The average accuracy, sensitivity, specificity, and percent volume error were 98.4%, 91.1%, 99.1%, and 7.2%, respectively. Computerized CT liver volumetry would require substantially less

  20. Postconditioning ameliorates lipid peroxidation in liver ischemia-reperfusion injury in rats Pós-condicionamento melhora a peroxidação lipídica na lesão de isquemia-reperfusão hepática em ratos

    Directory of Open Access Journals (Sweden)

    Antonio Roberto Franchi Teixeira

    2009-02-01

    Full Text Available PURPOSE: Liver ischemia-reperfusion injury is a phenomenon presents in events like liver resections and transplantation. The restoration of blood flow may leads to local and systemic injury. Several techniques have been developed in order to avoid or ameliorate ischemia-reperfusion injury in clinical situations. The application of a sttuter reperfusion after the ischemic event (postconditioning could alters the hydrodynamics and stimulates endogenous mechanisms that attenuate the reperfusion injury. The present study was designed to evaluate the potential protective effect of postconditioning in a model of ischemia-reperfusion in rats. METHODS: Hepatic anterior pedicle of median and left anterolateral segments were exposed and clamped for 1 hour. Two hours later, clamp was released in two different ways: Control Group (n=7: clamp was release straightforward; Postconditioning Group (n=7: clamp was released intermittently. Lipid peroxidation (malondialdehyde and expression of the glutathione-s-transferase-α-3 gene were studied. RESULTS: Lipid peroxidation was significantly decreased in ischemic and non-ischemic liver by postconditioning. GST- α3 gene was overexpressed in postconditioned group, but not significantly. CONCLUSION: Postconditioning induced hepatoprotection by reducing lipid peroxidation in the ischemic and non-ischemic liver.OBJETIVO: A lesão de isquemia-reperfusão hepática é um fenômeno presente em eventos tais como ressecções hepáticas e transplante de fígado. A restauração do fluxo sangüíneo após a isquemia gera lesões locais e sistêmicas. Várias técnicas foram desenvolvidas com o objetivo de evitar ou diminuir a lesão de isquemia-reperfusão hepática em situações clínicas. A utilização da reperfusão intermitente após o evento isquêmico (pós-condicionamento pode alterar a hidrodinâmica e estimular mecanismos endógenos que atenuam o dano da reperfusão. O presente estudo foi realizado para avaliar o

  1. Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats

    Directory of Open Access Journals (Sweden)

    Arruda Marcio Jose Cristiano de

    2006-01-01

    Full Text Available INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia, or sham procedures (control, followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10-7 to 3 x 10-4 was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains

  2. Fiber optic measurement of intracellular pH in intact rat liver using pH-sensitive dyes

    Science.gov (United States)

    Felberbauer, Franz; Graf, Juerg

    1991-09-01

    The pH-sensitive fluorescent dye 1,3-dihydroxy-pyrene-6,8-disulfonic acid (DHPDS) was used to measure intracellular pH (pHi) from the surface fluorescence of the isolated perfused rate liver. 1 micrometers of the diacetyl ester of DHPDS was added to the perfusate. The dye readily accumulated in hepatocytes where it was hydrolyzed to form the fluorescent pH indicator. Surface fluorescence was excited by focusing monochromatic light from a spectrofluorometer onto the end of a fiber light guide that illuminated a part of the liver surface. Two excitation wavelengths were used, one where fluorescence intensity was pH sensitive, the other at the isosbestic point. Emitted light was collected by a second fiber optic and returned to the emission side of the spectrometer. A ratio was computed between fluorescence intensities at the pH-sensitive excitation peak wavelength and the isosbestic wavelength, thus yielding measurement insensitive to changes in dye concentration and in excitation light intensity. Intracellular calibration of dye fluorescence was done by clamping pHi to perfusate pH with the use of the cell membrane H+/K+ -ionophore Nigericin. The method was used to monitor changes in pHi caused by addition and removal of NH4Cl. Data obtained in the perfused liver were in good agreement with those reported for isolated liver cells. The technique appears adequate to determine hepatocellular pH in the liver and will allow study of regulatory mechanisms of hepatocyte pHi in the intact organ.

  3. Quantum coherence spectroscopy to measure dietary fat retention in the liver.

    Science.gov (United States)

    Lindeboom, Lucas; de Graaf, Robin A; Nabuurs, Christine I; van Ewijk, Petronella A; Hesselink, Matthijs K C; Wildberger, Joachim E; Schrauwen, Patrick; Schrauwen-Hinderling, Vera B

    2016-08-18

    The prevalence of fatty liver reaches alarming proportions. Fatty liver increases the risk for insulin resistance, cardiovascular disease, and nonalcoholic steatohepatitis (NASH). Although extensively studied in a preclinical setting, the lack of noninvasive methodologies hampers our understanding of which pathways promote hepatic fat accumulation in humans. Dietary fat retention is one of the pathways that may lead to fatty liver. The low (1.1%) natural abundance (NA) of carbon-13 ((13)C) allows use of (13)C-enriched lipids for in vivo MR studies. Successful implementation of such methodology, however, is challenging due to low sensitivity of (13)C-magnetic resonance spectroscopy ((13)C-MRS). Here, we investigated the use of 1-dimensional gradient enhanced heteronuclear single quantum coherence (ge-HSQC) spectroscopy for the in vivo detection of hepatic (1)H-[(13)C]-lipid signals after a single high-fat meal with (13)C-labeled fatty acids in 5 lean and 6 obese subjects. Postprandial retention of orally administered (13)C-labeled fatty acids was significant (P < 0.01). Approximately 1.5% of the tracer was retained in the liver after 6 hours, and retention was similar in both groups (P = 0.92). Thus, a substantial part of the liver fat can originate directly from storage of meal-derived fat. The ge-HSQC can be used to noninvasively reveal the contribution of dietary fat to the development of hepatic steatosis over time.

  4. Relationship between liver PCB content and biochemical and morphometric measures in bream (Abramis brama) from Rybinsk Reservoir

    Energy Technology Data Exchange (ETDEWEB)

    Tillitt, D.E.; Zajicek, J.L. [NBS, Columbia, MO (United States); Chuiko, G.M.; Flerov, B.A.; Stepanova, V.M.; Zhelnin, Y.Y.; Pod`gornaya, V.A. [IBIW, Borok (Russian Federation)

    1995-12-31

    PCBs are widely distributed in aquatic environments throughout the world, due to local contamination and global transport. However, little is known of the local distribution of PCBs in Rybinsk Reservoir, Russia. The Rybinsk Reservoir, constructed in the 1940`s, is the largest artificial waterbody in Europe (4,550 km{sup 2}) and provides drinking water for cities in the surrounding area. Industrialization in Cherepovetz, a city at the northeastern portion of the reservoir including the largest metallurgical facility in Europe, has resulted in chemical contamination of the reservoir. The objective of this study was to investigate the extent of PCB contamination in Bream taken from six locations in the reservoir and to compare the chemical analyses with biochemical and morphometric indicators of fish health. Concentrations of PCBs ranged from non-detected to 3.4 ug/g of liver, with the greatest concentrations found in fish taken near the industrialized area. The pattern of the PCB congeners in the livers of Bream taken near Cherepovetz closely resembled that of the standard Aroclor 1254. PCB content was negatively correlated with protein content and acetylcholinesterase (AChE) activity in Bream liver. Other morphometric factors and biochemical measures varied among locations, but were unrelated to concentrations of PCBs in the livers of Bream.

  5. Value of serum liver fatty acid-binding protein in monitoring of hepatic function after the ischemia-reperfusion injury%血清肝型脂肪酸结合蛋白在大鼠肝脏缺血再灌注损伤的早期诊断价值

    Institute of Scientific and Technical Information of China (English)

    门贺伟; 杨龙; 张荣信; 薛振毅; 蔡金贞; 张雅敏

    2012-01-01

    Objective To investigate the diagnostic value and significance of serum liver fatty acid-binding protein (L-FABP) in hepatic ischemia-reperfusion injury in rat.Methods Male Wistar rats were randomly divided into three groups:sham operation group (group A) ; reperfusion after 15 min of ischemia group (group B) ; reperfusion after 30 min of ischemia group (group C).Each group was divided into 6 subgroups based on the time of reperfusion (15 min,1 h,3 h,6 h,1 d,3 d).The model of hepatic ischemia-reperfusion injury was established,the level of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and L-FABP were tested at each time point and the expression of L-FABP was tested by Immunohistochemical Fluorescence.The pathological changes observed in the liver and evaluated the changes by Suzuki's scoring system.Results Compared with group A,the changes of serum L-FABP:increased after 15 min of reperfusion [(0.57 ± 0.14) μg/L,P < 0.05],reached the peak after 3 h of reperfusion [(1.70 ± 0.26) μg/L,P < 0.05] and returned to normal at 3 d [(0.16 ± 0.05) μg/L,P >0.05] ; the changes of serum ALT and AST:no significant increase after 15min of reperfusion,reach the top at 6h and the level was still higher than normal at 3 d (P < 0.05) ; L-FABP in liver tissue:the expression was decreased after 15min of reperfusion (0.148 ± 0.047,P < 0.05),reached to the trough at 3 h (0.071 ± 0.019,P < 0.05) and returned to normal at 3 d (0.142 ± 0.047,P > 0.05).Compared with group B,the level of serum L-FABP,AST and ALT in group C were significandy increased at each time point (P < 0.05),and the expression of L-FABP was significantly decreased (P < 0.05),the pathological changes were significantly worse.Conclusion Compared with the traditional indicator of liver function (ALT,AST),L-FABP is the more sensitive indicator to monitor the hepatic ischemia-reperfusion injury,and it consistents with the changes in the liver tissue pathology.%目的 探讨血清

  6. 应用S-腺苷蛋氨酸预处理在大鼠肝脏缺血再灌注损伤中的保护作用%The Protective Effect of S-adenosylmethionine on Liver Ischemia Reperfusion Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    柯文波; 郑启昌; 何亮; 李俊; 熊俊

    2011-01-01

    Objective To investigate the protection and mechanism of S-adenosylmethionine pretreatment on hepatic ischemia- reperfusion injury in rats. Methods Three groups of animals ( n = 54) were studied: Sham group (laparotomy alone), ischemia repefusion( I/R) and pre-treatment with S-adenosylmethionine(SAM)group. Pretreatment group received intraperitoneal injection of SAM 2 hr before ischemia. Blood was sampled from inferior venacava at 0,3 and 6 hr after reperfusion and tested for ALT,AST,liver tissue were detected for oxidative stress reactive oxygen species(ROS) , mitochondrial energy metabolism of adenosine triphosphate( ATP) .energy charge( EC) and preparation of pathology in mitochondrial ultrastructure was observed under transmission electron microscope. Results SAM group ALT, AST, ROS were significantly lower than in the I/R group while the ATP, EC was significantly higher than in the I/R group. This changes were statistically significant(P < 0.01 ). In I/R group there is a significant damage of ultrastructure namely the mitochondria which was reduced in number and swelling of the apparent crest blurred the low-density matix. The SAM group when compared with 1/R group have significant reduction in the degree of injury. Conclusion SAM inhibits the mitochondrial lipid peroxidation, increases ATP production and ultimately improves the level of mitochondrial energy metabolism,which effectively reduces the liver ischemia-reperfusion injury.%目的 研究S-腺苷蛋氨酸预处理对大鼠肝脏缺血再灌注损伤的保护作用及其机制.方法 将54只大鼠随机分为假手术组、缺血再灌注(I/R)组和S-腺苷蛋氨酸预处理(S-arleneyslmethioaine,SAM)组.SAM组大鼠缺血前2 h行腹腔注射SAM预处理.假手术组仅做分离,不阻断肝门;其余两组大鼠均在阻断肝门左、中叶肝蒂60 min后复流,并于再灌注0、3和6 h抽取下腔静脉血检测ALT、AST;切取肝组织检测氧化应激活性氧(ROS)、线粒体能量代谢指

  7. Dataset on force measurements of needle insertions into two ex-vivo human livers.

    Science.gov (United States)

    de Jong, Tonke L; Dankelman, Jenny; van den Dobbelsteen, John J

    2017-04-01

    A needle-tissue interaction experiment has been carried out, by inserting the inner needle of a trocar needle into two ex-vivo human livers. The dataset contains the forces that act on the needle during insertion and retraction into the livers. In addition, a MATLAB code file is included that provides base-level analysis of the data and generates force-position diagrams of the needle insertions. The dataset is available on Mendeley Data (do1i:10.17632/94s7xd9mzt.2), and is made publicly available to enable other researchers to use it for their own research purposes. For further interpretation and discussion of the data, one is referred to the associated research article entitled "PVA matches human liver in needle-tissue interaction" de Jong et al., 2017.

  8. Direct measurement of the initial proton extrusion to oxygen uptake ratio accompanying succinate oxidation by rat liver mitochondria.

    OpenAIRE

    Setty, O H; Shrager, R I; Bunow, B; Reynafarje, B; Lehninger, A L; Hendler, R W

    1986-01-01

    The problem of obtaining very early ratios for the H+/O stoichiometry accompanying succinate oxidation by rat liver mitochondria was attacked using new techniques for direct measurement rather than extrapolations based on data obtained after mixing and the recovery of the electrode from initial injection of O2. Respiration was quickly initiated in a thoroughly mixed O2-containing suspension of mitochondria under a CO atmosphere by photolysis of the CO-cytochrome c oxidase complex-. Fast respo...

  9. Ischemia-driven angiogenesis.

    Science.gov (United States)

    Dor, Y; Keshet, E

    1997-11-01

    New blood vessels usually develop in places where they are most needed. A prime example of neovascularization representing a positive feedback response to insufficient perfusion is the development of collateral blood vessels in the ischemic myocardium and leg. The recent discoveries of hypoxia-inducible transcription and angiogenic factors have provided important mechanistic links between the metabolic consequences of ischemia and compensatory angiogenesis. Vascular endothelial growth factor (VEGF) has emerged as the key mediator of ischemia-driven angiogenesis. Environmental stresses, including hypoxia, hypoglycemia, and hypoferremia, upregulate VEGF expression at both the transcriptional and posttranscriptional levels. VEGF acts in turn on adjacent vascular beds expressing cognate receptors and induces sprouting and capillary growth toward the ischemic tissue. In addition to expanding the vasculature at sites where existing vessels have been occluded or obliterated, VEGF also functions to match the vascular density according to development and physiologic increases in oxygen consumption. Fine adjustment of the vasculature includes a step of oxygen-regulated vascular pruning mediated by VEGF in its capacity as a survival factor for newly formed vessels. Pathologic settings of ischemia-driven angiogenesis include a major component of stress-induced angiogenesis during tumor neovascularization and abnormal vessel growth associated with retinopathies. The latter represents an excessive angiogenic response to conditions of severe retinal ischemia. Further insights into the mechanism of stress-induced angiogenesis are likely to suggest new ways to augment growth of collateral vessels and to restrain unwarranted neovascularization in tumors and retinopathies. (Trends Cardiovasc Med 1997;7:289-294). © 1997, Elsevier Science Inc.

  10. Comparative Study on the Effect of Plantago psyllium and Ocimum basilicum Seeds on Anthropometric Measures in Nonalcoholic Fatty Liver Patients

    Science.gov (United States)

    Akbarian, Shahab-Aldin; Asgary, Sedigheh; Feizi, Awat; Iraj, Bijan; Askari, Gholamreza

    2016-01-01

    Background: Due to the attribution of fatty liver with some chronic diseases such as obesity, finding a way to control obesity can be useful for the management of fatty liver. This study was performed to assess the effects of Plantago psyllium (PP) and Ocimum basilicum (OB) on anthropometric measurements in people with hepatic steatosis. Methods: All patients with nonalcoholic fatty liver disease (NAFLD) were enrolled in this four-arm parallel, randomized, and single blind trial. They randomly assigned into four groups receiving (1) OB 10 g/day; (2) PP 10 g/day; (3) mix of OB and PP 10 g/day; and (4) control group without placebo for 12 weeks. Anthropometric measurements were assessed during study baseline and after 12 weeks intervention. The data were analyzed using paired sample t-test for within group and analysis of covariance for between groups. Results: In within group analysis, weight and body mass index show a significant reduction after 12 weeks intervention. In addition, soft lean mass and lean body mass were decreased in PP and mixed of PP and OB groups significantly; another group (OB) shows the same result for mass body fat. Although in intervention groups, we see considerable reduction, between group changes did not demonstrate the same consequences. Conclusions: The results of this study showed that administration of OB, PP, or mix of them for 12 weeks does not affect any of the anthropometric measures in NAFLD. PMID:27761216

  11. Liver Fat Measured by MR Spectroscopy: Estimate of Imprecision and Relationship with Serum Glycerol, Caeruloplasmin and Non-Esterified Fatty Acids.

    Science.gov (United States)

    France, Michael; Kwok, See; Soran, Handrean; Williams, Steve; Ho, Jan Hoong; Adam, Safwaan; Canoy, Dexter; Liu, Yifen; Durrington, Paul N

    2016-07-08

    Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantitative estimation of liver fat. Knowledge of its imprecision, which comprises biological variability and measurement error, is required to design therapeutic trials with measurement of change. The role of adipocyte lipolysis in ectopic fat accumulation remains unclear. We examined the relationship between liver fat content and indices of lipolysis, and determine whether lipolysis reflects insulin resistance or metabolic liver disease. Imprecision of measurement of liver fat was estimated from duplicate measurements by MRS at one month intervals. Patients provided fasting blood samples and we examined the correlation of liver fat with indices of insulin resistance, lipolysis and metabolic liver disease using Kendall Tau statistics. The coefficient of variation of liver fat content was 14.8%. Liver fat was positively related to serum insulin (T = 0.48, p = 0.042), homeostasis model assessment (HOMA)-B% (T = -0.48, p = 0.042), and body mass index (BMI) (T = 0.59, p = 0.012); and inversely related to HOMA-S% (T = -0.48, p = 0.042), serum glycerol (T = -0.59, p = 0.014), and serum caeruloplasmin (T = 0.055, p = 0.047). Our estimate of total variability in liver fat content (14.8%) is nearly twice that of the reported procedural variability (8.5%). We found that liver fat content was significantly inversely related to serum glycerol but not to non-esterified fatty acids (NEFA), suggesting progressive suppression of lipolysis. Reduction of caeruloplasmin with increasing liver fat may be a consequence or a cause of hepatic steatosis.

  12. Liver Fat Measured by MR Spectroscopy: Estimate of Imprecision and Relationship with Serum Glycerol, Caeruloplasmin and Non-Esterified Fatty Acids

    Directory of Open Access Journals (Sweden)

    Michael France

    2016-07-01

    Full Text Available Magnetic resonance spectroscopy (MRS is a non-invasive method for quantitative estimation of liver fat. Knowledge of its imprecision, which comprises biological variability and measurement error, is required to design therapeutic trials with measurement of change. The role of adipocyte lipolysis in ectopic fat accumulation remains unclear. We examined the relationship between liver fat content and indices of lipolysis, and determine whether lipolysis reflects insulin resistance or metabolic liver disease. Imprecision of measurement of liver fat was estimated from duplicate measurements by MRS at one month intervals. Patients provided fasting blood samples and we examined the correlation of liver fat with indices of insulin resistance, lipolysis and metabolic liver disease using Kendall Tau statistics. The coefficient of variation of liver fat content was 14.8%. Liver fat was positively related to serum insulin (T = 0.48, p = 0.042, homeostasis model assessment (HOMA-B% (T = −0.48, p = 0.042, and body mass index (BMI (T = 0.59, p = 0.012; and inversely related to HOMA-S% (T = −0.48, p = 0.042, serum glycerol (T = −0.59, p = 0.014, and serum caeruloplasmin (T = 0.055, p = 0.047. Our estimate of total variability in liver fat content (14.8% is nearly twice that of the reported procedural variability (8.5%. We found that liver fat content was significantly inversely related to serum glycerol but not to non-esterified fatty acids (NEFA, suggesting progressive suppression of lipolysis. Reduction of caeruloplasmin with increasing liver fat may be a consequence or a cause of hepatic steatosis.

  13. Protective effect of glycine on liver injury during liver transplantation

    Institute of Scientific and Technical Information of China (English)

    WANG Yao-sheng; YAN Ye-hong; ZOU Xun-feng

    2010-01-01

    @@ Multiple procedures of liver transplantation bring conditions producing cold ischemia-reperfusion (I/R) injury. During cold storage, the graft organ is subjected to cold ischemia, also known as hypoxia injury. After reperfusion, although hypoxic condition has been ameliorated, reoxygenation of the graft liver can produce not only reperfusion injury including generation of oxygen free radical, lipoperoxidation and calcium overload, but also aggravate the hypoxia damage, involving endothelial cell (EC) damage, Kupffer cell (KC) activation, and adherence of neutrophils and platelets to Ecs. Clinically, I/R injury is one of the major problems complicating liver transplantation, and can ultimately result in serious complications such as primary nonfunction and delayed graft function, which may lead to the need of urgent retransplantation. Therefore, the therapeutic strategies of attenuating graft I/R injury are clinically significant and might improve overall graft function and survival.

  14. Quercetin protects rat skeletal muscle from ischemia reperfusion injury.

    Science.gov (United States)

    Ekinci Akdemir, Fazile Nur; Gülçin, İlhami; Karagöz, Berna; Soslu, Recep

    2016-01-01

    In this study, we investigated the potential beneficial effects of quercetin on skeletal muscle ischemia reperfusion injury. Twenty-four Sprague-Dawley type rats were randomly divided into four groups. In the sham group, only gastrocnemius muscle were removed and given no quercetin. In ischemia group, all the femoral artery, vein and collaterals were occluded in the left hindlimb by applying tourniquate under general anaesthesia for three hours but reperfusion was not done. In the Quercetin + Ischemia reperfusion group, quercetin (200 mg kg(-1) dose orally) was given during one-week reoperation and later ischemia reperfusion model was done. Finally, gastrocnemius muscle samples were removed to measure biochemical parameters. The biomarkers, MDA levels, SOD, CAT and GPx activities, were evaluated related to skeletal muscle ischemia reperfusion injury. MDA levels reduced and SOD, CAT and GPx activities increased significantly in Quercetin + Ischemia reperfusion group. Results clearly showed that Quercetin have a protective role against oxidative damage induced by ischemia reperfusion in rats.

  15. 1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents.

    Directory of Open Access Journals (Sweden)

    Cilius Esmann Fonvig

    Full Text Available This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children.Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8-18 years.In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS, and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009 when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002. No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol.Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.

  16. Liver Stiffness Measurement among Patients with Chronic Hepatitis B and C

    DEFF Research Database (Denmark)

    Christiansen, Karen M; Mössner, Belinda K; Hansen, Janne F

    2014-01-01

    viral hepatitis and valid LSM using Fibroscan. Information about liver biopsy, antiviral treatment, and clinical outcome was obtained from medical records and national registers. The study included 845 patients: 597 (71%) with hepatitis C virus (HCV), 235 (28%) with hepatitis B virus (HBV) and 13 (2...

  17. Measurement of liver function for patients with cirrhosis by 13C-methacetin breath test compared with Child-Pugh score and routine liver function tests

    Institute of Scientific and Technical Information of China (English)

    LIU Yun-xiang; HUANG Liu-ye; WU Cheng-rong; CUI Jun

    2006-01-01

    @@ 13C-methacetin breath test was used for the evaluation of liver function, as for quantitative data could be achieved using this method, it had the characteristics of safety,quantification, and repetition and got recognition gradually through the world.1,2 We began this 13C-methacetin test to assess liver function of patients with cirrhosis from January 2002. The aim of this study was to explore the characteristic of this test for liver function evaluation and explore the correlation of this method with some clinical liver biochemical parameters and Child-Pugh score.

  18. Effects of hyperbaric oxygen (HBO, as pre-conditioning in liver of rats submitted to periodic liver ischemia/reperfusion Efeitos da oxigenoterapia hiperbárica como pré-condicionamento em fígados de ratos submetidos à lesão hepática de isquemia/reperfusão intermitente

    Directory of Open Access Journals (Sweden)

    Diego Elias da Silva Caldeira

    2013-01-01

    Full Text Available PURPOSE: to assess the effect of hyperbaric oxygen (HBO as pre-conditioning on periodic liver ischemia/reperfusion injury. METHODS: Thirty-six male Wistar rats were divided into 4 groups (SHAM, I/R , HBO-I/R and CONTROL. The surgical technique consisted of total clamping of the hepatic pedicle for 15 min followed by twice repeated reperfusion for 5 min (unclamping. HBO was applied in a collective chamber (simultaneous exposure of 4 rats directly pressurized with oxygen at 2 ATA for 60 min. Hepatic mitochondrial function was determined using samples of the median lobe obtained after exactly 5 min of reperfusion for the analysis of mitochondrial respiration based on the determination of states 3 and 4, the respiratory control ratio and the transition of mitochondrial permeability (mitochondrial swelling.Data were analyzed by the Mann-Whitney test and the level of significance was set at p OBJETIVO: Avaliar os efeitos da oxigenoterapia hiperbárica (HBO, como pré-condicionamento, em lesão hepática de isquemia/reperfusão intermitente. MÉTODOS: Foram avaliados 36 ratos Wistar machos, distribuídos em 4 grupos (SHAM, I/R , HBO - I/R e CONTROLE. A técnica operatória consistiu em pinçamento total do pedículo hepático durante 15min, seguido de reperfusão por 5 min (desclampeamento, por duas vezes. A aplicação de HBO foi realizada em câmara coletiva (exposição simultânea de 4 ratos diretamente pressurizada com oxigênio a 2ATA, durante 60min. Determinou-se a função mitocondrial hepática através de amostras do lobo mediano colhidas com exatos 5min de reperfusão para análise da respiração mitocondrial, através da determinação dos estados 3 e 4, razão de controle respiratório e transição de permeabilidade mitocondrial (intumescimento osmótico - swelling mitocondrial.Os resultados foram analisados pelo teste de Mann-Whitney e foi considerado significativo todo valor de p < 0,05. RESULTADOS: Houve diferença estatistica

  19. Measurement of liver iron concentration by superconducting quantum interference device biomagnetic liver susceptometry validates serum ferritin as prognostic parameter for allogeneic stem cell transplantation.

    Science.gov (United States)

    Jacobi, Nicole; Herich, Lena

    2016-10-01

    There are conflicting data regarding the role of serum ferritin (SF) as surrogate parameter for iron overload as an independent prognostic factor for outcome after allogeneic stem cell transplantation (SCT). Superconducting quantum interference device (SQUID) biomagnetic liver susceptometry, a noninvasive measurement of iron overload, allows measurement of the interference of an exteriorly applied small but highly constant magnetic field by the paramagnetic liver storage iron. By measuring the true iron load of patients through SQUID, we wanted to assess the effect of iron overload on patients undergoing SCT. We conducted a single-center retrospective analysis (1994-2010), comparing the effect of SF and liver iron content measured by SQUID shortly before transplantation on overall survival (OS), event-free survival (EFS), and transplant-related mortality (TRM) in 142 patients (median age 54.5 yr, range 5.6-75 yr) undergoing SCT (80% reduced intensity regimen). Patients were subdivided into five groups: myelodysplastic syndrome, de novo acute myeloid leukemia (AML), secondary AML, primary myelofibrosis, and others. Correlation between SF and SQUID was significant (r = 0.6; P 1000 ng/mL (P = 0.003). A significant association between SQUID and fungal infection was also seen (P = 0.004). For patients with SQUID ≥1000, the risk of proven fungal infection was increased 3.08-fold (95% CI 1.43-6.63). A similar association between SF >1000 and fungal infection was shown (P = 0.01). In univariate analysis, age was a prognostic factor for TRM (P = 0.034, HR 1.04, CI 1.00-1.08). SF ≥1000 was associated with OS (P = 0.033, HR 2.09, CI 1.06-4.11) and EFS (P = 0.016, HR 2.15, 95% CI 1.15-4.10). In multivariate analysis on EFS, only age and SF >1000 remained as independent factors (HR 1.027, P = 0.040, 95% CI 1.001-1.054 and HR 2.058, P = 0.034, 95% CI 1.056-4.008, respectively). The multivariate analysis on TRM left age and SQUID values ≥1000 in the final model (HR 1.045, P

  20. Liver stiffness measurement in cirrhotic patient — Implications of disease activity and treatment efficacy

    Directory of Open Access Journals (Sweden)

    Huang-Wei Xu

    2012-12-01

    Full Text Available Liver stiffness measurement (LSM is a noninvasive method for the diagnosis of hepatic fibrosis. The aim of this study was to evaluate the effects of hepatitis activity and antiviral therapy on LSM in cirrhotic patients. Consecutive patients with compensated hepatic cirrhosis were enrolled for LSM. The medical records of hepatitis activity and antiviral therapy before enrollment were reviewed. Patients were stratified into inactive, fluctuating, and active groups by serial change of alanine transaminase level. For chronic hepatitis C, patients were stratified into sustained virological response (SVR and non-SVR (NSVR by effect of antiviral treatment. LSM results were compared among different groups. A total of 163 patients (mean age = 57.2 ± 11.0 years were enrolled. The median (range LSM values were 9.6 (4.2–20.6, 10.25 (3.9–49.6, and 15.75 (4.8–61.5 kPa in the inactive, fluctuating, and active groups, respectively. Patients in the active group had significantly higher LSM values. For chronic hepatitis C, median (range LSM values were 16.6 (8.1–61.5, 22.9 (11.1–37.4, and 11.2 (3.9–27.0 kPa in patients without antiviral therapy, in NSVR, and in SVR groups, respectively. Patients with SVR had significantly lower LSM values. For chronic hepatitis B, median (range LSM values were 11.8 (5.1–46.6, 16.85 (4.2–48, and 10.6 (4.3–46.4 kPa kPa in patients without oral nucleos(tide analogue (NA therapy, with NA < 12, and ≧12 months, respectively. There was a significantly lower LSM value in patients with NA therapy≧12 months. There were low LSM values in cirrhotic patients without hepatitis activity, as well as with SVR in chronic hepatitis C and long-term NA therapy in chronic hepatitis B.

  1. sup 31 P spin-lattice relaxation time measurements in biological systems; Heart, liver, kidney and erythrocytes of rat

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Eiji; Maeda, Munehiro; Kuki, Satoru; Tsukamoto, Kenji; Kawakami, Tsuyoshi; Seo, Yoshiteru; Murakami, Masataka; Watari, Hiroshi (National Inst. for Physiological Sciences, Okazaki, Aichi (Japan))

    1989-08-01

    Spin-lattice relaxation time (T{sub 1}) of phosphorus compounds in the perfused heart, liver, kidney and erythrocytes of rats were measured by the DESPOT (Driven-equilibrium single-pulse observation of T{sub 1}) method at 8.45 T. This method is a rapid and accurate technique for the measurement of T{sub 1} values. T{sub 1} values of phosphomonoesters (PME), 2, 3-diphosphoglycerate (DPG), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and three phosphates of ATP were ranged from 0.15 {plus minus} 0.02 sec (beta-ATP in the liver) to 8.5 {plus minus} 1.6 sec (PDE in the kidney). T{sub 1} value of beta-ATP in the liver was 1/4-1/5 of those in the mandibular gland, heart, erythrocytes and kidney. T{sub 1} values obtained from biological materials are useful for selecting the optimal pulse repetition times and pulse angles to maximize the signal-to-noise ratio of {sup 13}P spectra, and for correcting distortions of signal intensities in the spectra. (author).

  2. Effects of Kupffer cell inactivation on graft survival and liver regeneration after partial liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    Hang-Yu Luo; Shan-Fang Ma; Ji-Fu Qu; De-Hu Tian

    2015-01-01

    BACKGROUND: Gadolinium chloride (GdCl3) selectively in-activates Kupffer cells and protects against ischemia/reperfu-sion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplan-tation (PLTx) is not clear. This study was to investigate the role of GdCl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process. METHODS: PLTx (30% partial liver transplantation) was per-formed using Kamada's cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose (5 mg/kg) and high-dose (10 mg/kg) GdCl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regen-eration by PCNA staining and BrdU uptake, apoptosis by TU-NEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting. RESULTS: GdCl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine amino-transferase and aspartate aminotransferase (P>0.05). GdCl3 pretreatment induced apoptosis and inhibited IL-6 overex-pression and STAT3 phosphorylation after PLTx in graft tissues. CONCLUSION: Kupffer cells may contribute to the liver re-generation after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway.

  3. Ischemia and hepatic reperfusion: is it possible to reduce hepatic alterations?

    Science.gov (United States)

    Lanteri, Raffaele; Greco, Raffaele; Licitra, Edelweiss; Di Benedetto, Fabrizio; Li Destri, Giovanni; Di Cataldo, Antonio

    2003-01-01

    Our aim was to evaluate liver damage after ischemia and reperfusion, and at the same time test the effectiveness of some drugs in preventing these alterations. For this study, we utilized 50 rats divided into four groups: three underwent hepatic ischemia through occlusion of the portal vein and hepatic artery for 30 min, and one underwent a sham operation. In all groups, hepatic enzymes and bilirubine were tested at 2 h, 3 h, 4 h, 24 h, and 30 h. The drugs utilized were: L-arginine, donor of nitric oxide, and L-canavanine, inhibitor of nitric oxide synthase (NOS). Our data showed that the drugs tested could make an improvement in hepatic function after ischemia/reperfusion, preventing its damage. These preliminary results could suggest a clinical application in order to prolong ischemic period during liver transplantation or liver resection in cirrhotic patients.

  4. Effect of pyrrolidine dithiocarbamate on hepatic vascular stress gene expression during ischemia and reperfusion.

    Science.gov (United States)

    Lee, Chan-Ho; Kim, Sung-Ho; Lee, Sun-Mee

    2008-10-24

    Pyrrolidine dithiocarbamate, an antioxidant and a potent inhibitor of nuclear factor-kappa B (NF-kappaB), is known to have protective effect against ischemia and reperfusion injury. This study examined the cytoprotective mechanism of pyrrolidine dithiocarbamate against the microcirculatory failure caused by hepatic ischemia and reperfusion. Rats were subjected to 60 min of hepatic ischemia followed by 5 h of reperfusion. Pyrrolidine dithiocarbamate (100 mg/kg) or the vehicle was administered intraperitoneally 24 h before ischemia. The level of serum aminotransferases and hepatic lipid peroxides significantly increased, and the glutathione contents fell in the ischemia/reperfusion group. Pyrrolidine dithiocarbamate prevented the increase in the level of serum enzymes and hepatic lipid peroxides, and the decrease in the glutathione contents. The NF-kappaB DNA-binding activity was inhibited by a pre-treatment with pyrrolidine dithiocarbamate. Ischemia and reperfusion significantly increased the mRNA expression of the endothelin-1 and endothelin ET(B) receptor, which was prevented by pyrrolidine dithiocarbamate. There were significant increases in the mRNA expressions of inducible nitric oxide synthase, tumor necrosis factor-alpha, and cyclooxygenase-2, in the livers after ischemia and reperfusion. These increases were attenuated by the pyrrolidine dithiocarbamate treatment. In a rat model of hepatic ischemia and reperfusion, our results suggest that the hepatoprotective actions of pyrrolidine dithiocarbamate may be mediated in part through the modulation of imbalanced expression of vascular stress genes.

  5. Ambroxol alleviates hepatic ischemia reperfusion injury by antioxidant and antiapoptotic pathways.

    Science.gov (United States)

    Jiang, K; Wang, X; Mao, X; Lao, H; Zhang, J; Wang, G; Cao, Y; Tong, I; Zhang, F

    2013-01-01

    Hepatic ischemia/reperfusion (HI/R) injury is a common pathologic process caused by many clinical settings, such as liver resection, liver transplantation, hypovolemic shock, and trauma. The use of ambroxol, which acts as a mucolytic agent, provides antioxidant and anti-inflammatory effects. A rat model of HI/R was induced by clamping the hepatic artery, the hepatoportal vein, and the bile duct with a vascular clamp for 30 minutes followed by reperfusion for 6 hours under anesthesia. The sham group underwent laparotomy without hepatic ischemia. The ambroxol group was injected into the tail vein in the ambroxol group 5 minutes before HI/R at one dose of 20 mg/kg, 80 mg/kg, or 140 mg/kg. The control group underwent the same procedure as the ambroxol group but with administration of physiological saline. Liver injury was evaluated by biochemical and histopathological examinations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in serum samples. Superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA), and glutathione (GSH) were spectrophotometrically measured. Furthermore, caspase-3, Bcl-2 and Bax expression as well as the level of c-Jun N-terminal kinases (JNK) we estimated activation. Wistar rats that received 20, 80 mg or 140 mg of ambroxol displayed reduced HI/R injury compared with controls. Use of ambroxol reduced the histologic injury and significantly decreased serum ALT and AST levels. In addition, ambroxol enhanced the activity of hepatic tissue SOD and CAT, increasing GSH but decreasing MDA tissue contents. In the ambroxol group, Bcl-2 expression was increased and Bax and caspase-3 decreased compared with the controls. Furthermore, ambroxol reduced levels of phosphorylated JNK (P ambroxol attenuated rat HI/R through upregulation of intracellular antioxidant and anti-apoptotic signaling pathways. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Prospective comparison of liver stiffness measurements between two point wave elastography methods: Virtual ouch quantification and elastography point quantification

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hyun Suk; Lee, Jeong Min; Yoon, Jeong Hee; Lee, Dong Ho; Chang, Won; Han, Joon Koo [Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-09-15

    To prospectively compare technical success rate and reliable measurements of virtual touch quantification (VTQ) elastography and elastography point quantification (ElastPQ), and to correlate liver stiffness (LS) measurements obtained by the two elastography techniques. Our study included 85 patients, 80 of whom were previously diagnosed with chronic liver disease. The technical success rate and reliable measurements of the two kinds of point shear wave elastography (pSWE) techniques were compared by χ{sup 2} analysis. LS values measured using the two techniques were compared and correlated via Wilcoxon signed-rank test, Spearman correlation coefficient, and 95% Bland-Altman limit of agreement. The intraobserver reproducibility of ElastPQ was determined by 95% Bland-Altman limit of agreement and intraclass correlation coefficient (ICC). The two pSWE techniques showed similar technical success rate (98.8% for VTQ vs. 95.3% for ElastPQ, p = 0.823) and reliable LS measurements (95.3% for VTQ vs. 90.6% for ElastPQ, p = 0.509). The mean LS measurements obtained by VTQ (1.71 ± 0.47 m/s) and ElastPQ (1.66 ± 0.41 m/s) were not significantly different (p = 0.209). The LS measurements obtained by the two techniques showed strong correlation (r = 0.820); in addition, the 95% limit of agreement of the two methods was 27.5% of the mean. Finally, the ICC of repeat ElastPQ measurements was 0.991. Virtual touch quantification and ElastPQ showed similar technical success rate and reliable measurements, with strongly correlated LS measurements. However, the two methods are not interchangeable due to the large limit of agreement.

  7. Why and how to measure renal function in patients with liver disease.

    Science.gov (United States)

    Piano, Salvatore; Romano, Antonietta; Di Pascoli, Marco; Angeli, Paolo

    2017-01-01

    Patients with advanced liver disease frequently have impaired renal function. Both acute kidney injury (AKI) and chronic kidney disease (CKD) are quite common in patients with cirrhosis and both are associated with a worse prognosis in these patients. A careful assessment of renal function is highly important in these patients to help physicians determine their diagnosis, prognosis and therapeutic management and to define transplantation strategies (liver transplantation alone vs simultaneous liver and kidney transplantation). Although they are still widely used in clinical practice, conventional biomarkers of renal function such as serum creatinine have several limitations in these patients. Recent progress has been made in the evaluation of renal function and new diagnostic criteria for AKI have been proposed. However, certain issues such as the noninvasive assessment of the glomerular filtration rate and/or improvement in the differential diagnosis between hepatorenal syndrome and acute tubular necrosis must still be addressed. The purposes of this paper are: (i) to highlight the importance of the evaluation of renal function in patients with cirrhosis; (ii) to review the state of the art in the assessment of renal function in these patients as well as advances that we expect will be made to improve the accuracy of available tools. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Oligodendrogenesis after Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Ruilan eZhang

    2013-10-01

    Full Text Available AbstractNeural stem cells in the subventricular zone (SVZ of the lateral ventricle of adult rodent brain generate oligodendrocyte progenitor cells (OPCs that disperse throughout the corpus callosum and striatum where some of OPCs differentiate into mature oligodendrocytes. Studies in animal models of stroke demonstrate that cerebral ischemia induces oligodendrogenesis during brain repair processes. This article will review evidence of stroke-induced proliferation and differentiation of OPCs that are either resident in white matter or are derived from SVZ neural progenitor cells and of therapies that amplify endogenous oligodendrogenesis in ischemic brain.

  9. Optical properties of normal and thermally coagulated chicken liver tissue measured ex-vivo with diffuse reflectance

    Science.gov (United States)

    Hafeez-Ullah; Atif, M.; Firdous, S.; Mehmood, M. S.; Hamza, M. Y.; Imran, M.; Hussain, G.; Ikram, M.

    2011-02-01

    The purpose of the present study is to determine the optical properties of normal and thermally coagulated chicken liver at 720, 740, 770, 810, 825 and 840 nm wavelengths of laser irradiation. So, we were able to evaluate these optical properties (absorption and scattering coefficients) with ex-vivo study using Kubelka Munk Model (KMM) from the radial dependence of the diffuse reflectance with femtosecond pulsed laser in near IR region. These coefficients were significantly increased with coagulation. The penetration depths of the diffused light have been reported to a maximum value of 8.12 ± 0.36 mm in normal liver and 2.49 ± 0.17 mm in coagulated liver at 840 nm showing increasing behavior towards IR region. The Monte Carlo simulation was used to check the theoretical validation of measured optical properties of the tissue that showed a good match with our experimental results. We believe that these differences in optical properties will be helpful for the understanding arid optimal use of laser applications in medicine and differential diagnosis of tissues by using different optical methods. Especially for the investigation of biological tissue for photodynamic therapy (PDT), the knowledge of the specific optical properties and their thermo-induced changes is important.

  10. Measuring the effect of a Western diet on liver tissue architecture by FLIM autofluorescence and harmonic generation microscopy.

    Science.gov (United States)

    Ranjit, Suman; Dvornikov, Alexander; Dobrinskikh, Evgenia; Wang, Xiaoxin; Luo, Yuhuan; Levi, Moshe; Gratton, Enrico

    2017-07-01

    The phasor approach to auto-fluorescence lifetime imaging was used to identify and characterize a long lifetime species (LLS) (~7.8 ns) in livers of mice fed with a Western diet. The size of the areas containing this LLS species depends on the type of diet and the size distribution shows Western diet has much larger LLS sizes. Combination of third harmonic generation images with FLIM identified the LLS species with fat droplets and the droplet size distribution was estimated. Second harmonic generation microscopy combined with phasor FLIM shows that there is an increase in fibrosis with a Western diet. A new decomposition in three components of the phasor plot shows that a Western diet is correlated with a higher fraction of free NADH, signifying more reducing condition and more glycolytic condition. Multiparametric analysis of phasor distribution shows that from the distribution of phasor points, a Western diet fed versus a low fat diet fed samples of mice livers can be separated. The phasor approach for the analysis of FLIM images of autofluorescence in liver specimens can result in discovery of new fluorescent species and then these new fluorescent species can help assess tissue architecture. Finally integrating FLIM and second and third harmonic analysis provides a measure of the advancement of fibrosis as an effect of diet.

  11. Plasma osteopontin in acute liver failure

    DEFF Research Database (Denmark)

    Srungaram, Praveen; Rule, Jody A; Yuan, He Jun

    2015-01-01

    BACKGROUND: Osteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function...... in the setting of massive hepatocyte injury. METHODS: OPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1....../mL; range 2.6-86.4). RA and SF post op patients had elevated OPN levels (37ng/mL and 198ng/mL respectively), well below those of the ALF patients. Median OPN levels were highest in acetaminophen (3603ng/mL) and ischemia-related ALF (4102ng/mL) as opposed to viral hepatitis (706ng/mL), drug-induced liver...

  12. Warm vs. cold perfusion techniques to rescue rodent liver grafts.

    Science.gov (United States)

    Schlegel, Andrea; Kron, Philipp; Graf, Rolf; Dutkowski, Philipp; Clavien, Pierre-Alain

    2014-12-01

    A variety of liver perfusion techniques have been proposed to protect liver grafts prior to implantation. We compared hypothermic and normothermic oxygenated perfusion techniques in a rat liver transplant model, using higher risk grafts obtained after cardiac arrest (DCD). Rat livers were subjected to 30 or 60 min in situ warm ischemia, without application of heparin. Livers were excised and stored for 4 h at 4°C, mimicking DCD organ procurement, followed by conventional organ transport. In experimental groups, DCD liver grafts received a 4 h normothermic oxygenated perfusion through the portal vein and the hepatic artery instead of cold storage. The perfusate consisted of either full blood or leukocyte-depleted blood (normothermic groups). Other livers underwent hypothermic oxygenated perfusion (HOPE) for 1 h after warm ischemia and 4 h cold storage (HOPE group). Liver injury was assessed during machine perfusion and after isolated liver reperfusion, and by orthotopic liver transplantation (OLT). DCD livers, subjected to normothermic perfusion, disclosed reduced injury and improved survival compared to cold storage after limited warm ischemia of 30 min (70%; 7/10), but failed to protect from lethal injury in grafts exposed to 60 min warm ischemia (0%; 0/10). This finding was consistent with Kupffer and endothelial cell activation in cold stored and normothermic perfused livers. In contrast, HOPE protected from hepatocyte and non-parenchymal cell injury and led to 90% (9/10) and 63% (5/8) animal survival after 30 and 60 min of donor warm ischemia, respectively. This is the first evidence that HOPE is superior to normothermic oxygenated perfusion in a clinically relevant model through modulation of the innate immunity and endothelial cell activation. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  13. The Hepatoprotective Effect of Sodium Nitrite on Cold Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Wei Li

    2012-01-01

    Full Text Available Liver ischemia-reperfusion injury is a major cause of primary graft non-function or initial function failure post-transplantation. In this study, we examined the effects of sodium nitrite supplementation on liver IRI in either Lactated Ringer's (LR solution or University of Wisconsin (UW solution. The syngeneic recipients of liver grafts were also treated with or without nitrite by intra-peritoneal injection. Liver AST and LDH release were significantly reduced in both nitrite-supplemented LR and UW preservation solutions compared to their controls. The protective effect of nitrite was more efficacious with longer cold preservation times. Liver histological examination demonstrated better preserved morphology and architecture with nitrite treatment. Hepatocellular apoptosis was significantly reduced in the nitrite-treated livers compared their controls. Moreover, liver grafts with extended cold preservation time of 12 to 24 hours demonstrated improved liver tissue histology and function post-reperfusion with either the nitrite-supplemented preservation solution or in nitrite-treated recipients. Interestingly, combined treatment of both the liver graft and recipient did not confer protection. Thus, nitrite treatment affords significant protection from cold ischemic and reperfusion injury to donor livers and improves liver graft acute function post-transplantation. The results from this study further support the potential for nitrite therapy to mitigate ischemia-reperfusion injury in solid organ transplantation.

  14. Liver kinetics of glucose analogs measured in pigs by PET: importance of dual-input blood sampling

    DEFF Research Database (Denmark)

    Munk, O L; Bass, L; Roelsgaard, K

    2001-01-01

    parameters, because of ignorance of the dual blood supply from the hepatic artery and the portal vein to the liver. METHODS: Six pigs underwent PET after [15O]carbon monoxide inhalation, 3-O-[11C]methylglucose (MG) injection, and [18F]FDG injection. For the glucose scans, PET data were acquired for 90 min....... Hepatic arterial and portal venous blood samples and flows were measured during the scan. The dual-input function was calculated as the flow-weighted input. RESULTS: For both MG and FDG, the compartmental analysis using arterial input led to systematic underestimation of the rate constants for rapid blood...

  15. Optical fluorescence spectroscopy to detect hepatic necrosis after normothermic ischemia: animal model

    Science.gov (United States)

    Romano, Renan A.; Vollet-Filho, Jose D.; Pratavieira, Sebastião.; Fernandez, Jorge L.; Kurachi, Cristina; Bagnato, Vanderlei S.; Castro-e-Silva, Orlando; Sankarankutty, Ajith K.

    2015-06-01

    Liver transplantation is a well-established treatment for liver failure. However, the success of the transplantation procedure depends on liver graft conditions. The tissue function evaluation during the several transplantation stages is relevant, in particular during the organ harvesting, when a decision is made concerning the viability of the graft. Optical fluorescence spectroscopy is a good option because it is a noninvasive and fast technique. A partial normothermic hepatic ischemia was performed in rat livers, with a vascular occlusion of both median and left lateral lobes, allowing circulation only for the right lateral lobe and the caudate lobe. Fluorescence spectra under excitation at 532 nm (doubled frequency Nd:YAG laser) were collected using a portable spectrometer (USB2000, Ocean Optics, USA). The fluorescence emission was collected before vascular occlusion, after ischemia, and 24 hours after reperfusion. A morphometric histology analysis was performed as the gold standard evaluation - liver samples were analyzed, and the percentage of necrotic tissue was obtained. The results showed that changes in the fluorescence emission after ischemia can be correlated with the amount of necrosis evaluated by a morphometric analysis, the Pearson correlation coefficient of the generated model was 0.90 and the root mean square error was around 20%. In this context, the laser-induced fluorescence spectroscopy technique after normothermic ischemia showed to be a fast and efficient method to differentiate ischemic injury from viable tissues.

  16. Apoptosis of rat liver in cold preser vation with custom-designed K YL solution

    Institute of Scientific and Technical Information of China (English)

    Li Li; Chun-Man Li; Bing-Yan Zhang; Ming-Dao Hu; Xiao-Yan Li; Jiang-Hua Ran; Ming Huang

    2007-01-01

    BACKGROUND:A suitable perfusate is very important in reducing various problems in liver preservation, prolonging the time of organ preservation and enhancing the quality of donor tissue. University of Wisconsin (UW) solution is the most successful solution for preserving multiple organs at present, but it has many shortcomings. We set out to develop a new liver preservation solution (KYL solution) and study its effects on apoptosis in rat liver undergoing cold preservation. METHODS: Using non-circulated isolated perfused rat liver (IPRL), we randomly preserved Sprague-Dawley rat livers for 0, 4, 8, 16, 24, and 48 hours with KYL solution or UW solution. The effects were assessed by measuring the content of free radicals in Krebs-Henseleit solution and the intracellular calcium content of hepatocytes, assessing hepatocellular apoptosis and related-gene expression, and observing the morphological changes in liver. To evaluate the protection by KYL and UW solutions in rat liver perfusion and preservation, we chosed normal saline for negative comparison. RESULTS: The intracellular calcium content of the liver preserved in KYL solution was less than that preserved in UW solution. At every different period of preservation, the malonaldehyde and superoxide dismutase content in Krebs-Henseleit solution, the percentage of apoptotic cells and the expression patterns of apoptosis-related-genes were similar in livers preserved in KYL and UW solutions. Morphological changes in the two groups were almost the same. The variables in both groups were better than those of livers preserved in normal saline. Both KYL and UW solutions protected rat liver from ischemia-reperfusion injury. CONCLUSIONS:KYL solution is superior to UW solution in preventing calcium overload. More severe hepatocyte damage may appear in the KYL group than in the UW group and the effect of KYL solution on apoptosis in rat liver preservation is similar to that of UW solution.

  17. Defining the Most Accurate Measurable Dimension(s of the Liver in Predicting Liver Volume Based on CT Volumetery and Reconstruction

    Directory of Open Access Journals (Sweden)

    Reza Saadat Mostafavi

    2010-05-01

    Full Text Available Background/Objective: The presence of liver volume has a great effect on diagnosis and management of different diseases such as lymphoproliferative conditions. "nPatients and Methods: Abdominal CT scan of 100 patients without any findings for liver disease (in history and imaging was subjected to volumetry and reconstruction. Along with the liver volume, in axial series, the AP diameter of the left lobe (in midline and right lobe (mid-clavicular and lateral maximum diameter of the liver in the mid-axiliary line and maximum diameter to IVC were calculated. In the coronal mid-axillary and sagittal mid-clavicular plane, maximum superior-inferior dimensions were calculated with their various combinations (multiplying. Regression analysis between dimensions and volume were performed. "nResults: The most accurate combination was the superior inferior sagittal dimension multiplied by AP diameter of the right lobe (R squared 0.78, P-value<0.001 and the most solitary dimension was the lateral dimension to IVC in the axial plane (R squared 0.57, P-value<0.001 with an interval of 9-11cm for 68% of normal. "nConclusion: We recommend the lateral maximum diameter of liver from surface to IVC in the axial plane in ultrasound for liver volume prediction with an interval of 9-11cm for 68% of normal. Out of this range is regarded as abnormal.

  18. Split liver transplantation.

    Science.gov (United States)

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  19. Accurate in vivo dielectric properties of liver from 500 MHz to 40 GHz and their correlation to ex vivo measurements.

    Science.gov (United States)

    Farrugia, L; Wismayer, P Schembri; Mangion, L Zammit; Sammut, C V

    2016-01-01

    In this article, we report on the characterization of the dielectric properties of in vivo rat liver at 36.4°C from 500 MHz up to 40 GHz with less than 5% uncertainty. The measured data were fitted to a Cole-Cole model and dielectric parameters are presented together with their respective 95% confidence interval. The root mean square error is 0.42. Moreover, ex vivo measurements were conducted in situ at 1, 2, 4 and 6 min after animal death and are compared to in vivo measurements. The results show that immediate changes in [Formula: see text]and [Formula: see text] are within experimental uncertainty, and therefore changes between in vivo and published ex vivo dielectric properties can be attributed to tissue hydration.

  20. Metabolic response of perfused livers to various oxygenation conditions.

    Science.gov (United States)

    Orman, Mehmet A; Ierapetritou, Marianthi G; Androulakis, Ioannis P; Berthiaume, Francois

    2011-12-01

    Isolated liver perfusion systems have been used to characterize intrinsic metabolic changes in liver as a result of various perturbations, including systemic injury, hepatotoxin exposure, and warm ischemia. Most of these studies were done using hyperoxic conditions (95% O(2)) but without the use of oxygen carriers in the perfusate. Prior literature data do not clearly establish the impact of oxygenation, and in particular that of adding oxygen carriers to the perfusate, on the metabolic functions of the liver. Therefore, herein the effects of oxygen delivery in the perfusion system on liver metabolism were investigated by comparing three modes of oxygenation. Rat livers were perfused via the portal and hepatic veins at a constant flow rate of 3 mL/min/g liver in a recirculating perfusion system. In the first group, the perfusate was equilibrated in a membrane oxygenator with room air (21% O(2)) before entering the liver. In the second group, the perfusate was equilibrated with a 95% O(2)/5% CO(2) gas mixture. In the third group, the perfusate was supplemented with washed bovine red blood cells (RBCs) at 10% hematocrit and also equilibrated with the 95% O(2)/5% CO(2) gas mixture. Oxygen and CO(2) gradients across the liver were measured periodically with a blood gas analyzer. The rate of change in the concentration of major metabolites in the perfusate was measured over time. Net extracellular fluxes were calculated from these measurements and applied to a stoichiometric-based optimization problem to determine the intracellular fluxes and active pathways in the perfused livers. Livers perfused with RBCs consumed oxygen at twice the rate observed using hyperoxic (95% O(2)) perfusate without RBCs, and also produced more urea and ketone bodies. At the flow rate used, the oxygen supply in perfusate without RBCs was just sufficient to meet the average oxygen demand of the liver but would be insufficient if it increased above baseline, as is often the case in response to

  1. Glutamine supplemented parenteral nutrition prevents intestinal ischemia- reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Guo-Hao Wu; Hao Wang; Yan-Wei Zhang; Zhao-Han Wu; Zhao-Guang Wu

    2004-01-01

    AIM: To examine whether glutamine prevents the injury to the intestinal mucosa after intestinal ischemia-reperfusion (I/R) in rats.METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups: a standard parenteral nutrition (PN)group (n = 10); an I/R-PN group (n = 10); an I/R-glutamine enriched PN (I/R-Gln) group (n = 10). The superior mesenteric artery (SMA) was clamped. After 60 min of ischemia, reperfusion was initiated and infusion was started. All rats received isocaloric and isonitrogenous nutritional support for 48 h. Spleen, liver, mesenteric lymph nodes (MLN), and intestinal segments were removed for morphological and biochemical analyses, and blood samples were collected for bacterial culture and measurement of endotoxin levels.The permeability of intestinnal mucosa was assayed by measurement of D-(-)-lactate levels in plasma.RESULTS: In I/R-PN group, extensive epithelial atrophy was observed, mucosal thickness, villous height, crypt depth and villous surface area were decreased significantly compared with PN group, whereas these findings did not occur in the I/R-Gln group. The incidence of intestinal bacterial translocation to spleen, liver, MLN, and blood was significantly higher in I/R-PN group than that in other groups.Plasma endotoxin levels significantly increased in the I/R-PN group compared with the I/R-Gln group. Remarkably higher values of D-(-)-lactate were also detected in PN group compared with that in I/R-Gln group.CONCLUSION: Glutamine protects the morphology and function of intestinal mucosa from injury after I/R in rats.

  2. 普拉克索在减轻小鼠肝缺血再灌注损伤中应用%Pramipexole reduce liver ischemia-reperfusion injury in mice by protecting the mitochondrial function

    Institute of Scientific and Technical Information of China (English)

    李培磊; 王天宇; 展洋洋; 傅志仁

    2016-01-01

    Objective To investigate the influence of pramipexole(PPX)in liver ishemia reperfusion(I/ R). Methods The healthy male mice were ramdonly divided into 4 groups:Sham + DMSO group,Sham + PPX group,I/ R + DMSO group,I/ R + PPX group. The mice in Sham groups underwent sham procedure,while the mice in I/ R groups underwent liver I/ R with Pringle's methods. DMSO and PPX(1 mg/ kg)were intraperitoneal injected 30 minutes before operation. Liver function was detected by examining the serum ALT/AST,the morphological changes and apoptosisin in liver tissue were observed 3,6,24 hours after reperfusion,the level of MDA,HNE, SOD were examinded to assess the level of oxidative stress in the liver. RCR,ADP/ O and level of ATP were detected to assess the mi-tochondrial function in the liver. Results Compared with I/ R + DMSO group,mice in I/ R + PPX group displayed significantly pre-served liver funcion as characterized by reduced serum ALT/ AST level,less histological damage and apoptosisin. Mechanistic studies revealed that the protection effect of PPX was associated with protection of hepatic mitochondrial function as manifested by oxidative stress index and the level of RCR、ADP/ O、ATP. Conclusion Our results indicate that PPX might provide protection for livers against I/ R-induced injury by protecting hepatic mitochondrial function.%目的:探讨普拉克索(PPX)对小鼠缺血再灌注(I/ R)后肝损伤的影响及机制。方法选择健康、雄性 C57BL/6小鼠40只,随机分为4组:Sham + DMSO 组、Sham + PPX 组、I/ R + DMSO 组、I/ R + PPX 组,每组各10只。Sham 组小鼠仅接受中线开腹、游离肝十二指肠韧带及关腹操作;I/ R 通过 Pringle 法诱导肝缺血再灌注模型。DMSO 和 PPX(1 mg/ kg)均在术前30 min腹腔注射。再灌注3、6、24 h 后检测血清谷丙转氨酶/谷草转氨酶(ALT/ AST)水平,观察肝形态学变化;TUNEL 染色了解肝细胞凋亡情况;通过试剂

  3. Does experience play a role in the ability to perform liver stiffness measurements by means of supersonic shear imaging (SSI)?

    Science.gov (United States)

    Grădinaru-Taşcău, Oana; Sporea, Ioan; Bota, Simona; Jurchiş, Ana; Popescu, Alina; Popescu, Mădălina; Şirli, Roxana; Szilaski, Milana

    2013-09-01

    The aim of this study was to identify if the experience of the examiner does plays a role in the ability to perform liver stiffness (LS) measurements by means of supersonic shear imaging (SSI) due to the lack of recommendation regarding this issue. The study included 371 consecutive subjects (42% men and 58% women, with a median age of 48 years, ranging between 17-85 years) with or without hepatopathies, in which LS was evaluated with an AixplorerTM ultrasound system (SuperSonic Imagine S.A., Aix-en-Provence, France). Reliable LS measurements by means of SSI were defined as the median value of 5 LS measurements expressed in kilopascals (kPa). The SSI measurements were performed by a novice (with less than 300 abdominal ultrasound examinations performed) or by a more experienced operator (with approximately 500 ultrasound examinations performed). The results of both operators were compared. The novice performed 57.4% and the more experienced operator 42.6% of the SSI measurements. The more experienced operator had a higher rate of reliable examinations as compared with the novice: 87.4% vs. 72.8% (p =0.001). The rate of reliable measurements was similar for novice and experienced operator in patients with a normal weight (BMI SSI and leads to achieving more reliable LS measurements especially in obese subjects.

  4. Simple Reversed-Phase HPLC Method with Spectrophotometric Detection for Measuring Acetaminophen-Protein Adducts in Rat Liver Samples

    Directory of Open Access Journals (Sweden)

    Miteshkumar Acharya

    2012-01-01

    Full Text Available A simple reversed-phase HPLC method for measuring hepatic levels of acetaminophen- (APAP- protein adduct following an overdose of APAP was developed. An aliquot of liver homogenate in phosphate-buffered saline pH 7.4 (PBS was placed on a Nanosep centrifugal device, which was centrifuged to obtain a protein residue. This residue was incubated with a solution of p-aminobenzoic acid (PABA, the internal standard, and bacterial protease in PBS, transferred to a Nanosep centrifugal device, and centrifuged. A 100 μL portion of the filtrate was analyzed on a YMC-Pack ODS-AMQ C18 column, using 100 mM potassium dihydrogen phosphate-methanol-acetic acid (100 : 0.6 : 0.1 as the mobile phase, a flow rate of 1 mL/min, and photometric detection at 254 nm. PABA and APAP-cystein-S-yl (APAP-Cys eluted at ~14.7 min and 22.7 min, respectively. Method linearity, based on on-column concentrations of APAP-Cys, was observed over the range 0.078–40 μg. Recoveries of APAP-Cys from spiked blank liver homogenates ranged from ~83% to 91%. Limits of detection and of quantification of APAP-Cys, based on column concentrations, were 0.06 μg and 0.14 μg, respectively. RSD values for interday and intraday analyses of a blank liver homogenate spiked with APAP-Cyst at three levels were, in all cases, ≤1.0% and <1.5%, respectively. The proposed method was found appropriate for comparing the antidotal properties of N-acetylcysteine and taurine in a rat model of APAP poisoning.

  5. Effect of electromagnetic radiofrequency radiation on the rats' brain, liver and kidney cells measured by comet assay.

    Science.gov (United States)

    Trosić, Ivancica; Pavicić, Ivan; Milković-Kraus, Sanja; Mladinić, Marin; Zeljezić, Davor

    2011-12-01

    The goal of study was to evaluate DNA damage in rat's renal, liver and brain cells after in vivo exposure to radiofrequency/microwave (Rf/Mw) radiation of cellular phone frequencies range. To determine DNA damage, a single cell gel electrophoresis/comet assay was used. Wistar rats (male, 12 week old, approximate body weight 350 g) (N = 9) were exposed to the carrier frequency of 915 MHz with Global System Mobile signal modulation (GSM), power density of 2.4 W/m2, whole body average specific absorption rate SAR of 0.6 W/kg. The animals were irradiated for one hour/day, seven days/week during two weeks period. The exposure set-up was Gigahertz Transversal Electromagnetic Mode Cell (GTEM--cell). Sham irradiated controls (N = 9) were apart of the study. The body temperature was measured before and after exposure. There were no differences in temperature in between control and treated animals. Comet assay parameters such as the tail length and tail intensity were evaluated. In comparison with tail length in controls (13.5 +/- 0.7 microm), the tail was slightly elongated in brain cells of irradiated animals (14.0 +/- 0.3 microm). The tail length obtained for liver (14.5 +/- 0.3 microm) and kidney (13.9 +/- 0.5 microm) homogenates notably differs in comparison with matched sham controls (13.6 +/- 0.3 microm) and (12.9 +/- 0.9 microm). Differences in tail intensity between control and exposed animals were not significant. The results of this study suggest that, under the experimental conditions applied, repeated 915 MHz irradiation could be a cause of DNA breaks in renal and liver cells, but not affect the cell genome at the higher extent compared to the basal damage.

  6. A metabolic index of ischemic injury for perfusion-recovery of cadaveric rat livers.

    Directory of Open Access Journals (Sweden)

    Sinem Perk

    Full Text Available With over 110,000 patients waiting for organ transplantation, the current crisis in organ transplantation is based on a lack of donors after brain-death (DBD. A very large alternative pool of donor organs that remain untapped are the donors after cardiac death (DCD, recovered after cardiac activity has ceased and therefore sustained some ischemic injury. Machine perfusion has been proposed as a novel modality of organ preservation and treatment to render such cadaveric organs, and in particular livers, transplantable. Two key issues that remain unaddressed are how to assess whether a DCD liver is damaged beyond repair, and whether machine perfusion has rendered an injured organ sufficiently viable for transplantation. In this work, we present a metabolic analysis of the transient responses of cadaveric rat livers during normothermic machine perfusion (NMP, and develop an index of ischemia that enables evaluation of the organ ischemic injury level. Further, we perform a discriminant analysis to construct a classification algorithm with >0.98 specificity to identify whether a given perfused liver is ischemic or fresh, in effect a precursor for an index of transplantability and a basis for the use of statistical process control measures for automated feedback control of treatment of ischemic injury in DCD livers. The analyses yield an index based on squared prediction error (SPE as log(SPE >1.35 indicating ischemia. The differences between metabolic functions of fresh and ischemic livers during perfusion are outlined and the metabolites that varied significantly for ischemic livers are identified as ornithine, arginine, albumin and tyrosine.

  7. A metabolic index of ischemic injury for perfusion-recovery of cadaveric rat livers.

    Science.gov (United States)

    Perk, Sinem; Izamis, Maria-Louisa; Tolboom, Herman; Uygun, Basak; Berthiaume, Francois; Yarmush, Martin L; Uygun, Korkut

    2011-01-01

    With over 110,000 patients waiting for organ transplantation, the current crisis in organ transplantation is based on a lack of donors after brain-death (DBD). A very large alternative pool of donor organs that remain untapped are the donors after cardiac death (DCD), recovered after cardiac activity has ceased and therefore sustained some ischemic injury. Machine perfusion has been proposed as a novel modality of organ preservation and treatment to render such cadaveric organs, and in particular livers, transplantable. Two key issues that remain unaddressed are how to assess whether a DCD liver is damaged beyond repair, and whether machine perfusion has rendered an injured organ sufficiently viable for transplantation. In this work, we present a metabolic analysis of the transient responses of cadaveric rat livers during normothermic machine perfusion (NMP), and develop an index of ischemia that enables evaluation of the organ ischemic injury level. Further, we perform a discriminant analysis to construct a classification algorithm with >0.98 specificity to identify whether a given perfused liver is ischemic or fresh, in effect a precursor for an index of transplantability and a basis for the use of statistical process control measures for automated feedback control of treatment of ischemic injury in DCD livers. The analyses yield an index based on squared prediction error (SPE) as log(SPE) >1.35 indicating ischemia. The differences between metabolic functions of fresh and ischemic livers during perfusion are outlined and the metabolites that varied significantly for ischemic livers are identified as ornithine, arginine, albumin and tyrosine.

  8. Liver kinetics of glucose analogs measured in pigs by PET: importance of dual-input blood sampling

    DEFF Research Database (Denmark)

    Munk, O L; Bass, L; Roelsgaard, K;

    2001-01-01

    Metabolic processes studied by PET are quantified traditionally using compartmental models, which relate the time course of the tracer concentration in tissue to that in arterial blood. For liver studies, the use of arterial input may, however, cause systematic errors to the estimated kinetic....... Hepatic arterial and portal venous blood samples and flows were measured during the scan. The dual-input function was calculated as the flow-weighted input. RESULTS: For both MG and FDG, the compartmental analysis using arterial input led to systematic underestimation of the rate constants for rapid blood...... of conventional arterial sampling underestimated these parameters compared with independent measurements of hepatic flow and hepatic blood volume. In contrast, the linear Gjedde-Patlak analysis, being less informative but more robust, gave similar parameter estimates (K, V) with both input functions...

  9. Selective gene expression in focal cerebral ischemia.

    Science.gov (United States)

    Jacewicz, M; Kiessling, M; Pulsinelli, W A

    1986-06-01

    Regional patterns of protein synthesis were examined in rat cortex made ischemic by the occlusion of the right common carotid and middle cerebral arteries. At 2 h of ischemia, proteins were pulse labeled with intracortical injections of a mixture of [3H]leucine, [3H]isoleucine, and [3H]proline. Newly synthesized proteins were analyzed by two-dimensional gel fluorography, and the results correlated with local CBF, measured with [14C]iodoantipyrine as tracer. Small blood flow reductions (CBF = 50-80 ml 100 g-1 min-1) were accompanied by a modest inhibition in synthesis of many proteins and a marked increase in one protein (Mr 27,000). With further reduction in blood flow (CBF = 40 ml 100 g-1 min-1), synthesis became limited to a small group of proteins (Mr 27,000, 34,000, 73,000, 79,000, and actin) including two new polypeptides (Mr 55,000 and 70,000). Severe ischemia (CBF = 15-25 ml 100 g-1 min-1) caused the isoelectric modification of several proteins (Mr 44,000, 55,000, and 70,000) and induced synthesis of another protein (Mr 40,000). Two polypeptides (Mr 27,000 and 70,000) dominated residual protein synthesis in severe ischemia. The changes in protein synthesis induced by different grades of ischemia most likely comprise a variation of the so-called "heat shock" or "stress" response found in all eukaryotic cells subjected to adverse conditions. Since heat shock genes are known to confer partial protection against anoxia and a variety of other noxious insults, their induction may be a factor in limiting the extent of ischemic tissue damage.

  10. Liver Facts

    Science.gov (United States)

    ... Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Facts How the Liver Works The liver is one ... Camps for kids Contacting my donor family Data Facts about living donation Financing a transplant Matching organs ...

  11. 硫化氢在肝硬化大鼠肝脏缺血再灌注损伤中的保护作用%Protective Effect of Hydrogen Sulfide on Hepatic Ischemia-reperfusion Injury in Rats with Liver Cirrhosis

    Institute of Scientific and Technical Information of China (English)

    牟燕; 魏来; 陈文雁; 王雯婷; 刘芝; 孔高茵

    2013-01-01

    [Objective]To study the effect of sodium hydrosulfide (NaHS ,a donor of hydrogen sulfide) precondi-tioning on liver function change after hepatic ischemia-reperfusion(IR) injury in rats with liver cirrhosis ,and explore the role of mitochondrial ATP-sensitive postassium channel(mitoK-ATP ) in it .[Methods]Thirty two rats with liver cirrhosis were randomly divided into four groups ( n=8) including sham operated group(sham group) ,hepatic IR in-jury group(HIRI group) ,NaHS preconditioning group(NaHS group) and NaHS+ mitoK-ATP group(group 5-HD) .The inferior vena cava blood were collected at the end of reperfusion and liver function indexes such as total bil-irubin(TBIL) ,direct bilirubin(DBIL) ,alanine transaminase(ALT) and aspartate aminotransferase(AST) were com-pared .[Results]At the end of reperfusion ,TBIL ,DBIL ,ALT and AST in group HIRI ,group NaHS and group 5-HD were obviously higher than those in sham group .There was no significant difference between group HIRI and group 5-HD .The indexes of group NaHS were lower than those in group HIRI and group 5-HD ( P < 0 .05) .[Conclusion]NaHS preconditioning can improve the ability of liver cirrhosis rats against hepatic IR injury ,which may be completed by opening mitoK-AT P .%[目的]研究硫化氢(NaHS)预处理对肝硬化大鼠肝脏缺血再灌注后肝功能变化的影响,并探讨线粒体ATP敏感性钾通道(mitoK-ATP)在其中发挥的作用。[方法]32只肝硬化大鼠随机分为四组( n =8),包括假手术组(Sham组),肝脏缺血再灌注损伤组(HIRI组),NaHS预处理组(NaHS组)和NaHS + mitoK-ATP通道阻断剂预处理组(5-HD组)。再灌注末取腔静脉血检测并比较肝功能指标:总胆红素(TBIL)、直接胆红素(DBIL)、谷丙转氨酶(ALT)和谷草转氨酶(AST)浓度。[结果]再灌注末,HIRI组、NaHS组和5-HD组TBIL、DBIL、ALT和AST浓度明显高于Sham组,HIRI组和5-HD组

  12. Intra-Tissue Pressure Measurement in Ex Vivo Liver Undergoing Laser Ablation with Fiber-Optic Fabry-Perot Probe.

    Science.gov (United States)

    Tosi, Daniele; Saccomandi, Paola; Schena, Emiliano; Duraibabu, Dinesh Babu; Poeggel, Sven; Leen, Gabriel; Lewis, Elfed

    2016-04-15

    We report the first-ever intra-tissue pressure measurement performed during 1064 nm laser ablation (LA) of an ex vivo porcine liver. Pressure detection has been performed with a biocompatible, all-glass, temperature-insensitive Extrinsic Fabry-Perot Interferometry (EFPI) miniature probe; the proposed methodology mimics in-vivo treatment. Four experiments have been performed, positioning the probe at different positions from the laser applicator tip (from 0.5 mm to 5 mm). Pressure levels increase during ablation time, and decrease with distance from applicator tip: the recorded peak parenchymal pressure levels range from 1.9 kPa to 71.6 kPa. Different pressure evolutions have been recorded, as pressure rises earlier in proximity of the tip. The present study is the first investigation of parenchymal pressure detection in liver undergoing LA: the successful detection of intra-tissue pressure may be a key asset for improving LA, as pressure levels have been correlated to scattered recurrences of tumors by different studies.

  13. Intra-Tissue Pressure Measurement in Ex Vivo Liver Undergoing Laser Ablation with Fiber-Optic Fabry-Perot Probe

    Directory of Open Access Journals (Sweden)

    Daniele Tosi

    2016-04-01

    Full Text Available We report the first-ever intra-tissue pressure measurement performed during 1064 nm laser ablation (LA of an ex vivo porcine liver. Pressure detection has been performed with a biocompatible, all-glass, temperature-insensitive Extrinsic Fabry-Perot Interferometry (EFPI miniature probe; the proposed methodology mimics in-vivo treatment. Four experiments have been performed, positioning the probe at different positions from the laser applicator tip (from 0.5 mm to 5 mm. Pressure levels increase during ablation time, and decrease with distance from applicator tip: the recorded peak parenchymal pressure levels range from 1.9 kPa to 71.6 kPa. Different pressure evolutions have been recorded, as pressure rises earlier in proximity of the tip. The present study is the first investigation of parenchymal pressure detection in liver undergoing LA: the successful detection of intra-tissue pressure may be a key asset for improving LA, as pressure levels have been correlated to scattered recurrences of tumors by different studies.

  14. Application of localized {sup 31}P MRS saturation transfer at 7 T for measurement of ATP metabolism in the liver: reproducibility and initial clinical application in patients with non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Valkovic, Ladislav [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); Gajdosik, Martin; Chmelik, Marek; Trattnig, Siegfried [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Traussnigg, Stefan; Kienbacher, Christian; Trauner, Michael [Medical University of Vienna, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Vienna (Austria); Wolf, Peter; Krebs, Michael [Medical University of Vienna, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Vienna (Austria); Bogner, Wolfgang [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); Krssak, Martin [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Vienna, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Vienna (Austria)

    2014-07-15

    Saturation transfer (ST) phosphorus MR spectroscopy ({sup 31}P MRS) enables in vivo insight into energy metabolism and thus could identify liver conditions currently diagnosed only by biopsy. This study assesses the reproducibility of the localized {sup 31}P MRS ST in liver at 7 T and tests its potential for noninvasive differentiation of non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH). After the ethics committee approval, reproducibility of the localized {sup 31}P MRS ST at 7 T and the biological variation of acquired hepato-metabolic parameters were assessed in healthy volunteers. Subsequently, 16 suspected NAFL/NASH patients underwent MRS measurements and diagnostic liver biopsy. The Pi-to-ATP exchange parameters were compared between the groups by a Mann-Whitney U test and related to the liver fat content estimated by a single-voxel proton ({sup 1}H) MRS, measured at 3 T. The mean exchange rate constant (k) in healthy volunteers was 0.31 ± 0.03 s{sup -1} with a coefficient of variation of 9.0 %. Significantly lower exchange rates (p < 0.01) were found in NASH patients (k = 0.17 ± 0.04 s{sup -1}) when compared to healthy volunteers, and NAFL patients (k = 0.30 ± 0.05 s{sup -1}). Significant correlation was found between the k value and the liver fat content (r = 0.824, p < 0.01). Our data suggest that the {sup 31}P MRS ST technique provides a tool for gaining insight into hepatic ATP metabolism and could contribute to the differentiation of NAFL and NASH. (orig.)

  15. Early Diagnosis of Intestinal Ischemia Using Urinary and Plasma Fatty Acid Binding Proteins

    NARCIS (Netherlands)

    Thuijls, Geertje; van Wijck, Kim; Grootjans, Joep; Derikx, Joep P. M.; van Bijnen, Annemarie A.; Heineman, Erik; Dejong, Cornelis H. C.; Buurman, Wim A.; Poeze, Martijn

    2011-01-01

    Objective: This study aims at improving diagnosis of intestinal ischemia, by measuring plasma and urinary fatty acid binding protein (FABP) levels. Methods: Fifty consecutive patients suspected of intestinal ischemia were included and blood and urine were sampled at time of suspicion. Plasma and uri

  16. Uncalibrated continuous cardiac output measurement in liver transplant patients: LiDCOrapid™ system versus pulmonary artery catheter.

    Science.gov (United States)

    Costa, Maria Gabriella; Chiarandini, Paolo; Scudeller, Luigia; Vetrugno, Luigi; Pompei, Livia; Serena, Giovanni; Buttera, Stefania; Della Rocca, Giorgio

    2014-06-01

    The aim of the study was to assess the level of agreement between continuous cardiac output estimated by uncalibrated pulse-power analysis (PulseCOLiR) and intermittent (ICO) and continuous cardiac output (CCO) obtained using a pulmonary artery catheter (PAC). Prospective cohort study. University hospital intensive care unit. Twenty patients after liver transplantation. Pulmonary artery catheters were placed in all patients, and ICO and CCO were determined using thermodilution. PulseCOLiR measurements were made using a LiDCOrapid(TM) (LiDCO Ltd, Cambridge, UK). ICO data were determined after intensive care unit admission and every 8 hours until the 48th postoperative hour. CCO and PulseCOLiR measurements were recorded simultaneously at these same time intervals as well as hourly. For the 8-hour data set (140 data pairs), the mean bias and percentage errors (PE) were, respectively,-0.10 L/min and 39.2% for ICO versus PulseCOLiR and 0.79 L/min and 34.6% for CCO versus PulseCOLiR. For the hourly comparison of CCO versus PulseCOLiR (980 data pairs), the bias was 0.75 L/min and the PE 37%. To assess the ability to measure change, a 4-quadrant plot was produced for each pair of methods. The performance of PulseCOLiR was moderate in detecting changes in ICO. In conclusion, the uncalibrated PulseCOLir method should not be used as a substitute for the thermodilution technique for the monitoring of cardiac output in liver transplant patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia/reperfusion injury

    NARCIS (Netherlands)

    Bos, Eelke M.; Snijder, Pauline M.; Jekel, Henrike; Weij, Michel; Leemans, Jaklien C.; van Dijk, Marcory C. F.; Hillebrands, Jan-Luuk; Lisman, Ton; van Goor, Harry; Leuvenink, Henri G. D.

    Hydrogen sulfide (H2S) can induce a reversible hypometabolic state, which could protect against hypoxia. In this study we investigated whether H2S could protect livers from ischemia/reperfusion injury (IRI). Male C57BL/6 mice were subjected to partial hepatic IRI for 60 min. Animals received 0 (IRI)

  18. Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia/reperfusion injury.

    NARCIS (Netherlands)

    Bos, E.M.; Snijder, P.M.; Jekel, H.; Weij, M.; Leemans, J.C.; Dijk, M.C.R.F. van; Hillebrands, J.L.; Lisman, T.; Goor, H. van; Leuvenink, H.G.

    2012-01-01

    Hydrogen sulfide (H(2) S) can induce a reversible hypometabolic state, which could protect against hypoxia. In this study we investigated whether H(2) S could protect livers from ischemia/reperfusion injury (IRI). Male C57BL/6 mice were subjected to partial hepatic IRI for 60 min. Animals received 0

  19. Lower limb ischemia and multiple organ dysfunction syndrome following wasp Sting

    Directory of Open Access Journals (Sweden)

    Jeyakanth T

    2015-05-01

    Full Text Available Wasp stings are commonly encountered in tropical countries. Various manifestations after wasp sting have been described. We report 66-years old healthy female developed lower limb ischemia, myocardial infarction, renal, liver and hematological involvement following multiple wasp stings. She was fully recovered after two weeks of treatment

  20. Optical monitoring and detection of spinal cord ischemia.

    Directory of Open Access Journals (Sweden)

    Rickson C Mesquita

    Full Text Available Spinal cord ischemia can lead to paralysis or paraparesis, but if detected early it may be amenable to treatment. Current methods use evoked potentials for detection of spinal cord ischemia, a decades old technology whose warning signs are indirect and significantly delayed from the onset of ischemia. Here we introduce and demonstrate a prototype fiber optic device that directly measures spinal cord blood flow and oxygenation. This technical advance in neurological monitoring promises a new standard of care for detection of spinal cord ischemia and the opportunity for early intervention. We demonstrate the probe in an adult Dorset sheep model. Both open and percutaneous approaches were evaluated during pharmacologic, physiological, and mechanical interventions designed to induce variations in spinal cord blood flow and oxygenation. The induced variations were rapidly and reproducibly detected, demonstrating direct measurement of spinal cord ischemia in real-time. In the future, this form of hemodynamic spinal cord diagnosis could significantly improve monitoring and management in a broad range of patients, including those undergoing thoracic and abdominal aortic revascularization, spine stabilization procedures for scoliosis and trauma, spinal cord tumor resection, and those requiring management of spinal cord injury in intensive care settings.

  1. CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice

    Directory of Open Access Journals (Sweden)

    Crockett Elahé T

    2007-05-01

    Full Text Available Abstract Background Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R. P-selectin and the intercellular adhesion molecule (ICAM-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration, and the interactions of neutrophils with hepatocytes in the liver. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury, indicating that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1 in neutrophil infiltration and liver injury during early and late phases of liver I/R. Methods Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null mice underwent 90 minutes of partial liver ischemia followed by various periods of reperfusion (6, 15 h, and a survival study. Liver injury was assessed by plasma level of alanine aminotransferase (ALT and histopathology. The plasma cytokines, TNF-α, IL-6, MIP-2 and KC, were measured by ELISA. Results Reperfusion caused significant hepatocellular injury in both wild-type and P/I null mice as was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil infiltration into the ischemic livers of both wild-type and P/I null mice. Although the levels of ALT and neutrophil infiltration were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. The plasma cytokine data of TNF-α and IL-6 followed a similar pattern to ALT data, and no significant difference was found between the wild-type and P/I null groups. In contrast, a significant difference in KC and MIP-2 chemokine levels was observed between the wild-type and P/I null mice. Additionally, the survival study showed a trend towards increased survival in the P/I null group. Conclusion While ICAM-1 and P

  2. An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure.

    Science.gov (United States)

    Roberts, Dean W; Lee, William M; Hinson, Jack A; Bai, Shasha; Swearingen, Christopher J; Stravitz, R Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M; Rule, Jody; Fontana, Robert J; Ganger, Daniel; Reddy, K Rajender; Liou, Iris; Fix, Oren; James, Laura P

    2017-04-01

    A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC; a sensitive and specific quantitative analytic assay) to detect acetaminophen protein adducts. We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal-Wallis test or rank-sum test for continuous variables. AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222-1027) vs 3678 (range, 394-8289) for those without (P acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with

  3. Does Dexpantenol Protect the Kidney from Ischemia-Reperfusion Injury?

    Directory of Open Access Journals (Sweden)

    Sezen ÖZKISACIK

    2011-05-01

    Full Text Available OBJECTIVES: Tissue injury occurs following reperfusion after creation of ischemia. Plenty of chemical agents have been shown to protect from such an injury. We planned to evaluate the protective effect of dexpanthenol (dxp in ischemia-reperfusion injury. MATERIAL and METHODS: 24 adult rats were used and divided into 3 groups. A right nephrectomy was performed through a median laparotomy incision in all groups. Additionally, in group 1 (sham group, left nephrectomy was made 6 hours later without creation of ischemia. In group 2 (Saline group, the left kidney was left ischemic for 1 hour and reperfusion was established for 6 hours. Saline was administered intraperitoneally thirty minutes before creation of ischemia and just before reperfusion. In group 3 (Dexpanthenol group, the left kidney was left ischemic for 1 hour and reperfusion was established for 6 hours. Dxp (500 mg/kg was administered intraperitoneally thirty minutes before creation of ischemia and just before reperfusion. A left nephrectomy was performed at the end of the 6 hours of reperfusion. Nephrectomy specimens were histopathologically analysed for congestion, inflammation and necrosis. Tissue NO, glutathione reductase, catalase and MDA levels were measured. RESULTS: There was no significant differences between the groups histopathologically or biochemically. CONCLUSION: Dexpanthenol is the biologically active form of pantothenic acid and has an antioxidant effect. Our study was not in correlation with the literature regarding a protective effect of dxp on various organs via its antioxidant effect.

  4. Normobaric Oxygen Therapy for Scleral Ischemia or Melt

    Directory of Open Access Journals (Sweden)

    Farideh Sharifipour

    2012-01-01

    Full Text Available Purpose: To investigate the efficacy of normobaric oxygen (NBO therapy for treatment of scleral ischemia or melt. Methods: This prospective interventional case series includes 9 eyes of 8 patients with scleral ischemia or melt of diverse etiologies. Following the failure of conventional medical and/or surgical therapy to improve ischemia or upon clinical deterioration, NBO was initiated. All patients received 100% NBO at flow rate of 10 liters/minute by face mask for 1 hour, twice daily until complete vascularization of ischemic areas. Main outcome measures were improvement of scleral ischemia and healing of conjunctival epithelial defects. Results: NBO therapy led to epithelialization and vascularization of the ischemic sclera in all eyes; the repair process began 3-4 days after NBO had been initiated and was completed in 18.1±4.7 (range, 10-25 days. All patients remained stable over a 9-month follow-up period. Conclusion: NBO therapy seems effective for treatment of scleral ischemia or melt, and hence can be considered as a non-invasive alternative to surgical intervention in these conditions.

  5. Semi-automatic liver tumor segmentation with hidden Markov measure field model and non-parametric distribution estimation.

    Science.gov (United States)

    Häme, Yrjö; Pollari, Mika

    2012-01-01

    A novel liver tumor segmentation method for CT images is presented. The aim of this work was to reduce the manual labor and time required in the treatment planning of radiofrequency ablation (RFA), by providing accurate and automated tumor segmentations reliably. The developed method is semi-automatic, requiring only minimal user interaction. The segmentation is based on non-parametric intensity distribution estimation and a hidden Markov measure field model, with application of a spherical shape prior. A post-processing operation is also presented to remove the overflow to adjacent tissue. In addition to the conventional approach of using a single image as input data, an approach using images from multiple contrast phases was developed. The accuracy of the method was validated with two sets of patient data, and artificially generated samples. The patient data included preoperative RFA images and a public data set from "3D Liver Tumor Segmentation Challenge 2008". The method achieved very high accuracy with the RFA data, and outperformed other methods evaluated with the public data set, receiving an average overlap error of 30.3% which represents an improvement of 2.3% points to the previously best performing semi-automatic method. The average volume difference was 23.5%, and the average, the RMS, and the maximum surface distance errors were 1.87, 2.43, and 8.09 mm, respectively. The method produced good results even for tumors with very low contrast and ambiguous borders, and the performance remained high with noisy image data.

  6. Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126.

    Science.gov (United States)

    Chen, Fan; Du, Yang; Esposito, Elga; Liu, Yi; Guo, Shuzhen; Wang, Xiaoying; Lo, Eng H; Xing, Changhong; Ji, Xunming

    2015-12-01

    Emerging data suggest that exosomal microRNA (miRNA) may provide potential biomarkers in acute ischemic stroke. However, the effects of ischemia-reperfusion on total versus exosomal miRNA responses in circulating blood remain to be fully defined. Here, we quantified levels of miR-126 in whole serum versus exosomes extracted from serum and compared these temporal profiles against reperfusion and outcomes in a rat model of acute focal cerebral ischemia. First, in vitro experiments confirmed the vascular origin and changes in miR-126 in brain endothelial cultures subjected to oxygen-glucose deprivation. Then in vivo experiments were performed by inducing permanent or transient focal cerebral ischemia in rats, and total serum and exosomal miR-126 levels were quantified, along with measurements of infarction and neurological outcomes. Exosomal levels of miR-126 showed a transient reduction at 3 h post-ischemia that appeared to normalize back close to pre-ischemic baselines after 24 h. There were no detectable differences in exosomal miR-126 responses in permanent or transient ischemia. Serum miR-126 levels appeared to differ in permanent versus transient ischemia. Significant reductions in serum miR-126 were detected at 3 h after permanent ischemia but not transient ischemia. By 24 h, serum miR-126 levels were back close to baseline in both permanent and transient ischemia. Overall, there were no correlations between serum miR-126 and exosomal miR-126. This proof-of-concept study suggests that changes in serum miR-126 may be able to distinguish severe permanent ischemia from milder injury after transient ischemia.

  7. Neuronal autophagy in cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Feng Xu; Jin-Hua Gu; Zheng-Hong Qin

    2012-01-01

    Autophagy has evolved as a conserved process for the bulk degradation and recycling of cytosolic components,such as long-lived proteins and organelles.In neurons,autophagy is important for homeostasis and protein quality control and is maintained at relatively low levels under normal conditions,while it is upregulated in response to pathophysiological conditions,such as cerebral ischemic injury.However,the role of autophagy is more complex.It depends on age or brain maturity,region,severity of insult,and the stage of ischemia.Whether autophagy plays a beneficial or a detrimental role in cerebral ischemia depends on various pathological conditions.In this review,we elucidate the role of neuronal autophagy in cerebral ischemia.

  8. Animal models of cerebral ischemia

    Science.gov (United States)

    Khodanovich, M. Yu.; Kisel, A. A.

    2015-11-01

    Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

  9. CT- and MRI-based volumetry of resected liver specimen: Comparison to intraoperative volume and weight measurements and calculation of conversion factors

    Energy Technology Data Exchange (ETDEWEB)

    Karlo, C., E-mail: christoph.karlo@usz.c [Institute of Diagnostic Radiology, Department of Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Reiner, C.S.; Stolzmann, P. [Institute of Diagnostic Radiology, Department of Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Breitenstein, S. [Department of Visceral Surgery, University Hospital of Zurich (Switzerland); Marincek, B. [Institute of Diagnostic Radiology, Department of Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Weishaupt, D. [Institute for Radiology and Radiodiagnostics, City Hospital Triemli, Zurich (Switzerland); Frauenfelder, T. [Institute of Diagnostic Radiology, Department of Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland)

    2010-07-15

    Objective: To compare virtual volume to intraoperative volume and weight measurements of resected liver specimen and calculate appropriate conversion factors to reach better correlation. Methods: Preoperative (CT-group, n = 30; MRI-group, n = 30) and postoperative MRI (n = 60) imaging was performed in 60 patients undergoing partial liver resection. Intraoperative volume and weight of the resected liver specimen was measured. Virtual volume measurements were performed by two readers (R1,R2) using dedicated software. Conversion factors were calculated. Results: Mean intraoperative resection weight/volume: CT: 855 g/852 mL; MRI: 872 g/860 mL. Virtual resection volume: CT: 960 mL(R1), 982 mL(R2); MRI: 1112 mL(R1), 1115 mL(R2). Strong positive correlation for both readers between intraoperative and virtual measurements, mean of both readers: CT: R = 0.88(volume), R = 0.89(weight); MRI: R = 0.95(volume), R = 0.92(weight). Conversion factors: 0.85(CT), 0.78(MRI). Conclusion: CT- or MRI-based volumetry of resected liver specimen is accurate and recommended for preoperative planning. A conversion of the result is necessary to improve intraoperative and virtual measurement correlation. We found 0.85 for CT- and 0.78 for MRI-based volumetry the most appropriate conversion factors.

  10. Perfusion measurement of the whole upper abdomen of patients with and without liver diseases: Initial experience with 320-detector row CT

    Energy Technology Data Exchange (ETDEWEB)

    Kanda, Tomonori, E-mail: k_a@hotmail.co.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); Yoshikawa, Takeshi, E-mail: yoshikaw@med.kobe-u.ac.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); Fujisawa, Yasuko, E-mail: yasuko1.fujisawa@toshiba.co.jp [Toshiba Medical Systems Co., 1385 Shimoishigami, Otawara 324-0036 (Japan); Kanata, Naoki, E-mail: takikina12345@yahoo.co.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); Yamaguchi, Masato, E-mail: masato03310402@yahoo.co.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); Seo, Yasushi, E-mail: yseo@med.kobe-u.ac.jp [Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate, School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); Yano, Yoshihiko, E-mail: yanoyo@med.kobe-u.ac.jp [Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate, School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); Koyama, Hisanobu, E-mail: hkoyama@med.kobe-u.ac.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); Kitajima, Kazuhiro, E-mail: kazu10041976@yahoo.co.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); Takenaka, Daisuke, E-mail: daisuket@med.kobe-u.ac.jp [Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017 (Japan); and others

    2012-10-15

    Objectives: To report initial experience of upper abdominal perfusion measurement with 320-detector row CT (CTP) for assessment of liver diseases and therapeutic effects. Materials and methods: Thirty-eight patients who were suspected of having a liver disease underwent CTP. There were two patients with liver metastases, two with hemangiomas, and four with cirrhosis (disease group). CTP was repeated for four patients with cirrhosis or hepatocellular carcinoma (HCC) after therapy. Hepatic arterial and portal perfusion (HAP and HPP) and arterial perfusion fraction (APF), and arterial perfusion (AP) of pancreas, spleen, stomach, and intra-portal HCC were calculated. For disease-free patients (normal group), the values were compared among liver segments and among pancreatic and gastric parts. The values were compared between groups and before and after therapy. Results: No significant differences were found in the normal group except between APFs for liver segments 3 and 5, and fundus and antrum. Mean HAP and APF for the disease group were significantly higher than for the normal group. APF increased after partial splenic embolization or creation of a transjugular intrahepatic portosystemic shunt. HPP increased and AP of intra-portal HCC decreased after successful radiotherapy. Conclusions: 320-Detector row CT makes it possible to conduct perfusion measurements of the whole upper abdomen. Our preliminary results suggested that estimated perfusion values have the potential to be used for evaluation of hepatic diseases and therapeutic effects.

  11. Protective effects of prostaglandin E1 perfusion against spinal cord ischemia-reperfusion injury in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    Xifan Mei; Yansong Wang; Chang Liu

    2008-01-01

    BACKGROUND: Prostaglandin E1 (PGE1) is known to be protective in ischemia-reperfusion of heart, lung, renal, and liver tissue. It still remains to be determined whether PGE1 exhibits similar protection against spinal cord ischemia-reperfusion injury in a rabbit model. OBJECTIVE: To observe the large, ventral horn, motor neurons of the spinal cord, as well as limb function, and to investigate whether perfusion of PGE1 exhibits protective effects against spinal cord ischemia-reperfusion injury in a rabbit model. DESIGN, TIME AND SETTING: Controlled observation. The experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between June and October 2007. MATERIALS: Twenty male, New Zealand white rabbits, weighing 2.0 kg and of mixed gender, were used in the present study. The following chemicals and compounds were used: prostaglandin El injectable powder, as well as malondialdehyde and ATPase kits. Animal intervention was in accordance with animal ethical standards. METHODS: We separated rabbits into control and experimental groups randomly, with 10 rabbits in each group. Rabbits were used as spinal cord ischemia models by segmentally cross-clamping the infrarenal aorta. The control group was subsequently perfused for five minutes with blood and saline solution, and the experimental group was perfused for 5 minutes with blood and saline solution containing PGE1 (100 ng/kg/min). MAIN OUTCOME MEASURES: The neurological function of the hind limbs was assessed 12, 24, and 48 hours after model establishment. All animals were sacrificed and spinal cords were harvested for histological analyses. The large motor neurons in the ventral horn of L1-7 were observed by inverted microscope. RESULTS: All 20 rabbits were included in the final analysis, without any loss. In the ventral horn of the L5-7 segments, there were more large motor neurons that appeared viable in the experimental group than the control group (P<0

  12. The protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    XIN Xiao-ming; MA Lian-long; GAO Yong-feng; WANG Hao; WANG Xiao-dan; ZHU Yu-yun; GAO Yun-sheng

    2008-01-01

    Objective To study the protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats. Methods Fourty SD rats were randomly divided into 5 groups (8 animals in each group) : sham-operated control group (A), hepatic ischemia-reperfusion group (B), 200 mg·kg-1 400 mg·kg-1 800 mg·kg-1 betaine hydrochloride + hepatic ischemia-reperfusion group (C、D、E). betaine hydrochloride was administered to animals byoral route in group C、D、E for 7 days before ischemia. A、B group was administered with NS. Made the animal model of part hepatic ischemia-reperfusion. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in the blood and themalondialdehyde (MDA), superoxide dismutase (SOD), protein content in hepatic tissue were determined after the liver had been reperfused for 24 hours; the hepatic tissue was examined under lightmieroscope and the cell apoptosis was demonstrated with flow cytometry. Results ALT, AST, MDA increased and SOD decreased significantly in B group when compared those in the A group (P<0.05), Hepatic apoptosis was significantly increased; ALT, AST, MDA decreased and SOD increased significantly in betaine hydrochloride 200 mg·kg-1(C) group when compared those in the B group(P<0.05). Hepatic apoptosis was significantly lower, The histologic changes of the liver tissue under lightmicroscope in the C group was more easer than in the I/R group (B). Conclusions Betaine hydrochloride has the ability to scavenge oxygen free radical (OFR), reduce lipid peroxidation and inhibition of apoptosis. So it can protect the rats liver damaged by ischemia-reperfusion.

  13. Regional protein synthesis in rat brain following acute hemispheric ischemia.

    Science.gov (United States)

    Dienel, G A; Pulsinelli, W A; Duffy, T E

    1980-11-01

    Regional protein synthesis was measured in rat brain at intervals up to 48 h following occlusion of the four major arteries to the brain for either 10 or 30 min. Four-vessel occlusions produces ischemia in the cerebral hemispheres and oligemia in the midbrain-diencephalon and brainstem. During the hour following 10 min of ischemia, protein synthesis, measured by incorporation of [14C]valine into protein, was inhibited in the cerebral cortex by 67%. Normal rates of protein synthesis were attained within 4 h of recirculation. In rats subjected to 30 min of ischemia, protein synthesis was inhibited by 83% during the first hour of recirculation in the cortex, caudate-putamen, and hippocampus. Recovery of protein synthesis in these regions was slow (25-48 h). The midbrain-diencephalon showed less inhibition, 67%, and faster recovery (by 12 h). Protein synthesis was unaffected in the brainstem. [14C]Autoradiography revealed that the pyramidal neurons of the hippocampus and areas of the caudate and cortex failed to recover normal rates of protein synthesis even after 48 h. The accumulation of TCA-soluble [14C]valine was enhanced (55-65%) in the cortex, caudate, and hippocampus after 30 min of ischemia; the increase persisted for 12 h. A smaller rise in [14C]valine content (30%) and more rapid normalization of valine accumulation (by 7 h) were observed in the midbrain-diencephalon; no changes were found in the brainstem. In the cortex, recovery was more rapid when the duration of ischemia was reduced. Thus, the degree of inhibition of protein synthesis, the accumulation of valine in the tissue, and the length of time required to reestablish normal values for these processes were dependent on both the severity and the duration of the ischemic insult. Restoration of normal rates of protein synthesis after ischemia was slow compared with the normalization of cerebral energy metabolites.

  14. Fiber-Optic Temperature and Pressure Sensors Applied to Radiofrequency Thermal Ablation in Liver Phantom: Methodology and Experimental Measurements

    Directory of Open Access Journals (Sweden)

    Daniele Tosi

    2015-01-01

    Full Text Available Radiofrequency thermal ablation (RFA is a procedure aimed at interventional cancer care and is applied to the treatment of small- and midsize tumors in lung, kidney, liver, and other tissues. RFA generates a selective high-temperature field in the tissue; temperature values and their persistency are directly related to the mortality rate of tumor cells. Temperature measurement in up to 3–5 points, using electrical thermocouples, belongs to the present clinical practice of RFA and is the foundation of a physical model of the ablation process. Fiber-optic sensors allow extending the detection of biophysical parameters to a vast plurality of sensing points, using miniature and noninvasive technologies that do not alter the RFA pattern. This work addresses the methodology for optical measurement of temperature distribution and pressure using four different fiber-optic technologies: fiber Bragg gratings (FBGs, linearly chirped FBGs (LCFBGs, Rayleigh scattering-based distributed temperature system (DTS, and extrinsic Fabry-Perot interferometry (EFPI. For each instrument, methodology for ex vivo sensing, as well as experimental results, is reported, leading to the application of fiber-optic technologies in vivo. The possibility of using a fiber-optic sensor network, in conjunction with a suitable ablation device, can enable smart ablation procedure whereas ablation parameters are dynamically changed.

  15. Effect of Salvianolic Acid B on Mitochondrial Function of Cerebral Ischemia in Mice

    Institute of Scientific and Technical Information of China (English)

    JIANG Yufeng; LUO Xuechun; WANG Ximei; FANG Lei; HUANG Qifu

    2009-01-01

    The effects of salvianolic acid B (SalB) on the mitochondrial membrane potential (MMP), calcium, and apoptosis of neurons with cerebral ischemia in mice were investigated using an acute cerebral ischemia model established by ligating the bilateral common carotid arteries in mica. The MMP, the intracellular cal-cium concentration, and the apoptosis rate of cortical neurons were measured at 6 min, 12 min, 18 min, 24 min, and 30 min after cerebral ischemia by a flow cytometer. The experiments show that SalB increases the MMP and reduces the intracellular calcium and the apoptosis rate at different stages of the cerebral ischemia in mice. The results show that the protective mechanism of SalB on cerebral ischemia enhances the MMP and maintains intracellular calcium homeostasis.

  16. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930137 Effects of selective and non-selectiveβ-adrenoreceptor blockers on portal hemody-namics in patients with liver cirrhosis.HUANGTianwei(黄天卫),et al.1st Affili Hosp,DalianMed Coll.Chin J Digest 1992;12(3):145-147.Effects of selective(atenolol)and non-selec-tive(propranolol)β-adrenoreceptor blockerson portal hemodynamics in patients with livercirrhosis were measured by pulsed Doppler du-

  17. Effects of ulinastatin on renal ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Cong-cong CHEN; Zi-ming LIU; Hui-hua WANG; Wei HE; Yi WANG; Wei-dong WU

    2004-01-01

    AIM: To investigate the effect and possible mechanism of ulinastatin on renal ischemia-reperfusion injury in rats.METHODS: Male Sprague-Dawley rats were subjected to 45-min bilateral renal ischemia, treated with intravenously 12 500 U ulinastatin at 30 min prior to ischemia and at the beginning of reperfusion, compared with a nontreated group without ulinastatin and a sham-operation group without bilateral renal ischemia. After 0 h, 2 h, 6 h, 12 h, and 24 h of reperfusion, serum creatinine and blood urea nitrogen were measured for the assessment of renal function, renal sections were used for histologic grading of renal injury, for immunohistochemical localization of Bcl-2 and heat shock protein 70. Renal ultrastructure was observed through a transmission electron microscope.RESULTS: Ulinastatin significantly reduced the increase in blood urea nitrogen and creatinine produced by renal ischemia-reperfusion, suggesting an improvement in renal function. Ulinastatin reduced the histologic evidence of renal damage associated with ischemia-reperfusion and accompanied with an up-regulation in the expression of Bcl-2 protein, but it had no significent effect on the expression of HSP 70. Ulinastatin also significantly reduced kidney ultrastructure damage caused by renal ischemia-reperfusion. CONCLUSION: The protease inhibitor, ulinastatin,reduced the renal dysfunction and injury associated with ischemia-reperfusion of the kidney. The protective effect of ulinastatin might be associated with the up-regulation of Bcl-2 expression and the effect on membrane fragility.

  18. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  19. Liver Hemangioma

    Science.gov (United States)

    ... in your liver, even if it's a benign mass. There's no evidence that an untreated liver hemangioma can lead to liver ... of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...

  20. Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Clausen, Bettina Hjelm; Degn, Matilda; Martin, Nellie Anne

    2014-01-01

    after ischemia. Brain inflammation, liver acute phase response (APR), spleen and blood leukocyte profiles, along with plasma microvesicle analysis, were evaluated.ResultsWe found that both XPro1595 and etanercept significantly improved functional outcomes, altered microglial responses, and modified APR......, spleen T cell and microvesicle numbers, but without affecting infarct volumes.ConclusionsOur data suggest that XPro1595 and etanercept improve functional outcome after focal cerebral ischemia by altering the peripheral immune response, changing blood and spleen cell populations and decreasing granulocyte...

  1. Controversies in cardiovascular care: silent myocardial ischemia

    Science.gov (United States)

    Hollenberg, N. K.

    1987-01-01

    The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.

  2. [Correlation of liver stiffness measured by FibroTouch and FibroScan with Ishak fibrosis score in patients with chronic hepatitis B].

    Science.gov (United States)

    Chen, G F; Ping, J; Gu, H T; Zhao, Z M; Zhou, Y; Xing, F; Tao, Y Y; Mu, Y P; Liu, P; Liu, C H

    2017-02-20

    Objective: To investigate the correlation of liver stiffness measured by FibroTouch (FT) and FibroScan (FS) with Ishak fibrosis score in patients with chronic hepatitis B. Methods: A total of 313 patients with chronic hepatitis B who visited Department of Liver Cirrhosis in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2014 to May 2016 were enrolled. All the patients underwent liver biopsy, and FT and FS were used to determine liver stiffness measurement (LSM). Serum biochemical parameters were measured, and the aspartate aminotransferase-to-platelet ratio index (APRI) in a multi-parameter model of liver fibrosis and fibrosis-4 (FIB-4) index were calculated. The consistency between the results of four noninvasive examinations and Ishak fibrosis score was compared. The t-test was used for comparison of LSM determined by FT and FS. Pearson correlation analysis was used investigate the correlation between LSM determined by FT and FS; Spearman correlation analysis was used to investigate the correlation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and Knodell score with LSM determined by FT and FS; the correlation between LSM determined by FT and FS and fibrosis stage was analyzed by partial correlation analysis adjusted by Knodell score for liver inflammatory activity; Spearman correlation analysis was used for APRI, FIB-4, and fibrosis stage. Based on the Ishak fibrosis score, the receiver operating characteristic (ROC) curve was used to analyze the values of four noninvasive methods in the diagnosis of liver fibrosis. Results: There was no significant difference in LSM measured by FT and FS in all patients (15.75±9.42 kPa vs 15.42±10.52 kPa, P > 0.05) and Pearson correlation analysis indicated a significant positive correlation between them (r = 0.858, P correlated with LSM determined by FT and FS. There was a significant positive correlation between LSM determined by FT and

  3. (1)H-MRS measured ectopic fat in liver and muscle is associated with the metabolic syndrome in Danish girls but not in boys with overweight and obesity

    DEFF Research Database (Denmark)

    Nissen, A; Fonvig, C E; Chabanova, E;

    2016-01-01

    MetS and ectopic fat may offer clinical relevance. OBJECTIVES: To investigate the prevalence of MetS, or components hereof, and ectopic fat accumulation in liver and skeletal muscle tissue in children, as well as interactions between these. METHODS: Two-hundred-and-sixteen children and adolescents (95...... boys) with overweight/obesity were investigated, as well as 47 controls (22 boys) with normal weight. The assessments included anthropometry, fasting blood biochemistry and blood pressure measurements. Liver and muscle lipid contents were assessed by proton magnetic resonance spectroscopy. RESULTS: We...

  4. Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia.

    Science.gov (United States)

    Chen, Yingzhu; Yi, Qiong; Liu, Gang; Shen, Xue; Xuan, Lihui; Tian, Ye

    2013-02-01

    Myelin sheath, either in white matter or in other regions of brain, is vulnerable to ischemia. The specific events involved in the progression of ischemia in white matter have not yet been elucidated. The aim of this study was to determine histopathological alterations in cerebral white matter and levels of myelin basic protein (MBP) in ischemia-injured brain tissue during the acute and subacute phases of central nervous injury following whole-brain ischemia. The whole cerebral ischemia model (four-vessel occlusion (4-VO)) was established in adult Sprague-Dawley rats and MBP gene expression and protein levels in the brain tissue were measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at 2 days, 4 days, 7 days, 14 days, and 28 days following ischemia. Demyelination was determined by Luxol fast blue myelin staining, routine histopathological staining, and electron microscopy in injured brain tissue. Results showed that edema, vascular dilation, focal necrosis, demyelination, adjacent reactive gliosis and inflammation occurred 7 days after ischemia in HE staining and recovered to control levels at 28 days. The absence of Luxol fast blue staining and vacuolation was clearly visible at 7 days, 14 days, and 28 days. Semiquantitative analysis showed that the transparency of myelin had decreased significantly by 7 days, 14 days, and 28 days. Demyelination and ultrastructual changes were detected 7 days after ischemia. The relative levels of MBP mRNA decreased 2 days after ischemia and this trend continued throughout the remaining four points in time. The MBP levels measured using ELISA also decreased significantly at 2 days and 4 days, but they recovered by 7 days and returned to control levels by 14 days. These results suggest that the impact of ischemia on cerebral white matter is time-sensitive and that different effects may follow different courses over time.

  5. Anterior Segment Ischemia after Strabismus Surgery

    Science.gov (United States)

    Göçmen, Emine Seyhan; Atalay, Yonca; Evren Kemer, Özlem; Sarıkatipoğlu, Hikmet Yavuz

    2017-01-01

    A 46-year-old male patient was referred to our clinic with complaints of diplopia and esotropia in his right eye that developed after a car accident. The patient had right esotropia in primary position and abduction of the right eye was totally limited. Primary deviation was over 40 prism diopters at near and distance. The patient was diagnosed with sixth nerve palsy and 18 months after trauma, he underwent right medial rectus muscle recession. Ten months after the first operation, full-thickness tendon transposition of the superior and inferior rectus muscles (with Foster suture) was performed. On the first postoperative day, slit-lamp examination revealed corneal edema, 3+ cells in the anterior chamber and an irregular pupil. According to these findings, the diagnosis was anterior segment ischemia. Treatment with 0.1/5 mL topical dexamethasone drops (16 times/day), cyclopentolate hydrochloride drops (3 times/day) and 20 mg oral fluocortolone (3 times/day) was initiated. After 1 week of treatment, corneal edema regressed and the anterior chamber was clean. Topical and systemic steroid treatment was gradually discontinued. At postoperative 1 month, the patient was orthophoric and there were no pathologic symptoms besides the irregular pupil. Anterior segment ischemia is one of the most serious complications of strabismus surgery. Despite the fact that in most cases the only remaining sequel is an irregular pupil, serious circulation deficits could lead to phthisis bulbi. Clinical properties of anterior segment ischemia should be well recognized and in especially risky cases, preventative measures should be taken. PMID:28182149

  6. Liver volume measurement: reason of the difference between in vivo CT-volumetry and intraoperative ex vivo determination and how to cope it

    Directory of Open Access Journals (Sweden)

    Niehues SM

    2010-08-01

    Full Text Available Abstract Purpose Volumetric assessment of the liver regularly yields discrepant results between pre- and intraoperatively determined volumes. Nevertheless, the main factor responsible for this discrepancy remains still unclear. The aim of this study was to systematically determine the difference between in vivo CT-volumetry and ex vivo volumetry in a pig animal model. Material and Methods Eleven pigs were studied. Liver density assessment, CT-volumetry and water displacement volumetry was performed after surgical removal of the complete liver. Known possible errors of volume determination like resection or segmentation borders were eliminated in this model. Regression analysis was performed and differences between CT-volumetry and water displacement determined. Results Median liver density was 1.07 g/ml. Regression analysis showed a high correlation of r2 = 0.985 between CT-volumetry and water displacement. CTvolumetry was found to be 13% higher than water displacement volumetry (p Conclusion In this study the only relevant factor leading to the difference between in vivo CT-volumetry and ex vivo water displacement volumetry seems to be blood perfusion of the liver. The systematic difference of 13 percent has to be taken in account when dealing with those measures.

  7. Sirt1 in cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Kevin B Koronowski

    2015-01-01

    Full Text Available Cerebral ischemia is among the leading causes of death worldwide. It is characterized by a lack of blood flow to the brain that results in cell death and damage, ultimately causing motor, sensory, and cognitive impairments. Today, clinical treatment of cerebral ischemia, mostly stroke and cardiac arrest, is limited and new neuroprotective therapies are desperately needed. The Sirtuin family of oxidized nicotinamide adenine dinucleotide (NAD +-dependent deacylases has been shown to govern several processes within the central nervous system as well as to possess neuroprotective properties in a variety of pathological conditions such as Alzheimer′s Disease, Parkinson′s Disease, and Huntington′s Disease, among others. Recently, Sirt1 in particular has been identified as a mediator of cerebral ischemia, with potential as a possible therapeutic target. To gather studies relevant to this topic, we used PubMed and previous reviews to locate, select, and resynthesize the lines of evidence presented here. In this review, we will first describe some functions of Sirt1 in the brain, mainly neurodevelopment, learning and memory, and metabolic regulation. Second, we will discuss the experimental evidence that has implicated Sirt1 as a key protein in the regulation of cerebral ischemia as well as a potential target for the induction of ischemic tolerance.

  8. Sirt1 in cerebral ischemia

    Science.gov (United States)

    Koronowski, Kevin B.; Perez-Pinzon, Miguel A.

    2015-01-01

    Cerebral ischemia is among the leading causes of death worldwide. It is characterized by a lack of blood flow to the brain that results in cell death and damage, ultimately causing motor, sensory, and cognitive impairments. Today, clinical treatment of cerebral ischemia, mostly stroke and cardiac arrest, is limited and new neuroprotective therapies are desperately needed. The Sirtuin family of oxidized nicotinamide adenine dinucleotide (NAD+)-dependent deacylases has been shown to govern several processes within the central nervous system as well as to possess neuroprotective properties in a variety of pathological conditions such as Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease, among others. Recently, Sirt1 in particular has been identified as a mediator of cerebral ischemia, with potential as a possible therapeutic target. To gather studies relevant to this topic, we used PubMed and previous reviews to locate, select, and resynthesize the lines of evidence presented here. In this review, we will first describe some functions of Sirt1 in the brain, mainly neurodevelopment, learning and memory, and metabolic regulation. Second, we will discuss the experimental evidence that has implicated Sirt1 as a key protein in the regulation of cerebral ischemia as well as a potential target for the induction of ischemic tolerance. PMID:26819971

  9. The Effect of a Lifestyle Modification Education on Adiposity Measures in Overweight and Obese Nonalcoholic Fatty Liver Disease Patients

    Science.gov (United States)

    Arab, Arman; Askari, Gholamreza; Golshiri, Parastoo; Feizi, Awat; Hekmatnia, Ali; Iraj, Bijan; Nourian, Mojgan

    2017-01-01

    Background: Obesity is increasingly associated with nonalcoholic fatty liver disease (NAFLD) and weight loss through a combination of dietary modifications and increased physical activity is a primary goal of therapy in this disease. Therefore, this study was conducted to evaluate the effects of a lifestyle modification education on adiposity measures, physical activity, and total calorie intake in overweight and obese NAFLD patients. Methods: During 8 weeks, 82 obese patients were randomly assigned into either an intervention group (n = 41) receiving a lifestyle modification education or to a control group (n = 41) receiving usual care. Total calorie intake, physical activity, and body composition indices were measured before and after the intervention. Results: Thirty-six patients in intervention group and 33 in control group completed the study. The analysis of body composition variables did not show any significant reduction for percent of body fat, abdominal circumference, waist to hip ratio, visceral fat area, age matched of body, and soft lean mass (SLM) of the trunk (P > 0.05). On the other hand, a significant reduction in weight, body mass index, mass of body fat (MBF), SLM, and MBF of the trunk was observed after 2 months of intervention compared to the controls (P < 0.05). A significant reduction was observed in total calorie intake of intervention group as compared to the control group. Physical activity status did not show any significant improvements after 2 months of intervention. Conclusions: Our lifestyle modification education and its guidelines could be used in obese patients with NAFLD to improve their body composition measurements and to lose weight. This could result in significant long-term benefits in NAFLD patients.

  10. Serial measurement of Doppler hepatic hemodynamic parameters for the diagnosis of acute rejection after live donor liver transplantation.

    Science.gov (United States)

    Sugimoto, Hiroyuki; Kato, Koichi; Hirota, Masashi; Takeda, Shin; Kamei, Hideya; Nakamura, Taro; Kiuchi, Tetsuya; Nakao, Akimasa

    2009-09-01

    To elucidate the role of Doppler hepatic hemodynamic parameters as surrogate markers of acute rejection (AR) after live donor liver transplantation (LDLT), serial Doppler measurements were prospectively performed during the first 2 weeks after LDLT to compare the longitudinal hepatic hemodynamic changes between patients with histologically proven AR and patients without histologically proven AR. Forty-six patients that had undergone adult-to-adult LDLT using a right lobe graft were enrolled in this study. The portal venous maximum velocity (PVV; cm/second), portal venous flow volume, hepatic arterial peak systolic velocity, hepatic arterial pulsatility index, hepatic venous maximum velocity, hepatic venous pulsatility index, and splenic arterial pulsatility index were measured. Fourteen patients were diagnosed by biopsy to have clinically relevant AR. Markedly increased PVV was seen soon after surgery and gradually decreased in both patients with clinically relevant AR and patients without clinically relevant AR. This serial change of decreasing PVV was significantly greater in patients with clinically relevant AR (P patients with clinically relevant AR was significantly lower than that in patients without clinically relevant AR (PVV on postoperative day 6: 35.6 +/- 21.3 versus 58.3 +/- 27.1 cm/second, respectively, P = 0.0080). A PVV cutoff value of 20.2 cm/second demonstrated the best accuracy for predicting clinically relevant AR. The sensitivity and specificity for predicting clinically relevant AR were 92.9% and 87.1%, respectively. The area under the curve was 0.94. In conclusion, serial Doppler measurement of hepatic parameters in LDLT is useful for the diagnosis of clinically relevant AR. Clinically relevant AR should therefore be suspected when a marked unexpected decrease in the PVV is observed.

  11. Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

    Directory of Open Access Journals (Sweden)

    Youichi Kawano

    Full Text Available Along with the increasing need for living-donor liver transplantation (LDLT, the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH. The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038, demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001. Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

  12. Measurement of real-time tissue elastography in a phantom model and comparison with transient elastography in pediatric patients with liver diseases

    Science.gov (United States)

    Schenk, Jens-Peter; Alzen, Gerhard; Klingmüller, Volker; Teufel, Ulrike; Sakka, Saroa El; Engelmann, Guido; Selmi, Buket

    2014-01-01

    PURPOSE We aimed to determine the comparability of real-time tissue elastography (RTE) and transient elastography (TE) in pediatric patients with liver diseases. MATERIALS AND METHODS RTE was performed on the Elasticity QA Phantom Model 049 (Computerized Imaging Reference Systems Company Inc., Norfolk, Virginia, USA), which has five areas with different levels of stiffness. RTE measurements of relative stiffness (MEAN [mean value of tissue elasticity], AREA [% of blue color-coded stiffer tissue]) in the phantom were compared with the phantom stiffness specified in kPa (measurement unit of TE). RTE and TE were performed on 147 pediatric patients with various liver diseases. A total of 109 measurements were valid. The participants had following diseases: metabolic liver disease (n=25), cystic fibrosis (n=20), hepatopathy of unknown origin (n=11), autoimmune hepatitis (n=12), Wilson’s disease (n=11), and various liver parenchyma alterations (n=30). Correlations between RTE and TE measurements in the patients were calculated. In addition, RTE was performed on a control group (n=30), and the RTE values between the patient and control groups were compared. RESULTS The RTE parameters showed good correlation in the phantom model with phantom stiffness (MEAN/kPa, r=−0.97; AREA/kPa, r=0.98). However, the correlation of RTE and TE was weak in the patient group (MEAN/kPa, r=−0.23; AREA/kPa, r=0.24). A significant difference was observed between the patient and control groups (MEAN, P = 5.32 e-7; AREA, P = 1.62 e-6). CONCLUSION In the phantom model, RTE was correlated with kPa, confirming the presumed comparability of the methods. However, there was no direct correlation between RTE and TE in patients with defined liver diseases under real clinical conditions. PMID:24317333

  13. Progression of biopsy-measured liver fibrosis in untreated patients with hepatitis C infection: non-Markov multistate model analysis.

    Directory of Open Access Journals (Sweden)

    Peter Bacchetti

    Full Text Available BACKGROUND: Fibrosis stages from liver biopsies reflect liver damage from hepatitis C infection, but analysis is challenging due to their ordered but non-numeric nature, infrequent measurement, misclassification, and unknown infection times. METHODS: We used a non-Markov multistate model, accounting for misclassification, with multiple imputation of unknown infection times, applied to 1062 participants of whom 159 had multiple biopsies. Odds ratios (OR quantified the estimated effects of covariates on progression risk at any given time. RESULTS: Models estimated that progression risk decreased the more time participants had already spent in the current stage, African American race was protective (OR 0.75, 95% confidence interval 0.60 to 0.95, p = 0.018, and older current age increased risk (OR 1.33 per decade, 95% confidence interval 1.15 to 1.54, p = 0.0002. When controlled for current age, older age at infection did not appear to increase risk (OR 0.92 per decade, 95% confidence interval 0.47 to 1.79, p = 0.80. There was a suggestion that co-infection with human immunodeficiency virus increased risk of progression in the era of highly active antiretroviral treatment beginning in 1996 (OR 2.1, 95% confidence interval 0.97 to 4.4, p = 0.059. Other examined risk factors may influence progression risk, but evidence for or against this was weak due to wide confidence intervals. The main results were essentially unchanged using different assumed misclassification rates or imputation of age of infection. DISCUSSION: The analysis avoided problems inherent in simpler methods, supported the previously suspected protective effect of African American race, and suggested that current age rather than age of infection increases risk. Decreasing risk of progression with longer time already spent in a stage was also previously found for post-transplant progression. This could reflect varying disease activity, with recent progression indicating

  14. Correlation between Heart, Liver and Pancreas Hemosiderosis Measured by MRI T2* among Thalassemia Major Patients from Iran.

    Science.gov (United States)

    Azarkeivan, Azita; Hashemieh, Mozhgan; Shirkavand, Afshan; Sheibani, Kourosh

    2016-02-01

    Major thalassemia patients need lifelong transfusions. The consequence of these repeated transfusions is iron accumulation in different organs. The main aim of the present study was to investigate the correlation between heart, liver and pancreas hemosiderosis in thalassemic patients from Iran. This cross-sectional study was conducted on 164 major thalassemia patients at Zafar Adult Thalassemia Center, a referral thalassemia center in Tehran, Iran, from May to November 2014.  All patients were on regular blood transfusion at 2-4 week intervals to keep their hemoglobin at a level of 7-9 gr/dL before each transfusion. Demographic data were gathered from patients' history. MRI T2* of liver, heart and pancreas were performed for all patients. There were a moderate correlation between pancreatic T2* and cardiac T2* relaxation times (r = 0.42, P pancreas and liver (r = 0.41, P pancreas and liver T2* relaxation times indicate that relying on liver MRI T2* to predict the exact condition of pancreas or heart iron overload might not be a reliable approach in thalassemia major patients. Our findings suggest the advantage of using pancreas and heart MRI T2* as a non-invasive method for estimation of iron overload instead of relying on liver MRI T2*.

  15. in vivo ischemia monitoring array for endoscopic surgery.

    Science.gov (United States)

    Tahirbegi, Islam Bogachan; Mir, Mònica; Schostek, Sebastian; Schurr, Marc; Samitier, Josep

    2014-11-15

    An array with all-solid-state, potentiometric, miniaturized sensors for pH and potassium was developed to be introduced into the stomach or other sectors of the digestive tract by means of flexible endoscopy. These sensors perform continuous and simultaneous measurement of extracellular pH and potassium. This detection seeks to sense ischemia in the gastric mucosa inside the stomach, an event indicative of local microvascular perfusion and tissue oxygenation status. Our array is proposed as a medical tool to identify the occurrence of the ischemia after gastrointestinal or gastroesophageal anastomosis. The stability and feasibility of the miniaturized working and reference electrodes integrated in the array were studied under in vitro conditions, and the behavior of the potassium and pH ion-selective membranes were optimized to work under acidic gastric conditions with high concentrations of HCl. The array was tested in vivo in pigs to measure the ischemia produced by clamping the blood flow into the stomach. Our results indicate that ischemic and reperfusion states can be sensed in vivo and that information on tissue damage can be collected by this sensor array. The device described here provides a miniaturized, inexpensive, and mass producible sensor array for detecting local ischemia caused by unfavorable anastomotic perfusion and will thus contribute to preventing anastomotic leakage and failure caused by tissue necrosis.

  16. Mixed models in cerebral ischemia study

    Directory of Open Access Journals (Sweden)

    Matheus Henrique Dal Molin Ribeiro

    2016-06-01

    Full Text Available The data modeling from longitudinal studies stands out in the current scientific scenario, especially in the areas of health and biological sciences, which induces a correlation between measurements for the same observed unit. Thus, the modeling of the intra-individual dependency is required through the choice of a covariance structure that is able to receive and accommodate the sample variability. However, the lack of methodology for correlated data analysis may result in an increased occurrence of type I or type II errors and underestimate/overestimate the standard errors of the model estimates. In the present study, a Gaussian mixed model was adopted for the variable response latency of an experiment investigating the memory deficits in animals subjected to cerebral ischemia when treated with fish oil (FO. The model parameters estimation was based on maximum likelihood methods. Based on the restricted likelihood ratio test and information criteria, the autoregressive covariance matrix was adopted for errors. The diagnostic analyses for the model were satisfactory, since basic assumptions and results obtained corroborate with biological evidence; that is, the effectiveness of the FO treatment to alleviate the cognitive effects caused by cerebral ischemia was found.

  17. Protection against ischemia-reperfusion injury in aged liver donor by induction of exogenous hTERT gene%外源hTERT基因转染对老年大鼠供肝缺血再灌注损伤的防护作用

    Institute of Scientific and Technical Information of China (English)

    靳斌; 王伟; 刘泽阳; 李广振; 杜刚; 张宗利; 韩立涛; 黄国振; 唐振宇

    2013-01-01

    Objective To investigate the liver ischemia-reperfusion (I/R) injury of adult and aged rats.Exogenous human telomerase reverse transcriptase (hTERT) gene was transferred into aged rats' liver before liver transplantation,and then the effects of the gene on cell apoptosis caused by I/R injury were observed.Methods Wistar rats were divided into two groups,with adult rats (5 months) in group Ⅰ and aged rats (16 ~ 18 months) in group Ⅱ.After transplantation,ALT content,chronic oxidative stress,lipid peroxidation related indicators including vitamin C and vitamin E,the content of superoxide dismutase (SOD),catalase (CAT) and malondialdehyde (MDA) were tested.The aged rats were divided into 3 groups:group A were pretreated with exogenous hTERT gene,group B with adenovirus vector and group C with physiologic saline.The indicators were detected to analyze the effects of exogenous hTERT gene on I/R injury.Results Contents of vitamin C,vitamin E,SOD,CAT were lower in group Ⅱ than in group Ⅰ (P < 0.05) ; MDA and ALT were higher in group Ⅱ than in group Ⅰ (P < 0.05).The apoptotic index and ALT level were significantly lower in group A than in group B and C (P < 0.05),while telomerase activity was increased and histological injury was milder in group A.Conclusion Compared with that in the adult rats,the I/R injury in aged liver donors were severer.Exogenous hTERT gene induction offers protection against I/R injury in aged liver.%目的 研究老年大鼠与成年大鼠肝脏缺血再灌注损伤的程度;在肝移植前将外源端粒酶逆转录酶(TERT)基因导入老年大鼠供肝内,移植成功后观察该基因对老年大鼠供肝缺血再灌注损伤的影响.方法 Wistar大鼠共分为2组:Ⅰ组为成年大鼠(5个月),Ⅱ组为老年大鼠(16~18个月).移植成功后,检测ALT、维生素C和维生素E含量,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)及丙二醛(MDA)含量,比较两组缺血再灌注损伤

  18. A new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities.

    Science.gov (United States)

    Noh, Young; Lee, Yunhwan; Seo, Sang Won; Jeong, Jee H; Choi, Seong Hye; Back, Joung Hwan; Woo, Sook-Young; Kim, Geon Ha; Shin, Ji Soo; Kim, Chi Hun; Cho, Hanna; Park, Joon Sung; Lee, Jong-Min; Hong, Chang Hyung; Kim, Sang Yun; Lee, Jae-Hong; Kim, Seong Yoon; Park, Kee Hyung; Han, Seol-Heui; Cheong, Hae-Kwan; Na, Duk L

    2014-04-01

    The Clinical Research Center for Dementia of South Korea (CREDOS) group developed a new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities (WMHs). In this study, we aimed to evaluate the validity of the CREDOS ischemia classification system. A total of 352 patients with cognitive impairments were included. Their WMH scores were rated using the CREDOS WMH visual rating scale. These patients were divided into 3 groups according to the CREDOS ischemia classification system. The volume of WMH was also automatically measured. The number of lacunes and microbleeds (MBs) were counted. The CREDOS ischemia classification system was revised with factor analysis using vascular risk factors and cerebrovascular disease (CVD) markers (WMH volume, lacunes, and MBs). External validation was performed in another group of patients with cognitive impairment using multinomial logistic regression analysis. The CREDOS WMH visual rating scale showed excellent correlation with the automatically measured volume of WMH. The factor analysis showed that the severe group was expanded to D3P1 and D3P2 in the revised CREDOS ischemia classification system. In the validation group, the presence of vascular risk factors and the severity of CVD markers could be distinguished according to the revised CREDOS ischemia classification. We validated a newly developed classification system for ischemia. This simple visual classification system was capable of providing information on vascular risk factors and CVD markers by simply rating WMH on magnetic resonance imaging.

  19. Thromboxane A2 release in ischemia and reperfusion of free flaps in rats, studied by microdialysis.

    Science.gov (United States)

    Ionac, M; Schaefer, D; Geishauser, M

    2001-02-01

    Several studies have implicated enhanced eicosanoid production in reperfusion injury. The reported study investigated the use of microdialysis in the in vivo measurement of thromboxane levels during reperfusion in ischemic and reperfused experimental free muscle flaps. Microdialysis probes were inserted, via a guide, into the gracilis and semitendinosus free flap in the rat. The probe was perfused at a flow of 5 microl/min, with samples collected at intervals of 20 min, and analyzed by the ELISA technique. Animals were randomly distributed into three groups. After ischemic periods of 2, 4, and 6 hr, respectively, the free muscle flaps were revascularized on the contralateral femoral vessels. The mean thromboxane level during ischemia was 1785.34 +/- 124.81 pg/ml. The mean levels of thromboxane rose significantly (p ischemia group, 192.33 percent in the 4-hr ischemia group, and 294.69 percent in the 6-hr ischemia group, and correlated well with histologic observations. The results suggest that a microdialysis technique, combined with a sensitive assay for measuring thromboxane, is a useful method for in vivo monitoring of inflammatory processes during ischemia and reperfusion. The evolution of thromboxane release following 6 hr of ischemia indicates that this mediator may be involved in facilitation of cell death, following ischemia and reperfusion, since its tissue level correlates with histologic tissue damage.

  20. 肠脂肪酸结合蛋白在急腹症患者中鉴别急性肠缺血的价值%The value of serum intestinal fatty acid binding protein measurement in discriminating intestinal ischemia in patients with acute abdomen

    Institute of Scientific and Technical Information of China (English)

    石卉; 吴本俨; 刘文徽; 苏斌斌; 李婷婷

    2012-01-01

    目的 评估肠脂肪酸结合蛋白( I-FABP)在急腹症患者中鉴别急性肠缺血的价值.方法 2009年11月至2011年8月解放军总医院151例住院急腹症患者及17例健康对照者纳入本研究,测定其血清I-FABP水平,根据ROC曲线计算I-FABP诊断急性肠缺血的临界值、敏感性、特异性、阳性似然比、阴性似然比、阳性预测值、阴性预测值,评估其诊断及鉴别诊断价值.结果 151例急腹症患者中急性肠缺血24例,非肠缺血127例.肠缺血组的I-FABP水平[(109.67 ±48.82)μg/L]明显高于非肠缺血组[(36.78±11.25) μg/L]和健康对照组[(8.33±6.25) μg/L],P值均<0.01.I-FABP的诊断临界值为87.52 μg/L,I-FABP诊断急性肠缺血的敏感度为0.762,阴性预测值为0.963,阳性似然比3.05,阴性似然比0.24.结论 血清I-FABP用于鉴别急腹症中急性肠缺血患者具有临床诊断价值.%Objective To assess the differential diagnostic value of serum intestinal fatty acid binding protein (I-FABP) in distinguishing intestinal ischemia patients from acute abdomen patients.Methods A total of 151 patients with acute abdomen and 17 healthy controls from the PLA General Hospital were enrolled from November,2009 to August,2011. Serum I-FABP levels were measured by ELISA.According to the ROC curve,the cut-off value,sensitivity,specificity,positive likelihood ratio (PLR),negative likelihood ratio ( NLR),positive predietive value (PPV) and negative predictive value (NPV) were calculated. Results Of the 151 acute abdomen patients,there were 24 intestinal ischemia patients and 127 without intestinal ischemia.Serum I-FABP level in intestinal ischemia group [( 109.67 ±48.82) μg/L]was significantly higher than those in patients without intestinal ischemia [(36.78 ± 11.25) μg/L]and healthy controls[(8.33 ±6.25) μg/L]( all P values <0.01 ).The serum I-FABP cut-off value for the diagnosis of intestinal ischemia was 87.52 μg/L.Serum I-FABP was efficient in terms of

  1. Factors associated with the impossibility to obtain reliable liver stiffness measurements by means of Acoustic Radiation Force Impulse (ARFI) elastography—Analysis of a cohort of 1031 subjects

    Energy Technology Data Exchange (ETDEWEB)

    Bota, Simona, E-mail: bota_simona1982@yahoo.com; Sporea, Ioan, E-mail: isporea@umft.ro; Sirli, Roxana, E-mail: roxanasirli@gmail.com; Popescu, Alina, E-mail: alinamircea.popescu@gmail.com; Danila, Mirela, E-mail: mireladanila@gmail.com; Jurchis, Ana, E-mail: ana.jurchis@yahoo.com; Gradinaru-Tascau, Oana, E-mail: bluonmyown@yahoo.com

    2014-02-15

    Introduction: Acoustic Radiation Force Impulse (ARFI) elastography is a non-invasive technique for liver fibrosis assessment. Aim: To assess the feasibility of ARFI elastography in a large cohort of subjects and to identify factors associated with impossibility to obtain reliable liver stiffness (LS) measurements by means of this technique. Methods: Our retrospective study included 1031 adult subjects with or without chronic liver disease. In each subject LS was assessed by means of ARFI elastography. Failure of ARFI measurements was defined if no valid measurement was obtained after at least 10 shots and unreliable in the following situations: fewer than 10 valid shots; or median value of 10 valid measurements with a success rate (SR) < 60% and/or an interquartile range interval (IQR) ≥ 30%. Results: Failure of LS measurements by means of ARFI was observed in 4 subjects (0.3%), unreliable measurements in 66 subjects (6.4%), so reliable measurements were obtained in 961 subjects (93.3%). In univariant analysis, the following risk factors were associated with failed and unreliable measurements: age over 58 years (OR = 0.49; 95% CI 0.30–0.80, p = 0.005), male gender (OR = 0.58; 95% CI 0.34–0.94, p = 0.04), BMI > 27.7 kg/m{sup 2} (OR = 0.23, 95% CI 0.13–0.41, p < 0.0001). In multivariate analysis all the factors mentioned above were independently associated with the risk of failed and unreliable measurements. Conclusions: Reliable LS measurements by means of ARFI elastography were obtained in 93.3% of cases. Older age, higher BMI and male gender were associated with the risk of failed and unreliable measurements, but their influence is limited as compared with Transient Elastography.

  2. UCP-2 gene knock-out alleviates ischemia/reperfusion-induced injury of high fat diet induced fatty liver%解耦联蛋白-2基因敲除减轻高脂饮食诱导小鼠脂肪肝缺血再灌注损伤

    Institute of Scientific and Technical Information of China (English)

    程锐; 王帅; 刘涛; 王春友; 万赤丹

    2010-01-01

    dehydrogenase (LDH) in hver tissues, and alanine tronsaminase (ALT), and asparate amin-otransferase (AST) in serum were determed. The pathologic changes were also examined. Results After feed-ing on high fat diet for 6 mouths, the model of fatty liver in mice was established. Western blotting con-firmed that the expression of UCP-2 mRNA was inhibited completely, and the expression level in group C was higher than in group B. The ALT, AST, ATP, ROS and LDH levels in group A were (55.33± 5.51), (128.33±7.02) U/L, (28.00±2.00) nmol/L, (165.33±7.09), (1176.00±22.27) U/prot, those in group B were (25.00±4.58), (85.33±4.51) U/L, (24.33±4.16) nmol/L, (147.33± 7.51), and (707.33±31.64) U/prot, and those in group C were (142.67±13.01), (220.67±7.02) U/L, (8.67±1.53 ) nmol/L, (65.00±5.00), (1748.33±42.52) U/prot, respectively. There was significant difference between group A and group C. Pathologic examination revealed that in group A, the ischemia-reperfusion-induced injury was milder than in group C. Conclusion Inhibiting the expression of UCP-2 attenuates the I/R injury of mouse fatty liver.

  3. Liver regeneration.

    Science.gov (United States)

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  4. Myocardial ischemia, carotid, and peripheral arterial disease and their interrelationship in type 2 diabetes patients

    DEFF Research Database (Denmark)

    Poulsen, Mikael K; Henriksen, Jan Erik; Dahl, Jordi;

    2009-01-01

    for the first time and age-matched nondiabetic reference subjects (n = 40) were screened for myocardial ischemia, carotid, and peripheral arterial disease by means of myocardial perfusion scintigraphy, carotid artery ultrasonography, and peripheral ankle and toe systolic blood pressure measurements. RESULTS......: In the T2DM patients, the prevalence of myocardial ischemia, carotid, and peripheral arterial disease was 30%, 42%, and 15%, respectively, almost three times higher than in the reference subjects (P = 0.007, P = 0.001, and P = 0.09, respectively). T2DM patients with myocardial ischemia, carotid...

  5. Curcumin reduces inflammatory reactions following transient cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Jing Zhao; Shanshan Yu; Lan Li; Xuemei Lin; Yong Zhao

    2011-01-01

    Inflammatory reactions are important pathophysiological mechanisms of ischemic brain injury. The present study analyzed the anti-inflammatory characteristics of curcumin via myeloperoxidase activity and nitric oxide content after 2-hour ischemia/24-hour reperfusion in Sprague Dawley rats. In addition, expressions of nuclear factor kappa B, tumor necrosis factor-α and interleukin-1β protein were measured. Curcumin significantly reduced myeloperoxidase and nitric oxide synthase activities and suppressed expressions of nuclear factor kappa B, tumor necrosis factor-a, and interleukin-1β in ischemia/reperfusion brain tissue. Results suggested that the neuroprotective effect of curcumin following cerebral ischemia/reperfusion injury could be associated with inhibition of inflammatory reactions.

  6. Altered acetylcholinesterase levels in the spinal cord anterior horn and dorsal root ganglion following sciatic nerve ischemia

    Institute of Scientific and Technical Information of China (English)

    Zhenjun Yang; Pei Wang; Songhe Yang; Jingfeng Xue

    2009-01-01

    BACKGROUND: Peripheral nerve ischemia has been shown to result in ischemic fiber degeneration and axoplasmic transport disturbance. However, the effect on acetylcholinesterase (AChE) expression in relevant cells following sciatic nerve ischemia remains unclear. OBJECTIVE: To observe AChE concentration changes following peripheral nerve ischemia. DESIGN, TIME AND SETTING: The present comparative observation, neuroanatomical experiment was performed at the Central Laboratory Animal of Chengde Medical College between 2006 and 2007. MATERIALS: A total of 20 healthy, adult, Wistar rats were randomized into two groups (n = 10): 8-day ischemia and 14-day ischemia. METHODS: Ischemia injury was induced in the unilateral sciatic nerve (experimental side) through ligation of the common iliac artery. The contralateral side received no intervention, and served as the control side. Rats in the 8-day ischemia and 14-day ischemia groups were allowed to survive for 8 and 14 days, respectively. MAIN OUTCOME MEASURES: The L5 lumbar spinal cord and the L5 dorsal root ganglion were removed from both sides and sectioned utilizing a Leica vibrating slicer. AChE cellular expression was detected using Karnovsky-Root, and the number of AChE-positive cells and average gray value were analyzed using a MiVnt image analysis system. RESULTS: In the 8-day ischemia group, AChE-positive cell numbers were significantly less in the dorsal root ganglion and spinal cord anterior horn of the experimental side, but the average gray value was significantly greater, compared with the control side (P < 0.05). These changes were more significant in the 14-day ischemia group than in the 8-day ischemia group (P < 0.01). CONCLUSION: Peripheral nerve ischemia leads to decreased AChE expression in the associated cells in a time-dependent manner.

  7. Influence of Tissue Microstructure on Shear Wave Speed Measurements in Plane Shear Wave Elastography: A Computational Study in Lossless Fibrotic Liver Media.

    Science.gov (United States)

    Wang, Yu; Jiang, Jingfeng

    2017-07-01

    Shear wave elastography (SWE) has been used to measure viscoelastic properties for characterization of fibrotic livers. In this technique, external mechanical vibrations or acoustic radiation forces are first transmitted to the tissue being imaged to induce shear waves. Ultrasonically measured displacement/velocity is then utilized to obtain elastographic measurements related to shear wave propagation. Using an open-source wave simulator, k-Wave, we conducted a case study of the relationship between plane shear wave measurements and the microstructure of fibrotic liver tissues. Particularly, three different virtual tissue models (i.e., a histology-based model, a statistics-based model, and a simple inclusion model) were used to represent underlying microstructures of fibrotic liver tissues. We found underlying microstructures affected the estimated mean group shear wave speed (SWS) under the plane shear wave assumption by as much as 56%. Also, the elastic shear wave scattering resulted in frequency-dependent attenuation coefficients and introduced changes in the estimated group SWS. Similarly, the slope of group SWS changes with respect to the excitation frequency differed as much as 78% among three models investigated. This new finding may motivate further studies examining how elastic scattering may contribute to frequency-dependent shear wave dispersion and attenuation in biological tissues.

  8. Dictionary-Driven Ischemia Detection From Cardiac Phase-Resolved Myocardial BOLD MRI at Rest.

    Science.gov (United States)

    Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A

    2016-01-01

    Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP-BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP-BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson's r=0.84) with respect to infarct size. When advances in automated registration and segmentation of CP-BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique.

  9. Clinical Neuroimaging of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawara, Jyoji [Nakamura Memorial Hospital, Sapporo (Japan)

    1999-06-01

    Notice points in clinical imaging of cerebral ischemia are reviewed. When cerebral blood flow is determined in acute stage of cerebral embolism (cerebral blood flow SPECT), it is important to find area of ischemic core and ischemic penumbra. When large cortex area is assigned to ischemic penumbra, thrombolytic therapy is positively adapted, but cautious correspondence is necessary when ischemic core is recognized. DWI is superior in the detection of area equivalent to ischemic core of early stage, but, in imaging of area equivalent to ischemic penumbra, perfusion image or distribution image of cerebral blood volume (CBV) by MRI need to be combined. Luxury perfusion detected by cerebral blood flow SPECT in the cases of acute cerebral embolism suggests vascular recanalization, but a comparison with CT/MRI and continuous assessment of cerebral circulation dynamics were necessary in order to predict brain tissue disease (metabolic abnormality). In hemodynamic cerebral ischemia, it is important to find stage 2 equivalent to misery perfusion by quantification of cerebral blood flow SPECT. Degree of diaschisis can indicate seriousness of brain dysfunction for lacuna infarct. Because cerebral circulation reserve ability (perfusion pressure) is normal in all areas of the low cerebral blood flow by diaschisis mechanism, their areas are easily distinguished from those of hemodynamic cerebral ischemia. (K.H.)

  10. Predictive Modeling of Cardiac Ischemia

    Science.gov (United States)

    Anderson, Gary T.

    1996-01-01

    The goal of the Contextual Alarms Management System (CALMS) project is to develop sophisticated models to predict the onset of clinical cardiac ischemia before it occurs. The system will continuously monitor cardiac patients and set off an alarm when they appear about to suffer an ischemic episode. The models take as inputs information from patient history and combine it with continuously updated information extracted from blood pressure, oxygen saturation and ECG lines. Expert system, statistical, neural network and rough set methodologies are then used to forecast the onset of clinical ischemia before it transpires, thus allowing early intervention aimed at preventing morbid complications from occurring. The models will differ from previous attempts by including combinations of continuous and discrete inputs. A commercial medical instrumentation and software company has invested funds in the project with a goal of commercialization of the technology. The end product will be a system that analyzes physiologic parameters and produces an alarm when myocardial ischemia is present. If proven feasible, a CALMS-based system will be added to existing heart monitoring hardware.

  11. Omega-3 fatty acids reduce hepatic steatosis and consequently attenuate ischemia-reperfusion injury following partial hepatectomy in rats

    NARCIS (Netherlands)

    H.A. Marsman; M. Heger; J.J. Kloek; S.L. Nienhuis; F.J.W. ten Kate; T.M. van Gulik

    2011-01-01

    Aim: The aim of this study was to investigate omega-3 fatty acids (FAs) treatment of experimental steatosis and the consequent effect on ischemia-reperfusion (IR) injury. Background: Fatty livers are more susceptible to IR injury and display decreased regenerative capacity. Consequently, restriction

  12. Effects of a Calcium Bentonite Clay in Diets Containing Aflatoxin when Measuring Liver Residues of Aflatoxin B₁ in Starter Broiler Chicks.

    Science.gov (United States)

    Fowler, Justin; Li, Wei; Bailey, Christopher

    2015-08-26

    Research has shown success using clay-based binders to adsorb aflatoxin in animal feeds; however, no adsorbent has been approved for the prevention or treatment of aflatoxicosis. In this study, growth and relative organ weights were evaluated along with a residue analysis for aflatoxin B₁ in liver tissue collected from broiler chickens consuming dietary aflatoxin (0, 600, 1200, and 1800 µg/kg) both with and without 0.2% of a calcium bentonite clay additive (TX4). After one week, only the combined measure of a broiler productivity index was significantly affected by 1800 µg/kg aflatoxin. However, once birds had consumed treatment diets for two weeks, body weights and relative kidney weights were affected by the lowest concentration. Then, during the third week, body weights, feed conversion, and the productivity index were affected by the 600 µg/kg level. Results also showed that 0.2% TX4 was effective at reducing the accumulation of aflatoxin B₁ residues in the liver and improving livability in birds fed aflatoxin. The time required to clear all residues from the liver was less than one week. With evidence that the liver's ability to process aflatoxin becomes relatively efficient within three weeks, this would imply that an alternative strategy for handling aflatoxin contamination in feed could be to allow a short, punctuated exposure to a higher level, so long as that exposure is followed by at least a week of a withdrawal period on a clean diet free of aflatoxin.

  13. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Jun Li

    Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

  14. Antioxidant effects of xanthohumol and functional impact on hepatic ischemia-reperfusion injury.

    Science.gov (United States)

    Hartkorn, Andreas; Hoffmann, Florian; Ajamieh, Hussam; Vogel, Susanne; Heilmann, Jörg; Gerbes, Alexander L; Vollmar, Angelika M; Zahler, Stefan

    2009-10-01

    Therapeutic effects of dietary flavonoids have been attributed mainly to their antioxidant capacity. Xanthohumol (1), a prominent flavonoid of the hop plant, Humulus lupulus, was investigated for its antioxidant potential and for its effect on NF-kappaB activation. To examine the biological relevance of 1, a hepatic ischemia/reperfusion model was chosen as a widely accepted model of oxidative stress generation. The impact of 1 on endogenous antioxidant systems, on the NF-kappaB signal transduction pathway as well as on apoptotic parameters, and on hepatic tissue damage was evaluated. Compound 1 markedly decreased the level of reactive oxygen species in vitro. Furthermore, levels of enzymatic and nonenzymatic antioxidants were restored after pretreatment in postischemic hepatic tissue, and lipid peroxidation was attenuated. NF-kappaB activity was reduced in vitro as well as in hepatic tissue after ischemia/reperfusion upon pretreatment with 1. In addition, the phosphorylation of Akt was markedly inhibited. Surprisingly, 1 decreased the expression of the antiapoptotic protein Bcl-X and increased caspase-3 like-activity, a proapoptotic parameter. Moreover, hepatic tissue damage as well as TNF-alpha levels increased in xanthohumol-pretreated liver tissue after ischemia/reperfusion. In summary, xanthohumol did not protect against ischemia/reperfusion injury in rat liver, despite its antioxidant and NF-kappaB inhibitory properties.

  15. Role of Nuclear Factor kappaB in Intestine Injury Induced by Hepatic Ischemia Reperfusion

    Institute of Scientific and Technical Information of China (English)

    陈俊华; 王国斌

    2004-01-01

    Summary: The role of nuclear factor kappaB in intestine injury induced by hepatic ischemia reperfusion was investigated. Eighteen male Wistar rats were divided into 3 groups randomly: sham operation group (group A), hepatic ischemia reperfusion group (group B) and hepatic ischemia reperfusion plus pyrrolidine dithiocarbamate (PDTC) group (group C). The rats in group A were only subjected to laparotomy, those in group B underwent partial hepatic ischemia reperfusion (ischemia for 1 h and reperfusion for 2 h) and those in group C underwent the same procedure as that of group B but received PDTC 200 mg/kg i.v. before and after ischemia. After reperfusion, tissues of jejunum and venous blood were obtained for measurement of TNF-α, MDA and MPO. The levels of TNF-α in jejunum and venous blood, the levels of MPO in jejunum in group B were significantly higher than those in group A and group C (P<0.05). There was no significant different in the levels of MDA between group B and group C. The severity of histological intestinal injury in group B and group C was similar. Hepatic ischemia reperfusion caused intestine injury, NF-kappaB may play an important role in this course and the targeting of upstream components of the inflammatory response, such as NF-kappaB, may have important therapeutic applications.

  16. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Seyed Mojtaba Hosseini; Mohammad Farahmandnia; Zahra Razi; Somayeh Delavarifar; Benafsheh Shakibajahromi

    2015-01-01

    Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the lfuorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These ifndings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

  17. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Seyed Mojtaba Hosseini

    2015-01-01

    Full Text Available Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the fluorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These findings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

  18. Caffeic acid ameliorates early and delayed brain injuries after focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Yu ZHOU; San-hua FANG; Yi-lu YE; Li-sheng CHU; Wei-ping ZHANG; Meng-ling WANG; Er-qing WEI

    2006-01-01

    Aim: To investigate the effects of caffeic acid on early and delayed injuries after focal cerebral ischemia in rats, and the possible relation to 5-lipoxygenase inhibition. Methods: Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in Sprague-Dawley rats. Caffeic acid (10 and 50 mg/kg) was ip injected for 5 d after ischemia. The brain injuries were observed, and the levels of cysteinyl leukotrienes and leukotriene B4 in the brain tissue were measured. Results: Caffeic acid (50 mg/kg) ameliorated neurological dysfunction and neuron loss, and decreased infarct volume 24 h after ischemia; it attenuated brain atrophy, infarct volume, and particularly astrocyte proliferation 14 d after ischemia. In addition, it reduced the production of leukotrienes (5-lipoxygenase metabolites) in the ischemic hemispheres 3 h and 7 d after ischemia. Conclusion: Caffeic acid has protective effect on both early and delayed injuries after focal cerebral ischemia in rats; and this effect may partly relate to 5-lipoxygenase inhibition.

  19. Kidney ischemia and reperfunsion syndrome: effect of lidocaine and local postconditioning

    Directory of Open Access Journals (Sweden)

    IGOR NAGAI YAMAKI

    Full Text Available ABSTRACT Objective: to evaluate the effects of blocking the regulation of vascular tone on the ischemia and reperfusion syndrome in rats through the use of lidocaine in the postconditioning technique. Methods: we randomized 35 rats into seven groups of five animals: Group 1- Control; Group 2- Ischemia and Reperfusion; Group 3- Ischemia, Reperfusion and Saline; Group 4- Ischemic Postconditioning; Group 5- Ischemic Postconditioning and Saline; Group 6- Lidocaine; Group 7- Ischemic Postconditioning and Lidocaine. Except for the control group, all the others were submitted to renal ischemia for 30 minutes. In postconditioning groups, we performed ischemia and reperfusion cycles of five minutes each, applied right after the main ischemia. In saline and lidocaine groups, we instilled the substances at a rate of two drops per minute. To compare the groups, we measured serum levels of urea and creatinine and also held renal histopathology. Results: The postconditioning and postconditioning + lidocaine groups showed a decrease in urea and creatinine values. The lidocaine group showed only a reduction in creatinine values. In histopathology, only the groups submitted to ischemic postconditioning had decreased degree of tubular necrosis. Conclusion: Lidocaine did not block the effects of postconditioning on renal ischemia reperfusion syndrome, and conferred better glomerular protection when applied in conjunction with ischemic postconditioning.

  20. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

    Science.gov (United States)

    Pachori, Alok S.; Melo, Luis G.; Hart, Melanie L.; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D.; Stahl, Gregory L.; Pratt, Richard E.; Dzau, Victor J.

    2004-08-01

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  1. The response of GABAergic and cholinergic neurons to transient cerebral ischemia.

    Science.gov (United States)

    Francis, A; Pulsinelli, W

    1982-07-15

    The vulnerability of striatal and hippocampal neurons to ischemia was studied by measuring the activity of neurotransmitter-related enzymes after transient forebrain ischemia in rats. Activities of glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) were measured 6 h to 8 days after 20, 30 or 40 min of forebrain ischemia, as markers for GABAergic and cholinergic neurons respectively. Transient forebrain ischemia resulted in depression of striatal GAD activity while striatal CAT and hippocampal GAD activities were unaffected. Striatal GAD activity progressively decreased during the first 24 h postischemia and remained depressed 5--8 days later, suggesting irreversible damage to this population of neurons. The stability of striatal CAT and hippocampal GAD activity indicates that these cells were resistant to the present ischemic conditions.

  2. Protective effect of ischemic preconditioning on liver

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To study the protective effect of ischemicpreconditioning (IPC) on the hepatic ischemia-reperfusion injury.Methods: The model of rat liver subjected to ischemia/reperfusion (I/R) injury was made. All 24 mice were divided randomly into 3 groups and anesthetized by 2% sodium pentobarbital (30-40 mg/kg). The enzyme activity of AST, ALT, LDH, SOD and the content of LPO were assayed respectively. Specimens were observed under transmission electron microscope.Results: IPC prevented the increase of ALT, AST and LDH in the blood and that of LPO in the tissues (P<0.05), and maintained high level of SOD in the tissues (P<0.05).Conclusions: IPC has protective effect on the liver function.

  3. Assessment of liver fibrosis by Fibroscan as compared to liver biopsy in biliary atresia

    OpenAIRE

    Shen, Qiu-Long; Chen, Ya-Jun; Wang, Zeng-Meng; Zhang, Ting-Chong; Pang, Wen-Bo; Shu, Jun; Peng, Chun-Hui

    2015-01-01

    AIM: To evaluate liver stiffness measurement (LSM) using non-invasive transient elastography (Fibroscan) in comparison with liver biopsy for assessment of liver fibrosis in children with biliary atresia (BA).

  4. Liver Immunology

    Science.gov (United States)

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  5. Arachidonic Acid and Cerebral Ischemia Risk: A Systematic Review of Observational Studies

    Directory of Open Access Journals (Sweden)

    Mai Sakai

    2014-11-01

    Full Text Available Background: Arachidonic acid (ARA is a precursor of various lipid mediators. ARA metabolites such as thromboxane A2 cause platelet aggregation and vasoconstriction, thus may lead to atherosclerotic disease. It is unclear whether dietary ARA influences the ARA-derived lipid mediator balance and the risk for atherosclerotic diseases, such as cerebral ischemia. Considering the function of ARA in atherosclerosis, it is reasonable to focus on the atherothrombotic type of cerebral ischemia risk. However, no systematic reviews or meta-analyses have been conducted to evaluate the effect of habitual ARA exposure on cerebral ischemia risk. We aimed to systematically evaluate observational studies available on the relationship between ARA exposure and the atherothrombotic type of cerebral ischemia risk in free-living populations. Summary: The PubMed database was searched for articles registered up to June 24, 2014. We designed a PubMed search formula as follows: key words for humans AND brain ischemia AND study designs AND ARA exposure. Thirty-three articles were reviewed against predefined criteria. There were 695 bibliographies assessed from the articles that included both ARA and cerebral ischemia descriptions. Finally, we identified 11 eligible articles and categorized them according to their reporting and methodological quality. We used the Strengthening the Reporting of Observational Studies in Epidemiology Statement (STROBE checklist to score the reporting quality. The methodological quality was qualitatively assessed based on the following aspects: subject selection, ARA exposure assessment, outcome diagnosis, methods for controlling confounders, and statistical analysis. We did not conduct a meta-analysis due to the heterogeneity among the studies. All eligible studies measured blood ARA levels as an indicator of exposure. Our literature search did not identify any articles that evaluated dietary ARA intake and tissue ARA as assessments of

  6. Real-Time Visualization of Tissue Ischemia

    Science.gov (United States)

    Bearman, Gregory H. (Inventor); Chrien, Thomas D. (Inventor); Eastwood, Michael L. (Inventor)

    2000-01-01

    A real-time display of tissue ischemia which comprises three CCD video cameras, each with a narrow bandwidth filter at the correct wavelength is discussed. The cameras simultaneously view an area of tissue suspected of having ischemic areas through beamsplitters. The output from each camera is adjusted to give the correct signal intensity for combining with, the others into an image for display. If necessary a digital signal processor (DSP) can implement algorithms for image enhancement prior to display. Current DSP engines are fast enough to give real-time display. Measurement at three, wavelengths, combined into a real-time Red-Green-Blue (RGB) video display with a digital signal processing (DSP) board to implement image algorithms, provides direct visualization of ischemic areas.

  7. MELD score measured day 10 after orthotopic liver transplantation predicts death and re-transplantation within the first year

    DEFF Research Database (Denmark)

    Rostved, Andreas A; Lundgren, Jens D; Hillingsø, Jens

    2016-01-01

    day 1 the MELD score significantly diversified and was higher in the poor outcome group (MELD score quartile 4 versus quartile 1-3 at day 10: HR 5.1, 95% CI: 2.8-9.0). This association remained after adjustment for non-identical blood type, autoimmune liver disease and hepatocellular carcinoma...

  8. Acute limb ischemia in cancer patients: should we surgically intervene?

    LENUS (Irish Health Repository)

    Tsang, Julian S

    2012-02-01

    BACKGROUND: Cancer patients have an increased risk of venous thromboembolic events. Certain chemotherapeutic agents have also been associated with the development of thrombosis. Reported cases of acute arterial ischemic episodes in cancer patients are rare. METHODS: Patients who underwent surgery for acute limb ischemia associated with malignancy in a university teaching hospital over a 10-year period were identified. Patient demographics, cancer type, chemotherapy use, site of thromboembolism, treatment and outcome were recorded. RESULTS: Four hundred nineteen patients underwent surgical intervention for acute arterial ischemia, 16 of these patients (3.8%) had associated cancer. Commonest cancer sites were the urogenital tract (n = 5) and the lungs (n = 5). Eight patients (50%) had been recently diagnosed with cancer, and four (25%) of these cancers were incidental findings after presentation with acute limb ischemia. Four patients (25%) developed acute ischemia during chemotherapy. The superficial femoral artery was the most frequent site of occlusion (50%), followed by the brachial (18%) and popliteal (12%) arteries. All patients underwent thromboembolectomy, but two (12%) patients subsequently required a bypass procedure. Six patients (37%) had limb loss, and in-patient mortality was 12%. Histology revealed that all occlusions were due to thromboembolism, with no tumor cells identified. At follow-up, 44% of patients were found to be alive after 1 year. CONCLUSION: Cancer and chemotherapy can predispose patients to acute arterial ischemia. Unlike other reports that view this finding as a preterminal event most appropriately treated by palliative measures, in this series, early diagnosis and surgical intervention enabled limb salvage and patient survival.

  9. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

  10. Liver disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  11. Liver Disease

    Science.gov (United States)

    ... stay still. Liver disease has many causes. Infection Parasites and viruses can infect the liver, causing inflammation ... beyond. National Institute of Diabetes and Digestive and Kidney Diseases. http://digestive.niddk.nih.gov/ddiseases/pubs/ ...

  12. Hemostasis and the diseased liver : a study on hemostatic disorders in liver disease and liver transplantation

    NARCIS (Netherlands)

    C.M. Bakker (Minke)

    1993-01-01

    textabstractIn this thesis studies on hemostatic disorders in liver cirrhosis and liver transplantation have been described. Aims of the work were to further investigate; 1. Whether (low-grade) DIC occurs in liver cirrhosis applying new quantitative tests, measuring thrombin-antithrombin Ill complex

  13. Comparison of serial serum ferritin measurements and liver iron concentration assessed by MRI in adult transfused patients with sickle cell disease.

    Science.gov (United States)

    Tsitsikas, Dimitris A; Nzouakou, Ruben; Ameen, Venus; Sirigireddy, Bala; Amos, Roger J

    2014-02-01

    Transfused patients with sickle cell disease (SCD) are at risk of iron overload and identifying such patients is important to prevent associated complications. Our aim was to assess the efficacy of serial serum ferritin (SF) measurements in identifying patients with hepatic iron overload as assessed by liver MRI and its usefulness in guiding decision making regarding chelation therapy. We retrospectively compared the results of 49 liver MRI scans (LS) with the median serum ferritin (MSF) values for 28 patients in our institution. We found a nonlinear increment of MSF with increasing liver iron concentration (LIC). 18.4% and 47.4% of abnormal LSs corresponded to MSF serum ferritin measurements in adult transfused patients with sickle cell disease have a low sensitivity for identifying patients with iron overload and are of limited value in guiding decision making regarding initiation or monitoring of chelation therapy. The iron status of such high risk patients should be assessed by more definitive ways such as MRI. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. The effects of simultaneous revascularization on the expression of TNF-α during bile duct ischemia-reperfusion injury in rats liver transplantation%双重血流同时开放对大鼠肝移植胆管TNF-α表达的影响

    Institute of Scientific and Technical Information of China (English)

    张毅; 冉艳; 叶启发

    2008-01-01

    目的 探讨门静脉、肝动脉双重血流同时开放对大鼠肝移植胆道缺血/再灌注(I/R)损伤中的TNF-α表达的影响.方法 选用雄性SD大鼠建立大鼠自体原位肝移植模型,随机分为双重血流同时开放组(P组)、门静脉先开放组(N组)和假手术对照组(S组),供肝再灌注后检测血清ALT、AST、GGT、AKP、TBiL及DBiL水平,比色法测定髓过氧化物酶(MPO)含量,RT-PCR法检测胆管组织TNF-α、mRNA表达.结果 肝脏再灌注后6 h及24 h两个时点P组的GGT水平明显低于N组水平(P<0.05);肝脏再灌注后24 h,P组的AKP、TBiL、DBiL水平及胆管损伤病理学评分明显低于N组水平(P<0.05);再灌注后6 h,N组大鼠肝组织的MPO含量明显高于P组(P<0.05);供肝再灌注后2h、6h,P组大鼠肝组织TNF-α mRNA的相对表达水平明显低于N组(P<0.05).结论 门静脉、肝动脉双重血流同时开放,有利于减轻肝移植物胆管组织的I/R损伤;其机制可能与TNF-α表达水平的降低以及中性粒细胞(PMN)浸润的减少有关.%Objective To investigate the effects of simultaneous hepatic artery and portal revaseularization on the expression of TNF-α during bile duet ischemia-reperfusion injury in rats liver transplantation.Methods Male Spragne-Dawley rats were used to establish an autologous orthotopic liver transphmtation model.Model rats were random divided two groups,simultaneous revascularization group(sroup P)and portal vein revascularization group(group N).The animals were separately killed at the 2nd hour,6th hour and 24th hour after reperfusion.Plasma samples were collected for ALT,AST,GGT,AKP,TBiL and DBiL test.Bile duct tissues were collected to detect the histolosical changes,MPO activit,and the expression of TNF-α mRNA.Results The serum levels of GGT in group P was significantly lower than that in group N at the 6th hour and 24th hour after reperfusion(P<0.05).And the serum levels of AKP,TBiL and DBiL and the morphological scores of

  15. Role of Coronary Calcium Scoring in the Assessment of Physiological Ischemia in Patients with Intermediate Stenosis

    Science.gov (United States)

    Horie, Kazunori; Kikuchi, Yuichi; Takizawa, Kaname; Inoue, Naoto

    2015-01-01

    Although coronary artery calcium (CAC) is an established marker of coronary atherosclerosis, whether it also reflects the physiological significance is unknown. This study aims to evaluate if CAC could indicate physiological ischemia in intermediate stenosis defined by an invasive fractional flow reserve (FFR). CAC score (CACS) derived from either whole coronary arteries or individual arteries was measured by computed tomography among patients with intermediate de novo lesions (percent diameter stenosis from 30% to less than 70%). All stenoses were evaluated by invasive FFR; lesions with an FFR ≤ 0.80 were considered significant. We enrolled 119 patients with 143 lesions. Of these, 42 lesions (29.4%) demonstrated significant ischemia by FFR measurement. FFR values had modest but significant correlations with CACS in individual arteries with intermediate stenosis (r = − 0.290; p stenosis had 71.4% sensitivity and 67.3% specificity as a predictor of significant ischemia at a cut off value of 145.9. Multivariable analysis showed that percent diameter stenosis and CACS in individual arteries with intermediate stenosis were independent predictors for significant ischemia. By net reclassification improvement analysis, CACS in individual arteries with intermediate stenosis provided incremental prediction for significant ischemia over minimum lumen diameter, percent diameter stenosis, and lesion length. CACS measured in each artery, but not the total CACS, provides additional information as to whether an angiographically intermediate stenosis within the artery is significant enough to cause myocardial ischemia. PMID:26648671

  16. Protective effects of ischemic preconditioning and application of lipoic acid prior to 90 min of hepatic ischemia in a rat model

    Institute of Scientific and Technical Information of China (English)

    Friedrich Duenschede; Ines Gockel; Alexandra K Kiemer; Theodor Junginger; Kirsten Erbes; Nina Riegler; Patrick Ewald; Achim Kircher; Stefanie Westermann; Arno Schad; Imke Miesmer; Simon Albrecht-Sch(o)ck

    2007-01-01

    AIM: To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning (IP) as well as pharmacologic pretreatment by αα-lipoic acid (LA).METHODS: Several groups of rats were compared:sham operated animals, non-pretreated animals (nt),animals receiving IP (10 min of ischemia by clamping of the portal triad and 10 min of reperfusion) prior to sustained ischemia, animals receiving selective ischemic preconditioning (IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 min of reperfusion)prior to sustained ichemia, and animals receiving 500μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia.RESULTS: Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA (19±2 vs 10±1, P<0.05 and 29±5 vs 12±1,P<0.05). Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment (3.1±0.3 vs 1.8±0.2, P<0.05). Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation (LPO) in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towards anti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death.CONCLUSION: IP, consisting of 10 min of ischemia and 10 min of reperfusion, protects only partly against ischemia/reperfusion injury of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia,possibly by downregulation of pro-apoptotic Bax.

  17. Microdialysis-based analysis of interstitial NO in situ: NO synthase-independent NO formation during myocardial ischemia.

    Science.gov (United States)

    Martin, Claus; Schulz, Rainer; Post, Heiner; Boengler, Kerstin; Kelm, Malte; Kleinbongard, Petra; Gres, Petra; Skyschally, Andreas; Konietzka, Ina; Heusch, Gerd

    2007-04-01

    Nitric oxide (NO) synthesis by NO synthases (NOS) requires oxygen. However, although counterintuitive, NO synthesis is increased in ischemic myocardium. Accordingly, mechanisms independent of the NOS pathway have been suggested to contribute to NO synthesis during ischemia. NO initiates detrimental as well as protective mechanisms in a concentration-dependent manner, thus aggravating or improving the outcome of ischemia. The aim of this study was to measure in situ interstitial NO concentrations in parallel to infarct size in anaesthetized pigs subjected to myocardial ischemia/reperfusion. The contribution of NOS-independent pathways to NO synthesis was studied using NOS blockade. Interstitial NO measurements, based on microdialysis combined with the oxyhemoglobin method, were made during 90 min of moderate or severe ischemia and subsequent reperfusion. To examine the effect of NOS inhibition, an initial 30-min ischemic period was followed 60 min later by a second 30-min ischemic period with intracoronary infusion of S-ethyl-isothiourea. During ischemia, the interstitial NO concentration increased for about 30 min and then remained constant at this elevated level. The increase in NO concentration by 253+/-82 nmol/L during moderate and 565+/-169 nmol/L during severe ischemia correlated inversely with subendocardial blood flow (r=-0.76). NOS inhibition increased coronary arterial pressure and decreased the interstitial basal NO concentration and tissue nitrite content. However, it did not diminish the increase in interstitial NO concentration during ischemia. NOS-independent pathways are significantly involved in NO synthesis during myocardial ischemia.

  18. (1)H-MRS measured ectopic fat in liver and muscle is associated with the metabolic syndrome in Danish girls but not in boys with overweight and obesity

    DEFF Research Database (Denmark)

    Nissen, A; Fonvig, Cilius E; Chabanova, E.

    2016-01-01

    BACKGROUND: The metabolic syndrome (MetS) is a complication to overweight and obesity, which can be observed already in childhood. Ectopic lipid accumulation in muscle and liver has been shown to associate with the development of insulin resistance and dyslipidemia. Thus, the interaction between...... boys) with overweight/obesity were investigated, as well as 47 controls (22 boys) with normal weight. The assessments included anthropometry, fasting blood biochemistry and blood pressure measurements. Liver and muscle lipid contents were assessed by proton magnetic resonance spectroscopy. RESULTS: We...... observed an odds ratio in girls with overweight/obesity of 12.2 (95% confidence interval: [3.8; 49.0]) for exhibiting MetS when hepatic steatosis was present, whereas no association was observed in boys with overweight/obesity (odds ratio 0.7 [0.2; 2.7]). The odds ratio of exhibiting MetS in the presence...

  19. Recipient twin limb ischemia with postnatal onset.

    Science.gov (United States)

    Broadbent, Roland Spencer

    2007-02-01

    After the occurrence of 3 local cases of limb ischemia in newborn twins, we reviewed the literature to investigate this combination systematically. This review reveals a distinct condition: postnatal onset limb ischemia affecting recipient twins in twin-twin transfusion syndrome.

  20. Retinal ischemia and embolism. Causes and outcomes

    NARCIS (Netherlands)

    Wijman, C.A.C.

    2007-01-01

    The ocular fundus allows direct visualization of the retinal vasculature, blood vessels that are part of the cerebral circulation. Unraveling the causes of retinal ischemia may provide further insight in the pathophysiological processes that underlie cerebral ischemia. The primary aim of the studies

  1. The effect of Allium sativum on ischemic preconditioning and ischemia reperfusion induced cardiac injury

    Directory of Open Access Journals (Sweden)

    Bhatti Rajbir

    2008-01-01

    Full Text Available In the present study, the effect of garlic (Allium sativum extract on ischemic preconditioning and ischemia-reperfusion induced cardiac injury has been studied. Hearts from adult albino rats of Wistar strain were isolated and immediately mounted on Langendorff′s apparatus for retrograde perfusion. After 15 minutes of stabilization, the hearts were subjected to four episodes of 5 min ischemia, interspersed with 5 min reperfusion (to complete the protocol of ischemic preconditioning, 30 min global ischemia, followed by 120 min of reperfusion. In the control and treated groups, respective interventions were given instead of ischemic preconditioning. The magnitude of cardiac injury was quantified by measuring Lactate Dehydrogenase and creatine kinase concentration in the coronary effluent and myocardial infarct size by macroscopic volume method. Our study demonstrates that garlic extract exaggerates the cardio protection offered by ischemic preconditioning and per se treatment with garlic extract also protects the myocardium against ischemia reperfusion induced cardiac injury.

  2. Detection of renal ischemia by in situ microdialysis - an experimental study

    DEFF Research Database (Denmark)

    Keller, Anna Krarup

    Purpose: Acute vascular thrombosis of the renal artery or vein is a feared and devastating complication after renal operations, especially transplantation. The aim of the present study was to evaluate microdialysis as a possible new tool for fast and reliable detection of renal ischemia...... was placed outside, on the renal capsule. The contra lateral kidney was removed. After two hours of baseline measurements, ischemia was introduced by clamping the renal artery or vein in the first two groups. Microdialysis samples were taken every thirty minutes during baseline and the following five hours...... in a porcine model. Material and methods: Twenty healthy anesthetized pigs were randomized to experiments on left or right kidney and into three groups: arterial ischemia (n=8); venous ischemia (n=8) and controls (n=4). One microdialysis catheter was inserted superficially in the renal cortex and one...

  3. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction...... the prevalence of ambulatory or transient myocardial ischemia is lower than in patients with chronic, stable coronary artery disease. A greater proportion of ischemic episodes, however, are silent than in other subgroups with ischemic heart disease. Early after the infarction, transient myocardial ischemia...... exhibits a circadian variation with a peak activity occurring in the late evening hours. Patients with non-Q wave infarction have more transient myocardial ischemia, whereas thrombolytic therapy seems to result in less residual ischemia. Exercise testing is more sensitive than ambulatory monitoring...

  4. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction...... the prevalence of ambulatory or transient myocardial ischemia is lower than in patients with chronic, stable coronary artery disease. A greater proportion of ischemic episodes, however, are silent than in other subgroups with ischemic heart disease. Early after the infarction, transient myocardial ischemia...... exhibits a circadian variation with a peak activity occurring in the late evening hours. Patients with non-Q wave infarction have more transient myocardial ischemia, whereas thrombolytic therapy seems to result in less residual ischemia. Exercise testing is more sensitive than ambulatory monitoring...

  5. Acetaldehyde Adducts in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Mashiko Setshedi

    2010-01-01

    Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

  6. In vivo measurement of extravasation of silver nanoparticles into liver extracellular space by push-pull-based continuous monitoring system.

    Science.gov (United States)

    Su, Cheng-Kuan; Hung, Ching-Wen; Sun, Yuh-Chang

    2014-06-05

    With the increasing prevalence of silver nanoparticles (AgNPs) in various products, whether such AgNPs will introduce new injury mechanisms from new pathologies remains to be determined. From the toxicokinetic viewpoint, it is vital to have in-depth knowledge of their in vivo transport kinetics and extravasation phenomenon. By combining push-pull perfusion sampling, in-tube solid phase extraction, and inductively coupled plasma mass spectrometry, we used an in vivo push-pull-based continuous monitoring system to investigate in vivo transport kinetics of extracellular AgNPs in living rat liver with a detection limit and temporal resolution of 0.64μgL(-1) and 10min, respectively. Before administration into living rats, the pre-incubation in DMEM with 10% FBS for 8h was adopted as the optimized exposure condition for the used AgNPs. After repeated-dose treatments, we observed a higher concentration of AgNPs in the liver extracellular space, suggesting that AgNP clearance by the reticuloendothelial system (RES) may be blocked by a prior administration of AgNPs. Future studies on AgNP distribution in different liver compartments (blood stream, extracellular space and Kupffer cells/hepatocytes) are necessary for defining the risks and benefits of AgNP applications.

  7. Liver steatosis in pre-transplant liver biopsies can be quantified rapidly and accurately by nuclear magnetic resonance analysis.

    Science.gov (United States)

    Bertram, Stefanie; Myland, Cathrin; Swoboda, Sandra; Gallinat, Anja; Minor, Thomas; Lehmann, Nils; Thie, Michael; Kälsch, Julia; Pott, Leona; Canbay, Ali; Bajanowski, Thomas; Reis, Henning; Paul, Andreas; Baba, Hideo A

    2017-02-01

    Donor livers marginally acceptable or acceptable according to extended criteria are more frequently transplanted due to the growing discrepancy between demand and availability of donor organs. One type of marginally acceptable graft is a steatotic donor liver, because it is more sensitive to ischemia-reperfusion injury. Thus, quantitative assessment of steatosis is crucial prior to liver transplantation. Extent of steatosis of 49 pre-reperfusion liver biopsies from patients who received orthotopic liver transplantation was assessed by three techniques: semi-quantitative histological evaluation, computerized histomorphometry, and NMR-based estimation of fat content. The findings were correlated to clinical data and to histological examination of corresponding post-reperfusion biopsies for quantification of ischemia-reperfusion injury. We found that values obtained through all three assessment methods were positively correlated. None of the values obtained by the three applied methods correlated with clinical outcome or extent of ischemia-reperfusion injury. Quantitative evaluation of steatosis by NMR yields results comparable to histological and morphometrical assessment. This technique is rapid (livers, and provides results that can be used when evaluation by a pathologist is not available.

  8. How effective are alprostadil and hydrocortisone on reperfusion injury in kidney after distant organ ischemia?

    Directory of Open Access Journals (Sweden)

    Ali Ebrahimi

    2013-01-01

    Full Text Available Background: After reestablishment of blood flow to ischemic limb recirculation of free radicals may cause ischemia-reperfusion injury in many organs. This study designed to investigate effects of hydrocortisone and alprostadil distant injury to kidneys by both measuring biochemical markers of oxidative stress and histopathologic examination in an experimental rat model of hind limb ischemia-reperfusion. Materials and Methods: This study conducted in Isfahan University of Medical Sciences during 2011-2012. Ischemia was established by infra renal aortic clamping for 60 min in 32 male Wistar rats. Animals were divided into those receiving alprostadil (group ischemia-reperfusion plus alprostadil (IR/A, n = 8, those receiving hydrocortisone (group ischemia-reperfusion plus hydrocortisone (IR/H, n = 8, control group (group ischemia-reperfusion (IR, n = 8, and sham group (n = 8. After 120 min of reperfusion both kidneys were removed. Levels of superoxide dismutase (SOD, malondialdehyde (MDA, and glutathione (GSH as indirect markers of oxidative injury was measured. Finally all data in different groups were compared using the analysis of variance (ANOVA test by Statistical Package for Social Sciences (SPSS version 16. Results: Administration of alprostadil or hydrocortisone does not improve the biochemical parameters of oxidative injury including MDA and SOD. However, statistically significant difference was seen in GSH level among sham and IR groups. Mean (΁ standard deviation (SD concentration of GSH in IR, IR/A, IR/H, and sham groups were 1028.77 (72.65, 924.82 (70.66, 1000.28 (108.77, and 846.69 (163.52, respectively (P = 0.015. Histopathological study of specimens did not show any significant changes between groups. Conclusion: Alprostadil and hydrocortisone do not improve the kidney GSH, SOD, and MDA level and kidney releases its GSH reserve during ischemia-reperfusion event, and another point is that, 3 h of ischemia-reperfusion does not develop

  9. Hyperlipidemia affects neuronal nitric oxide synthase expression in brains of focal cerebral ischemia rat model

    Institute of Scientific and Technical Information of China (English)

    Jianji Pei; Liqiang Liu; Jinping Pang; Xiaohong Tian

    2008-01-01

    BACKGROUND: Hyperlipidemia, a risk factor for ischemic cerebrovascular disease, may mediate production of neuronal nitric oxide synthase (nNOS) to induce increased nitric oxide levels, resulting in brain neuronal injury. OBJECTIVE: To investigate effects of hyperlipidemia on brain nNOS expression, and to verify changes in infarct volume and pathology during reperfusion, as well as neuronal injury following ischemia/reperfusion in a rat model of focal cerebral ischemia. DESIGN, TIME AND SETTING: Complete, randomized grouping experiment was performed at the Laboratory of Physiology, Shanxi Medical University from March 2005 to March 2006. MATERIALS: A total of 144 eight-week-old, male, Wistar rats, weighing 160-180 g, were selected. A rat model of middle cerebral artery occlusion was established by suture method after 4 weeks of formulated diet. Nitric oxide kit and rabbit anti-rat nNOS kit were respectively purchased from Nanjing Jiancheng Bioengineering Institute, China and Wuhan Boster Biological Technology, Ltd., China. METHODS: The rats were equally and randomly divided into high-fat diet and a normal diet groups. Rats in the high-fat diet group were fed a high-fat diet, consisting of 10% egg yolk powder, 5% pork fat, and 0.5% pig bile salt combined with standard chow to create hyperlipidemia. Rats in the normal diet group were fed a standard rat chow. A total of 72 rats in both groups were randomly divided into 6 subgroups: sham-operated, 4-hour ischemia, 4-hour ischemia/2-hour reperfusion, 4-hour ischemia/4-hour reperfusion, 4-hour ischemia/6-hour reperfusion, and 4-hour ischemia/12-hour reperfusion, with 12 rats in each subgroup. MAIN OUTCOME MEASURES: nNOS expression was measured by immunohistochemistry, and pathomorphology changes were detected by hematoxylin-eosin staining. Infarct volume and nitric oxide levels were respectively measured using 2, 3, 5-triphenyltetrazolium chloride (TTC) and immunohistochemistry. RESULTS: In the ischemic region, pathology

  10. The effects of farm management practices on liver fluke prevalence and the current internal parasite control measures employed on Irish dairy farms.

    Science.gov (United States)

    Selemetas, Nikolaos; Phelan, Paul; O'Kiely, Padraig; de Waal, Theo

    2015-01-30

    Fasciolosis caused by Fasciola hepatica is responsible for major production losses in cattle farms. The objectives of this study were to assess the effect of farm management practices on liver fluke prevalence on Irish dairy farms and to document the current control measures against parasitic diseases. In total, 369 dairy farms throughout Ireland were sampled from October to December 2013, each providing a single bulk tank milk (BTM) sample for liver fluke antibody-detection ELISA testing and completing a questionnaire on their farm management. The analysis of samples showed that cows on 78% (n=288) of dairy farms had been exposed to liver fluke. There was a difference (P0.05) between positive and negative farms in (a) the grazing of dry cows together with replacement cows, (b) whether or not grazed grassland was mowed for conservation, (c) the type of drinking water provision system, (d) spreading of cattle manure on grassland or (e) for grazing season length (GSL; mean=262.5 days). Also, there were differences (Pcontrol strategy.

  11. [Tonic pupil caused by ischemia].

    Science.gov (United States)

    Wilhelm, H

    1989-01-01

    Tonic pupil is usually an idiopathic condition. In some cases, the cause of the ciliary ganglion lesion leading to tonic pupils is obvious. Rarely ischemia causes a lesion of the ciliary ganglion or the short ciliary nerves due to the good blood supply of the ciliary ganglion. Only two cases of tonic pupils in the course of giant cell arteritis are mentioned in the literature, but tonic pupils are probably much more common with this disease. Five cases are demonstrated here. All had associated ischemic optic neuropathy, and stagnation of the blood flow in the supratrochlear artery could be demonstrated in two cases by Doppler sonography. Tonic pupils may also occur when an oclusion of the internal carotid artery resolves, probably because of transient stasis of the orbital blood flow. In another case, tonic pupils were associated with choroidal ischemia (proved by video fluorescent angiography) of unknown origin. The diagnosis of tonic pupils was made by pharmacological testing for cholinergic hypersensitivity with 0.1% pilocarpine.

  12. Metabolic Adaptation to Muscle Ischemia

    Science.gov (United States)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  13. Reproducibility of Intra- and Inter-scanner Measurements of Liver Fat Using Complex Confounder-corrected Chemical Shift Encoded MRI at 3.0 Tesla

    Science.gov (United States)

    Wu, Bing; Han, Wei; Li, Zhenhong; Zhao, Yonghua; Ge, Mingmei; Guo, Xueqing; Wu, Xinhuai

    2016-01-01

    The purpose of this study was to prospectively evaluate the reproducibility of the proton density fat-fraction (PDFF) of the liver using the IDEAL algorithm, a quantitative confounder-corrected chemical-shift-encoded MRI method. Data were obtained from 15 volunteers on four different days. The first and the third examinations were conducted on scanner one with one-week intervals, while the second and the fourth tests were performed on scanner two with same time interval. For each test, two MR scans were performed, one before and one after a meal. Regions-of-interest measurements were manually calculated to estimate the PDFF in the right and left lobes on the PDFF images. Reproducibility was measured using the intra-class correlation coefficient (ICC). The ICCs of the PDFF in the right and left lobes were 0.935 and 0.878, respectively. The intra-scanner ICCs of the right lobe before and after a meal or at a one-week interval were 0.924 and 0.953, respectively. The inter-scanner ICCs of PDFF the next day and at a one-week interval were 0.920 and 0.864, respectively. The PDFF of liver derived from IDEAL demonstrated high intra- and inter-scanner measurement reproducibility. The PDFF of the right lobe before a meal was more reproducible than after-meal measurements. PMID:26763303

  14. Assessment of liver volume with spiral computerized tomography scanning: predicting liver volume by age and height

    Directory of Open Access Journals (Sweden)

    Madhu Sharma

    2016-07-01

    Conclusions: Liver volume is a reliable index of liver size and measurement of liver volume with spiral CT is useful method. Spiral CT can be utilized for measurement of liver volume for such purpose. [Int J Res Med Sci 2016; 4(7.000: 3020-3023

  15. Benign Liver Tumors

    Science.gov (United States)

    ... A Life After Diagnosis Support for Chronic Illness Corporate Partnerships Interview with Kristen Hanks Liver Lowdown July ... Disease , Liver Transplant , Liver Cancer , Liver Tumor , Liver Failure Help Fight Liver Disease We rely upon donations ...

  16. What Is Liver Cancer?

    Science.gov (United States)

    ... Research? Liver Cancer About Liver Cancer What Is Liver Cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  17. Role of Hydrogen Sulfide in Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Dongdong Wu

    2015-01-01

    Full Text Available Ischemia-reperfusion (I/R injury is one of the major causes of high morbidity, disability, and mortality in the world. I/R injury remains a complicated and unresolved situation in clinical practice, especially in the field of solid organ transplantation. Hydrogen sulfide (H2S is the third gaseous signaling molecule and plays a broad range of physiological and pathophysiological roles in mammals. H2S could protect against I/R injury in many organs and tissues, such as heart, liver, kidney, brain, intestine, stomach, hind-limb, lung, and retina. The goal of this review is to highlight recent findings regarding the role of H2S in I/R injury. In this review, we present the production and metabolism of H2S and further discuss the effect and mechanism of H2S in I/R injury.

  18. Oxidative DNA damage after transplantation of the liver and small intestine in pigs

    DEFF Research Database (Denmark)

    Loft, S; Larsen, P N; Rasmussen, A

    1995-01-01

    Oxidative damage is thought to play an important role in ischemia/reperfusion injury, including the outcome of transplantation of the liver and intestine. We have investigated oxidative DNA damage after combined transplantation of the liver and small intestine in 5 pigs. DNA damage was estimated...... to DNA results from reperfusion of transplanted small intestine and liver in pigs, as estimated from the readily excreted repair product 8-oxodG....

  19. Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo.

    Science.gov (United States)

    Schulz, Rainer; Gres, Petra; Skyschally, Andreas; Duschin, Alexej; Belosjorow, Sergej; Konietzka, Ina; Heusch, Gerd

    2003-07-01

    During myocardial ischemia, connexin 43 (Cx43) is dephosphorylated in vitro, and the subsequent opening of gap junctions formed by two opposing Cx43 hexamers was suggested to propagate ischemia/reperfusion injury. Reduction of infarct size (IS) by ischemic preconditioning (IP) involves activation of protein kinase C (PKC) and p38 mitogen activated protein kinase (MAPK), both of which can phosphorylate Cx43. We now studied in anesthetized pigs whether IP impacts on Cx43 phosphorylation by measuring the density of non-phosphorylated and total Cx43 (confocal laser) during normoperfusion and 90-min ischemia in non-preconditioned and preconditioned hearts. Co-localization of PKCalpha, p38MAPKalpha, and p38MAPKbeta with Cx43 and the activity of p38MAPK were assessed. IP by 10 min ischemia and 15 min reperfusion reduced IS. Non-phosphorylated Cx43 remained unchanged during ischemia in preconditioned hearts, while it increased from 35+/-3 to 75+/-8 AU (P<0.05) in non-preconditioned hearts. Co-localization of PKCalpha, p38MAPKalpha, and p38MAPKbeta with Cx43 during ischemia increased only in preconditioned hearts. While the ischemia-induced increase in p38MAPKalpha activity was comparable in preconditioned and non-preconditioned hearts, p38MAPKbeta activity was increased only in preconditioned hearts. Blockade of p38MAPK by SB203580 attenuated the IS-reduction and the increased p38MAPK-Cx43 co-localization by IP. We conclude that IP increases co-localization of protein kinases with Cx43 and preserves phosphorylation of Cx43 during ischemia.

  20. Apoptosis of motor neurons in the spinal cord after ischemia reperfusion injury delayed paraplegia in rabbits

    Institute of Scientific and Technical Information of China (English)

    Liu Bibo; Liu Miao; Ma Wei; Wang Duoning

    2007-01-01

    Objective To clarify the pathologic change of the motor neuron on spinal cord ischemia reperfusion injury delayed paraplegia. Methods The infrarenal aorta of White New Zealand rabbits (n=24) was occluded for 26 minutes using two bulldog clamps. Rabbits were killed after 8, 24, 72, or 168 hours (n=6 per group), respectively. The clamps was placed but never clamped in sham-operated rabbits (n=24). The lumbar segment of the spinal cord (L5 to L7) was used for morphological studies, including hematoxylin and eosin staining, the expression of bcl-2 and bax proteins in spinal cord was detected with immunohistochemistry. The apoptotic neurons in spinal cord were measured with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end-labeling of DNA fragments (TUNEL) staining. Results Delayed paraplegia occurred in all rabbits of ischemia reperfusion group at 16-24 hours, but not in sham groups. Motor neurons were selectively lost at 7 days after transient ischemia. After ischemia, the positive expression of bcl-2 protein were in the sham controls but decreased significantly as compared with that of the IR group (P<0.01), especially in 72 hours reperfusion. The positive expression of bax protein were also in the sham controls, but increased in the IR group, especially in 72 hours reperfusion; In addition, TUNEL study demonstrated that no cells were positively labeled until 24 hours after ischemia, but nuclei of some motor neurons were positively labeled at peak after ischemia reperfusion at 72 hours. Conclusion Spinal cord ischemia in rabbits induces morphological and biochemical changes suggestive of apoptosis. These data raise the possibility that apoptosis contributes to neuronal cell death after spinal cord ischemia reperfusion.

  1. Gastric Tissue Damage Analysis Generated by Ischemia: Bioimpedance, Confocal Endomicroscopy, and Light Microscopy

    Science.gov (United States)

    Beltran, Nohra E.; Garcia, Laura E.; Garcia-Lorenzana, Mario

    2013-01-01

    The gastric mucosa ischemic tissular damage plays an important role in critical care patients' outcome, because it is the first damaged tissue by compensatory mechanism during shock. The aim of the study is to relate bioimpedance changes with tissular damage level generated by ischemia by means of confocal endomicroscopy and light microscopy. Bioimpedance of the gastric mucosa and confocal images were obtained from Wistar male rats during basal and ischemia conditions. They were anesthetized, and stain was applied (fluorescein and/or acriflavine). The impedance spectroscopy catheter was inserted and then confocal endomicroscopy probe. After basal measurements and biopsy, hepatic and gastric arteries clamping induced ischemia. Finally, pyloric antrum tissue was preserved in buffered formaldehyde (10%) for histology processing using light microscopy. Confocal images were equalized, binarized, and boundary defined, and infiltrations were quantified. Impedance and infiltrations increased with ischemia showing significant changes between basal and ischemia conditions (P < 0.01). Light microscopy analysis allows detection of general alterations in cellular and tissular integrity, confirming gastric reactance and confocal images quantification increments obtained during ischemia. PMID:23841094

  2. Gastric Tissue Damage Analysis Generated by Ischemia: Bioimpedance, Confocal Endomicroscopy, and Light Microscopy

    Directory of Open Access Journals (Sweden)

    Nohra E. Beltran

    2013-01-01

    Full Text Available The gastric mucosa ischemic tissular damage plays an important role in critical care patients’ outcome, because it is the first damaged tissue by compensatory mechanism during shock. The aim of the study is to relate bioimpedance changes with tissular damage level generated by ischemia by means of confocal endomicroscopy and light microscopy. Bioimpedance of the gastric mucosa and confocal images were obtained from Wistar male rats during basal and ischemia conditions. They were anesthetized, and stain was applied (fluorescein and/or acriflavine. The impedance spectroscopy catheter was inserted and then confocal endomicroscopy probe. After basal measurements and biopsy, hepatic and gastric arteries clamping induced ischemia. Finally, pyloric antrum tissue was preserved in buffered formaldehyde (10% for histology processing using light microscopy. Confocal images were equalized, binarized, and boundary defined, and infiltrations were quantified. Impedance and infiltrations increased with ischemia showing significant changes between basal and ischemia conditions (. Light microscopy analysis allows detection of general alterations in cellular and tissular integrity, confirming gastric reactance and confocal images quantification increments obtained during ischemia.

  3. Matrix Metalloproteinase-2 (MMP-2) Gene Deletion Enhances MMP-9 Activity, Impairs PARP-1 Degradation, and Exacerbates Hepatic Ischemia and Reperfusion Injury in Mice.

    Science.gov (United States)

    Kato, Hiroyuki; Duarte, Sergio; Liu, Daniel; Busuttil, Ronald W; Coito, Ana J

    2015-01-01

    Hepatic ischemia and reperfusion injury (IRI) is an inflammatory condition and a significant cause of morbidity and mortality after surgery. Matrix metalloproteinases (MMPs) have been widely implicated in the pathogenesis of inflammatory diseases. Among the different MMPs, gelatinases (MMP-2 and MMP-9) are within the most prominent MMPs detected during liver IRI. While the role of MMP-9 in liver damage has been fairly documented, direct evidence of the role for MMP-2 activity in hepatic IRI remains to be established. Due to the lack of suitable inhibitors to target individual MMPs in vivo, gene manipulation is as an essential tool to assess MMP direct contribution to liver injury. Hence, we used MMP-2-/- deficient mice and MMP-2+/+ wild-type littermates to examine the function of MMP-2 activity in hepatic IRI. MMP-2 expression was detected along the sinusoids of wild-type livers before and after surgery and in a small population of leukocytes post-IRI. Compared to MMP-2+/+ mice, MMP-2 null (MMP-2-/-) mice showed exacerbated liver damage at 6, 24, and 48 hours post-reperfusion, which was fatal in some cases. MMP-2 deficiency resulted in upregulation of MMP-9 activity, spontaneous leukocyte infiltration in naïve livers, and amplified MMP-9-dependent transmigration of leukocytes in vitro and after hepatic IRI. Moreover, complete loss of MMP-2 activity impaired the degradation of poly (ADP-ribose) polymerase (PARP-1) in extensively damaged livers post-reperfusion. However, the administration of a PARP-1 inhibitor to MMP-2 null mice restored liver preservation to almost comparable levels of MMP-2+/+ mice post-IRI. Deficient PARP-1 degradation in MMP-2-null sinusoidal endothelial cells correlated with their increased cytotoxicity, evaluated by the measurement of LDH efflux in the medium. In conclusion, our results show for the first time that MMP-2 gene deletion exacerbates liver IRI. Moreover, they offer new insights into the MMP-2 modulation of inflammatory responses

  4. Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

    Science.gov (United States)

    Turamanlar, Ozan; Özen, Oğuz Aslan; Songur, Ahmet; Yağmurca, Murat; Akçer, Sezer; Mollaoğlu, Hakan; Aktaş, Cevat

    2015-01-01

    Background: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA) on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250–300 grams) were used in this study. Rats were randomly divided into six groups including one control (Group 1), one sham (Group 2), two ischemia-reperfusion (Groups 3 and 4) and two treatment groups (Groups5 and 6). Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6) intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities as well as malondialdehyde (MDA) and nitricoxide (NO) levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose. There were

  5. Myocardial Ischemia Caused by Subepicardial Hematoma

    Science.gov (United States)

    Grieshaber, Philippe; Nef, Holger; Böning, Andreas; Niemann, Bernd

    2017-01-01

    Background Bleeding from bypass anastomosis leakage occurs early after coronary artery bypass grafting. Later, once the anastomosis is covered by intima, spontaneous bleeding is unlikely. Case Description A 63-year-old male patient developed a pseudoaneurysm-like, subepicardial late-term bleeding resulting in a hematoma that compromised coronary artery flow by increasing extracoronary pressure. This resulted in severe angina pectoris (Canadian Cardiovascular Society IV) and myocardial ischemia within the affected area. After surgical removal of the hematoma and repair of the anastomosis, the patient's symptoms disappeared and no signs of myocardial ischemia were present. Conclusion Surgical removal is an efficient therapy for subepicardial hematoma inducing myocardial ischemia.

  6. Liver Transplant

    Science.gov (United States)

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  7. Liver anatomy.

    Science.gov (United States)

    Abdel-Misih, Sherif R Z; Bloomston, Mark

    2010-08-01

    Understanding the complexities of the liver has been a long-standing challenge to physicians and anatomists. Significant strides in the understanding of hepatic anatomy have facilitated major progress in liver-directed therapies--surgical interventions, such as transplantation, hepatic resection, hepatic artery infusion pumps, and hepatic ablation, and interventional radiologic procedures, such as transarterial chemoembolization, selective internal radiation therapy, and portal vein embolization. Without understanding hepatic anatomy, such progressive interventions would not be feasible. This article reviews the history, general anatomy, and the classification schemes of liver anatomy and their relevance to liver-directed therapies. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Use of linear radiofrequency device in liver resection

    Directory of Open Access Journals (Sweden)

    Stojanović Miroslav P.

    2010-01-01

    Full Text Available Background/Aim. Linear radiofrequency device (LRFD is disposable tool designed for liver parenchyma transection using controlled radiofrequency to 'seal' blood vessels and bile ducts, making liver resection easier and safer compared to classical resectional techniques. The aim of this study was to determine real value of the LRFD compared to the standard 'keliclasia' technique. Methods. This prospective study analyzed the significant intraoperative parameters and postoperative results of the 200 patients who underwent surgery at the Surgery Clinic of Clinical Centre in Niš, between January 1, 2001, and January 1, 2009. The patients were divided into two groups: the control Keli group (144 patients with the 'keliclasia' resection technique and the control RF group (with resection performed using LRFD - Tissue Link / Dissection Sealer (DS - 3.0 (56 patients. The following parameters were analyzed: duration of liver ischemia, liver parenchyma transection time, intraoperative blood loss, significant intraoperative and postoperative complication rate, duration of hospitalization and mortality. Results. LRFD was used in 56 liver resections. The average duration of liver ischemia in the RF group was shorter than in the Keli group (7 versus 22 minutes. Parenchymal liver transection was significantly slower in the RF group than in the Keli group (2.05 versus 4.34 cm2/minutes, respectively. There was less intraoperative bleeding using LRFD 'Keliclasia' tehniquethan in the control group (390 mL compared to 420 mL, respectively. After the use of LRFD two cases of biliary leak and 4 pleural effusions were registered. Conclusion. LRFD is simple device for safe liver transection with decreased need for liver ischemia and singificant reducing of the intraoperative blood loss. High price for disposable device and slow parenchyma transection are disadvantages of this device.

  9. Differential effects of eugenol against hepatic inflammation and overall damage induced by ischemia/re-perfusion injury.

    Science.gov (United States)

    Abd El Motteleb, Dalia M; Selim, Sally A; Mohamed, Ahmed M

    2014-01-01

    Liver injuries, liver tumor resection, and liver transplantation are known to be responsible for ischemia/reperfusion (I/R) injury that, in turn, gives rise to liver damage. This study was undertaken to investigate the possible protective effect of eugenol against the damage induced by I/R in rat livers as well as to explore possible mechanisms of action. Male rats were divided into four groups: sham-operated, I/R only, and two groups that received 10 or 100 mg eugenol/kg/day (Eug10 and Eug100, respectively) for 15 days by gavage and were then subjected to I/R, i.e. an ischemia induced for 45 min followed by re-perfusion for 6 h. The rats were euthanized and liver tissues and blood collected for examination. The results showed that I/R induced massive hepatic structural and functional damage. Eug10-treated rats had improvement in both liver function and structure, and inhibition of I/R-induced increases in serum myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, as well as hepatic nuclear factor-κB (NF-κB) p65 and caspase-3 expression. Eug10 treatment also inhibited the degree of loss in reduced glutathione (GSH) and of rise in malondialdehyde (MDA) levels in liver tissues induced by I/R. In contrast, augmentation of liver damage induced by I/R was noted in Eug100-treated rats, with these hosts displaying significant increases in oxidant, inflammatory, and apoptotic markers relative to levels seen in I/R-only rats. The results of the present study provide the first evidence that a low dose of eugenol may protect the liver against I/R injury in part by decreasing levels of lipid peroxidation, down-regulating inflammatory mediators, and inhibiting apoptosis, and that a larger dose amplifies the liver injury via oxidant and inflammatory effects.

  10. Spironolactone Effect in Hepatic Ischemia/Reperfusion Injury in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Julio César Jiménez Pérez

    2016-01-01

    Full Text Available Introduction. Ischemia/reperfusion (IR injury, often associated with liver surgery, is an unresolved problem in the clinical practice. Spironolactone is an antagonist of aldosterone that has shown benefits over IR injury in several tissues, but its effects in hepatic IR are unknown. Objective. To evaluate the effect of spironolactone on IR-induced damage in liver. Materials and Methods. Total hepatic ischemia was induced in rats for 20 min followed by 60 min of reperfusion. Spironolactone was administered and hepatic injury, cytokine production, and oxidative stress were assessed. Results. After IR, increased transaminases levels and widespread acute inflammatory infiltrate, disorganization of hepatic hemorrhage trabeculae, and presence of apoptotic bodies were observed. Administration of SPI reduced biochemical and histological parameters of liver injury. SPI treatment increased IL-6 levels when compared with IR group but did not modify either IL-1β or TNF-α with respect to IR group. Regarding oxidative stress, increased levels of catalase activity were recorded in IR + SPI group in comparison with group without treatment, whereas MDA levels were similar in IR + SPI and IR groups. Conclusions. Spironolactone reduced the liver damage induced by IR, and this was associated with an increase in IL-6 production and catalase activity.

  11. GI ischemia in patients with portal vein thrombosis: a prospective cohort study.

    Science.gov (United States)

    Harki, Jihan; Plompen, Elisabeth P C; van Noord, Désirée; Hoekstra, Jildou; Kuipers, Ernst J; Janssen, Harry L A; Tjwa, Eric T T L

    2016-03-01

    GI ischemia is a concerning adverse event of portal vein thrombosis (PVT). Minimally invasive techniques, such as visible light spectroscopy (VLS), have greatly improved the ability to diagnose GI ischemia. The aim of this study was to assess the clinical presentation and characteristics of GI ischemia in patients with PVT. Patients with noncirrhotic, nonmalignant PVT were included in this prospective cohort study. Clinical symptoms of GI ischemia were assessed by a structured questionnaire, VLS, and radiologic evaluation of the mesenteric vasculature. VLS measurements were compared with those in patients with cirrhosis and with a reference population. We included 15 patients with chronic PVT and 1 patient with acute PVT (median age 46.1 years [interquartile range [IQR], 30.9-53.7]; 44% male). Decreased mucosal oxygenation in at least 1 location of the GI tract was found in 12 patients (75%). Compared with the reference population (median 60.0 [IQR, 56.2-61.7]), VLS measurements were mostly decreased in the descending duodenum in patients with PVT (median 55.5 [IQR, 52.3-58.8]; P = .02) and patients with cirrhosis (median 52.0 [IQR, 46.5-54.0], P = .003). Symptoms typical for GI ischemia, such as postprandial pain and exercise-induced pain, were reported in 10 patients (63%) with PVT. In patients with extension of thrombosis into the superior mesenteric vein and splenic vein and/or presence of hypercoagulability, decreased VLS measurements were observed compared with historical control subjects. In patients with chronic PVT, GI ischemia is frequent. VLS enables objective and quantitative determination of GI mucosal ischemia. Onset of abdominal symptoms such as postprandial pain should prompt the physician to re-evaluate extent, cause, and treatment of PVT. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  12. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

    Science.gov (United States)

    Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  13. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats