Sample records for preconditioning prevents postischemic

  1. Preconditioning with soluble guanylate cyclase activation prevents postischemic inflammation and reduces nitrate tolerance in heme oxygenase-1 knockout mice

    PubMed Central

    Wang, Walter Z.; Wang, Meifang; Durante, William; Korthuis, Ronald J.

    2013-01-01

    Previously we have shown that, unlike wild-type mice (WT), heme oxygenase-1 knockout (HO-1?/?) mice developed nitrate tolerance and were not protected from inflammation caused by ischemia-reperfusion (I/R) when preconditioned with a H2S donor. We hypothesized that stimulation (with BAY 41-2272) or activation (with BAY 60-2770) of soluble guanylate cyclase (sGC) would precondition HO-1?/? mice against an inflammatory effect of I/R and increase arterial nitrate responses. Intravital fluorescence microscopy was used to visualize leukocyte rolling and adhesion to postcapillary venules of the small intestine in anesthetized mice. Relaxation to ACh and BAY compounds was measured on superior mesenteric arteries isolated after I/R protocols. Preconditioning with either BAY compound 10 min (early phase) or 24 h (late phase) before I/R reduced postischemic leukocyte rolling and adhesion to sham control levels and increased superior mesenteric artery responses to ACh, sodium nitroprusside, and BAY 41-2272 in WT and HO-1?/? mice. Late-phase preconditioning with BAY 60-2770 was maintained in HO-1?/? and endothelial nitric oxide synthase knockout mice pretreated with an inhibitor (dl-propargylglycine) of enzymatically produced H2S. Pretreatment with BAY compounds also prevented the I/R increase in small intestinal TNF-?. We speculate that increasing sGC activity and related PKG acts downstream to H2S and disrupts signaling processes triggered by I/R in part by maintaining low cellular Ca2+. In addition, BAY preconditioning did not increase sGC levels, yet increased the response to agents that act on reduced heme-containing sGC. Collectively these actions would contribute to increased nitrate sensitivity and vascular function. PMID:23771693

  2. Unique Transcriptional Profile of Sustained Ligand-Activated Preconditioning in Pre- and Post-Ischemic Myocardium

    PubMed Central

    Ashton, Kevin J.; Tupicoff, Amanda; Williams-Pritchard, Grant; Kiessling, Can J.; See Hoe, Louise E.; Headrick, John P.; Peart, Jason N.

    2013-01-01

    Background Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. Methodology/Principal Findings Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (?1.3-fold change, FDR?5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip. Conclusions Protection via SLP is associated with transcriptional repression of inflammation/immunity, up-regulation of sarcomeric elements and natriuretic peptides, and modulation of cell stress, growth and development, while conventional protective molecules are unaltered. PMID:23991079

  3. Plasmin Inhibitors Prevent Leukocyte Accumulation and Remodeling Events in the Postischemic Microvasculature

    PubMed Central

    Reichel, Christoph A.; Lerchenberger, Max; Uhl, Bernd; Rehberg, Markus; Berberich, Nina; Zahler, Stefan; Wymann, Matthias P.; Krombach, Fritz

    2011-01-01

    Clinical trials revealed beneficial effects of the broad-spectrum serine protease inhibitor aprotinin on the prevention of ischemia-reperfusion (I/R) injury. The underlying mechanisms remained largely unclear. Using in vivo microscopy on the cremaster muscle of male C57BL/6 mice, aprotinin as well as inhibitors of the serine protease plasmin including tranexamic acid and ?-aminocaproic acid were found to significantly diminish I/R-elicited intravascular firm adherence and (subsequent) transmigration of neutrophils. Remodeling of collagen IV within the postischemic perivenular basement membrane was almost completely abrogated in animals treated with plasmin inhibitors or aprotinin. In separate experiments, incubation with plasmin did not directly activate neutrophils. Extravascular, but not intravascular administration of plasmin caused a dose-dependent increase in numbers of firmly adherent and transmigrated neutrophils. Blockade of mast cell activation as well as inhibition of leukotriene synthesis or antagonism of the platelet-activating-factor receptor significantly reduced plasmin-dependent neutrophil responses. In conclusion, our data suggest that extravasated plasmin(ogen) mediates neutrophil recruitment in vivo via activation of perivascular mast cells and secondary generation of lipid mediators. Aprotinin as well as the plasmin inhibitors tranexamic acid and ?-aminocaproic acid interfere with this inflammatory cascade and effectively prevent postischemic neutrophil responses as well as remodeling events within the vessel wall. PMID:21364954

  4. Plasmin inhibitors prevent leukocyte accumulation and remodeling events in the postischemic microvasculature.

    PubMed

    Reichel, Christoph A; Lerchenberger, Max; Uhl, Bernd; Rehberg, Markus; Berberich, Nina; Zahler, Stefan; Wymann, Matthias P; Krombach, Fritz

    2011-01-01

    Clinical trials revealed beneficial effects of the broad-spectrum serine protease inhibitor aprotinin on the prevention of ischemia-reperfusion (I/R) injury. The underlying mechanisms remained largely unclear. Using in vivo microscopy on the cremaster muscle of male C57BL/6 mice, aprotinin as well as inhibitors of the serine protease plasmin including tranexamic acid and ?-aminocaproic acid were found to significantly diminish I/R-elicited intravascular firm adherence and (subsequent) transmigration of neutrophils. Remodeling of collagen IV within the postischemic perivenular basement membrane was almost completely abrogated in animals treated with plasmin inhibitors or aprotinin. In separate experiments, incubation with plasmin did not directly activate neutrophils. Extravascular, but not intravascular administration of plasmin caused a dose-dependent increase in numbers of firmly adherent and transmigrated neutrophils. Blockade of mast cell activation as well as inhibition of leukotriene synthesis or antagonism of the platelet-activating-factor receptor significantly reduced plasmin-dependent neutrophil responses. In conclusion, our data suggest that extravasated plasmin(ogen) mediates neutrophil recruitment in vivo via activation of perivascular mast cells and secondary generation of lipid mediators. Aprotinin as well as the plasmin inhibitors tranexamic acid and ?-aminocaproic acid interfere with this inflammatory cascade and effectively prevent postischemic neutrophil responses as well as remodeling events within the vessel wall. PMID:21364954

  5. Tandem action of exercise training and food restriction completely preserves ischemic preconditioning in the aging heart

    Microsoft Academic Search

    P. Abete; G. Testa; G. Galizia; F. Mazzella; D. Della Morte; D. de Santis; C. Calabrese; F. Cacciatore; G. Gargiulo; N. Ferrara; G. Rengo; V. Sica; C. Napoli; F. Rengo

    2005-01-01

    Ischemic preconditioning (IP) has been proposed as an endogenous form of protection against ischemia reperfusion injury. IP, however, does not prevent post-ischemic dysfunction in the aging heart but may be partially corrected by exercise training and food restriction. We investigated the role of exercise training combined with food restriction on restoring IP in the aging heart. Effects of IP against

  6. A selective M1 and M3 receptor antagonist, penehyclidine hydrochloride, prevents postischemic LTP: involvement of NMDA receptors.

    PubMed

    Ma, Teng-Fei; Zhou, Li; Wang, Yun; Qin, Shou-Jun; Zhang, Yuan; Hu, Bin; Yan, Jing-Zhi; Ma, Xing; Zhou, Cheng-Hua; Gu, Shu-Ling

    2013-12-01

    Our previous and other studies have confirmed that a selective M1 and M3 receptor antagonist, Penehyclidine hydrochloride (PHC), has neuroprotection activity in cerebral ischemia. However, the precise mechanisms of protection of PHC are still elusive. In this study we analyzed PHC-mediated neuroprotection on a model of brain ischemia (oxygen and glucose deprivation), named postischemic LTP (i-LTP). We found that the activation of NMDA receptor was required for the induction of i-LTP. Compared with scopolamine, PHC could prevent it due to selectively blocking M1 receptor, not M2 receptor, to decrease NMDAR activation. Our findings further showed that the inhibition of SK2 channels occluded the prevention of PHC on NMDAR activation. Furthermore, we confirmed that PHC exerted its roles through directly disinhibition of SK2 channels by blocking M1 receptor and subsequent restricting PKC activation. Moreover, our studies further revealed the critical roles of SK2 channels in i-LTP. Thus, the mechanisms of PHC in brain protection may be involved in suppression of NMDAR by regulation of SK2 channels. Our results obtained in effects of PHC on i-LTP further provided a better understanding of the therapy strategy during stroke and identified potential therapeutic targets to prevent development of ischemia. PMID:23813456

  7. Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts

    Microsoft Academic Search

    Dirk Bruegger; Markus Rehm; Matthias Jacob; Daniel Chappell; Mechthild Stoeckelhuber; Ulrich Welsch; Peter Conzen; Bernhard F Becker

    2008-01-01

    INTRODUCTION: Postischemic injury to the coronary vascular endothelium, in particular to the endothelial glycocalyx, may provoke fluid extravasation. Shedding of the glycocalyx is triggered by redox stress encountered during reperfusion and should be alleviated by the radical scavenger nitric oxide (NO). The objective of this study was to investigate the effect of exogenous administration of NO during reperfusion on both

  8. ISCHEMIC PRECONDITIONING PREVENTS PROTEIN AGGREGATION AFTER TRANSIENT CEREBRAL ISCHEMIA

    PubMed Central

    Liu, C.; Chen, S.; Kamme, F.; Hu, B.R.

    2012-01-01

    Transient cerebral ischemia leads to protein aggregation mainly in neurons destined to undergo delayed neuronal death after ischemia. This study utilized a rat transient cerebral ischemia model to investigate whether ischemic preconditioning is able to alleviate neuronal protein aggregation, thereby protecting neurons from ischemic neuronal damage. Ischemic preconditioning was introduced by a sublethal 3 min period of ischemia followed by 48 h of recovery. Brains from rats with either ischemic preconditioning or sham-surgery were then subjected to a subsequent 7 min period of ischemia followed by 30 min, 4, 24, 48 and 72 h of reperfusion. Protein aggregation and neuronal death were studied by electron and confocal microscopy, as well as by biochemical analyses. Seven minutes of cerebral ischemia alone induced severe protein aggregation after 4 h of reperfusion mainly in CA1 neurons destined to undergo delayed neuronal death (which took place after 72 h of reperfusion). Ischemic preconditioning reduced significantly protein aggregation and virtually eliminated neuronal death in CA1 neurons. Biochemical analyses revealed that ischemic preconditioning decreased accumulation of ubiquitin-conjugated proteins (ubi-proteins) and reduced free ubiquitin depletion after brain ischemia. Furthermore, ischemic preconditioning also reduced redistribution of heat shock cognate protein 70 and Hdj1 from cytosolic fraction to protein aggregate-containing fraction after brain ischemia. These results suggest that ischemic preconditioning decreases protein aggregation after brain ischemia. PMID:15939539

  9. Postischemic Treatment With Ethyl Pyruvate Prevents Adenosine Triphosphate Depletion, Ameliorates Inflammation, and Decreases Thrombosis in a Murine Model of Hind-Limb Ischemia and Reperfusion

    PubMed Central

    Crawford, Robert S.; Albadawi, Hassan; Atkins, Marvin D.; Jones, John J.; Conrad, Mark F.; Austen, William G.; Fink, Mitchell P.; Watkins, Michael T.

    2011-01-01

    Introduction Experiments were designed to investigate the effects of ethyl pyruvate (EP) in a murine model of hind-limb ischemia-reperfusion (IR) injury. Methods C57BL6 mice underwent 90 minutes of unilateral ischemia followed by 24 hours of reperfusion using two treatment protocols. For the preischemic treatment (pre-I) protocol, mice (n = 6) were given 300 mg/kg EP before ischemia, followed by 150 mg/kg of EP just before reperfusion and at 6 hours and 12 hours after reperfusion. In a postischemic treatment (post-I) protocol, mice (n = 7) were treated with 300 mg/kg EP at the end of the ischemic period, then 15 minutes later, and 2 hours after reperfusion and 150 mg/kg of EP at 4 hours, 6 hours, 10 hours, 16 hours, and 22 hours after reperfusion. Controls mice for both protocols were treated with lactated Ringers alone at time intervals identical to EP. Skeletal muscle levels of adenosine triphosphate (ATP), interleukin-1?, keratinocyte chemoattractant protein, and thrombin antithrombin-3 complex were measured. Skeletal muscle architectural integrity was assessed microscopically. Results ATP levels were higher in mice treated with EP compared with controls under the both treatment protocols (p = 0.02). Interleukin-1?, keratinocyte chemoattractant protein, thrombin antithrombin-3 complex (p < 0.05), and the percentage of injured fibers (p < 0.0001) were significantly decreased in treated versus control mice under the both protocols. Conclusion Muscle fiber injury and markers of tissue thrombosis and inflammation were reduced, and ATP was preserved with EP in pre-I and post-I protocols. Further investigation of the efficacy of EP to modulate IR injury in a larger animal model of IR injury is warranted. PMID:21217488

  10. Ischemic preconditioning prevents the impairment of hypoxic coronary vasodilatation caused by ischemia/reperfusion: role of adenosine A1/A3 and bradykinin B2 receptor activation.

    PubMed

    Giannella, E; Mochmann, H C; Levi, R

    1997-09-01

    We previously reported that hypoxic coronary vasodilatation (HCVD) is initiated by endothelial NO and sustained by adenosine. Prolonged ischemia/reperfusion impairs endothelium-dependent coronary vasodilatation, whereas transient ischemia (ie, preconditioning) protects the myocardium from subsequent ischemic events. Accordingly, we assessed whether prolonged ischemia/reperfusion impairs HCVD and whether preconditioning prevents this dysfunction. HCVD, elicited in isolated guinea pig hearts by a 1-minute exposure to 100% N2, consisted of an approximately 70% increase in coronary flow associated with enhanced nitrite/nitrate and adenosine overflow (+40% and 5-fold, respectively). After 30-minute global ischemia and 20-minute reperfusion, HCVD was decreased by approximately 60%, and the increases in nitrite/nitrate and adenosine overflow were abolished. Preconditioning (ie, three cycles of 5-minute global ischemia+5-minute reperfusion) prevented the impairment of HCVD and fully restored the increase in nitrite/nitrate overflow, but not that of adenosine. The protective effect of preconditioning was mimicked by perfusion with the adenosine A1 receptor agonist N6-cyclopentyladenosine and prevented by the A1 receptor antagonist N-0861. In addition, the A3 receptor agonist N6-(3-iodobenzyl)adenosine-5'-N-methyl-carboxamide had a similar protective effect. The bradykinin B2 receptor antagonist HOE 140 abolished the protective effect of preconditioning, whereas the NO synthase inhibitor N(omega)-methyl-L-arginine and the cycloxygenase inhibitor indomethacin did not. Our data indicate that preconditioning restores HCVD by a process that is triggered by activation of adenosine A1/A3 and bradykinin B2 receptors. The action of bradykinin is independent of NO and prostacyclin production. Once restored by preconditioning, HCVD is mediated by NO but no longer sustained by adenosine. PMID:9285644

  11. Preconditioning Against Myocardial Dysfunction After Ischemia andReperfusion by an ca1Adrenergic Mechanism

    Microsoft Academic Search

    Anirban Banerjee; Cristee Locke-Winter; Elizabeth C. Brew; Charles B. Cairns; Dennis D. Bensard

    Preconditioning may findreadyapplicability inhumansfacing scheduled global cardiac ischemia- reperfusion (IR)during bypass ortransplantation, wheresucha maneuver isfeasible before arrest. Our objective was todelineate andexploit theendogenous preconditioning mechanismtriggered bytransient ischemia (TI)andthereby attenuate myocardial postischemic mechanical dysfunction byclinically acceptable means. Preconditioning by2 minutesofTIfollowed by10minutesofnormalperfusion protected isolated ratleft ventricle function assessed after 20minutes ofglobal, 37°Cischemia and40 minutesofreperfusion. Finalrecoveryofdeveloped pressure(DP)was improved(91.5±l.9%o of equilibration DP versusunconditioned IRcontrol,

  12. Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia–reperfusion injury after 30 minutes of hypoxia\\/ischemia in porcine hearts

    Microsoft Academic Search

    P. A Fedalen; V Piacentino; V Jeevanandam; C Fisher; J Greene; K. B Margulies; S. R Houser; S Furukawa; A. K Singhal; B. I Goldman

    2003-01-01

    BackgroundHearts from non–heart-beating organ donors are not transplanted because of risk of ischemia-reperfusion injury. We tested whether pharmacologic pre-conditioning with adenosine and the Na+\\/H+ exchanger inhibitor, cariporide, combined with controlled reperfusion, would prevent injury in porcine hearts that had sustained 30 minutes of hypoxia\\/ischemia in closed-chest animals.

  13. Quercetin Improves Postischemic Recovery of Heart Function in Doxorubicin-Treated Rats and Prevents Doxorubicin-Induced Matrix Metalloproteinase-2 Activation and Apoptosis Induction

    PubMed Central

    Barteková, Monika; Šimon?íková, Petra; Fogarassyová, Mária; Ivanová, Monika; Okruhlicová, ?udmila; Tribulová, Narcisa; Dovinová, Ima; Baran?ík, Miroslav

    2015-01-01

    Quercetin (QCT) is flavonoid that possesses various biological functions including anti-oxidative and radical-scavenging activities. Moreover, QCT exerts some preventive actions in treatment of cardiovascular diseases. The aim of present study was to explore effects of prolonged administration of QCT on changes induced by repeated application of doxorubicin (DOX) in rat hearts. We focused on the ultrastructure of myocardium, matrix metalloproteinases (MMPs), biometric parameters, and apoptosis induction. Our aim was also to examine effects of QCT on ischemic tolerance in hearts exposed to chronic effects of DOX, and to determine possible mechanisms underlying effects of QCT. Our results showed that QCT prevented several negative chronic effects of DOX: (I) reversed DOX-induced blood pressure increase; (II) mediated improvement of deleterious effects of DOX on ultrastructure of left ventricle; (III) prevented DOX-induced effects on tissue MMP-2 activation; and (iv) reversed effects of DOX on apoptosis induction and superoxide dismutase inhibition. Moreover, we showed that rat hearts exposed to effects of QCT were more resistant to ischemia/reperfusion injury. Effects of QCT on modulation of ischemic tolerance were linked to Akt kinase activation and connexin-43 up-regulation. Taken together, these results demonstrate that prolonged treatment with QCT prevented negative chronic effects of DOX on blood pressure, cellular damage, MMP-2 activation, and apoptosis induction. Moreover, QCT influenced myocardial responses to acute ischemic stress. These facts bring new insights into mechanisms of QCT action on rat hearts exposed to the chronic effects of DOX. PMID:25872140

  14. Hypoxia Preconditioned Mesenchymal Stem Cells Prevent Cardiac Fibroblast Activation and Collagen Production via Leptin

    PubMed Central

    Chen, Panpan; Wu, Rongrong; Zhu, Wei; Jiang, Zhi; Xu, Yinchuan; Chen, Han; Zhang, Zhaocai; Chen, Huiqiang; Zhang, Ling; Yu, Hong; Wang, Jian'an; Hu, Xinyang

    2014-01-01

    Aims Activation of cardiac fibroblasts into myofibroblasts constitutes a key step in cardiac remodeling after myocardial infarction (MI), due to interstitial fibrosis. Mesenchymal stem cells (MSCs) have been shown to improve post-MI remodeling an effect that is enhanced by hypoxia preconditioning (HPC). Leptin has been shown to promote cardiac fibrosis. The expression of leptin is significantly increased in MSCs after HPC but it is unknown whether leptin contributes to MSC therapy or the fibrosis process. The objective of this study was to determine whether leptin secreted from MSCs modulates cardiac fibrosis. Methods Cardiac fibroblast (CF) activation was induced by hypoxia (0.5% O2). The effects of MSCs on fibroblast activation were analyzed by co-culturing MSCs with CFs, and detecting the expression of ?-SMA, SM22?, and collagen I?I in CFs by western blot, immunofluorescence and Sirius red staining. In vivo MSCs antifibrotic effects on left ventricular remodeling were investigated using an acute MI model involving permanent ligation of the left anterior descending coronary artery. Results Co-cultured MSCs decreased fibroblast activation and HPC enhanced the effects. Leptin deficit MSCs from Ob/Ob mice did not decrease fibroblast activation. Consistent with this, H-MSCs significantly inhibited cardiac fibrosis after MI and mediated decreased expression of TGF-?/Smad2 and MRTF-A in CFs. These effects were again absent in leptin-deficient MSCs. Conclusion Our data demonstrate that activation of cardiac fibroblast was inhibited by MSCs in a manner that was leptin-dependent. The mechanism may involve blocking TGF-?/Smad2 and MRTF-A signal pathways. PMID:25116394

  15. Preconditioning Balloons

    NSDL National Science Digital Library

    Integrated Teaching and Learning Program,

    Students use balloons (a polymer) to explore preconditioning—a viscoelastic material behavior that is important to understand when designing biomedical devices. They improve their understanding of preconditioning by measuring the force needed to stretch a balloon to the same displacement multiple times. Students gain experience in data collection and graph interpretation.

  16. Left ventricular dysfunction and disturbed O 2utilization in stunned myocardium: influence of ischemic preconditioning

    Microsoft Academic Search

    Ulrich Sunderdiek; Simone Schmitz-Spanke; Bernhard Korbmacher; Emmeran Gams; Jochen D Schipke

    2001-01-01

    Objective: Myocardial dysfunction during postischemic reperfusion is frequently reported only in terms of left ventricular (LV) systolic properties. We additionally assessed diastolic properties, the cardiovascular tone and in particular, the relation between ventricular function and myocardial oxygen consumption. Moreover, these measures are investigated after cardioprotection via ischemic preconditioning (IP). However, this phenomenon is not fully understood, and therefore cardioprotective methods

  17. Supplemental l-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury

    Microsoft Academic Search

    Hiroki Sato; Zhi-Qing Zhao; D. Scott McGee; Mark W. Williams; John W. Hammon; J. Vinten-Johansen

    1995-01-01

    Unenhanced hypothermic cardioplegia does not prevent postischemic endothelial and contractile dysfunction in hearts subjected to antecedent regional or global ischemia. This study tested the hypothesis that supplementing blood cardioplegic solution and reperfusion with the nitric oxide precursor l-arginine would preserve endothelial function, reduce infarct size, and reverse postcardioplegia regional contractile dysfunction by the L-arginine-nitric oxide pathway. In 23 anesthetized dogs,

  18. Towards a dynamical network view of brain ischemia and reperfusion. Part II: a post-ischemic neuronal state space

    PubMed Central

    DeGracia, Donald J.

    2011-01-01

    The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the “ischemic cascade”. This is the second in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. We here build the bistable network model of brain ischemia. The central concept is that of a post-ischemic state space. Ischemia, as a quantitative perturbation, is envisioned to push the brain through a series of four phenotypes as a function of the amount of ischemia: the homeostatic, preconditioned, delayed neuronal death and necrotic phenotypes. The phenotypes are meta-stable attractors in the landscape of the post-ischemic state space. The sequence of the phenotypes derives from the mutual antagonism between damage mechanisms and stress responses, each conceived as aggregate ensemble variables. The competition between damage mechanisms and stress responses is posited to have the form of a bistability. Application of bistability to brain ischemia is grounded in the incontrovertible fact that post-ischemic neurons face the mutually exclusive decision to either live or die. PMID:21258657

  19. Equilibrative nucleoside transporter 1 (ENT1) regulates postischemic blood flow during acute kidney injury in mice

    PubMed Central

    Grenz, Almut; Bauerle, Jessica D.; Dalton, Julee H.; Ridyard, Douglas; Badulak, Alexander; Tak, Eunyoung; McNamee, Eóin N.; Clambey, Eric; Moldovan, Radu; Reyes, German; Klawitter, Jost; Ambler, Kelly; Magee, Kristann; Christians, Uwe; Brodsky, Kelley S.; Ravid, Katya; Choi, Doo-Sup; Wen, Jiaming; Lukashev, Dmitriy; Blackburn, Michael R.; Osswald, Hartmut; Coe, Imogen R.; Nürnberg, Bernd; Haase, Volker H.; Xia, Yang; Sitkovsky, Michail; Eltzschig, Holger K.

    2012-01-01

    A complex biologic network regulates kidney perfusion under physiologic conditions. This system is profoundly perturbed following renal ischemia, a leading cause of acute kidney injury (AKI) — a life-threatening condition that frequently complicates the care of hospitalized patients. Therapeutic approaches to prevent and treat AKI are extremely limited. Better understanding of the molecular pathways promoting postischemic reflow could provide new candidate targets for AKI therapeutics. Due to its role in adapting tissues to hypoxia, we hypothesized that extracellular adenosine has a regulatory function in the postischemic control of renal perfusion. Consistent with the notion that equilibrative nucleoside transporters (ENTs) terminate adenosine signaling, we observed that pharmacologic ENT inhibition in mice elevated renal adenosine levels and dampened AKI. Deletion of the ENTs resulted in selective protection in Ent1–/– mice. Comprehensive examination of adenosine receptor–knockout mice exposed to AKI demonstrated that renal protection by ENT inhibitors involves the A2B adenosine receptor. Indeed, crosstalk between renal Ent1 and Adora2b expressed on vascular endothelia effectively prevented a postischemic no-reflow phenomenon. These studies identify ENT1 and adenosine receptors as key to the process of reestablishing renal perfusion following ischemic AKI. If translatable from mice to humans, these data have important therapeutic implications. PMID:22269324

  20. Immunizing Beef Calves: A Preconditioning Immunization Concept 

    E-print Network

    Faries Jr., Floron C.

    2000-12-20

    Properly vaccinating an entire herd, including pregnant cows, calves, replacement heifers and bulls, can prevent disease outbreaks caused by both dormant and incubating infections. This preconditioning immunization helps unborn, nursing and weanling...

  1. Oxygen Consumption and Mitochondrial Membrane Potential in Postischemic Myocardium

    Microsoft Academic Search

    Kazuaki Nishio; Noburu Konno; Yoshihisa Arata; Ryuji Ueda; Katumiti Iijima; Toshiki Iwata; Takashi Katagiri

    Oxygen consumption may be disproportionately high relative to contractile function in postischemic reperfused myocardium.\\u000a The study reported in this chapter investigated the mechanism of the dissociation between oxygen consumption and contractile\\u000a function in postischemic reperfused myocardium using isolated rat hearts. Mitochondrial dysfunction secondary to increased\\u000a calcium uptake has been implicated as an important mediator of reperfusion injury in the heart.

  2. Repairing brain after stroke: a review on post-ischemic neurogenesis.

    PubMed

    Wiltrout, Charles; Lang, Bradley; Yan, Yiping; Dempsey, Robert J; Vemuganti, Raghu

    2007-06-01

    Stroke is devastating as currently no therapies are available that can prevent stroke-induced neurological dysfunction in humans. With the recent observations that acute insults to adult brain stimulate new neuronal formation in various species of animals, optimism is building for a possible regeneration of stroke-damaged brain. This article reviewed the advances in the understanding of the molecular mechanisms of the various steps of neurogenesis with an emphasis on the endogenous mediators and exogenous promoters of neural progenitor proliferation, migration and survival in the post-ischemic adult brain. PMID:17531349

  3. EEG, CT and neurosonographic findings in patients with postischemic seizures

    Microsoft Academic Search

    Susanna Horner; Xiu-Shi Ni; Margret Duft; Kurt Niederkorn; Helmut Lechner

    1995-01-01

    Seventy-two patients with postischemic seizures were evaluated with electroencephalography (EEG), computerized tomography (CT) and neurosonography. There were 24% early-onset and 76% late-onset initial seizures. Early-onset seizure was more likely to be simple partial (53%), whereas late-onset seizure was more likely to be primarily generalized (56%). 76% early-onset and 80% late-onset seizures were single. Status epilepticus was more frequent in early-onset

  4. Effects of estrogen on postischemic pial artery reactivity to ADP

    PubMed Central

    Li, Min; Zeynalov, Emil; Li, Xiaoling; Miyazaki, Chikao; Koehler, Raymond C.; Littleton-Kearney, Marguerite T.

    2011-01-01

    Objective To determine if (1) ischemia alters pial artery responsiveness to the partially nitric oxide (NO)–dependent dilator ADP, (2) the alteration depends on 17?-estradial (E2), and (3) NO contributes to E2 protective effects. Methods Response to ADP and the non–NO-dependent dilator PGE2 were examined through closed cranial windows. Ovariectomized (OVX) and E2-replaced (E25, 0.025 mg; or E50, 0.05 mg) rats were subjected to 15-minute forebrain ischemia and 1-hour reperfusion. Endothelial NO synthase (eNOS) expression was determined in pre- and post-ischemic isolated cortical microvessels. Results In OVX rats, ischemia depressed pial responses to ADP but not to PGE2. Both doses of E2 maintained responses to ADP and had no effect on the response to PGE2. eNOS inhibition decreased the ADP response by 60% in the E25 rats and 50% in the E50 rats but had no effect in the OVX rats. Compared to the OVX group, microvessel expression of eNOS was increased by E2, but postischemic eNOS was unchanged in both groups. Conclusions The nearly complete loss of postischemic dilation to ADP suggests that normal non-NO-mediated dilatory mechanisms may be acutely impaired after ischemic injury. Estrogen’s protective action on ADP dilation may involve both NO- and non-NO-mediated mechanisms. PMID:19347762

  5. Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine A 1 receptor agonist

    Microsoft Academic Search

    Mark Beenhakker; Rick C.-S. Lin; Margaret F. Carter; Ian A. Paul; Norbert Bischofberger; Kenneth A. Jacobson

    1996-01-01

    Agonists of adenosine A1 receptors have been frequently proposed as candidates for clinical development in treatment of cerebral ischemia and stroke. Numerous experimental studies have shown that pre- and postischemic administration of these drugs results in a very significant reduction of postischemic brain damage. However, only a few studies determined the impact of cerebral ischemia and drug treatment on postischemic

  6. Permanent Reduction of Seizure Threshold in Post-Ischemic CA3 Pyramidal Neurons

    E-print Network

    Cossart, Rosa

    Permanent Reduction of Seizure Threshold in Post-Ischemic CA3 Pyramidal Neurons PATRICE CONGAR thresh- old in post-ischemic CA3 pyramidal neurons. J. Neurophysiol. 83: 2040­2046, 2000. The effects of ischemia were examined on CA3 pyramidal neurons recorded in hippocampal slices 2­4 mo after a global

  7. Expression of neurotrophin receptors by proliferating glia in postischemic hippocampal CA1 sector of adult monkeys

    Microsoft Academic Search

    Anton B. Tonchev; Nadezhda B. Boneva; Desislav B. Kaplamadzhiev; Mitsuru Kikuchi; Yoshimi Mori; Shunya Sahara; Tetsumori Yamashima

    2008-01-01

    Transient global cerebral ischemia elicits a nearly total neuronal cell death in the hippocampal CA1 sector, accompanied by a marked microglial and astroglial proliferation. The molecular mechanisms regulating the postischemic glial reaction in the primate brain remain obscure. Here we present in situ evidence that proliferating postischemic microglia in adult monkey CA1 sector express the neurotrophin receptor TrkA, while activated

  8. Postischemic thyroxin stimulates renal mitochondrial adenine nucleotide translocator activity.

    PubMed

    Boydstun, I; Najjar, S; Kashgarian, M; Carpenter, T; Siegel, N

    1995-04-01

    Postischemic thyroxin (T4) enhances restitution of cellular ATP and accelerates recovery of renal function. This effect is not related to global improvement in cell integrity. To determine the mechanism by which recovery of cellular ATP is enhanced, the effect of T4 on mitochondrial ATP production was evaluated using specific inhibitor stop assays for mitochondrial phosphate transport and ADP translocator activity. Rats were subjected to 45-min renal ischemia and given normal saline (NS, 0.5 ml) or T4 (20 micrograms/kg) during the reflow period. By 30-min reflow; the values for apparent endpoint of phosphate transport (PiTm, nmol Pi/mg mitochondrial protein) had recovered to rates seen in nonischemic animals (10.3 +/- 0.9) and remained stable at 120 min. T4 treatment did not affect PiTm. In contrast, the apparent endpoint of ADP transport (ADPTm, nmol ADP/mg mitochondrial protein) was dramatically decreased in NS rats at 30-min (6.7 +/- 0.5) and 120-min (13.7 +/- 1.0) reflow compared with nonischemic control rats (24.7 +/- 2.4). T4 significantly improved ADPTm by 30 min (10.1 +/- 0.6, P < 0.05). By 120 min T4 stimulated ADPTm (37.7 +/- 5.2, P < 0.05) to exceed nonischemic control values. These data suggest the following: 1) postischemic mitochondrial PiTm recovers to control values by 30 min of reflow; 2) T4 does not augment PiTm; 3) renal ischemia causes a dramatic decrease in mitochondrial ADPTm; 4) postischemic T4 significantly enhances mitochondrial nucleotide transport at 30-min reflow; 5) by 120-min reflow, T4 rats have ADPTm which exceeds control values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7733309

  9. PRECONDITIONING BLOCK TOEPLITZ MATRICES

    Microsoft Academic Search

    THOMAS K. HUCKLE; DIMITRIOS NOUTSOS

    2007-01-01

    We investigate the spectral behavior of preconditioned block Toeplitz matrices with small non- Toeplitz blocks. These matrices have a quite different behavior than scalar or mulitlevel Toeplitz matrices. Based on the connection between Toeplitz and Hankel matrices we derive some negative results on eigenvalue clustering for ill-conditioned block Toeplitz matrices. Furthermore, we identify Block Toeplitz matrices that are easy to

  10. miR-15b Suppression of Bcl-2 Contributes to Cerebral Ischemic Injury and is Reversed by Sevoflurane Preconditioning

    PubMed Central

    Shi, Hong; Sun, Bao-liang; Zhang, Jia; Lu, Shiduo; Zhang, Pengyue; Wang, Hailian; Yu, Qiong; Stetler, R Anne; Vosler, Peter S.; Chen, Jun; Gao, Yanqin

    2014-01-01

    Ischemic neuroprotection afforded by sevoflurane preconditioning has been previously demonstrated, yet the underlying mechanism is poorly understood and likely affects a wide range of cellular activities. Several individual microRNAs have been implicated in both the pathogenesis of cerebral ischemia and cellular survival, and are capable of affecting a range of target mRNA. Conceivably, sevoflurane preconditioning may lead to alterations in ischemia-induced microRNA expression that may subsequently exert neuroprotective effects. We first examined the microRNA expression profile following transient cerebral ischemia in rats and the impact of sevoflurane preconditioning. Microarray analysis revealed that 3 microRNAs were up-regulated (>2.0 fold) and 9 were down-regulated (< 0.5 fold) following middle cerebral artery occlusion (MCAO) compared to sham controls. In particular, miR-15b was expressed at significantly high levels after MCAO. Preconditioning with sevoflurane significantly attenuated the upregulation of miR-15b at 72h after reperfusion. Bcl-2, an anti-apoptotic gene involved in the pathogenesis of cerebral ischemia, has been identified as a direct target of miR-15b. Consistent with the observed downregulation of miR-15b in sevoflurane-preconditioned brain, post-ischemic Bcl-2 expression was significantly increased by sevoflurane preconditioning. We identified the 3’-UTR of Bcl-2 as the target for miR-15b. Molecular inhibition of miR-15b was capable of mimicking the neuroprotective effect of sevoflurane preconditioning, suggesting that the suppression of miR-15b due to sevoflurane contributes to its ischemic neuroprotection. Thus, sevoflurane preconditioning may exert its anti-apoptotic effects by reducing the elevated expression of miR-15b following ischemic injury, allowing its target proteins, including Bcl-2, to be translated and expressed at the protein level. PMID:23469855

  11. Mitochondrial ROS production and subsequent ERK phosphorylation are necessary for temperature preconditioning of isolated ventricular myocytes

    PubMed Central

    Bhagatte, Y; Lodwick, D; Storey, N

    2012-01-01

    Hypothermia and hypothermic preconditioning are known to be profoundly cardioprotective, but the molecular mechanisms of this protection have not been fully explained. In this study, temperature preconditioning (16?°C) was found to be cardioprotective in isolated adult rat ventricular myocytes, enhancing contractile recovery and preventing calcium dysregulation after oxidative stress. Hypothermic preconditioning preserved mitochondrial function by delaying the pathological opening of the mitochondrial permeability transition pore (mPTP), whereas transient mPTP flickering remained unaltered. For the first time, reactive oxygen species (ROS) from the mitochondria are shown to be released exclusively during the hypothermic episodes of the temperature-preconditioning protocol. Using a mitochondrially targeted ROS biosensor, ROS release was shown during the brief bursts to 16?°C of temperature preconditioning. The ROS scavenger N-(2-mercaptopropionyl) glycine attenuated ROS accumulation during temperature preconditioning, abolishing the protective delay in mPTP opening. Temperature preconditioning induces ROS-dependant phosphorylation of the prosurvival kinase extracellular signal-regulated kinase (ERK)1/2. ERK1/2 activation was shown to be downstream of ROS release, as the presence of a ROS scavenger during temperature preconditioning completely blocked ERK1/2 activation. The cardioprotective effects of temperature preconditioning on mPTP opening were completely lost by inhibiting ERK1/2 activation. Thus, mitochondrial ROS release and ERK1/2 activation are both necessary to signal the cardioprotective effects of temperature preconditioning in cardiac myocytes. PMID:22764104

  12. Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

    PubMed

    Zarubina, I V; Shabanov, P D

    2009-03-01

    Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia. PMID:19529857

  13. An improved algorithm of fiber tractography demonstrates postischemic cerebral reorganization

    NASA Astrophysics Data System (ADS)

    Liu, Xiao-dong; Lu, Jie; Yao, Li; Li, Kun-cheng; Zhao, Xiao-jie

    2008-03-01

    In vivo white matter tractography by diffusion tensor imaging (DTI) accurately represents the organizational architecture of white matter in the vicinity of brain lesions and especially ischemic brain. In this study, we suggested an improved fiber tracking algorithm based on TEND, called TENDAS, for tensor deflection with adaptive stepping, which had been introduced a stepping framework for interpreting the algorithm behavior as a function of the tensor shape (linear-shaped or not) and tract history. The propagation direction at each step was given by the deflection vector. TENDAS tractography was used to examine a 17-year-old recovery patient with congenital right hemisphere artery stenosis combining with fMRI. Meaningless picture location was used as spatial working memory task in this study. We detected the shifted functional localization to the contralateral homotypic cortex and more prominent and extensive left-sided parietal and medial frontal cortical activations which were used directly as seed mask for tractography for the reconstruction of individual spatial parietal pathways. Comparing with the TEND algorithms, TENDAS shows smoother and less sharp bending characterization of white matter architecture of the parietal cortex. The results of this preliminary study were twofold. First, TENDAS may provide more adaptability and accuracy in reconstructing certain anatomical features, whereas it is very difficult to verify tractography maps of white matter connectivity in the living human brain. Second, our study indicates that combination of TENDAS and fMRI provide a unique image of functional cortical reorganization and structural modifications of postischemic spatial working memory.

  14. Post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin can reduce ischemia reperfusion injury.

    PubMed

    Shimbo, Daisuke; Abumiya, Takeo; Shichinohe, Hideo; Nakayama, Naoki; Kazumata, Ken; Houkin, Kiyohiro

    2014-03-20

    Despite successful revascularization, reperfusion after prolonged ischemia causes ischemia reperfusion (I/R) injury. Recruitment and activation of neutrophils is thought to be a key event causing I/R injury. We examined whether post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier without neutrophils, could reduce I/R injury in a rat transient middle cerebral artery occlusion (MCAO) model. Male Sprague-Dawley rats were subjected to 2-h MCAO and then were divided into three groups: (1) LEH group (n=7) infused with LEH (Hb concentration of 6g/dl, 10ml/kg/h) through the recanalized internal carotid artery for 2h, (2) vehicle group (n=8) infused with saline (10ml/kg/h) in the same manner as the LEH group, and (3) control group (n=9) subjected to recanalization only. After 24-h reperfusion, all rats were tested for neurological score and then sacrificed to examine infarct and edema volumes, myeloperoxidase (MPO) expression, matrix metalloproteinase-9 (MMP-9) expression and activity, and reactive oxygen species (ROS) production. Compared with the control group and the vehicle group, the LEH group showed a significantly better neurological score and significantly smaller infarct and edema volumes. MPO expression, MMP-9 expression and activity, and ROS production in the LEH group were also significantly lower than those in the control and vehicle groups. The results in the present study suggest that post-ischemic intra-arterial infusion of LEH can reduce I/R injury through reducing the effect of MMP-9, most likely produced by neutrophils. This therapeutic strategy may be a promising candidate to prevent I/R injury after thrombolysis and/or thromboectomy. PMID:24486612

  15. Hypoxic preconditioning protects rat hearts against ischemia-reperfusion injury via the arachidonate12-lipoxygenase/transient receptor potential vanilloid 1 pathway.

    PubMed

    Lu, Ming-Jen; Chen, Yih-Sharng; Huang, Ho-Shiang; Ma, Ming-Chieh

    2014-07-01

    Hypoxic preconditioning (HPC) protects rat hearts against ischemia-reperfusion (IR) injury. However, the role of transient receptor potential vanilloid 1 (TRPV1) in HPC-mediated cardioprotection remains unknown. TRPV1 is activated by endovanilloid 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], which is synthesized by arachidonate 12-lipoxygenase (ALOX12). Therefore, we examined whether HPC protects the myocardium against IR via the ALOX12/TRPV1 pathway. Compared to hearts of rats kept in room air, the hearts of rats kept in air with 10 % oxygen for 4 weeks had better post-ischemic recovery and less tissue damage when subjected to 30-min global ischemia and 4-h reflow in a Langendorff apparatus. Capsazepine, a specific TRPV1 blocker, administered 5 min before reperfusion markedly attenuated the effects of HPC, confirming that TRPV1 is a downstream effector in HPC-mediated cardioprotection. HPC resulted in the upregulation of ALOX12 and myocardial 12(S)-HETE, and prevented IR-induced 12(S)-HETE reduction. In addition, sarcolemmal ALOX12 expression in HPC hearts mainly co-localized with TRPV1 expression. Blockade of ALOX12 by cinnamyl-3,4-dihydroxy-?-cyanocinnamate or baicalein abrogated the effects of HPC, baicalein also decreased 12(S)-HETE expression. Mimicking HPC by given 12(S)-HETE or capsaicin to baicalien-treated hearts enhanced cardiac recovery during reperfusion. The cardiac protein kinase C (PKC) isoforms ?, ?, ?, and ? were preferentially expressed in the sarcolemmal membrane of HPC-treated hearts, indicating their high intrinsic activation state. Capsazepine or co-treatment with baicalein attenuated translocation of PKC?, PKC? and PKC?, but not that of PKC?. We conclude that HPC reduces heart susceptibly to IR via ALOX12/TRPV1/PKC pathway, as shown by increased 12(S)-HETE expression in HPC hearts. PMID:24816396

  16. Estrogen replacement therapy in diabetic ovariectomized female rats potentiates postischemic leukocyte adhesion in cerebral venules via a RAGE-related process

    PubMed Central

    Xu, Hao-Liang; Vetri, Francesco; Lee, Hae-Kyung; Ye, Shuhua; Paisansathan, Chanannait; Mao, Lizhen; Tan, Fulong

    2009-01-01

    In this study, we tested the hypothesis that the documented transformation of 17?-estradiol (E2) from a counterinflammatory hormone in nondiabetic (ND) rats to a proinflammatory agent in rats with diabetes mellitus (DM) is due to an enhanced contribution from the receptor for advanced glycation end products (RAGE). Rhodamine 6G-labeled leukocytes were observed through a closed cranial window in rats. In vivo pial venular leukocyte adherence and infiltration were measured over 10 h reperfusion after transient forebrain ischemia in DM (streptozotocin) versus ND intact, ovariectomized (OVX), and E2-replaced (for 7–10 days) OVX (OVE) females. The role of RAGE was examined in two ways: 1) RAGE knockdown via topical application of RAGE antisense versus missense oligodeoxynucleotide or 2) intracerebroventricular injection of the RAGE decoy inhibitor, soluble RAGE. Among diabetic rats, the lowest levels of cortical RAGE mRNA and immunoreactivity of the RAGE ligand, AGE, were seen in OVX females, with significantly higher levels exhibited in intact and OVE females. However, results from the analysis of cortical RAGE protein only partially tracked those findings. When comparing ND to DM rats, cortical AGE immunoreactivity was significantly lower in OVE and intact females but similar in OVX rats. In DM rats, the level of postischemic leukocyte adhesion and infiltration (highest to lowest) was OVE > intact >> untreated OVX. In NDs, adhesion was highest in the untreated OVX group. Leukocyte extravasation was observed at >6 h postischemia but only in diabetic OVE and intact females and in ND OVX (untreated) rats. Pretreatment with RAGE antisense-oligodeoxynucleotide or soluble RAGE attenuated postischemic leukocyte adhesion and prevented infiltration but only in the diabetic OVE and intact groups. These results indicate that the exacerbation of postischemic leukocyte adhesion by chronic E2 replacement therapy in diabetic OVX females involves a RAGE-related mechanism. Targeting RAGE may restore the neuroprotective effect of E2 replacement therapy in diabetic females. PMID:19820198

  17. Chemical preconditioning-induced reactive astrocytosis contributes to the reduction of post-ischemic edema through aquaporin-4 downregulation

    Microsoft Academic Search

    Akihiko Hoshi; Teiji Yamamoto; Keiko Shimizu; Yoshihiro Sugiura; Yoshikazu Ugawa

    2011-01-01

    Aquaporins are a family of membrane proteins that promote the transmembrane diffusion of water. Aquaporin-4 (AQP4) is a predominant water channel protein in the brain and is concentrated in the end-feet of astrocytes. A critical question is what role astrocytic AQP4 plays in pathological conditions. Another matter to be elucidated is the relationship between morphological changes in astrocytes and AQP4

  18. Long-term effects of pre and post-ischemic exercise following global cerebral ischemia on astrocyte and microglia functions in hippocampus from Wistar rats.

    PubMed

    Lovatel, Gisele Agustini; Bertoldi, Karine; Elsnerb, Viviane Rostirola; Piazza, Francele Valente; Basso, Carla Giovana; Moysés, Felipe Dos Santos; Worm, Paulo Valdeci; Netto, Carlos Alexandre; Marcuzzo, Simone; Siqueira, Ionara Rodrigues

    2014-10-31

    Persistent effects of pre- and postischemic exercise on glial cells activation after global cerebral ischemia remains poorly understood. Here, we investigated the effect of both pre and postischemic treadmill exercise protocols (20min/day during 2 weeks) on glial cells immunostaining in the hippocampus of Wistar rats submitted to global ischemia. A synergistic effect between ischemia and postischemic exercise on the astrocytic area was demonstrated. Postischemic exercise partially reversed the ischemia-induced increase on the area occupied by microglia, without any effect of pre-ischemic protocol. In conclusion, postischemic exercise distinctly modulates astrocyte and microglia immunostaining in the hippocampal dentate gyrus following global cerebral ischemia in Wistar rats. PMID:25192647

  19. Volatile anesthetic-induced preconditioning.

    PubMed

    Swyers, T; Redford, D; Larson, D F

    2014-01-01

    The myocardium has an innate ability to protect itself from ischemic events. This protection occurs when the myocardium is exposed to a brief ischemic period prior to a more extreme ischemic event. This is termed ischemic preconditioning. Ischemic preconditioning induces a series of molecular pathways that protect the cardiac myocyte; first, for a period of 1-6 hours (early preconditioning) and, also, for a second period from 24-72 hours (delayed phase). The early preconditioning is mediated by the release of adenosine which induces a protective signal that is related to the mitochondrial KATP channel activation and activation of the ?-opioid and bradykinin receptors. The delayed phase is related to the induction of inducible nitric oxide synthase, superoxide dismutase and heat-shock proteins. Indirect evidence indicates that O2-derived free radicals are involved in the delayed phase, as noted in the early preconditioning phase. Applying ischemic preconditioning to clinical practice can be dangerous and difficult to implement in a controlled fashion. However, recent studies have shown that the use of volatile anesthetics, such as sevoflurane, isoflurane and desflurane, can mimic the early phase of ischemic preconditioning through a multi-pathway signaling of mitochondrial KATP channels. This important finding can easily be applied to clinical practice for patients undergoing surgery. It can also be significantly important for patients undergoing off-pump cardiac bypass surgery or cardiac bypass surgery where there is no cross-clamp or cardioplegia used where the probability of myocardial ischemia is greatly increased. This report will, therefore, discuss the mechanism, safety and efficacy of volatile anesthetics as inducers of cardiac preconditioning. PMID:24002781

  20. The divergent roles of autophagy in ischemia and preconditioning

    PubMed Central

    Sheng, Rui; Qin, Zheng-hong

    2015-01-01

    Autophagy is an evolutionarily conserved and lysosome-dependent process for degrading and recycling cellular constituents. Autophagy is activated following an ischemic insult or preconditioning, but it may exert dual roles in cell death or survival during these two processes. Preconditioning or lethal ischemia may trigger autophagy via multiple signaling pathways involving endoplasmic reticulum (ER) stress, AMPK/TSC/mTOR, Beclin 1/BNIP3/SPK2, and FoxO/NF-?B transcription factors, etc. Autophagy then interacts with apoptotic and necrotic signaling pathways to regulate cell death. Autophagy may also maintain cell function by removing protein aggregates or damaged mitochondria. To date, the dual roles of autophagy in ischemia and preconditioning have not been fully clarified. The purpose of the present review is to summarize the recent progress in the mechanisms underlying autophagy activation during ischemia and preconditioning. A better understanding of the dual effects of autophagy in ischemia and preconditioning could help to develop new strategies for the preventive treatment of ischemia. PMID:25832421

  1. ORGANELLES DO NOT COLOCALIZE WITH mRNA GRANULES IN POST-ISCHEMIC NEURONS

    E-print Network

    DeGracia, Donald J.

    of TA in post-ischemic neurons, such as the hippocampal CA1 re- gion, is one of the strongest predictorsRNA. Together, these results shed additional light on the identity of the mRNA granule by ruling out a direct Materials Antisera for -tubulin (T6199) and neurofilament (NF) H/M (N2912) were purchased from Sigma

  2. Blood cardioplegia enhanced with nitric oxide donor SPM5185 counteracts postischemic endothelial and ventricular dysfunction

    Microsoft Academic Search

    Katsuhiko Nakanishi; Zhi-Qing Zhao; J. Vinten-Johansen; Dudley A. Hudspeth; D. Scott McGee; John W. Hammon

    1995-01-01

    This study tested the hypothesis that enhancement of blood cardioplegia with the nitric oxide donor agent SPM-5185 inhibits postischemic left ventricular and coronary endothelial dysfunction. Eighteen anesthetized dogs supported by total vented bypass were subjected to 30 minutes of normothermic ischemia followed by 4° C multidose blood cardioplegia. Hearts received either standard blood cardioplegia (vehicle group; n = 6), blood

  3. Arterial spin labeling and dynamic susceptibility contrast CBF MRI in postischemic hyperperfusion,

    E-print Network

    Duong, Timothy Q.

    Arterial spin labeling and dynamic susceptibility contrast CBF MRI in postischemic hyperperfusion Texas Veterans Health Care System, San Antonio, Texas, USA Arterial spin labeling (ASL) and dynamic.76±0.14 seconds in normal pixels to 1.93±0.17 seconds in hyperperfusion pixels. Arterial transit time decreased

  4. 40 CFR 1065.518 - Engine preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...emission testing: (1) Cold-start transient cycle. Precondition the engine by running at least one hot-start transient cycle. We will precondition your engine by running two hot-start transient cycles. Immediately after...

  5. Cardiac genomic response following preconditioning stimulus

    Microsoft Academic Search

    Dipak K. Das; Nilanjana Maulik

    2006-01-01

    This review focuses on the genomic response following a preconditioning stimulus. Initial studies demonstrated that classical ischemic preconditioning mediated by cyclic episodes of short durations of reversible ischemia and reperfusion could result in the reprogramming of gene expression. Some of these genes are translated into proteins during the late preconditioning or so-called ''second window of protection''. Subsequent studies determined a

  6. Liver ischemia preconditions the heart against ischemia-reperfusion arrhythmias

    PubMed Central

    Noorbakhsh, Mohammad-Foad; Arab, Hossein-Ali; Kazerani, Hamid-Reza

    2015-01-01

    Objective(s): This study aimed to examine the hypothesis that an antiarrhythmic effect might be obtained by ischemic preconditioning of the liver, and also to characterize the potential underlying mechanisms. Materials and Methods: Male Wistar rats were anesthetized by thiopental sodium (50 mg/kg, IP) followed by IV injection of heparin (250 IU). Remote ischemic preconditioning (RIPC) was induced by 3 cycles of 5 min liver ischemia followed by 5 min of reperfusion. The hearts were excised within 5 min after the final cycle of preconditioning and perfused using Langendorff’s system. The isolated perfused hearts were subjected to 30 min global ischemia followed by 90 min reperfusion. The myocardial arrhythmias induced by ischemia- reperfusion (I/R) were determined in accordance with the guidelines of Lambeth Conventions. The potential role of KATP channels on RIPC was assessed by injection of glibenclamide (nonselective KATP blocker) or 5-hydroxydecanoate (mitochondrial KATP blocker) on rats 30 and 15 min before induction of RIPC in the liver, respectively. Results: Hepatic remote preconditioning of the heart significantly (P<0.0001) prevented the incidence of myocardial arrhythmias induced by I/R in the perfused hearts (5.33±1.54 vs. 32.33±6.44,). However, the protective effects of remote preconditioning was significantly (P<0.01) abolished by the KATP blocker, glibenclamide (25.5±4.9 vs. 5.33±1.54,). Conclusion: Hepatic RIPC may prevent the arrhythmias induced by I/R in the isolated perfused hearts via KATP channels. PMID:25810880

  7. Preconditioning for temporal video superresolution

    E-print Network

    Cooperstock, Jeremy R.

    Preconditioning for temporal video superresolution St´ephane Pelletier and Jeremy R. Cooperstock.pelletier@mail.mcgill.ca jer@cim.mcgill.ca Abstract Temporal superresolution produces a video sequence of high temporal resolution (HTR), i.e. frame rate, from a set of video sequences of low tem- poral resolution (LTR). A method

  8. Effect of hemodilution and hemoconcentration on postischemic alterations of microvessels in rabbit paired auricles

    Microsoft Academic Search

    L. A. Mikhailichenko; M. I. Reutov

    1996-01-01

    Morphometric parameters of microvessels in paired rabbit ears and blood sampled from the internal vein were studied after\\u000a ischemia reproduced under conditions of prior hemodilution and hemoconcentration. In hemodilution the postischemic alterations\\u000a were found to be more pronounced in microvessels of the left ear, while for the right the same was true for rheological characteristics\\u000a of the outflowing blood. Under

  9. The effectiveness of a preconditioning program on the incidence of running-related injuries in female novice runners: a randomised controlled trial

    Microsoft Academic Search

    S Zijlstra; I Buist; S W Bredeweg

    2011-01-01

    BackgroundThe incidence of running-related injuries (RRI) in (female) novice runners is high. Preconditioning programs have shown to be effective on the incidence of sports and overuse injuries in different populations.ObjectiveIs a preconditioning program effective for preventing RRIs in female novice runners?DesignThe prospective study is a large 2-arm randomised clinical trial. Participants were randomly assigned to a preconditioning group and a

  10. [Factors affecting the post-ischemic recuperation of isolated perfused rat heart].

    PubMed

    Tapsoba, Y A; Feuvray, D; de Leiris, J

    1980-08-01

    A number of cardioplegic solutions have been described for the reduction of cellular damage during ischemic cardiac arrest. Using an isolated working rat heart model, we have attempted to precise some of the factors affecting the post-ischemic recovery of myocardial tissue after a 30-min period of total ischemia at 37 degrees C. The results indicate that procaine (1 mM) is able to afford some protective against normothermic ischemia while this protective effect remains consistently lower than that of the St. Thomas' Hospital solution (procaine + high K+ + high Mg2+; JYNGE et al., 1977). On the other hand, hearts from rats of the Wistar strain consistently exhibit a significantly better degree of recovery than do hearts from rats of the Shermann strain. When hearts were perfused at different levels of preload (1 or 2 kPa) and afterload (8 or 10 kPa), post-ischemic recovery was better in hearts with lower levels of cardiac work. Glucose, insulin and DL-propranolol which have been shown to exert a protective effect in isolated rat hearts with regional ischemia failed to protect the heart in the present experimental conditions. No clear correlation does exist between the post-ischemic recovery and the enzymatic assessment of myocardial cell damage. PMID:6159859

  11. Prevention

    Cancer.gov

    NCI’s prevention research has a broad focus, from identifying environmental and lifestyle factors that influence cancer risk to studying the biology of how cancer develops and studying ways to disseminate prevention interventions.

  12. Preconditioning rabbit cardiomyocytes: role of pH, vacuolar proton ATPase, and apoptosis.

    PubMed Central

    Gottlieb, R A; Gruol, D L; Zhu, J Y; Engler, R L

    1996-01-01

    Ischemic preconditioning signals through protein kinase C (PKC) to protect against myocardial infarction. This protection is characterized by diminished intracellular acidification. Acidification is also a feature of apoptosis, and several agents act to prevent apoptosis by preventing acidification through activation of ion channels and pumps to promote cytoplasmic alkalinization. We characterized metabolic inhibition, recovery, and preconditioning through a PKC-dependent pathway in cardiomyocytes isolated from adult rabbit hearts. Preconditioning reduced loss of viability assessed by morphology and reduced DNA nicking. Blockade of the vacuolar proton ATPase (VPATPase) prevented the effect of preconditioning to reduce metabolic inhibition-induced acidosis, loss of viability, and DNA nicking. The beneficial effect of Na+/H+ exchange inhibition, which is thought to be effective through reduced intracellular Na+ and Ca++, was also abrogated by VPATPase blockade, suggesting that acidification even in the absence of Na+/H+ exchange may lead to cell death. We conclude that a target of PKC in mediating preconditioning is activation of the VPATPase with resultant attenuation of intracellular acidification during metabolic inhibition. Inhibition of the "death protease," interleukin-1-beta converting enzyme or related enzymes, also protected against the injury that followed metabolic inhibition. This observation, coupled with the detection of DNA nicking in cells subjected to metabolic inhibition, suggests that apoptotic cell death may be preventable in this model of ischemia/reperfusion injury. PMID:8636421

  13. Signal mechanism activated by erythropoietin preconditioning and remote renal preconditioning-induced cardioprotection

    Microsoft Academic Search

    Vishal Diwan; Ravi Kant; Amteshwar Singh Jaggi; Nirmal Singh; Dhandeep Singh

    2008-01-01

    It has been recently reported that release of erythropoietin could mediate the cardioprotective effects of remote renal preconditioning.\\u000a However, the mechanism of erythropoietin-mediated cardioprotection in remote preconditioning is still unexplored. Therefore,\\u000a the present study was designed to investigate the possible signal transduction pathway of erythropoietin-mediated cardioprotection\\u000a in remote preconditioning in rats. Remote renal preconditioning was performed by four episodes of

  14. Calcium activity and post-ischemic suppression of protein synthesis

    Microsoft Academic Search

    B. Djuricic; G. Röhn; W. Paschen; K.-A. Hossmann

    1995-01-01

    Increase in intracellular calcium concentration is a prominent feature of ischemia and has been considered a major factor in the initiation of ischemic pathology, which involves inhibition of protein synthesis. A reduction of calcium ion activity during and immediately after in vitro ischemia did not prevent inhibition of protein synthesis in hippocampae slices. When slices were overloaded with calcium by

  15. Weighted Graph Based Ordering Techniques for Preconditioned Conjugate Gradient Methods

    E-print Network

    Waterloo, University of

    Weighted Graph Based Ordering Techniques for Preconditioned Conjugate Gradient Methods Simon S: Preconditioned conjugate gradient, preconditioner, matrixordering, weighted graph Running Title: Weighted Graph's University, Kingston, Ontario. 1 #12;2 Weighted Graph Ordering for PCG Methods 1 Introduction Preconditioned

  16. Management of Preconditioned Calves and Impacts of Preconditioning.

    PubMed

    Hilton, W Mark

    2015-07-01

    When studying the practice of preconditioning (PC) calves, many factors need to be examined to determine if cow-calf producers should make this investment. Factors such as average daily gain, feed efficiency, available labor, length of the PC period, genetics, and marketing options must be analyzed. The health sales price advantage is an additional benefit in producing and selling PC calves but not the sole determinant of PC's financially feasibility. Studies show that a substantial advantage of PC is the selling of additional pounds at a cost of gain well below the marginal return of producing those additional pounds. PMID:26139187

  17. Prevention

    MedlinePLUS

    ... LinkedIn Twitter Digg Delicious Reddit StubmleUpon Print About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... try to avoid secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  18. A mouse model of peripheral postischemic dysesthesia: involvement of reperfusion-induced oxidative stress and TRPA1 channel.

    PubMed

    Sasaki, Atsushi; Mizoguchi, Shizuka; Kagaya, Kenta; Shiro, Mai; Sakai, Akiho; Andoh, Tsugunobu; Kino, Yurika; Taniguchi, Hiroyuki; Saito, Yukako; Takahata, Hiroki; Kuraishi, Yasushi

    2014-12-01

    Peripheral postischemic dysesthesia was examined behaviorally in mice and we investigated the underlying molecular mechanism with a focus on oxidative stress. Hind-paw ischemia was induced by tight compression of the ankle with a rubber band, and reperfusion was achieved by cutting the rubber tourniquet. We found that reperfusion after ischemia markedly provoked licking of the reperfused hind paw, which was significantly inhibited by systemic administration of the antioxidant N-acetyl-l-cysteine and the transient receptor potential (TRP) A1 channel blocker HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide]. Postischemic licking was also significantly inhibited by an intraplantar injection of another antioxidant, phenyl-N-tert-butylnitrone. The TRPV1 channel blocker BCTC [N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide] did not inhibit postischemic licking. An intraplantar injection of hydrogen peroxide elicited hind-paw licking, which was inhibited by N-acetyl-l-cysteine, phenyl-N-tert-butylnitrone, and HC-030031. Postischemic licking was not affected by chemical depletion of sensory C-fibers, but it was inhibited by morphine, which has been shown to inhibit the C- and A?-fiber-evoked responses of dorsal horn neurons. Interestingly, postischemic licking was not inhibited by gabapentin and pregabalin, which have been shown to inhibit the C-fiber- but not A?-fiber-evoked response. The present results suggest that ischemia-reperfusion induces oxidative stress, which activates TRPA1 channels to provoke postischemic licking. It has been suggested that this behavior is mediated by myelinated (probably A?-type) afferent fibers. Oxidative stress and TRPA1 channels may be potential targets to treat peripheral ischemia-associated dysesthesia. PMID:25228635

  19. Turfgrass evapotranspiration: Responses to shade preconditioning

    Microsoft Academic Search

    C. M. Feldhake; J. D. Butler; R. E. Danielson

    1985-01-01

    Sixteen minilysimeters were used in a study to determine the effect of preconditioning to shade on evapotranspiration (ET) by Kentucky bluegrass (Poa pratensis L. var ‘Merion’). Grass that had been preconditioned to 100, 71, 51, and 27% of possible photosynthetically active radiation (PAR) was subjected to full sun (100% PAR) or full shade (2% PAR) for one day periods. Canopy

  20. Preconditioning Techniques in Computational Fluid Dynamics

    Microsoft Academic Search

    E. Turkel

    1999-01-01

    An overview of preconditioning for the steady-state compressible inviscid fluid dynamic equations is presented. Extensions to the Navier-Stokes equations are also considered. These preconditioners are necessary for many algorithms in order to have the correct behavior at low speeds and to converge to the solution of the incompressible equations as the Mach number goes to zero. In addition, the preconditioning

  1. Roles of collateral arterial flow and ischemic preconditioning in protection of acutely ischemic myocardium.

    PubMed

    Jennings, Robert B; Wagner, Galen S

    2014-01-01

    The extent and rate at which necrosis develops in experimental acute myocardial infarction in the dog heart is presented together with an analysis of the role played by protective mechanisms in myocyte death. Preconditioning with ischemia delays but does not prevent myocyte death. Arterial collateral flows exceeding 30% of control flow essentially prevent myocyte death, while lesser amounts of collateral flow delay myocyte death to a variable extent. Flows of <0.09mlmin(-1)g(-1) wet exert no protective effect. Cell death occurs as quickly as it does with zero flow. Electrocardiography provides a means of detection of the preconditioned state in the dog heart in that the amount of ST elevation observed during the preconditioning episode is reduced during subsequent episodes of ischemia. Also, marked depression of arterial collateral flow can be detected by an increase in the duration of the QRS segment. PMID:24952922

  2. Pediatric cerebral stroke: susceptibility-weighted imaging may predict post-ischemic malignant edema.

    PubMed

    Bosemani, Thangamadhan; Poretti, Andrea; Orman, Gunes; Meoded, Avner; Huisman, Thierry A G M

    2013-10-01

    Susceptibility-weighted imaging (SWI) is an advanced MRI technique providing information on the blood oxygenation level. Deoxyhemoglobin is increased in hypoperfused tissue characterized by SWI-hypointensity, while high oxyhemoglobin concentration within hyperperfused tissue results in a SWI iso- or hyperintensity compared to healthy brain tissue. We describe a child with a stroke, where SWI in addition to excluding hemorrhage and delineating the thrombus proved invaluable in determining regions of hyperperfusion or luxury perfusion, which contributed further to the prognosis including an increased risk of developing post-ischemic malignant edema. PMID:24199819

  3. Cortical spreading depression-induced preconditioning in mouse neocortex is lamina specific.

    PubMed

    Gniel, Helen M; Martin, Rosemary L

    2013-06-01

    Cortical spreading depression (CSD) is able to confer neuroprotection when delivered at least 1 day in advance of an ischemic event. However, its ability to confer neuroprotection in a more immediate time frame has not previously been investigated. Here we have used mouse neocortical brain slices to study the effects of repeated episodes of CSD in layer V and layer II/III pyramidal neurons. In layer V, CSD evoked at 15-min intervals caused successively smaller membrane depolarizations and increases in intracellular calcium compared with the response to the first CSD. With an inter-CSD interval of 30 min this preconditioning effect was much less marked, indicating that preconditioning lasts between 15 and 30 min. A single episode of CSD also provided a degree of protection in oxygen-glucose deprivation (OGD) by significantly lengthening the time a cell could withstand OGD before anoxic depolarization occurred. In layer II/III pyramidal neurons no preconditioning by CSD on subsequent episodes of CSD was observed, demonstrating that the response of pyramidal neurons to repeated CSD is lamina specific. The A1 receptor antagonist 8-cyclopentyl theophylline (8-CPT) reduced the layer V preconditioning in a concentration-related manner. Inhibition of extracellular formation of adenosine by blocking ecto-5'-nucleotidase with ?,?-methyleneadenosine 5'-diphosphate prevented preconditioning in most but not all cells. Block of equilibrative nucleoside transporters 1 and 2 with dipyramidole alone or in combination with 6-[(4-nitrobenzyl)thio]-9-?-d-ribofuranosylpurine also prevented preconditioning in some but not all cells. These data provide evidence that rapid preconditioning of one CSD by another is primarily mediated by adenosine. PMID:23515796

  4. Mitochondrial reactive oxygen species: A double edged sword in ischemia/reperfusion vs preconditioning

    PubMed Central

    Kalogeris, Theodore; Bao, Yimin; Korthuis, Ronald J.

    2014-01-01

    Reductions in the blood supply produce considerable injury if the duration of ischemia is prolonged. Paradoxically, restoration of perfusion to ischemic organs can exacerbate tissue damage and extend the size of an evolving infarct. Being highly metabolic organs, the heart and brain are particularly vulnerable to the deleterious effects of ischemia/reperfusion (I/R). While the pathogenetic mechanisms contributing to I/R-induced tissue injury and infarction are multifactorial, the relative importance of each contributing factor remains unclear. However, an emerging body of evidence indicates that the generation of reactive oxygen species (ROS) by mitochondria plays a critical role in damaging cellular components and initiating cell death. In this review, we summarize our current understanding of the mechanisms whereby mitochondrial ROS generation occurs in I/R and contributes to myocardial infarction and stroke. In addition, mitochondrial ROS have been shown to participate in preconditioning by several pharmacologic agents that target potassium channels (e.g., ATP-sensitive potassium (mKATP) channels or large conductance, calcium-activated potassium (mBKCa) channels) to activate cell survival programs that render tissues and organs more resistant to the deleterious effects of I/R. Finally, we review novel therapeutic approaches that selectively target mROS production to reduce postischemic tissue injury, which may prove efficacious in limiting myocardial dysfunction and infarction and abrogating neurocognitive deficits and neuronal cell death in stroke. PMID:24944913

  5. The role of mitochondria in direct cell-to-cell connection dependent rescue of postischemic cardiomyoblasts.

    PubMed

    Pankotai, Eszter; Cselenyák, Attila; Rátosi, Orsolya; Lörincz, Judit; Kiss, Levente; Lacza, Zsombor

    2012-03-01

    In this in vitro study we induced ischemic injury on H9c2 rat cardiomyoblasts using the oxygen-glucose deprivation model (OGD). We monitored if the addition of healthy or mitochondria-depleted cells can save OGD treated cells from post-ischemic injury. We were able to significantly improve the surviving cell number of oxidatively damaged H9c2 cells by the addition of healthy cells to the culture. On the contrary, cells with disturbed mitochondria did not increase the number of surviving cells. High-resolution confocal time-lapse imaging also proved that mitochondria are drifting from cell-to-cell through tunneling membrane bridges, however, they do not get into the cytoplasm of the other cell. We conclude that addition of healthy cells to severly injured post-ischemic cardiomyoblasts can rescue them from death during the first 24h after reoxigenation. Grafted cells must maintain their mitochondria in an actively respiring state, and although cell contact is required for the mechanism, neither cell fusion nor organelle transfer occurs. This novel mechanism opens a new possiblity for cell-based cardiac repair in ischemic heart disease. PMID:21983690

  6. Pathways for ischemic cytoprotection: Role of sirtuins in caloric restriction, resveratrol, and ischemic preconditioning

    Microsoft Academic Search

    Kahlilia C Morris; Hung Wen Lin; John W Thompson; Miguel A Perez-Pinzon

    2011-01-01

    Caloric restriction (CR), resveratrol, and ischemic preconditioning (IPC) have been shown to promote protection against ischemic injury in the heart and brain, as well as in other tissues. The activity of sirtuins, which are enzymes that modulate diverse biologic processes, seems to be vital in the ability of these therapeutic modalities to prevent against cellular dysfunction and death. The protective

  7. Preconditioning the diabetic human myocardium

    PubMed Central

    Sivaraman, Vivek; Hausenloy, Derek J; Wynne, Abigail M; Yellon, Derek M

    2010-01-01

    Abstract Our objective was to determine whether human diabetic myocardium is amenable to the cardioprotective actions of ischaemic preconditioning. Human right atrial appendages were harvested from diabetic and non-diabetic patients undergoing elective coronary artery bypass graft surgery. The atrial trabeculae were isolated and subjected to 90 min. of hypoxia followed by 120 min. of reoxygenation, following which the percentage recovery of baseline contractile function was determined. The atrial trabeculae were randomized to: (i) controls (groups 1 and 3); (ii) standard hypoxic preconditioning (HPC) protocol consisting of 4 min. of hypoxia/16 min. of reoxygenation before the 90 min. index hypoxic period (groups 2 and 4); (iii) Prolonged HPC protocol consisting of: 7 min. of hypoxia /16 min. of reoxygenation before the index hypoxic period (group 5). In addition, basal levels of Akt phosphorylation were determined in right atrial appendages harvested from non-diabetic patients and diabetic patients to determine whether PI3K-Akt signalling is down-regulated in the diabetic heart. Standard HPC improved baseline contractile function in human atrial trabeculae harvested from non-diabetic patients (52.4 ± 3.8% with HPC versus 30.0 ± 3.2% in control: P= 0.001; N= 6/group), but not in atrial trabeculae isolated from diabetic patients (22.6 ± 3.3% with HPC versus 28.5 ± 1.9% in control: P > 0.05; N= 6/group). However, the prolonged HPC protocol did improve baseline contractile function in atrial trabeculae harvested from diabetic patients (42.0 ± 2.4% with HPC versus 28.5 ± 1.9% in control: P= 0.001; N? 6/group). Western blot analysis demonstrated lower levels of phosphorylated Akt in diabetic myocardium compared to non-diabetic myocardium (0.13 ± 0.03 arbitrary units versus 0.39 ± 0.11 arbitrary units: P= 0.047; N? 4/group). From the data obtained it appears that the threshold for preconditioning the diabetic myocardium is elevated which may be related to the down-regulation of the PI3K-Akt pathway. PMID:19508386

  8. Laser thermal preconditioning enhances dermal wound repair

    NASA Astrophysics Data System (ADS)

    Wilmink, Gerald J.; Carter, Terry; Davidson, Jeffrey M.; Jansen, E. Duco

    2008-02-01

    Preconditioning tissues with an initial mild thermal stress, thereby eliciting a stress response, can serve to protect tissue from subsequent stresses. Patients at risk for impaired healing, such as diabetics, can benefit from therapeutic methods which enhance wound repair. We present a laser thermal preconditioning protocol that accelerates cutaneous wound repair in a murine model. A pulsed diode laser (? = 1.86 ?m, ? p = 2 ms, 50 Hz, H = 7.64 mJ/cm2) was used to precondition mouse skin before incisional wounds were made. The preconditioning protocol was optimized in vitro and in vivo using hsp70 expression, cell viability, and temperature measurements as benchmarks. Hsp70 expression was non-invasively monitored using a transgenic mouse strain with the hsp70 promoter driving luciferase expression. Tissue temperature recordings were acquired in real time using an infrared camera. Wound repair was assessed by measuring hsp70 expression, biomechanical properties, and wound histology for up to 24 d. Bioluminescence (BLI) was monitored with the IVIS 200 System (Xenogen) and tensile properties with a tensiometer (BTC-2000). The in vivo BLI studies indicated that the optimized laser preconditioning protocol increased hsp70 expression by 15-fold. The tensiometer data revealed that laser preconditioned wounds are ~40% stronger than control wounds at 10 days post surgery. Similar experiments in a diabetic mouse model also enhanced wound repair strength. These results indicate that 1) noninvasive imaging methods can aid in the optimization of novel laser preconditioning methods; 2) that optimized preconditioning with a 1.86 ?m diode laser enhances early wound repair.

  9. Steps to translate preconditioning from basic research to the clinic

    PubMed Central

    Bahjat, Frances R; Gesuete, Raffaella; Stenzel-Poore, Mary P

    2012-01-01

    Efforts to treat cardiovascular and cerebrovascular diseases often focus on the mitigation of ischemia-reperfusion (I/R) injury. Many treatments or “preconditioners” are known to provide substantial protection against the I/R injury when administered prior to the event. Brief periods of ischemia itself have been validated as a means to achieve neuroprotection in many experimental disease settings, in multiple organ systems, and in multiple species suggesting a common pathway leading to tolerance. In addition, pharmacological agents that act as potent preconditioners have been described. Experimental induction of neuroprotection using these various preconditioning paradigms has provided a unique window into the brain’s endogenous protective mechanisms. Moreover, preconditioning agents themselves hold significant promise as clinical-stage therapies for prevention of I/R injury. The aim of this article is to explore several key steps involved in the preclinical validation of preconditioning agents prior to the conduct of clinical studies in humans. Drug development is difficult, expensive and relies on multi-factorial analysis of data from diverse disciplines. Importantly, there is no single path for the preclinical development of a novel therapeutic and no proven strategy to ensure success in clinical translation. Rather, the conduct of a diverse array of robust preclinical studies reduces the risk of clinical failure by varying degrees depending upon the relevance of preclinical models and drug pharmacology to humans. A strong sense of urgency and high tolerance of failure are often required to achieve success in the development of novel treatment paradigms for complex human conditions. PMID:23504609

  10. Aerobic exercise performance correlates with post-ischemic flow-mediated dilation of the brachial artery in young healthy men

    Microsoft Academic Search

    Emiliano Antonio Palmieri; Vittorio Palmieri; Pasquale Innelli; Emma Arezzi; Liberato Aldo Ferrara; Aldo Celentano; Serafino Fazio

    2005-01-01

    In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg\\/m2; mean (SD)

  11. Direct Evidence that Oxygen-Derived Free Radicals Contribute to Postischemic Myocardial Dysfunction in the Intact Dog

    Microsoft Academic Search

    Roberto Bolli; Mohamed O. Jeroudi; Bharat S. Patel; Coit M. Dubose; Edward K. Lai; Robert Roberts; Paul B. McCay

    1989-01-01

    Electron paramagnetic resonance (EPR) spectroscopy was used to investigate whether (i) the free radicals produced in the ``stunned'' myocardium (myocardium with postischemic contractile dysfunction) are derived from O2, (ii) inhibition of radical reactions improves function, and (iii) i.v. spin traps are effective. Open-chest dogs undergoing a 15-min coronary occlusion received an i.v. infusion of the spin trap, alpha -phenyl N-tert-butylnitrone

  12. Postischemic Hyperthermia Induced Caspase3 Activation in the Newborn Rat Brain after Hypoxia-Ischemia and Exacerbated the Brain Damage

    Microsoft Academic Search

    Hirotsugu Fukuda; Takuji Tomimatsu; Takeshi Kanagawa; Junwu Mu; Masatomo Kohzuki; Koichiro Shimoya; Takayoshi Hosono; Toru Kanzaki; Yuji Murata

    2003-01-01

    The effects of postischemic hyperthermia were investigated in the newborn rat brain after hypoxia-ischemia (HI). Seven-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 30 min, and divided into a hyperthermia group (rectal temperature at 39°C for 6 h) and a normothermia group. Hyperthermia resulted in an approximately 5-fold increase in activated caspase-3 24 h

  13. Noopept Reduces the Postischemic Functional and Metabolic Disorders in the Brain of Rats with Different Sensitivity to Hypoxia

    Microsoft Academic Search

    I. V. Zarubina; P. D. Shabanov

    2009-01-01

    Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to\\u000a hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg\\/kg) during 7 days after occlusion\\u000a of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved\\u000a their survival during the postischemic

  14. Behavioral/Systems/Cognitive Octopamine Mediates Thermal Preconditioning of the

    E-print Network

    Robertson, Meldrum

    ) in the metathoracic ganglion decreased during heat stress. We measured of physiological adaptations that have evolved to protect nervous systems from heat stress. Preconditioning locusts l OA) mimicked heat shock preconditioning and improved the thermotolerance of the motor pattern

  15. Xenon preconditioning: molecular mechanisms and biological effects

    PubMed Central

    2013-01-01

    Xenon is one of noble gases and has been recognized as an anesthetic for more than 50?years. Xenon possesses many of the characteristics of an ideal anesthetic, but it is not widely applied in clinical practice mainly because of its high cost. In recent years, numerous studies have demonstrated that xenon as an anesthetic can exert neuroprotective and cardioprotective effects in different models. Moreover, xenon has been applied in the preconditioning, and the neuroprotective and cardioprotective effects of xenon preconditioning have been investigated in a lot of studies in which some mechanisms related to these protections are proposed. In this review, we summarized these mechanisms and the biological effects of xenon preconditioning. PMID:23305274

  16. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

    SciTech Connect

    Li, Zhao [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States)] [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States); Jin, Zhu-Qiu, E-mail: zhu-qiu.jin@sdstate.edu [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States)] [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiac TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in normal mouse heart. IPC preserves the integrity of TJ structure and function that are vulnerable to IR injury.

  17. Ischemic preconditioning protects cardiomyocyte mitochondria through mechanisms independent of cytosol.

    PubMed

    Ruiz-Meana, Marisol; Núñez, Estefanía; Miro-Casas, Elisabet; Martínez-Acedo, Pablo; Barba, Ignasi; Rodriguez-Sinovas, Antonio; Inserte, Javier; Fernandez-Sanz, Celia; Hernando, Victor; Vázquez, Jesús; Garcia-Dorado, David

    2014-03-01

    Mitochondria play a central role in the protection conferred by ischemic preconditioning (IP) by not fully elucidated mechanisms. We investigated whether IP protects mitochondria against ischemia-reperfusion (IR) injury through mechanisms independent of cytosolic signaling. In isolated rat hearts, sublethal IR increased superoxide production and reduced complex-I- and II-mediated respiration in subsarcolemmal (SS), but not interfibrillar (IF) mitochondria. This effect of IR on mitochondrial respiration was significantly attenuated by IP. Similar results were obtained in isolated cardiac mitochondria subjected to in vitro IR. The reduction in SS mitochondrial respiration in the heart and in vitro model was paralleled by an increase in oxidized cysteine residues, which was also prevented by IP. IP was also protective in mitochondria submitted to lethal IR. The protective effect of IP against respiratory failure was unaffected by inhibition of mitochondrial KATP channels or mitochondrial permeability transition. However, IP protection was lost in mitochondria from genetically-modified animals in which connexin-43, a protein present in SS but not IF mitochondria, was replaced by connexin-32. Our results demonstrate the existence of a protective mitochondrial mechanism or "mitochondrial preconditioning" independent of cytosol that confers protection against IR-induced respiratory failure and oxidative damage, and requires connexin-43. PMID:24434643

  18. PARALLEL GLOBAL LINE JACOBI PRECONDITIONING IN NIMROD Carl Sovinec, LANL

    E-print Network

    Sovinec, Carl

    PARALLEL GLOBAL LINE JACOBI PRECONDITIONING IN NIMROD Carl Sovinec, LANL June 11, 1999 This note to warrant trying global line Jacobi preconditioning in parallel. Here, I discuss one parallel implementation this global preconditioning will reduce computation time and increase parallel efficiency significantly

  19. Essential role of EGFR in cardioprotection and signaling responses to A1 adenosine receptors and ischemic preconditioning.

    PubMed

    Williams-Pritchard, Grant; Knight, Matthew; Hoe, Louise See; Headrick, John P; Peart, Jason N

    2011-06-01

    Transactivation of epidermal growth factor receptor (EGFR) may contribute to specific protective responses (e.g. mediated by ?-opioid, bradykinin, or muscarinic receptors). No studies have assessed EGFR involvement in cardioprotection mediated by adenosine receptors (ARs), and the role of EGFR in ischemic preconditioning (IPC) is unclear. We tested EGFR, matrix metalloproteinase (MMP), and heparin-binding EGF (HB-EGF) dependencies of functional protection via A(1)AR agonism or IPC. Pretreatment of mouse hearts with 100 nM of A(1)AR agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) or IPC (3 × 1.5-min ischemia/2-min reperfusion) substantially improved recovery from 25-min ischemia, reducing left ventricular diastolic dysfunction up to 50% and nearly doubling pressure development and positive change in pressure over time (+dP/dt). Benefit with both CCPA and IPC was eliminated by inhibitors of EGFR tyrosine kinase (0.3 ?M AG1478), MMP (0.3 ?M GM6001), or HB-EGF ligand (0.3 ng/ml CRM197), none of which independently altered postischemic outcome. Phosphorylation of myocardial EGFR, Erk1/2, and Akt increased two- to threefold during A(1)AR agonism, with responses blocked by AG1478, GM6001, and CRM197. Studies in HL-1 myocytes confirm A(1)AR-dependent Erk1/2 phosphorylation is negated by AG1478 or GM6001, and reduced with CRM197 (as was Akt activation). These data collectively reveal that A(1)AR- and IPC-mediated functional protection is entirely EGFR and MMP dependent, potentially involving the HB-EGF ligand. Myocardial survival kinase activation (Erk1/2, Akt) by A(1)AR agonism is similarly MMP/HB-EGF/EGFR dependent. Thus MMP-mediated EGFR activation appears essential to cardiac protection and signaling via A(1)ARs and preconditioning. PMID:21460200

  20. Evidence for an essential role of reactive oxygen species in the genesis of late preconditioning against myocardial stunning in conscious pigs.

    PubMed Central

    Sun, J Z; Tang, X L; Park, S W; Qiu, Y; Turrens, J F; Bolli, R

    1996-01-01

    Conscious pigs underwent a sequence of 10 2-min coronary occlusions, each separated by 2 min of reperfusion, for three consecutive days (days 1, 2, and 3). On day 1, pigs received an i.v. infusion of a combination of antioxidants (superoxide dismutase, catalase, and N-2 mercaptopropionyl glycine; group II, n = 9), nisoldipine (group III, n = 6), or vehicle (group I [controls], n = 9). In the control group, systolic wall thickening (WTh) in the ischemic-reperfused region on day 1 remained significantly depressed for 4 h after the 10th reperfusion, indicating myocardial "stunning." On days 2 and 3, however, the recovery of WTh improved markedly, so that the total deficit of WTh decreased by 53% on day 2 and 56% on day 3 compared with day 1 (P < 0.01), indicating the development of a powerful cardioprotective response (late preconditioning against stunning). In the anti-oxidant-treated group, the total deficit of WTh on day 1 was 54% less than in the control group (P < 0.01). On day 2, the total deficit of WTh was 85% greater than that observed on day 1 and similar to that observed on day 1 in the control group. On day 3, the total deficit of WTh was 58% less than that noted on day 2 (P < 0.01). In the nisoldipine-treated group, the total deficit of WTh on day 1 was 53% less than that noted in controls (P < 0.01). On days 2 and 3, the total deficit of WTh was similar to the corresponding values in the control group. These results demonstrate that: (a) in the conscious pig, antioxidant therapy completely blocks the development of late preconditioning against stunning, indicating that the production of reactive oxygen species (ROS) on day 1 is the mechanism whereby ischemia induces the protective response observed on day 2; (b) antioxidant therapy markedly attenuates myocardial stunning on day 1, indicating that ROS play an important pathogenetic role in postischemic dysfunction in the porcine heart despite the lack of xanthine oxidase; (c) although the administration of a calcium-channel antagonist (nisoldipine) is as effective as antioxidant therapy in attenuating myocardial stunning on day 1, it has no effect on late preconditioning on day 2, indicating that the ability of antioxidants to block late preconditioning is not a nonspecific result of the mitigation of postischemic dysfunction on day 1. Generation of ROS during reperfusion is generally viewed as a deleterious process. Our finding that ROS contribute to the genesis of myocardial stunning but, at the same time, trigger the development of late preconditioning against stunning supports a complex pathophysiological paradigm, in which ROS play an immediate injurious role (as mediators of stunning) followed by a useful function (as mediators of subsequent preconditioning). PMID:8567981

  1. Implementation of Deflated Preconditioned Conjugate Gradient

    E-print Network

    Vuik, Kees

    -by-Step Optimizations ·Profiler for Advice ·Modularity and Readability Methodology #12;·DIA Format is best ·Spm% of bandwidth ·Clubbing Kernels ­ Reducing Memory Traffic Deflated Preconditioned Conjugate Gradient bE 1 #12;·Density Contrast 1000:1 · ·False Stop Two Phase Matrix 1 2 2 10 |||| |||| 0 k kexact X XX #12

  2. Preconditioned Iterative Regularization Ill--Posed Problems

    E-print Network

    Plemmons, Robert J.

    Preconditioned Iterative Regularization for Ill--Posed Problems Martin Hanke, \\Lambda James Nagy y for solving large scale structured linear systems Hf = g + j, arising from the discretization of ill­ posed regularized for solving ill­posed problems by using the spectral decomposition of the preconditioner. Key

  3. Preconditioning and tolerance against cerebral ischaemia

    PubMed Central

    Dirnagl, Ulrich; Becker, Kyra; Meisel, Andreas

    2009-01-01

    Neuroprotection and brain repair in patients after acute brain damage are still major unfulfilled medical needs. Pharmacological treatments are either ineffective or confounded by adverse effects. Consequently, endogenous mechanisms by which the brain protects itself against noxious stimuli and recovers from damage are being studied. Research on preconditioning, also known as induced tolerance, over the past decade has resulted in various promising strategies for the treatment of patients with acute brain injury. Several of these strategies are being tested in randomised clinical trials. Additionally, research into preconditioning has led to the idea of prophylactically inducing protection in patients such as those undergoing brain surgery and those with transient ischaemic attack or subarachnoid haemorrhage who are at high risk of brain injury in the near future. In this Review, we focus on the clinical issues relating to preconditioning and tolerance in the brain; specifically, we discuss the clinical situations that might benefit from such procedures. We also discuss whether preconditioning and tolerance occur naturally in the brain and assess the most promising candidate strategies that are being investigated. PMID:19296922

  4. Managing one master data – challenges and preconditions

    Microsoft Academic Search

    Risto Silvola; Olli Jaaskelainen; Hanna Kropsu-Vehkapera; Harri Haapasalo

    2011-01-01

    Purpose – This paper aims to provide a framework of the multidimensional concept of one master data. Preconditions required for successful one master data implementation and usage in large high-tech companies are presented and related current challenges companies have today are identified. Design\\/methodology\\/approach – This paper is qualitative in nature. First, literature was studied to find out the elements of

  5. Revealing Preconditions for Trustful Collaboration in CSCL

    ERIC Educational Resources Information Center

    Gerdes, Anne

    2010-01-01

    This paper analyses preconditions for trust in virtual learning environments. The concept of trust is discussed with reference to cases reporting trust in cyberspace and through a philosophical clarification holding that trust in the form of self-surrender is a common characteristic of all human co-existence. In virtual learning environments,…

  6. Preconditioning matrices for Chebyshev derivative operators

    NASA Technical Reports Server (NTRS)

    Rothman, Ernest E.

    1986-01-01

    The problem of preconditioning the matrices arising from pseudo-spectral Chebyshev approximations of first order operators is considered in both one and two dimensions. In one dimension a preconditioner represented by a full matrix which leads to preconditioned eigenvalues that are real, positive, and lie between 1 and pi/2, is already available. Since there are cases in which it is not computationally convenient to work with such a preconditioner, a large number of preconditioners were studied which were more sparse (in particular three and four diagonal matrices). The eigenvalues of such preconditioned matrices are compared. The results were applied to the problem of finding the steady state solution to an equation of the type u sub t = u sub x + f, where the Chebyshev collocation is used for the spatial variable and time discretization is performed by the Richardson method. In two dimensions different preconditioners are proposed for the matrix which arises from the pseudo-spectral discretization of the steady state problem. Results are given for the CPU time and the number of iterations using a Richardson iteration method for the unpreconditioned and preconditioned cases.

  7. Backward Analysis for Inferring Quantified Preconditions

    Microsoft Academic Search

    Tal Lev-AmiMooly Sagiv; Sumit Gulwani

    2007-01-01

    This paper presents a method to infer preconditions that contain quantifiers. Such invariants can quantify over an unbounded num- ber of storage locations and elements of arrays, and allow shape properties of programs that manipulate pointers and dynamically allocated data structures to be described concisely. The precondi- tions that are found ensure that any assertions that exist in the code

  8. Negative regulation of diacylglycerol kinase ? mediates adenosine-dependent hepatocyte preconditioning

    Microsoft Academic Search

    G Baldanzi; E Alchera; C Imarisio; M Gaggianesi; C Dal Ponte; M Nitti; C Domenicotti; W J van Blitterswijk; E Albano; A Graziani; R Carini

    2010-01-01

    In liver ischemic preconditioning (IP), stimulation of adenosine A2a receptors (A2aR) prevents ischemia\\/reperfusion injury by promoting diacylglycerol-mediated activation of protein kinase C (PKC). By concerting diacylglycerol to phosphatidic acid, diacylglycerol kinases (DGKs) act as terminator of diacylglycerol signalling. This study investigates the role of DGK in the development of hepatocyte IP. DGK activity and cell viability were evaluated in isolated

  9. Temporal assessment of vascular reactivity and functionality using MRI during postischemic proangiogenenic vascular remodeling.

    PubMed

    Huang, Chien-Hsiang; Shih, Yen-Yu Ian; Siow, Tiing-Yee; Hsu, Yi-Hua; Chen, Chiao-Chi V; Lin, Teng-Nan; Jaw, Fu-Shan; Chang, Chen

    2015-09-01

    Postischemic angiogenesis is an important recovery mechanism. Both arteries and veins are upregulated during angiogenesis, but eventually there are more angiogenic veins than arteries in terms of number and length. It is critical to understand how the veins are modulated after ischemia and then transitioned into angiogenic vessels during the proangiogenic stage to finally serve as a restorative strength to the injured area. Using a rat model of transient focal cerebral ischemia, the hypercapnic blood oxygen level-dependent (BOLD) response was used to evaluate vascular reactivity, while the hyperoxic BOLD and tissue oxygen level-dependent (TOLD) responses were used to evaluate the vascular functionality at 1, 3, and 7days after ischemia. Vessel-like venous signals appeared on R2* maps on days 3 and 7, but not on day 1. The large hypercapnic BOLD responses on days 3 and 7 indicated that these areas have high vascular reactivity. The temporal correlation between vascular reactivity and the immunoreactivity to desmin and VEGF further indicates that the integrity of vascular reactivity is associated with the pericyte coverage as regulated by the VEGF level. Vascular functionality remained low on days 1, 3, and 7, as reflected by the small hyperoxic BOLD and large hyperoxic TOLD responses, indicating the low oxygen consumption of the ischemic tissues. These functional changes in proangiogenic veins may be critical for angiogenesis. PMID:25944092

  10. [Energy corrective and antioxidative actions of cytoflavin during postischemic period of human dermal fibroblasts in vitro].

    PubMed

    Tiuriaeva, I I; Kuranova, M L; Gonchar, I V; Rozanov, Iu M

    2012-01-01

    The influence of metabolic drug Cytoflavin (CF) with antihypoxic and antioxidative properties on human dermal fibroblasts in a model of ischemia-reoxygenation in vitro was studied. It was revealed that the restoration of ATP synthesis in fibroblasts in the postischemic period was considerably accelerated (in 2.1 times) by the addition of CF to the culture medium. The drug had a cell protective effect of reducing cell mortality during the reoxygenation after ischemia by 2-2.7 times. CF effectively reduced the level of reactive oxygen species (ROS) in fibroblasts after H2O2 treatment which allowed maintaining their survival at the level of control cells. Pretreatment of the cells with CF for one day ensured the maintenance of normal levels of ROS during the investigated time period in the fibroblasts subjected to H2O2 treatment, and reduced H2O2-induced cell death by almost a third compared to control cells. The introduction of CF in culture medium after ischemia showed no influence on Hsp70 synthesis, but led to decrease in GRP78 synthesis, raised after ischemia, to the control level, indicating a resolve of the endoplasmic reticulum (ER) stress and functional normalization of ER. PMID:22997734

  11. LPS-Induced Delayed Preconditioning Is Mediated by Hsp90 and Involves the Heat Shock Response in Mouse Kidney

    PubMed Central

    Kaucsár, Tamás; Bodor, Csaba; Godó, Mária; Szalay, Csaba; Révész, Csaba; Németh, Zalán; Mózes, Miklós; Szénási, Gábor; Rosivall, László; S?ti, Csaba; Hamar, Péter

    2014-01-01

    Introduction We and others demonstrated previously that preconditioning with endotoxin (LPS) protected from a subsequent lethal LPS challenge or from renal ischemia-reperfusion injury (IRI). LPS is effective in evoking the heat shock response, an ancient and essential cellular defense mechanism, which plays a role in resistance to, and recovery from diseases. Here, by using the pharmacological Hsp90 inhibitor novobiocin (NB), we investigated the role of Hsp90 and the heat shock response in LPS-induced delayed renal preconditioning. Methods Male C57BL/6 mice were treated with preconditioning (P: 2 mg/kg, ip.) and subsequent lethal (L: 10 mg/kg, ip.) doses of LPS alone or in combination with NB (100 mg/kg, ip.). Controls received saline (C) or NB. Results Preconditioning LPS conferred protection from a subsequent lethal LPS treatment. Importantly, the protective effect of LPS preconditioning was completely abolished by a concomitant treatment with NB. LPS induced a marked heat shock protein increase as demonstrated by Western blots of Hsp70 and Hsp90. NB alone also stimulated Hsp70 and Hsp90 mRNA but not protein expression. However, Hsp70 and Hsp90 protein induction in LPS-treated mice was abolished by a concomitant NB treatment, demonstrating a NB-induced impairment of the heat shock response to LPS preconditioning. Conclusion LPS-induced heat shock protein induction and tolerance to a subsequent lethal LPS treatment was prevented by the Hsp90 inhibitor, novobiocin. Our findings demonstrate a critical role of Hsp90 in LPS signaling, and a potential involvement of the heat shock response in LPS-induced preconditioning. PMID:24646925

  12. PRECONDITIONING BEEF CALVES: ARE EXPECTED PREMIUMS SUFFICIENT TO JUSTIFY THE PRACTICE?

    Microsoft Academic Search

    Kevin C. Dhuyvetter

    2004-01-01

    The concept of preconditioning calves has been around for a long time, yet adoption of the practice has been slow. Current trends in the beef industry likely will increase interest in preconditioning programs. This research estimates premiums received for preconditioned calves and the expected returns from a preconditioning program. Preconditioned calves sold in the fall received a premium of approximately

  13. Preserving Symmetry in Preconditioned Krylov Subspace Methods

    NASA Technical Reports Server (NTRS)

    Chan, Tony F.; Chow, E.; Saad, Y.; Yeung, M. C.

    1996-01-01

    We consider the problem of solving a linear system Ax = b when A is nearly symmetric and when the system is preconditioned by a symmetric positive definite matrix M. In the symmetric case, one can recover symmetry by using M-inner products in the conjugate gradient (CG) algorithm. This idea can also be used in the nonsymmetric case, and near symmetry can be preserved similarly. Like CG, the new algorithms are mathematically equivalent to split preconditioning, but do not require M to be factored. Better robustness in a specific sense can also be observed. When combined with truncated versions of iterative methods, tests show that this is more effective than the common practice of forfeiting near-symmetry altogether.

  14. M-step preconditioned conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Adams, L.

    1983-01-01

    Preconditioned conjugate gradient methods for solving sparse symmetric and positive finite systems of linear equations are described. Necessary and sufficient conditions are given for when these preconditioners can be used and an analysis of their effectiveness is given. Efficient computer implementations of these methods are discussed and results on the CYBER 203 and the Finite Element Machine under construction at NASA Langley Research Center are included.

  15. Insights from knock-out models concerning postischemic release of TNFalpha from isolated mouse hearts.

    PubMed

    Reil, J-C; Gilles, S; Zahler, S; Brandl, A; Drexler, H; Hültner, L; Matrisian, L M; Welsch, U; Becker, B F

    2007-01-01

    The inflammatory cytokine tumor necrosis factor alpha (TNFalpha) is controversially discussed in ischemia/reperfusion damage of the heart. Purpose of this study was to elucidate cellular sources of TNFalpha and parameters which possibly influence its release in the heart following ischemia. Isolated hearts of mice were subjected to 15 min of global ischemia and 90 min of reperfusion. We employed hearts of various mice knock-out strains (interleukin-6(-/-), matrix metalloprotease-7(-/-), mast-cell deficient WBB6F1-Kit(W)/Kit(W-v), TNF-R1(-/-)) and wildtype mice, the latter perfused without and with infusion of cycloheximide or TNFalpha-cleaving-enzyme inhibitor (TAPI-2). Normoxic control hearts showed basal release of TNFalpha during the whole experiment. Immunohistology identified cardiac mast cells, macrophages and endothelial cells as main sources. TNFalpha release was stimulated during postischemic reperfusion, occurring in a two-peak pattern: directly after ischemia (0-10 min) and again after 60-90 min. The first peak mainly reflects tissue washout of TNFalpha accumulated during ischemia. The second, protracted peak arose continuously from the basal level and was abolished by protein synthesis inhibitor cycloheximide. Both properties are characteristic for de novo synthesis of TNFalpha, e.g., in cardiac muscle cells. However, immunohistological staining for TNFalpha failed in cardiomyocytes after 90 min of reperfusion. In contrast to hearts of TNF-R1(-/-) and Kit(W/W-v)-mice, those of IL-6(-/-) and MMP-7(-/-) mice lacked the late TNFalpha peak. TAPI did not suppress release of TNFalpha. While autostimulation via TNF-R1 also does not seem obligatory and mast cell can be ignored as source of the second peak, IL-6 may support de novo synthesis of TNFalpha. Additionally, TNFalpha release may essentially involve cleavage of membrane bound TNFalpha by MMP-7. PMID:17101148

  16. A limited role for regulatory T cells in post-ischemic neovascularization.

    PubMed

    Hellingman, A A; van der Vlugt, L E P M; Lijkwan, M A; Bastiaansen, A J N M; Sparwasser, T; Smits, H H; Hamming, J F; Quax, P H A

    2012-02-01

    Recently, it was demonstrated that arteriogenesis is enhanced in mice deficient in regulatory T cells (CD4(+) CD25(+) FoxP3(+) T cell), which can suppress effector T cell responses. The present study investigates the effects of these regulatory T cells on arteriogenesis in more detail by either specific expanding or depleting regulatory T cells. Hind limb ischemia was induced by electro-coagulation of the femoral artery in mice. Regulatory T cells were either expanded by injecting mice with a complex of interleukin (IL)-2 with the IL-2 monoclonal antibody JES6-1, or depleted by anti-CD25 antibody or diphtheria toxin injections in DEREG mice (depletion of regulatory T cells). Blood flow restoration was monitored using laser Doppler perfusion imaging. Collateral arteries were visualized by immunohistochemistry. Regulatory T cell expansion led to a moderate though significant suppression of blood flow restoration after ischemia induction. Surprisingly, depletion of regulatory T cells resulted in minor increase on blood flow recovery. However, collateral and capillary densities in the post-ischemic skeletal muscle were significantly increased in DEREG mice depleted for regulatory T cells. The presence of regulatory T cells after ischemia induction when analysed in non-depleted DEREG mice could be demonstrated by green fluorescent protein staining only in lymph nodes in the ischemic area, and not in the ischemic muscle tissue. The current study demonstrates that, even under conditions of major changes in regulatory T cell content, the contribution of regulatory T cells to the regulation of the arteriogenic response is only moderate. PMID:21426486

  17. On polynomial preconditioning for indefinite Hermitian matrices

    NASA Technical Reports Server (NTRS)

    Freund, Roland W.

    1989-01-01

    The minimal residual method is studied combined with polynomial preconditioning for solving large linear systems (Ax = b) with indefinite Hermitian coefficient matrices (A). The standard approach for choosing the polynomial preconditioners leads to preconditioned systems which are positive definite. Here, a different strategy is studied which leaves the preconditioned coefficient matrix indefinite. More precisely, the polynomial preconditioner is designed to cluster the positive, resp. negative eigenvalues of A around 1, resp. around some negative constant. In particular, it is shown that such indefinite polynomial preconditioners can be obtained as the optimal solutions of a certain two parameter family of Chebyshev approximation problems. Some basic results are established for these approximation problems and a Remez type algorithm is sketched for their numerical solution. The problem of selecting the parameters such that the resulting indefinite polynomial preconditioners speeds up the convergence of minimal residual method optimally is also addressed. An approach is proposed based on the concept of asymptotic convergence factors. Finally, some numerical examples of indefinite polynomial preconditioners are given.

  18. Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: the Involvement of Autophagy

    PubMed Central

    Wang, Haiping; Bower, Kimberly A.; Frank, Jacqueline A.; Xu, Mei; Luo, Jia

    2013-01-01

    Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. A sublethal preconditioning has been proposed as a neuroprotective strategy against several central nervous system (CNS) neurodegenerative diseases. We have recently demonstrated that autophagy is a protective response to alleviate ethanol toxicity. A modest hypoxic preconditioning (1% oxygen) did not cause neurotoxicity but induced autophagy (Tzeng et al., 2010). We therefore hypothesize that the modest hypoxic preconditioning may offer a protection against ethanol-induced neurotoxicity. We showed here that the modest hypoxic preconditioning (1% oxygen) for 8 hours significantly alleviated ethanol-induced death of SH-SY5Y neuroblastoma cells. Under the normoxia condition, cell viability in ethanol-exposed cultures (316 mg/dl for 48 hrs) was 49 ± 6% of untreated controls; however, with hypoxic preconditioning, cell viability in the ethanol-exposed group increased to 78 ± 7% of the controls (p < 0.05; n = 3). Bafilomycin A1, an inhibitor of autophagosome and lysosome fusion, blocked hypoxic preconditioning-mediated protection. Similarly, inhibition of autophagic initiation by wortmannin also eliminated hypoxic preconditioning-mediated protection. In contrast, activation of autophagy by rapamycin further enhanced neuroprotection caused by hypoxic preconditioning. Taken together, the results confirm that autophagy is a protective response against ethanol neurotoxicity and the modest hypoxic preconditioning can offer neuroprotection by activating autophagic pathways. PMID:23568540

  19. Neuroprotection by biodegradable PAMAM ester (e-PAM-R)-mediated HMGB1 siRNA delivery in primary cortical cultures and in the postischemic brain

    E-print Network

    Park, Jong-Sang

    , wherein HMGB1 expression was depleted in over 40% of neurons and astrocytes of the normal brain. Moreover cortical cultures and in the postischemic brain Il-Doo Kim a,1 , Chae-Moon Lim a,1 , Jung-Bin Kim a , HyeRNA transfection Primary cortical culture Brain ischemia MCAO Although RNA interference (RNAi)-mediated gene

  20. Effects of postischemic left ventricular pressure-volume unloading on contractile recovery and myocardial blood flow in the regionally stunned canine heart

    Microsoft Academic Search

    Alfred C. Nicolosi; John G. Markley; Gordon N. Olinger

    1999-01-01

    Objective: Myocardial stunning remains a clinical problem without definitive therapy. This study tested the hypothesis that mechanical therapy with a ventricular assist device would accelerate recovery of contractility in stunned myocardium by increasing the postischemic myocardial blood flow. Methods: Regional stunning was induced in dogs (25 kg) by 15 minutes of coronary occlusion and 180 minutes of reperfusion. One group

  1. The influence of delayed postischemic hyperthermia following transient focal ischemia: alterations of gene expression.

    PubMed

    Kim, Y; Truettner, J; Zhao, W; Busto, R; Ginsberg, M D

    1998-07-15

    We have recently shown that moderate hyperthermia, even if delayed, markedly enlarges the volume of an acute ischemic infarct. In the current study, we used in situ hybridization autoradiography to assess the effects of delayed hyperthermia on the regional expression of messenger RNA (mRNA) for the immediate early genes c-fos and c-jun, the inducible heat-shock protein 70 (hsp70) and glial fibrillary acid protein (GFAP) following 1 h of transient middle cerebral artery occlusion (MCAo) produced in rats by the insertion of an intraluminal suture. Sham-occluded rats were also studied. One day after MCAo, rats were placed into a heating chamber, where cranial temperature was either maintained at 37-38 degrees C (normothermic group) or was elevated to 40 degrees C (hyperthermic group) for 3 h. At either 2 or 24 h thereafter, brains were studied by in situ hybridization. Low-level constitutive c-fos and c-jun expression in sham-occluded rats was unaffected by delayed temperature manipulation. Prior MCAo decreased c-fos and c-jun mRNA in the affected striatum and overlying cortex. In rats studied 2 h after delayed hyperthermia, however, c-fos mRNA was markedly increased in ipsilateral cingulate cortex. By contrast, the pattern of c-jun mRNA was similar in rats with prior MCAo irrespective of delayed normothermia or hyperthermia: increased expression involved ipsilateral cingulate and paramedian cortical areas. Bilateral increases in hsp70 expression were produced by hyperthermia alone, and hsp70 mRNA was densely increased throughout the ischemic cortex and striatum following MCAo, while delayed hyperthermia altered this pattern by extending the zone of increased hsp70 message to cingulate and paramedian cortical areas at 2 h. GFAP mRNA was decreased within the previously ischemic field but increased in surrounding regions. The induction of c-fos and hsp70 message in tissue regions abutting zones of enhanced injury in brains with delayed postischemic hyperthermia indicates that these zones have been additionally stressed: these gene responses may possibly contribute to the protection of these threatened regions. PMID:9700696

  2. H(curl) Auxiliary Mesh Preconditioning

    SciTech Connect

    Kolev, T V; Pasciak, J E; Vassilevski, P S

    2006-08-31

    This paper analyzes a two-level preconditioning scheme for H(curl) bilinear forms. The scheme utilizes an auxiliary problem on a related mesh that is more amenable for constructing optimal order multigrid methods. More specifically, we analyze the case when the auxiliary mesh only approximately covers the original domain. The latter assumption is important since it allows for easy construction of nested multilevel spaces on regular auxiliary meshes. Numerical experiments in both two and three space dimensions illustrate the optimal performance of the method.

  3. Domain-decomposed preconditionings for transport operators

    NASA Technical Reports Server (NTRS)

    Chan, Tony F.; Gropp, William D.; Keyes, David E.

    1991-01-01

    The performance was tested of five different interface preconditionings for domain decomposed convection diffusion problems, including a novel one known as the spectral probe, while varying mesh parameters, Reynolds number, ratio of subdomain diffusion coefficients, and domain aspect ratio. The preconditioners are representative of the range of practically computable possibilities that have appeared in the domain decomposition literature for the treatment of nonoverlapping subdomains. It is shown that through a large number of numerical examples that no single preconditioner can be considered uniformly superior or uniformly inferior to the rest, but that knowledge of particulars, including the shape and strength of the convection, is important in selecting among them in a given problem.

  4. Preconditioned Multigrid Methods for Compressible Flow Calculations on Stretched Meshes

    Microsoft Academic Search

    Niles A. Pierce; Michael B. Giles

    1997-01-01

    Efficient preconditioned multigrid methods are developed for both inviscid and viscous flow applications. The work is motivated by the mixed results obtained using the standard approach of scalar preconditioning and full coarsened multigrid, which performs well for Euler calculations on moderately stretched meshes but is far less effective for turbulent Naiver–Stokes calculations, when the cell stretching becomes severe. In the

  5. Analysis and design of preconditioning methods for the Euler equations

    Microsoft Academic Search

    Marco Rodolfo Zaccanti

    1999-01-01

    Preconditioning of a system of equations at the differential level represents a relatively new area of research in convergence acceleration of discrete schemes for the fluid dynamics equations. This technique attempts to remove the intrinsic stiffness of the equations caused by the different time scales of the dynamic problem. Specifically, for the Euler equations, preconditioning aims at equalizing the speed

  6. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... false Preconditioning for tests. 183.220 Section 183...220 Preconditioning for tests. A boat must meet the following...at least 18 hours before the tests required by §§ 183.225...the motor and controls and the battery in lieu of this...

  7. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... false Preconditioning for tests. 183.220 Section 183...220 Preconditioning for tests. A boat must meet the following...at least 18 hours before the tests required by §§ 183.225...the motor and controls and the battery in lieu of this...

  8. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... false Preconditioning for tests. 183.220 Section 183...220 Preconditioning for tests. A boat must meet the following...at least 18 hours before the tests required by §§ 183.225...the motor and controls and the battery in lieu of this...

  9. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... false Preconditioning for tests. 183.220 Section 183...220 Preconditioning for tests. A boat must meet the following...at least 18 hours before the tests required by §§ 183.225...the motor and controls and the battery in lieu of this...

  10. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... false Preconditioning for tests. 183.220 Section 183...220 Preconditioning for tests. A boat must meet the following...at least 18 hours before the tests required by §§ 183.225...the motor and controls and the battery in lieu of this...

  11. Modern Preconditioned Eigensolvers for Spectral Image Segmentation and Graph Bisection

    E-print Network

    Knyazev, Andrew

    Modern Preconditioned Eigensolvers for Spectral Image Segmentation and Graph Bisection Workshop numerical solution of eigenvalue problems with the graph Laplacian. We discuss several modern preconditioned Innovation Center through the joint "Approaches to Combat Terrorism" Program Solicitation NSF 03-569. 1

  12. Negative regulation of diacylglycerol kinase theta mediates adenosine-dependent hepatocyte preconditioning.

    PubMed

    Baldanzi, G; Alchera, E; Imarisio, C; Gaggianesi, M; Dal Ponte, C; Nitti, M; Domenicotti, C; van Blitterswijk, W J; Albano, E; Graziani, A; Carini, R

    2010-06-01

    In liver ischemic preconditioning (IP), stimulation of adenosine A2a receptors (A2aR) prevents ischemia/reperfusion injury by promoting diacylglycerol-mediated activation of protein kinase C (PKC). By concerting diacylglycerol to phosphatidic acid, diacylglycerol kinases (DGKs) act as terminator of diacylglycerol signalling. This study investigates the role of DGK in the development of hepatocyte IP. DGK activity and cell viability were evaluated in isolated rat hepatocytes preconditioned by 10 min hypoxia followed by 10 min re-oxygenation or by the treatment with the A2aR agonist, CGS21680, and subsequently exposed to prolonged hypoxia. We observed that after IP or A2aR activation, a decrease in DGK activity was associated with the onset of hepatocyte tolerance to hypoxia. CGS21680-induced stimulation of A2aR specifically inhibited DGK isoform theta by activating RhoA-GTPase. Consistently, both siRNA-mediated downregulation of DGK theta and hepatocyte pretreatment with the DGK inhibitor R59949 induced cell tolerance to hypoxia. The pharmacological inhibition of DGK was associated with the diacylglycerol-dependent activation of PKC delta and epsilon and of their downstream target p38 MAPK. In conclusion, we unveil a novel signalling pathway contributing to the onset of hepatocyte preconditioning, which through RhoA-GTPase, couples A2aR to the downregulation of DGK. Such an inhibition is essential for the sustained accumulation of diacylglycerol required for triggering PKC-mediated survival signals. PMID:20057501

  13. Mitochondrial mechanisms in cerebral vascular control: shared signaling pathways with preconditioning.

    PubMed

    Busija, David W; Katakam, Prasad V

    2014-01-01

    Mitochondrial-initiated events protect the neurovascular unit against lethal stress via a process called preconditioning, which independently promotes changes in cerebrovascular tone through shared signaling pathways. Activation of adenosine triphosphate (ATP)-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels) is a specific and dependable way to induce protection of neurons, astroglia, and cerebral vascular endothelium. Through the opening of mitoKATP channels, mitochondrial depolarization leads to activation of protein kinases and transient increases in cytosolic calcium (Ca(2+)) levels that activate terminal mechanisms that protect the neurovascular unit against lethal stress. The release of reactive oxygen species from mitochondria has similar protective effects. Signaling elements of the preconditioning pathways also are involved in the regulation of vascular tone. Activation of mitoKATP channels in cerebral arteries causes vasodilation, with cell-specific contributions from the endothelium, vascular smooth muscles, and nerves. Preexisting chronic conditions, such as insulin resistance and/or diabetes, prevent preconditioning and impair relaxation to mitochondrial-centered responses in cerebral arteries. Surprisingly, mitochondrial activation after anoxic or ischemic stress appears to protect cerebral vascular endothelium and promotes the restoration of blood flow; therefore, mitochondria may represent an important, but underutilized target in attenuating vascular dysfunction and brain injury in stroke patients. PMID:24862206

  14. Fetal asphyctic preconditioning modulates the acute cytokine response thereby protecting against perinatal asphyxia in neonatal rats

    PubMed Central

    2013-01-01

    Background Perinatal asphyxia (PA) is a major cause of brain damage and neurodevelopmental impairment in infants. Recent investigations have shown that experimental sublethal fetal asphyxia (FA preconditioning) protects against a subsequent more severe asphyctic insult at birth. The molecular mechanisms of this protection have, however, not been elucidated. Evidence implicates that inflammatory cytokines play a protective role in the induction of ischemic tolerance in the adult brain. Accordingly, we hypothesize that FA preconditioning leads to changes in the fetal cytokine response, thereby protecting the newborn against a subsequent asphyctic insult. Methods In rats, FA preconditioning was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global PA was induced by placing the uterine horns, containing the pups, in a saline bath for 19 min. We assessed, at different time points after FA and PA, mRNA and protein expression of several cytokines and related receptor mRNA levels in total hemispheres of fetal and neonatal brains. Additionally, we measured pSTAT3/STAT3 levels to investigate cellular responses to these cytokines. Results Prenatally, FA induced acute downregulation in IL-1?, TNF-? and IL-10 mRNA levels. At 96 h post FA, IL-6 mRNA and IL-10 protein expression were increased in FA brains compared with controls. Two hours after birth, all proinflammatory cytokines and pSTAT3/STAT3 levels decreased in pups that experienced FA and/or PA. Interestingly, IL-10 and IL-6 mRNA levels increased after PA. When pups were FA preconditioned, however, IL-10 and IL-6 mRNA levels were comparable to those in controls. Conclusions FA leads to prenatal changes in the neuroinflammatory response. This modulation of the cytokine response probably results in the protective inflammatory phenotype seen when combining FA and PA and may have significant implications for preventing post-asphyctic perinatal encephalopathy. PMID:23351591

  15. Preconditioning Triggered by Carbon Monoxide (CO) Provides Neuronal Protection Following Perinatal Hypoxia-Ischemia

    PubMed Central

    Widerøe, Marius; Alves, Paula M.; Vercelli, Alessandro; Vieira, Helena L. A.

    2012-01-01

    Perinatal hypoxia-ischemia is a major cause of acute mortality in newborns and cognitive and motor impairments in children. Cerebral hypoxia-ischemia leads to excitotoxicity and necrotic and apoptotic cell death, in which mitochondria play a major role. Increased resistance against major damage can be achieved by preconditioning triggered by subtle insults. CO, a toxic molecule that is also generated endogenously, may have a role in preconditioning as low doses can protect against inflammation and apoptosis. In this study, the role of CO-induced preconditioning on neurons was addressed in vitro and in vivo. The effect of 1 h of CO treatment on neuronal death (plasmatic membrane permeabilization and chromatin condensation) and bcl-2 expression was studied in cerebellar granule cells undergoing to glutamate-induced apoptosis. CO's role was studied in vivo in the Rice-Vannucci model of neonatal hypoxia-ischemia (common carotid artery ligature +75 min at 8% oxygen). Apoptotic cells, assessed by Nissl staining were counted with a stereological approach and cleaved caspase 3-positive profiles in the hippocampus were assessed. Apoptotic hallmarks were analyzed in hippocampal extracts by Western Blot. CO inhibited excitotoxicity-induced cell death and increased Bcl-2 mRNA in primary cultures of neurons. In vivo, CO prevented hypoxia-ischemia induced apoptosis in the hippocampus, limited cytochrome c released from mitochondria and reduced activation of caspase-3. Still, Bcl-2 protein levels were higher in hippocampus of CO pre-treated rat pups. Our results show that CO preconditioning elicits a molecular cascade that limits neuronal apoptosis. This could represent an innovative therapeutic strategy for high-risk cerebral hypoxia-ischemia patients, in particular neonates. PMID:22952602

  16. A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts.

    PubMed

    Amini, Elham; Rezaei, Mohsen; Mohamed Ibrahim, Norlinah; Golpich, Mojtaba; Ghasemi, Rasoul; Mohamed, Zahurin; Raymond, Azman Ali; Dargahi, Leila; Ahmadiani, Abolhassan

    2014-09-01

    Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events. PMID:25195699

  17. Attenuation of Focal Cerebral Ischemic Injury Following Post-Ischemic Inhibition of Angiotensin Converting Enzyme (ACE) Activity in Normotensive Rat

    PubMed Central

    Panahpour, Hamdollah; Dehghani, Gholam Abbas

    2012-01-01

    Background Central renin angiotensin system has an important role on the cerebral microcirculation and metabolism. Our previous work showed that inhibition of angiotensin converting enzyme () activity prior to induction of ischemia protected the brain from severe ischemia/reperfusion (I/R) injuries. This study evaluated the impacts of post-ischemic inhibition of , enalapril, on brain infarction in normotensive rats. Methods Rats were anesthetized with chloral hydrate (400 mg/kg). Focal cerebral ischemia was induced by 60-min intraluminal occlusion of right middle cerebral artery (MCA). Intraperitoneal injection of enalapril (0.03 or 0.1 mg/kg) was done after MCA reopening (reperfusion). Neurological deficit score (NDS) was evaluated after 24 h and the animals randomly assigned for the assessments of infarction, absolute brain water content (ABWC) and index of brain edema Results Severe impaired motor functions (NDS = 2.78 ± 0.28), massive infarction (cortex = 214 ± 19 mm3, striatum = 86 ± 5 mm3) and edema (ABWC = 83.1 ± 0.46%) were observed in non-treated ischemic rats. Non-hypotensive dose of enalapril (0.03 mg/kg) significantly reduced NDS (1.5 ± 0.22), infarction (cortex = 102 ± 16 mm3, striatum = 38 ± 5 mm3) and edema (ABWC = 80.9 ± 0.81%). Enalapril at dose of 0.1 mg/kg significantly lowered arterial pressure could not improve NDS (2.0 ± 0.45) and reduce infarction (cortex = 166 ± 26 mm3, striatum = 71 ± 11 mm3). Conclusion Post-ischemic ACE inhibition in the normotensive rats without affecting arterial pressure protects the brain from reperfusion injuries; however, this beneficial action is masked by hypotension. PMID:23183619

  18. Arterial spin labeling and dynamic susceptibility contrast CBF MRI in postischemic hyperperfusion, hypercapnia, and after mannitol injection

    PubMed Central

    Tanaka, Yoji; Nagaoka, Tsukasa; Nair, Govind; Ohno, Kikuo; Duong, Timothy Q

    2011-01-01

    Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) are widely used to image cerebral blood flow (CBF) in stroke. This study examined how changes in tissue spin-lattice relaxation-time constant (T1), blood–brain barrier (BBB) permeability, and transit time affect CBF quantification by ASL and DSC in postischemic hyperperfusion in the same animals. In Group I (n=6), embolic stroke rats imaged 48?hours after stroke showed regional hyperperfusion. In normal pixels, ASL- and DSC-CBF linearly correlated pixel-by-pixel. In hyperperfusion pixels, ASL-CBF was significantly higher than DSC-CBF pixel-by-pixel (by 25%). T1 increased from 1.76±0.14?seconds in normal pixels to 1.93±0.17?seconds in hyperperfusion pixels. Arterial transit time decreased from 300?milliseconds in normal pixels to 200?milliseconds in hyperperfusion pixels. ?R2* profiles showed contrast-agent leakages in the hyperperfusion regions. In Group II (n=3) in which hypercapnic inhalation was used to increase CBF without BBB disruption, CBF increased overall but ASL- and DSC-CBF remained linearly correlated. In Group III (n=3) in which mannitol was used to break the BBB, ASL-CBF was significantly higher than DSC-CBF. We concluded that in normal tissue, ASL and DSC provide comparable quantitative CBF, whereas in postischemic hyperperfusion, ASL-CBF and DSC-CBF differed significantly because ischemia-induced changes in T1 and BBB permeability affected the two methods differently. PMID:21179070

  19. Mitigation of postischemic cardiac contractile dysfunction by CaMKII inhibition: effects on programmed necrotic and apoptotic cell death.

    PubMed

    Szobi, Adrian; Rajtik, Tomas; Carnicka, Slavka; Ravingerova, Tana; Adameova, Adriana

    2014-03-01

    While Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been suggested to be an important protein regulating heart function upon ischemia/reperfusion (I/R), the mechanisms responsible are not fully known. Furthermore, it is not known whether CaMKII activation can modulate necroptosis, a recently described form of programmed cell death. In order to investigate these issues, Langendroff-perfused rat hearts were subjected to global ischemia and reperfusion, and CaMKII inhibition was achieved by adding the CaMKII inhibitor KN-93 (0.5 ?mol/dm(3)) to the perfusion solution before the induction of ischemia. Immunoblotting was used to detect changes in expression of proteins modulating both necroptotic and apoptotic cell death. CaMKII inhibition normalized I/R induced increases in expression of necroptotic RIP1 and caspase-8 along with proteins of the intrinsic apoptotic pathway, namely cytochrome c and caspase-9. In addition, it increased the Bcl-2/Bax ratio and reduced caspase-3 and cleaved PARP1 content suggesting reduction of cell death. These changes coexisted with improvement of postischemic contractile function. On the other hand, there was no correlation between levels of pT287-CaMKII? and LVDP recovery after I/R. These results demonstrate for the first time that CaMKII inhibition may mitigate cardiac contractile dysfunction, at least partially, by limiting the contents of not only apoptotic, but also necroptotic proteins. Phosphorylation of CaMKII seems unlikely to determine the degree of postischemic recovery of contractile function. PMID:24347176

  20. Identification of a Novel Role for Sphingolipid Signaling in TNF ? and Ischemic Preconditioning Mediated Cardioprotection

    Microsoft Academic Search

    Sandrine Lecour; Robert M. Smith; Brian Woodward; Lionel H. Opie; Luc Rochette; Michael N. Sack

    2002-01-01

    TNF ? administration mimics ischemic preconditioning and neutralizing antibodies to TNF? and IL-1 ? abolish exercise-induced preconditioning. However, the pharmacology of TNF? 's cardioprotective effects and associated downstream signaling events has not been delineated. We evaluated the temporal and dose specific requirements of TNF ? to function as a preconditioning mimetic. Furthermore we postulated that the preconditioning effect of TNF

  1. Post-ischemic estradiol treatment reduced glial response and triggers distinct cortical and hippocampal signaling in a rat model of cerebral ischemia

    PubMed Central

    2012-01-01

    Background Estradiol has been shown to exert neuroprotective effects in several neurodegenerative conditions, including cerebral ischemia. The presence of this hormone prior to ischemia attenuates the damage associated with such events in a rodent model (middle cerebral artery occlusion (MCAO)), although its therapeutic value when administered post-ischemia has not been assessed. Hence, we evaluated the effects of estradiol treatment after permanent MCAO (pMCAO) was induced in rats, studying the PI3K/AKT/GSK3/?-catenin survival pathway and the activation of SAPK-JNK in two brain areas differently affected by pMCAO: the cortex and hippocampus. In addition, we analyzed the effect of estradiol on the glial response to injury. Methods Male rats were subjected to pMCAO and estradiol (0.04?mg/kg) was administered 6, 24, and 48?h after surgery. The animals were sacrificed 6?h after the last treatment, and brain damage was evaluated by immunohistochemical quantification of ‘reactive gliosis’ using antibodies against GFAP and Iba1. In addition, Akt, phospho-AktSer473, phospho-AktThr308, GSK3, phospho-GSK3Ser21/9, ?-catenin, SAPK-JNK, and pSAPK-JNKThr183/Tyr185 levels were determined in western blots of the ipsilateral cerebral cortex and hippocampus, and regional differences in neuronal phospho-Akt expression were determined by immunohistochemistry. Results The increases in the percentage of GFAP- (5.25-fold) and Iba1- (1.8-fold) labeled cells in the cortex and hippocampus indicate that pMCAO induced ‘reactive gliosis’. This effect was prevented by post-ischemic estradiol treatment; diminished the number of these cells to those comparable with control animals. pMCAO down-regulated the PI3K/AkT/GSK3/?-catenin survival pathway to different extents in the cortex and hippocampus, the activity of which was restored by estradiol treatment more efficiently in the cerebral cortex (the most affected region) than in the hippocampus. No changes in the phosphorylation of SAPK-JNK were observed 54?h after inducing pMCAO, whereas pMCAO did significantly decrease the phospho-AktSer473 in neurons, an effect that was reversed by estradiol. Conclusion The present study demonstrates that post-pMCAO estradiol treatment attenuates ischemic injury in both neurons and glia, events in which the PI3K/AKT/GSK3/?-catenin pathway is at least partly involved. These findings indicate that estradiol is a potentially useful treatment to enhance recovery after human ischemic stroke. PMID:22747981

  2. The preconditioning of major sudden stratospheric warmings

    NASA Astrophysics Data System (ADS)

    Bancalá, S.; Krüger, K.; Giorgetta, M.

    2012-02-01

    The preconditioning of major sudden stratospheric warmings (SSWs) is investigated with two long time series using reanalysis (ERA-40) and model (MAECHAM5/MPI-OM) data. Applying planetary wave analysis, we distinguish between wavenumber-1 and wavenumber-2 major SSWs based on the wave activity of zonal wavenumbers 1 and 2 during the prewarming phase. For this analysis an objective criterion to identify and classify the preconditioning of major SSWs is developed. Major SSWs are found to occur with a frequency of six and seven events per decade in the reanalysis and in the model, respectively, thus highlighting the ability of MAECHAM5/MPI-OM to simulate the frequency of major SSWs realistically. However, from these events only one quarter are wavenumber-2 major warmings, representing a low (˜0.25) wavenumber-2 to wavenumber-1 major SSW ratio. Composite analyses for both data sets reveal that the two warming types have different dynamics; while wavenumber-1 major warmings are preceded only by an enhanced activity of the zonal wavenumber-1, wavenumber-2 events are either characterized by only the amplification of zonal wavenumber-2 or by both zonal wavenumber-1 and zonal wavenumber-2, albeit at different time intervals. The role of tropospheric blocking events influencing these two categories of major SSWs is evaluated in the next step. Here, the composite analyses of both reanalysis and model data reveal that blocking events in the Euro-Atlantic sector mostly lead to the development of wavenumber-1 major warmings. The blocking-wavenumber-2 major warming connection can only be statistical reliable analyzed with the model time series, demonstrating that blocking events in the Pacific region mostly precede wavenumber-2 major SSWs.

  3. Effects of combined postischemic hypothermia and delayed N- tert-butyl- a-pheylnitrone (PBN) administration on histopathological and behavioral deficits associated with transient global ischemia in rats

    Microsoft Academic Search

    Alejandra J. Pazos; Edward J. Green; Raul Busto; Philip M. McCabe; R. C. Baena; Myron D. Ginsberg; Mordecai Y.-T. Globus; Neil Schneiderman; W. Dalton Dietrich

    1999-01-01

    Previous cerebral ischemia studies have reported the limitations of restricted periods of postischemic hypothermia in producing long-term neuroprotection. The present experiment attempts to determine whether delayed treatment with the free radical scavenger N-tert-butyl-a-phenylnitrone (PBN) is protective at 2 months following transient global forebrain ischemia, and whether additive effects can be observed when PBN is administered in combination with moderate hypothermia.

  4. Hepatic Branch Vagus Nerve Plays a Critical Role in the Recovery of Post-Ischemic Glucose Intolerance and Mediates a Neuroprotective Effect by Hypothalamic Orexin-A

    PubMed Central

    Harada, Shinichi; Yamazaki, Yui; Koda, Shuichi; Tokuyama, Shogo

    2014-01-01

    Orexin-A (a neuropeptide in the hypothalamus) plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve) is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse) administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve) with orexin-1 receptor and c-Fos (activated neural cells marker). These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A. PMID:24759941

  5. Preconditioning Outside Air: Cooling Loads from Building Ventilation 

    E-print Network

    Kosar, D.

    1998-01-01

    of the standard. To mitigate or nullify these additional weather loads, outdoor air preconditioning technologies are being promoted in combination with conventional HVAC operations downstream as a means to deliver the required fresh air and control humidity...

  6. Progress in Parallel Schur Complement Preconditioning for Computational Fluid Dynamics

    NASA Technical Reports Server (NTRS)

    Barth, Timothy J.; Chan, Tony F.; Tang, Wei-Pai; Chancellor, Marisa K. (Technical Monitor)

    1997-01-01

    We consider preconditioning methods for nonself-adjoint advective-diffusive systems based on a non-overlapping Schur complement procedure for arbitrary triangulated domains. The ultimate goal of this research is to develop scalable preconditioning algorithms for fluid flow discretizations on parallel computing architectures. In our implementation of the Schur complement preconditioning technique, the triangulation is first partitioned into a number of subdomains using the METIS multi-level k-way partitioning code. This partitioning induces a natural 2X2 partitioning of the p.d.e. discretization matrix. By considering various inverse approximations of the 2X2 system, we have developed a family of robust preconditioning techniques. A computer code based on these ideas has been developed and tested on the IBM SP2 and the SGI Power Challenge array using MPI message passing protocol. A number of example CFD calculations will be presented to illustrate and assess various Schur complement approximations.

  7. Preconditioned solenoidal basis method for incompressible fluid flows 

    E-print Network

    Wang, Xue

    2006-04-12

    This thesis presents a preconditioned solenoidal basis method to solve the algebraic system arising from the linearization and discretization of primitive variable formulations of Navier-Stokes equations for incompressible ...

  8. Attenuation of sensory preconditioning by noradrenaline depletion in the rat.

    PubMed

    Archer, T; Mohammed, A K; Danysz, W; Järbe, T U; Jonsson, G

    1986-04-01

    In order to investigate the effect of noradrenaline (NA) depletion upon an associative learning phenomenon, sensory preconditioning, rats were inflicted with either 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle (DNAB) or the locus coeruleus (LC), or with systemic injections of the NA neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). Using appropriate controls (the UP groups) sensory preconditioning was demonstrated clearly in the non-lesion conditions (Sham or saline), but was blocked or strongly attenuated in the DNAB and DSP4 conditions. LC lesions did not affect sensory preconditioning. These findings suggest that the loss of central NA may cause some disruption of some aspects of complex associative learning. The role of NA in sensory preconditioning may be relevant to current notions of NA function. PMID:3718664

  9. Preconditioning: myocardial function and energetics during coronary hypoperfusion and reperfusion

    Microsoft Academic Search

    Ulrich Sunderdiek; Simone Schmitz-Spanke; Bernhard Korbmacher; Emmeran Gams; Jochen D. Schipke

    2002-01-01

    Background. Ischemic preconditioning (IP) is gaining more acceptance as a protective method in beating heart surgery. Yet it remains controversial whether preconditioning can attenuate myocardial dysfunction during reperfusion after severe coronary hypoperfusion. We examined this issue and also the issue of whether this protection is mediated by adenosine A1 receptors.Methods. In isolated, blood-perfused rabbit hearts, the effects of IP (3

  10. An optimised preconditioning procedure for gas permeability measurement

    Microsoft Academic Search

    M. Carcassès; A. Abbas; J.-P. Ollivier; J. Verdier

    2002-01-01

    To study the permeability of cementitious materials; a procedure of drying out moisture before the actual measurement of this\\u000a property, normally called preconditioning, is an unavoidable necessity. In this study, the preconditioning procedure developed\\u000a by the authors earlier, is used to carry out the measurement of permeability to gases of 15 concrete compositions in order\\u000a to compare the different steps

  11. The Galvanotactic Migration of Keratinocytes is Enhanced by Hypoxic Preconditioning

    PubMed Central

    Guo, Xiaowei; Jiang, Xupin; Ren, Xi; Sun, Huanbo; Zhang, Dongxia; Zhang, Qiong; Zhang, Jiaping; Huang, Yuesheng

    2015-01-01

    The endogenous electric field (EF)-directed migration of keratinocytes (galvanotaxis) into wounds is an essential step in wound re-epithelialization. Hypoxia, which occurs immediately after injury, acts as an early stimulus to initiate the healing process; however, the mechanisms for this effect, remain elusive. We show here that the galvanotactic migration of keratinocytes was enhanced by hypoxia preconditioning as a result of the increased directionality rather than the increased motility of keratinocytes. This enhancement was both oxygen tension- and preconditioning time-dependent, with the maximum effects achieved using 2% O2 preconditioning for 6?hours. Hypoxic preconditioning (2% O2, 6?hours) decreased the threshold voltage of galvanotaxis to?preconditioning accelerated healing by 1.38-fold compared with the control conditions. Scavenging of the induced ROS by N-acetylcysteine (NAC) abolished the enhanced galvanotaxis and the accelerated healing by hypoxic preconditioning. Our data demonstrate a novel and unsuspected role of hypoxia in supporting keratinocyte galvanotaxis. Enhancing the galvanotactic response of cells might therefore be a clinically attractive approach to induce improved wound healing. PMID:25988491

  12. Analysis and design of preconditioning methods for the Euler equations

    NASA Astrophysics Data System (ADS)

    Zaccanti, Marco Rodolfo

    Preconditioning of a system of equations at the differential level represents a relatively new area of research in convergence acceleration of discrete schemes for the fluid dynamics equations. This technique attempts to remove the intrinsic stiffness of the equations caused by the different time scales of the dynamic problem. Specifically, for the Euler equations, preconditioning aims at equalizing the speed of propagation of the different waves of the hyperbolic problem. This 'fix' becomes particularly useful in the incompressible limit and in the neighborhood of the sonic point. Practical examples of application of preconditioning include modern transonic supercritical airfoils, and nearly incompressible flows with embedded regions where compressibility is important (e.g., low speed combustion). This study attempts the ambitious project of reviewing most of the work done in Euler preconditioning, while at the same time extending some of the existing methods and correcting their robustness problems. Several original contributions to the theory of Euler preconditioning are given, including a thorough exposition of the symmetrizability property of the preconditioned equations, a discussion of the positive definiteness property of the preconditioning matrix, and the study of the eigenvalues for the full form of the preconditioner. Considering the numerical implementation of the preconditioned methods using the Roe flux function, a scheme based on the classical one-Riemann problem normal to the cell interface is proposed, and its advantages over other formulations found in the literature, as well as its drawbacks, are discussed. Then, the analysis of several existing preconditioning methods is conducted, and the complete eigenvector structure of the equations preconditioned with the Van Leer- Lee-Roe matrix, the Turkel matrix, the Choi-Merkle matrix, and a few others, is obtained and analyzed. A comprehensive exploration of preconditioning in one and two spatial dimensions is attempted, which allows to better understand the properties of existing preconditioners. While this investigation suggests new interesting families of one-dimensional preconditioners, for the two-dimensional case the analysis is complete only for the sparse form of the preconditioner, and shows that in this instance it is not possible to remove all of the robustness problems usually found in Euler preconditioning. When considering the full form of the preconditioning matrix the analysis is not complete, because of the formidable algebraic problem involved. Nonetheless, some specific solutions are considered, and a few general conclusions are also drawn in this case. Finally, it is shown that there exist at least two sparse preconditioners that are sufficiently robust in computing stagnation point flow, while preserving the overall effectiveness of preconditioning for low speed flow. One of these matrices is a modification of the popular Turkel method. Using this matrix in regions of low Mach number, in conjunction with the Van Leer-Lee-Roe preconditioner in the transonic and supersonic parts of the flow field, allows to achieve a very robust and efficient preconditioning procedure for the entire Mach regime.

  13. Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

    PubMed Central

    Vaez, Haleh; Samadzadeh, Mehrban; Zahednezhad, Fahimeh; Najafi, Moslem

    2012-01-01

    Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibrate for 30 min then subjected to 30 min global ischemia. In the control group, the hearts were reperfused with drug free normal Krebs-Henseleit (K/H) solution before ischemia and during 120 min reperfusion. In the treatment groups, reperfusion was initiated with K/H solution containing different concentration of honey (0.25, 0.5, 1 and 2%) for 15 min and was resumed until the end of 120 min with normal K/H solution. Results: In the control group, VEBs number was 784±199, while in honey concentration of 0.25, 0.5, 1 and 2%, it decreased to 83±23 (P<0.001), 138±48 (P<0.01), 142±37 (P<0.001) and 157±40 (P<0.01), respectively. Number and duration of VT and time spent in reversible VF were also reduced by honey. In the control group, the infarct size was 54.1±7.8%, however; honey (0.25, 0.5, 1 and 2%) markedly lowered the value to 12.4±2.4, 12.7±3.3, 11.3±2.6 and 7.9±1.7 (P<0.001), respectively. Conclusion: Postischemic administration of natural honey in global ischemia showed protective effects against ischemia/reperfusion (I/R) injuries in isolated rat heart. Antioxidant and radical scavenging activity, lipoperoxidation inhibition, reduction of necrotized tissue, presence of rich energy sources, various type of vitamins, minerals and enzymes and formation of NO-contain metabolites may probably involve in those cardioprotective effects. PMID:24312792

  14. Acute Superoxide Radical Scavenging Reduces Blood Pressure but Does Not Influence Kidney Function in Hypertensive Rats with Postischemic Kidney Injury

    PubMed Central

    Miloradovi?, Zoran; Ivanov, Milan; Mihailovi?-Stanojevi?, Nevena; Gruji? Milanovi?, Jelica; Jovovi?, ?ur?ica; Vaji?, Una-Jovana; Markovi?-Lipkovski, Jasmina

    2014-01-01

    Acute kidney injury (AKI) is associated with significant morbidity and mortality in hypertensive surroundings. We investigated superoxide radical molecules influence on systemic haemodynamic and kidney function in spontaneously hypertensive rats (SHR) with induced postischemic AKI. Experiment was performed in anesthetized adult male SHR. The right kidney was removed, and left renal artery was subjected to ischemia by clamping for 40 minutes. The treated group received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5 minutes before, during, and 175 minutes after the period of reperfusion, while the control AKI group received the vehicle via the same route. All parameters were measured 24?h after renal reperfusion. TEMPOL treatment significantly decreased mean arterial pressure and total peripheral resistance (P < 0.05) compared to AKI control. It also increased cardiac output and catalase activity (P < 0.05). Lipid peroxidation and renal vascular resistance were decreased in TEMPOL (P < 0.05). Plasma creatinine and kidney morphological parameters were unchanged among TEMPOL treated and control groups. Our study shows that superoxide radicals participate in haemodynamic control, but acute superoxide scavenging is ineffective in glomerular and tubular improvement, probably due to hypertension-induced strong endothelial dysfunction which neutralizes beneficial effects of O2? scavenging. PMID:25050356

  15. Post-ischemic treatment with L-kynurenine sulfate exacerbates neuronal damage after transient middle cerebral artery occlusion.

    PubMed

    Gellért, L; Knapp, L; Németh, K; Herédi, J; Varga, D; Oláh, G; Kocsis, K; Menyhárt, A; Kis, Z; Farkas, T; Vécsei, L; Toldi, J

    2013-09-01

    Since brain ischemia is one of the leading causes of adult disability and death, neuroprotection of the ischemic brain is of particular importance. Acute neuroprotective strategies usually have the aim of suppressing glutamate excitotoxicity and an excessive N-methyl-d-aspartate (NMDA) receptor function. Clinically tolerated antagonists should antagonize an excessive NMDA receptor function without compromising the normal synaptic function. Kynurenic acid (KYNA) an endogenous metabolite of the tryptophan metabolism, may be an attractive neuroprotectant in this regard. The manipulation of brain KYNA levels was earlier found to effectively enhance the histopathological outcome of experimental ischemic/hypoxic states. The present investigation of the neuroprotective capacity of L-kynurenine sulfate (L-KYNs) administered systemically after reperfusion in a novel distal middle cerebral artery occlusion (dMCAO) model of focal ischemia/reperfusion revealed that in contrast with earlier results, treatment with L-KYNs worsened the histopathological outcome of dMCAO. This contradictory result indicates that post-ischemic treatment with L-KYNs may be harmful. PMID:23685169

  16. PKM? knockdown disrupts post-ischemic long-term potentiation via inhibiting postsynaptic expression of aminomethyl phosphonic acid receptors

    PubMed Central

    Cheng, Nan; Hu, Xiaoqiao; Tian, Tian; Lu, Wei

    2015-01-01

    Abstract Post-ischemic long-term potentiation (i-LTP) is a pathological form of plasticity that was observed in glutamate receptor-mediated neurotransmission after stroke and may exert a detrimental effect via facilitating excitotoxic damage. The mechanism underlying i-LTP, however, remains less understood. By employing electrophysiological recording and immunofluorescence assay on hippocampal slices and cultured neurons, we found that protein kinase M? (PKM?), an atypical protein kinase C isoform, was involved in enhancing aminomethyl phosphonic acid (AMPA) receptor (AMPAR) expression after i-LTP induction. PKM? knockdown attenuated postsynaptic expression of AMPA receptors and disrupted i-LTP. Consistently, we observed less neuronal death of cultured hippocampal cells with PKM? knockdown. Meanwhile, these findings indicate that PKM? plays an important role in i-LTP by regulating postsynaptic expression of AMPA receptors. This work adds new knowledge to the mechanism of i-LTP, and thus is helpful to find the potential target for clinical therapy of ischemic stroke.

  17. Iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET1 balance

    Microsoft Academic Search

    Masahiro Kawashima; Takayuki Nakamura; Sven Schneider; Brigitte Vollmar; Henning F Lausberg; Michael Bauer; Michael D Menger; Hans-Joachim Schäfers

    2003-01-01

    Background:Ischemia–reperfusion (I\\/R) injury of the lung involves increased pulmonary vascular resistance. Prostaglandins are thought to have a beneficial effect in lung transplantation, but their mechanism in I\\/R injury is unknown. We investigated whether iloprost, a stable prostacyclin analogue, prevents I\\/R-associated pulmonary vascular dysfunction and whether it affects endothelin-1 (ET-1) balance.

  18. Preconditioned Krylov subspace methods for solving nonsymmetric matrices from CFD applications

    E-print Network

    Zhang, Jun

    Preconditioned Krylov subspace methods for solving nonsymmetric matrices from CFD applications Jun arising computational dynamics (CFD) applications. preconditioned iterative methods consist of KrylovCGSTAB, GMRES and TFQMR. Numerical experiments, using several matrices arising various relevant CFD applications

  19. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 2012-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 ...Emission Control System Performance Warranty Short Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements...

  20. 40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...and canister preconditioning; refueling test. 86.153-98 Section 86.153-98...Otto-Cycle Complete Heavy-Duty Vehicles; Test Procedures § 86.153-98 Vehicle and canister preconditioning; refueling test. (a) Vehicle and canister...

  1. 40 CFR 85.2219 - Idle test with loaded preconditioning-EPA 91.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 2011-07-01 2011-07-01 false Idle test with loaded preconditioning-EPA 91. 85.2219...Emission Control System Performance Warranty Short Tests § 85.2219 Idle test with loaded preconditioning—EPA 91. (a)...

  2. 40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...and canister preconditioning; refueling test. 86.153-98 Section 86.153-98...Otto-Cycle Complete Heavy-Duty Vehicles; Test Procedures § 86.153-98 Vehicle and canister preconditioning; refueling test. (a) Vehicle and canister...

  3. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 2011-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 ...Emission Control System Performance Warranty Short Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements...

  4. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 2010-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 ...Emission Control System Performance Warranty Short Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements...

  5. 40 CFR 85.2219 - Idle test with loaded preconditioning-EPA 91.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 2012-07-01 2012-07-01 false Idle test with loaded preconditioning-EPA 91. 85.2219...Emission Control System Performance Warranty Short Tests § 85.2219 Idle test with loaded preconditioning—EPA 91. (a)...

  6. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 2013-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 ...Emission Control System Performance Warranty Short Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements...

  7. 40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...and canister preconditioning; refueling test. 86.153-98 Section 86.153-98...Otto-Cycle Complete Heavy-Duty Vehicles; Test Procedures § 86.153-98 Vehicle and canister preconditioning; refueling test. (a) Vehicle and canister...

  8. 40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...and canister preconditioning; refueling test. 86.153-98 Section 86.153-98...Otto-Cycle Complete Heavy-Duty Vehicles; Test Procedures § 86.153-98 Vehicle and canister preconditioning; refueling test. (a) Vehicle and canister...

  9. 40 CFR 92.125 - Pre-test procedures and preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 2013-07-01 false Pre-test procedures and preconditioning. 92.125 Section...POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.125 Pre-test procedures and preconditioning. (a)...

  10. 40 CFR 85.2219 - Idle test with loaded preconditioning-EPA 91.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 2013-07-01 2013-07-01 false Idle test with loaded preconditioning-EPA 91. 85.2219...Emission Control System Performance Warranty Short Tests § 85.2219 Idle test with loaded preconditioning—EPA 91. (a)...

  11. 40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...and canister preconditioning; refueling test. 86.153-98 Section 86.153-98...Otto-Cycle Complete Heavy-Duty Vehicles; Test Procedures § 86.153-98 Vehicle and canister preconditioning; refueling test. (a) Vehicle and canister...

  12. 40 CFR 85.2219 - Idle test with loaded preconditioning-EPA 91.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 2010-07-01 2010-07-01 false Idle test with loaded preconditioning-EPA 91. 85.2219...Emission Control System Performance Warranty Short Tests § 85.2219 Idle test with loaded preconditioning—EPA 91. (a)...

  13. Hypoxic preconditioning-induced mitochondrial protection is not disrupted in a cell model of mtDNA T8993G mutation-induced F1F0-ATP synthase defect: the role of mitochondrial permeability transition.

    PubMed

    Huang, Wen-Yi; Jou, Mei-Jie; Peng, Tsung-I

    2014-02-01

    Transient opening of the mitochondrial permeability transition pore plays a crucial role in hypoxic preconditioning-induced protection. Recently, the cyclophilin-D component of the mitochondrial permeability transition pore has been shown to interact with and regulate the F1F0-ATP synthase. However, the precise role of the F1F0-ATP synthase and the interaction between cyclophilin-D and F1F0-ATP synthase in the mitochondrial permeability transition pore and hypoxic preconditioning remain uncertain. Here we found that a 1-h hypoxic preconditioning delayed apoptosis and improved cell survival after stimulation with various apoptotic inducers including H2O2, ionomycin, and arachidonic acid in mitochondrial DNA T8993G mutation (NARP) osteosarcoma 143B cybrids, an F1F0-ATP synthase defect cell model. This hypoxic preconditioning protected NARP cybrid cells against focal laser irradiation-induced oxidative stress by suppressing reactive oxygen species formation and preventing the depletion of cardiolipin. Furthermore, the protective functions of transient opening of the mitochondrial permeability transition pore in both NARP cybrids and wild-type 143B cells can be augmented by hypoxic preconditioning. Disruption of the interaction between cyclophilin-D and F1F0-ATP synthase by cyclosporin A attenuated the mitochondrial protection induced by hypoxic preconditioning in both NARP cybrids and wild-type 143B cells. Our results demonstrate that the interaction between cyclophilin-D and F1F0-ATP synthase is important in the hypoxic preconditioning-induced cell protection. This finding improves our understanding of the mechanism of mitochondrial permeability transition pore opening in cells in response to hypoxic preconditioning, and will be helpful in further developing new pharmacological agents targeting hypoxia-reoxygenation injury and mitochondria-mediated cell death. PMID:24291231

  14. Is red blood cell a mediator of remote ischaemic preconditioning?

    PubMed

    Gopalakrishnan, Maya; Saurabh, Suman

    2014-12-01

    Remote ischaemic preconditioning is emerging as a promising clinical technique which can afford immediate protection against coronary ischaemia. The mechanisms which mediate the signal transduction from remote organ to the heart are still unclear. The role of ATP sensitive potassium channels in ischaemic preconditioning has been established. It is known that the red blood cell (RBC) acts as a mediator of local autoregulation in adjusting oxygen supply to demand by sensing hypoxia and releasing ATP locally to achieve vasodilatation in the adjacent vascular beds. Our hypothesis links these two known mechanisms. Remote ischaemic preconditioning and local RBC autoregulation might share a common mechanism using the ATP sensitive potassium channels. Therefore, we hypothesize that the signal transduction by RBC might be partly responsible for this protection against ischaemia. PMID:25468784

  15. Liquid hydrogen turbopump rapid start program. [thermal preconditioning using coatings

    NASA Technical Reports Server (NTRS)

    Wong, G. S.

    1973-01-01

    This program was to analyze, test, and evaluate methods of achieving rapid-start of a liquid hydrogen feed system (inlet duct and turbopump) using a minimum of thermal preconditioning time and propellant. The program was divided into four tasks. Task 1 includes analytical studies of the testing conducted in the other three tasks. Task 2 describes the results from laboratory testing of coating samples and the successful adherence of a KX-635 coating to the internal surfaces of the feed system tested in Task 4. Task 3 presents results of testing an uncoated feed system. Tank pressure was varied to determine the effect of flowrate on preconditioning. The discharge volume and the discharge pressure which initiates opening of the discharge valve were varied to determine the effect on deadhead (no through-flow) start transients. Task 4 describes results of testing a similar, internally coated feed system and illustrates the savings in preconditioning time and propellant resulting from the coatings.

  16. Thermal Preconditioning and Heat-Shock Protein 72 Preserve Synaptic Transmission during Thermal Stress

    E-print Network

    Robertson, Meldrum

    Thermal Preconditioning and Heat-Shock Protein 72 Preserve Synaptic Transmission during Thermal, exposing the mammalian CNS to nonle- thal heat stress (i.e., thermal preconditioning) increases levels that generates respiratory rhythm (the pre- Bo¨ tzinger complex), we show that thermal preconditioning has

  17. Recent Progress in Parallel Schur Complement Preconditioning for Computational Fluid

    NASA Technical Reports Server (NTRS)

    Barth, Tim; Kwak, Dochan (Technical Monitor)

    1997-01-01

    We consider preconditioning methods for nonself-adjoint advective-diffusive systems based on a nonoverlapping Schur complement procedure for arbitrary triangulated domains. The triangulation is first partitioned using the METIS multi-level $k$-way partitioning code. This partitioning of the triangulation induces a natural 2x2 partitioning of the demoralization matrix. By considering various inverse approximations of the 2x2 system we have developed a family of robust preconditioning techniques. The performance of these approximations will be discussed and numerous examples shown to illustrate the efficiency of the technique.

  18. Choice of Variables and Preconditioning for Time Dependent Problems

    NASA Technical Reports Server (NTRS)

    Turkel, Eli; Vatsa, Verr N.

    2003-01-01

    We consider the use of low speed preconditioning for time dependent problems. These are solved using a dual time step approach. We consider the effect of this dual time step on the parameter of the low speed preconditioning. In addition, we compare the use of two sets of variables, conservation and primitive variables, to solve the system. We show the effect of these choices on both the convergence to a steady state and the accuracy of the numerical solutions for low Mach number steady state and time dependent flows.

  19. Chronic Valproate Treatment Enhances Post-ischemic Angiogenesis and Promotes Functional Recovery in a Rat Model of Ischemic Stroke

    PubMed Central

    Wang, Zhifei; Tsai, Li-Kai; Munasinghe, Jeeva; Leng, Yan; Fessler, Emily Bame; Chibane, Fairouz; Leeds, Peter; Chuang, De-Maw

    2012-01-01

    Background and Purpose Enhanced angiogenesis facilitates neurovascular remodeling processes and promotes brain functional recovery after stroke. Previous studies from our laboratory demonstrated that valproate (VPA), a histone deacetylase (HDAC) inhibitor, protects against experimental brain ischemia. The present study investigated whether VPA could enhance angiogenesis and promote long-term functional recovery after ischemic stroke. Methods Male rats underwent middle cerebral artery occlusion (MCAO) for 60 minutes followed by reperfusion for up to 14 days. Assessed parameters were: locomotor function via rotarod test; infarct volume via T2-weighted magnetic resonance imaging; microvessel density via immunohistochemistry; relative cerebral blood flow (rCBF) via perfusion-weighted imaging; protein levels of pro-angiogenic factors via Western blotting; and matrix metalloproteinase (MMP)-2/9 activities via gelatin zymography. Results Post-ischemic VPA treatment robustly improved the rotarod performance of MCAO rats on days 7 and 14 after ischemia, and significantly reduced brain infarction on day 14. Concurrently, VPA markedly enhanced microvessel density, facilitated endothelial cell proliferation, and increased rCBF in the ipsilateral cortex. The transcription factor hypoxia-inducible factor (HIF)-1? and its downstream pro-angiogenic factors, vascular endothelial growth factor (VEGF) and MMP-2/9, were upregulated after MCAO and significantly potentiated by VPA in the ipsilateral cortex. Acetylation of histone-H3 and H4 was robustly increased by chronic VPA treatment. The beneficial effects of VPA on rotarod performance and microvessel density were abolished by HIF-1? inhibition. Conclusions Chronic VPA treatment enhances angiogenesis and promotes functional recovery after brain ischemia. These effects may involve HDAC inhibition and upregulation of HIF-1? and its downstream pro-angiogenic factors VEGF and MMP-2/9. PMID:22811460

  20. 40 CFR 86.1232-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...1) Gasoline- and methanol-fueled vehicles...preconditioned separately. If production evaporative canisters...per hour. (2) For methanol-fueled and flexible-fueled...prior to loading. If production evaporative canisters...of hydrocarbons, of methanol, or of methanol...

  1. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...1) Gasoline- and methanol-fueled vehicles...preconditioned separately. If production evaporative canisters...per hour. (2) For methanol-fueled and flexible-fueled...prior to loading. If production evaporative canisters...of hydrocarbons, of methanol, or of methanol...

  2. 40 CFR 86.1232-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...1) Gasoline- and methanol-fueled vehicles...preconditioned separately. If production evaporative canisters...per hour. (2) For methanol-fueled and flexible-fueled...prior to loading. If production evaporative canisters...of hydrocarbons, of methanol, or of methanol...

  3. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...1) Gasoline- and methanol-fueled vehicles...preconditioned separately. If production evaporative canisters...per hour. (2) For methanol-fueled and flexible-fueled...prior to loading. If production evaporative canisters...of hydrocarbons, of methanol, or of methanol...

  4. Planar amperometric oxygen sensor with improved preconditioning property

    Microsoft Academic Search

    Sung Hyuk Choi; Jeonghan Ha; Jae Ho Shin; Yong Suk Choi; Sang Hyun Han; Hakhyun Nam; Geun Sig Cha

    2001-01-01

    The feasibility of enhancing the preconditioning time property of the planar type amperometric oxygen sensor is investigated. A gas permeable membrane is formulated by incorporating hydrophilic polyurethane (HPU) into a one-component room temperature vulcanizing (RTV) silicone rubber matrix. Planar oxygen sensors are made by forming a recipient hydrogel layer on the base electrodes screen printed on a substrate, and by

  5. Dexmedetomidine Preconditioning Attenuates Cisplatin-Induced Ototoxicity in Zebrafish

    PubMed Central

    Min, Too Jae; Ha, Young Ran; Jeong, In young; Yoo, Ji young

    2014-01-01

    Objectives Utilisation of high-frequency drills is known to increase noise induced hearing loss due to increasing the damages of inner ear cells. This study aimed to investigate whether preconditioning by using dexmedetomidine (DEX) decreased the occurrence of ischemia in inner cells of the ear. Methods We utilised a transgenic zebrafish line Brn3C, and the embryos were collected from breeding adult zebrafish. Five-day-old larvae were cultured at the density of 50 embryos, and the larvae were classified into 4 groups: control, cisplatin group, DEX group, and DEX+yohimbine; adrenoreceptor blocker group. The DEX group was categorised into 3 subgroups by dosage; 0.1, 1, and 10 µM. Preconditioning was performed for 150 minutes and then exposed to cisplatin for 6 hours. The experiment was performed in 7 replicates for each group and the number of hair cells in 3 parts of the neuromasts of each fish was determined. Results Hair cell apoptosis by cisplatin was attenuated more significantly in the DEX preconditioning group than in the control group. However, the preconditioning effects were not blocked by yohimbine. Conclusion The results of this study suggest that hearing loss caused by vibration-induced noise could be reduced by using DEX and may occur through other mechanisms rather than adreno-receptors. PMID:25436046

  6. Minimal preconditioning effects observed for inflation tests of planar tissues.

    PubMed

    Tonge, Theresa K; Murienne, Barbara J; Coudrillier, Baptiste; Alexander, Stephen; Rothkopf, William; Nguyen, Thao D

    2013-11-01

    The purpose of this study is to investigate the effects of preconditioning on the deformation response of planar tissues measured by inflation tests. The inflation response of test specimens, including the bovine cornea, bovine and porcine sclera, and human skin, exhibited a negligible evolving deformation response when subjected to repeated pressure loading with recovery periods between cycles. Tissues obtained complete recovery to the reference state, and strain contours across the entire specimen were nearly identical at the maximum pressure of each load cycle. This repeatability was obtained regardless of strain history. These results suggest that negligible permanent change was induced in the microstructure by inflation testing. Additionally, we present data illustrating that a lack of a recovery period can result in an evolving deformation response to repeated loading that is commonly attributed to preconditioning. These results suggest that the commonly observed effects of preconditioning may be avoided by experimental design for planar tissues characterized by long collagen fibers arranged in the plane of the tissue. Specifically, if the test is designed to fully fix the specimen boundary during loading, adequate recovery periods are allowed after each load cycle, and loads are limited to avoid damage, preconditioning effects may be avoided for planar tissues. PMID:23897279

  7. Efficient Preconditioning of Laplacian Matrices for Computer Graphics Dilip Krishnan

    E-print Network

    Bernstein, Phil

    . It can therefore be used for a wide variety of computational photography problems, as well as several 3D; Keywords: matrix preconditioning, Laplacians, multigrid, mesh processing, computational photography Links Introduction A large number of problems in computer graphics and compu- tational photography are formulated

  8. Preconditioning of PWR steam generators to reduce radiation buildup

    SciTech Connect

    Beslu, P.; Masse, F.; Anthoni, S.; Galliano, N. (CEA Centre d'Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France))

    1992-08-01

    The purpose of the tests carried out on the CORELE loop was to determine whether preconditioning of steam generator tube surfaces could minimize the release rate of corrosion products. The test program and evaluation of the results obtained are included in this report.

  9. Interleukin-6 mediates exercise preconditioning against myocardial ischemia reperfusion injury.

    PubMed

    McGinnis, Graham Ripley; Ballmann, Christopher; Peters, Bridget; Nanayakkara, Gayani; Roberts, Michael; Amin, Rajesh; Quindry, John C

    2015-06-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine that protects against cardiac ischemia-reperfusion (I/R) injury following pharmacological and ischemic preconditioning (IPC), but the affiliated role in exercise preconditioning is unknown. Our study purpose was to characterize exercise-induced IL-6 cardiac signaling (aim 1) and evaluate myocardial preconditioning (aim 2). In aim 1, C57 and IL-6(-/-) mice underwent 3 days of treadmill exercise for 60 min/day at 18 m/min. Serum, gastrocnemius, and heart were collected preexercise, immediately postxercise, and 30 and 60 min following the final exercise session and analyzed for indexes of IL-6 signaling. For aim 2, a separate cohort of exercise-preconditioned (C57 EX and IL-6(-/-) EX) and sedentary (C57 SED and IL-6(-/-) SED) mice received surgical I/R injury (30 min I, 120 min R) or a time-matched sham operation. Ischemic and perfused tissues were examined for necrosis, apoptosis, and autophagy. In aim 1, serum IL-6 and IL-6 receptor (IL-6R), gastrocnemius, and myocardial IL-6R were increased following exercise in C57 mice only. Phosphorylated (p) signal transducer and activator of transcription 3 was increased in gastrocnemius and heart in C57 and IL-6(-/-) mice postexercise, whereas myocardial iNOS and cyclooxygenase-2 were unchanged in the exercised myocardium. Exercise protected C57 EX mice against I/R-induced arrhythmias and necrosis, whereas arrhythmia score and infarct outcomes were higher in C57 SED, IL-6(-/-) SED, and IL-6(-/-) EX mice compared with SH. C57 EX mice expressed increased p-p44/42 MAPK (Thr(202)/Tyr(204)) and p-p38 MAPK (Thr(180)/Tyr(182)) compared with IL-6(-/-) EX mice, suggesting pathway involvement in exercise preconditioning. Findings indicate exercise exerts cardioprotection via IL-6 and strongly implicates protective signaling originating from the exercised skeletal muscle. PMID:25820396

  10. Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke

    PubMed Central

    Ruscher, Karsten; Kuric, Enida; Liu, Yawei; Walter, Helene L; Issazadeh-Navikas, Shohreh; Englund, Elisabet; Wieloch, Tadeusz

    2013-01-01

    After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3+) and CD3+/CD4+ T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke. PMID:23632969

  11. Postischemic hyperperfusion on arterial spin labeled perfusion MRI is linked to hemorrhagic transformation in stroke.

    PubMed

    Yu, Songlin; Liebeskind, David S; Dua, Sumit; Wilhalme, Holly; Elashoff, David; Qiao, Xin J; Alger, Jeffry R; Sanossian, Nerses; Starkman, Sidney; Ali, Latisha K; Scalzo, Fabien; Lou, Xin; Yoo, Bryan; Saver, Jeffrey L; Salamon, Noriko; Wang, Danny J J

    2015-04-01

    The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR) = 4.8, 95% confidence interval (CI) 2.5 to 8.9, P < 0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P<0.001). There was a significant association between having hyperperfusion at any time point and HT (OR = 3.5, 95% CI 2.0 to 6.3, P < 0.001). There was a positive relationship between the grade of HT and time-hyperperfusion with the Spearman's rank correlation of 0.44 (P = 0.003). Arterial spin labeling hyperperfusion may provide an imaging marker of HT, which may guide the management of AIS patients post tissue-type plasminogen activator (tPA) and/or endovascular treatments. Late hyperperfusion should be given more attention to prevent high-grade HT. PMID:25564233

  12. Strategies for Study of Neuroprotection from Cold-preconditioning

    PubMed Central

    Mitchell, Heidi M.; White, David M.; Kraig, Richard P.

    2010-01-01

    Neurological injury is a frequent cause of morbidity and mortality from general anesthesia and related surgical procedures that could be alleviated by development of effective, easy to administer and safe preconditioning treatments. We seek to define the neural immune signaling responsible for cold-preconditioning as means to identify novel targets for therapeutics development to protect brain before injury onset. Low-level pro-inflammatory mediator signaling changes over time are essential for cold-preconditioning neuroprotection. This signaling is consistent with the basic tenets of physiological conditioning hormesis, which require that irritative stimuli reach a threshold magnitude with sufficient time for adaptation to the stimuli for protection to become evident. Accordingly, delineation of the immune signaling involved in cold-preconditioning neuroprotection requires that biological systems and experimental manipulations plus technical capacities are highly reproducible and sensitive. Our approach is to use hippocampal slice cultures as an in vitro model that closely reflects their in vivo counterparts with multi-synaptic neural networks influenced by mature and quiescent macroglia / microglia. This glial state is particularly important for microglia since they are the principal source of cytokines, which are operative in the femtomolar range. Also, slice cultures can be maintained in vitro for several weeks, which is sufficient time to evoke activating stimuli and assess adaptive responses. Finally, environmental conditions can be accurately controlled using slice cultures so that cytokine signaling of cold-preconditioning can be measured, mimicked, and modulated to dissect the critical node aspects. Cytokine signaling system analyses require the use of sensitive and reproducible multiplexed techniques. We use quantitative PCR for TNF-? to screen for microglial activation followed by quantitative real-time qPCR array screening to assess tissue-wide cytokine changes. The latter is a most sensitive and reproducible means to measure multiple cytokine system signaling changes simultaneously. Significant changes are confirmed with targeted qPCR and then protein detection. We probe for tissue-based cytokine protein changes using multiplexed microsphere flow cytometric assays using Luminex technology. Cell-specific cytokine production is determined with double-label immunohistochemistry. Taken together, this brain tissue preparation and style of use, coupled to the suggested investigative strategies, may be an optimal approach for identifying potential targets for the development of novel therapeutics that could mimic the advantages of cold-preconditioning. PMID:20834222

  13. Preconditioned iterative methods for Navier-Stokes control problems

    NASA Astrophysics Data System (ADS)

    Pearson, John W.

    2015-07-01

    PDE-constrained optimization problems are a class of problems which have attracted much recent attention in scientific computing and applied science. In this paper we discuss preconditioned iterative methods for a class of (time-independent) Navier-Stokes control problems, one of the main problems of this type in the field of fluid dynamics. Having detailed the Picard-type iteration we use to solve the problems and derived the structure of the matrix system to be solved at each step, we utilize the theory of saddle point systems to develop efficient preconditioned iterative solution techniques for these problems. We also require theory of solving convection-diffusion control problems, as well as a commutator argument to justify one of the components of the preconditioner.

  14. Preconditioning effects of intermittent stream flow on leaf litter decomposition

    Microsoft Academic Search

    D. Dieter; D. von Schiller; E. M. García-Roger; M. M. Sánchez-Montoya; R. Gómez; J. Mora-Gómez; F. Sangiorgio; J. Gelbrecht; K. Tockner

    Autumnal input of leaf litter is a pivotal energy source in most headwater streams. In temporary streams, however, water stress\\u000a may lead to a seasonal shift in leaf abscission. Leaves accumulate at the surface of the dry streambed or in residual pools\\u000a and are subject to physicochemical preconditioning before decomposition starts after flow recovery. In this study, we experimentally\\u000a tested

  15. Protein Tyrosine Nitration of the Flavin Subunit Is Associated with Oxidative Modification of Mitochondrial Complex II in the Post-ischemic Myocardium*S?

    PubMed Central

    Chen, Chwen-Lih; Chen, Jingfeng; Rawale, Sharad; Varadharaj, Saradhadevi; Kaumaya, Pravin P. T.; Zweier, Jay L.; Chen, Yeong-Renn

    2008-01-01

    Increased \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document} and NO production is a key mechanism of mitochondrial dysfunction in myocardial ischemia/reperfusion injury. A crucial segment of the mitochondrial electron transport chain is succinate ubiquinone reductase (SQR or Complex II). In SQR, oxidative impairment and deglutathionylation of the 70-kDa flavin protein occurs in the post-ischemic heart (Chen, Y. R., Chen, C. L., Pfeiffer, D. R., and Zweier, J. L. (2007) J. Biol. Chem. 282,32640 -3265417848555). To gain insights into the oxidative modification of the 70-kDa protein in the post-ischemic myocardium, we used the identified S-glutathionylated peptide (77AAFGLSEAGFNTACVTK93) of the 70-kDa protein as a chimeric epitope incorporating a “promiscuous” T cell epitope to generate a high titer polyclonal antibody, AbGSC90. Purified AbGSC90 showed a high binding affinity to isolated SQR. Antibodies of AbGSC90 moderately inhibited the electron transfer and superoxide generation activities of SQR. To test for protein nitration, rats were subjected to 30 min of coronary ligation followed by 24 h of reperfusion. Tissue homogenates were immunoprecipitated with AbGSC90 and probed with antibodies against 3-nitrotyrosine. Enhancement of protein tyrosine nitration was detected in the post-ischemic myocardium. Isolated SQR was subjected to in vitro protein nitration with peroxynitrite, leading to site-specific nitration at the 70-kDa polypeptide and impairment of SQR electron transfer activity. Protein nitration of SQR further impaired its protein-protein interaction with Complex III. Liquid chromatography/tandem mass spectrometry analysis indicated that Tyr-56 and Tyr-142 were involved in protein tyrosine nitration. When the isolated SQR was subjected to in vitro S-glutathionylation, oxidative modification and impairment mediated by peroxynitrite were significantly decreased, thus confirming the protective effect of S-glutathionylation from the oxidative damage of nitration. PMID:18682392

  16. Preconditioning the bidomain model with almost linear complexity

    NASA Astrophysics Data System (ADS)

    Pierre, Charles

    2012-01-01

    The bidomain model is widely used in electro-cardiology to simulate spreading of excitation in the myocardium and electrocardiograms. It consists of a system of two parabolic reaction diffusion equations coupled with an ODE system. Its discretisation displays an ill-conditioned system matrix to be inverted at each time step: simulations based on the bidomain model therefore are associated with high computational costs. In this paper we propose a preconditioning for the bidomain model either for an isolated heart or in an extended framework including a coupling with the surrounding tissues (the torso). The preconditioning is based on a formulation of the discrete problem that is shown to be symmetric positive semi-definite. A block LU decomposition of the system together with a heuristic approximation (referred to as the monodomain approximation) are the key ingredients for the preconditioning definition. Numerical results are provided for two test cases: a 2D test case on a realistic slice of the thorax based on a segmented heart medical image geometry, a 3D test case involving a small cubic slab of tissue with orthotropic anisotropy. The analysis of the resulting computational cost (both in terms of CPU time and of iteration number) shows an almost linear complexity with the problem size, i.e. of type nlog ?( n) (for some constant ?) which is optimal complexity for such problems.

  17. Preconditioning concepts in polymer flooding in high-salinity reservoirs; Laboratory investigations and case histories

    SciTech Connect

    Volz, H.; Maltin, B.K. (RWE-DEA AG (DE)); Sohn, W.O.

    1990-11-01

    In polymer-flood field projects with partially hydrolized polyacrylamide (PH PAA) solutions, the authors applied two methods of preconditioning: a preflush with fresh water and the use of a relatively small slug of a less-salt-sensitive polymer. Results of laboratory work that led to an improved preconditioning concept with polymer are described. Case histories of two projects with two different preconditioning processes are presented and discussed in detail.

  18. Delayed myocardial preconditioning induced by cobalt chloride in the rat: HIF-1? and iNOS involvement.

    PubMed

    Belaidi, Elise; Beguin, Pauline C; Levy, Patrick; Ribuot, Christophe; Godin-Ribuot, Diane

    2012-08-01

    We previously reported that acute exposure to intermittent hypoxia results in delayed cardioprotection against ischemia/reperfusion (I/R) injury and that the hypoxia-inducible factor (HIF)-1?, a transcriptional factor stabilized by hypoxia, as well as inducible nitric oxide synthase (iNOS) play a key role in this form of preconditioning. As cobalt chloride (CoCl(2)) is known to promote HIF-1? stabilization by inhibiting prolyl hydroxylase activity, we hypothesized that CoCl(2) could mimic the cardioprotective effects of hypoxia. Two groups of rats were administered 30 mg/kg twice of CoCl(2) or sterile water. Twenty-four hours later, hearts were perfused in Langendorff mode and subjected to an I/R protocol. Infarct size and functional recovery were studied. The role of iNOS was assessed by measuring myocardial iNOS content and by observing the effects of the iNOS inhibitor aminoguanidine (Ag, 100 ?m, prior to ischemia). The role of HIF-1? was investigated by preventing its stabilization using cadmium chloride (CdCl(2), 1 mg/kg), administered 1 h before cobalt treatment. Treatment by CoCl(2) significantly reduced myocardial infarction by 33% and increased coronary flow (CF) at reperfusion by 27% compared with control rats, and this was accompanied by a threefold increase in myocardial iNOS content. CdCl(2) pretreatment and Ag perfusion abolished the beneficial effects on both infarct size and CF. Thus, the hypoxia-sensitive transcription factor HIF-1? and iNOS appear to play a pivotal role in the delayed pharmacological myocardial preconditioning induced by cobalt, thus mimicking the effects of hypoxic preconditioning. These results underscore the importance of prolyl hydroxylases as potential therapeutic targets for cardioprotection. PMID:21480981

  19. 41 CFR 102-72.68 - What preconditions must be satisfied before an Executive agency may exercise the delegated...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...preconditions must be satisfied before an Executive agency may exercise the delegated authority to perform an individual ancillary...preconditions must be satisfied before an Executive agency may exercise the delegated authority to perform an individual...

  20. 41 CFR 102-72.68 - What preconditions must be satisfied before an Executive agency may exercise the delegated...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...preconditions must be satisfied before an Executive agency may exercise the delegated authority to perform an individual ancillary...preconditions must be satisfied before an Executive agency may exercise the delegated authority to perform an individual...

  1. Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4 dependent pathway

    E-print Network

    Paris-Sud XI, Université de

    Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber cell mobilization and skeletal muscle fiber regeneration via a paracrine Wnt dependent mechanism. Transplantation of hypoxic preconditioned murine MSC (HypMSC) enhanced skeletal muscle regeneration at day 7

  2. Weighted graph based ordering techniques for preconditioned conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Clift, Simon S.; Tang, Wei-Pai

    1994-01-01

    We describe the basis of a matrix ordering heuristic for improving the incomplete factorization used in preconditioned conjugate gradient techniques applied to anisotropic PDE's. Several new matrix ordering techniques, derived from well-known algorithms in combinatorial graph theory, which attempt to implement this heuristic, are described. These ordering techniques are tested against a number of matrices arising from linear anisotropic PDE's, and compared with other matrix ordering techniques. A variation of RCM is shown to generally improve the quality of incomplete factorization preconditioners.

  3. Preconditioned Krylov subspace methods for solving nonsymmetric matrices from CFD applications q

    E-print Network

    Zhang, Jun

    Preconditioned Krylov subspace methods for solving nonsymmetric matrices from CFD applications q dynamics (CFD) applications. The preconditioned iterative methods consist of Krylov subspace accelerators matrices arising from various relevant CFD applications, are reported. Ó 2000 Elsevier Science S.A. All

  4. A preconditioning mass matrix to accelerate the convergence to the steady Euler solutions using explicit schemes

    Microsoft Academic Search

    M. A. Storti; C. E. Baumann; S. R. Idelsohn

    1992-01-01

    The paper shows, with analytical and numerical results, how the use of a preconditioning mass matrix accelerates the convergence in zones with low Mach number and in zones with transonic flow. A preconditioning mass matrix is proposed which can be applied to any FEM\\/FVM that uses an explicit time marching scheme to find the steady state. The method's rate of

  5. 40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 false Preconditioned two speed idle test-EPA 91. 85.2220 Section 85.2220...Emission Control System Performance Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements...

  6. 40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 false Preconditioned two speed idle test-EPA 91. 85.2220 Section 85.2220...Emission Control System Performance Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements...

  7. 40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 false Preconditioned two speed idle test-EPA 91. 85.2220 Section 85.2220...Emission Control System Performance Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements...

  8. 40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 false Preconditioned two speed idle test-EPA 91. 85.2220 Section 85.2220...Emission Control System Performance Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements...

  9. HL-1 Myocytes Exhibit PKC and KATP Channel-Dependent Delta Opioid Preconditioning1,2

    E-print Network

    Wojcik, Edward J.

    HL-1 Myocytes Exhibit PKC and KATP Channel-Dependent Delta Opioid Preconditioning1,2 Elisabeth M. Opioid preconditioning protects the myocardium against ischemia/reperfusion (IR) injury. By enhancing cardiomyocyte viability, opioids can en- hance cardiac function and recovery from IR injury during acute cardiac

  10. Preconditioning via a Schur Complement Method: an Application in State Estimation

    E-print Network

    Blank, Luise - Naturwissenschaftliche Fakultät I

    Preconditioning via a Schur Complement Method: an Application in State Estimation #3; Luise Blank y complement is analyzed and applied for preconditioning symmetric matrices. In particular we eliminate the in modulo extreme eigenvalues by computing the Schur complement with respect to a coarse subspace, which cap

  11. An incomplete-factorization preconditioning using repeated red-black ordering

    Microsoft Academic Search

    Clemens W. Brand

    1992-01-01

    Summary The convergence of the conjugate gradient method for the iterative solution of large systems of linear equations depends on proper preconditioning matrices. We present an efficient incomplete-factorization preconditioning based on a specific, “repeated red-black” ordering scheme and cyclic reduction. For the Dirichlet model problem, we prove that the condition number increases asymptotically slower with the number of equations than

  12. Waveform preconditioning for clutter rejection in multipath for sparse distributed apertures

    Microsoft Academic Search

    T. Varslot; B. Yazici; C.-E. Yarman; M. Cheney; L. Scharf

    2007-01-01

    The idea of preconditioning transmit waveforms for optimal clutter rejection in radar imaging is presented. Waveform preconditioning involves determining a map on the space of transmit waveforms, and then applying this map to the waveforms before transmission. The work applies to systems with an arbitrary number of transmitand receive-antenna elements, and makes no assumptions about the elements being co-located. Waveform

  13. Aggravation of post-ischemic liver injury by overexpression of insulin-like growth factor binding protein 3

    PubMed Central

    Zhou, Lu; Koh, Hyoung-Won; Bae, Ui-Jin; Park, Byung-Hyun

    2015-01-01

    Insulin-like growth factor-1 (IGF-1) is known to inhibit reperfusion-induced apoptosis. IGF-binding protein-3 (IGFBP-3) is the major circulating carrier protein for IGF-1 and induces apoptosis. In this study, we determined if IGFBP-3 was important in the hepatic response to I/R. To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 cDNA (AdIGFBP-3) or an IGFBP-3 mutant devoid of IGF binding affinity but retaining IGFBP-3 receptor binding ability (AdIGFBP-3GGG). Mice subjected to I/R injury showed typical patterns of hepatocellular damage. Protein levels of IGFBP-3 were increased after reperfusion and showed a positive correlation with the extent of liver injury. Prior injection with AdIGFBP-3 aggravated liver injury: serum aminotransferases, prothrombin time, proinflammatory cytokines, hepatocellular necrosis and apoptosis, and neutrophil infiltration were markedly increased compared to control mice. A decrease in antioxidant potential and an upregulation of NADPH oxidase might have caused these aggravating effects of IGFBP-3. Experiments using HepG2 cells and N-acetylcysteine-pretreated mice showed a discernible effect of IGFBP-3 on reactive oxygen species generation. Lastly, AdIGFBP-3 abolished the beneficial effects of ischemic preconditioning and hypothermia. Mice treated with AdIGFBP-3GGG exhibited effects similar to those of AdIGFBP-3, suggesting a ligand-independent effect of IGFBP-3. Our results suggest IGFBP-3 as an aggravating factor during hepatic I/R injury. PMID:26073647

  14. Aggravation of post-ischemic liver injury by overexpression of insulin-like growth factor binding protein 3.

    PubMed

    Zhou, Lu; Koh, Hyoung-Won; Bae, Ui-Jin; Park, Byung-Hyun

    2015-01-01

    Insulin-like growth factor-1 (IGF-1) is known to inhibit reperfusion-induced apoptosis. IGF-binding protein-3 (IGFBP-3) is the major circulating carrier protein for IGF-1 and induces apoptosis. In this study, we determined if IGFBP-3 was important in the hepatic response to I/R. To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 cDNA (AdIGFBP-3) or an IGFBP-3 mutant devoid of IGF binding affinity but retaining IGFBP-3 receptor binding ability (AdIGFBP-3(GGG)). Mice subjected to I/R injury showed typical patterns of hepatocellular damage. Protein levels of IGFBP-3 were increased after reperfusion and showed a positive correlation with the extent of liver injury. Prior injection with AdIGFBP-3 aggravated liver injury: serum aminotransferases, prothrombin time, proinflammatory cytokines, hepatocellular necrosis and apoptosis, and neutrophil infiltration were markedly increased compared to control mice. A decrease in antioxidant potential and an upregulation of NADPH oxidase might have caused these aggravating effects of IGFBP-3. Experiments using HepG2 cells and N-acetylcysteine-pretreated mice showed a discernible effect of IGFBP-3 on reactive oxygen species generation. Lastly, AdIGFBP-3 abolished the beneficial effects of ischemic preconditioning and hypothermia. Mice treated with AdIGFBP-3(GGG) exhibited effects similar to those of AdIGFBP-3, suggesting a ligand-independent effect of IGFBP-3. Our results suggest IGFBP-3 as an aggravating factor during hepatic I/R injury. PMID:26073647

  15. [Prevention within the context of the healthcare reform in Russia].

    PubMed

    Shchepin, V O; Petruchuk, O E

    2004-01-01

    Healthcare and promotion of preventive care rendered to population of the Russian Federation are the main components of the whole social sphere. Perfection of the legal basis for the high-quality primary prevention is a precondition of success of the Russian healthcare reform as a whole. Implementation of social and medical prevention measures must turn into a united purpose for the activities of medical personnel, enterprise management and public organizations. Prevention issues belong to the sphere of combined economic and social interests of public and healthcare. PMID:15291331

  16. Parallelizable approximate solvers for recursions arising in preconditioning

    SciTech Connect

    Shapira, Y. [Israel Inst. of Technology, Haifa (Israel)

    1996-12-31

    For the recursions used in the Modified Incomplete LU (MILU) preconditioner, namely, the incomplete decomposition, forward elimination and back substitution processes, a parallelizable approximate solver is presented. The present analysis shows that the solutions of the recursions depend only weakly on their initial conditions and may be interpreted to indicate that the inexact solution is close, in some sense, to the exact one. The method is based on a domain decomposition approach, suitable for parallel implementations with message passing architectures. It requires a fixed number of communication steps per preconditioned iteration, independently of the number of subdomains or the size of the problem. The overlapping subdomains are either cubes (suitable for mesh-connected arrays of processors) or constructed by the data-flow rule of the recursions (suitable for line-connected arrays with possibly SIMD or vector processors). Numerical examples show that, in both cases, the overhead in the number of iterations required for convergence of the preconditioned iteration is small relatively to the speed-up gained.

  17. Role of miRs in Cardiac Preconditioning

    PubMed Central

    Salloum, Fadi N.; Yin, Chang; Kukreja, Rakesh C.

    2014-01-01

    Preconditioning of the heart by sub-lethal ischemia, mild heat shock or hypoxia have evolved as powerful experimental tools to discover novel signaling mechanisms in cardioprotection. The ultimate goal is to determine novel therapeutic targets for potential application in humans in protecting the heart against ischemia-related injuries. In recent years, there has been a tremendous interest in understanding the role of small non-coding RNAs, microRNAs (miRs), in cardiovascular diseases. miRs have been recognized as regulators of gene expression by destabilization and translational inhibition of target mRNAs. Studies have shown that several miRs including miR-1, miR-133, miR-21, miR-126, miR-320, miR-92a and miR-199a are regulated after preconditioning and play an active role in protection of the heart against ischemia/reperfusion injury. These miRs also drive the synthesis of important cardioprotective proteins including HSP-70, eNOS, iNOS, HSP-20, Sirt-1 and HIF-1?. We believe that identification and targeted delivery of miR(s) in the heart could have an immense therapeutic potential in reducing myocardial infarction in patients suffering from heart disease. PMID:20980922

  18. Functional preservation of hippocampal CA1 by low-dose GYKI-52466 preconditioning in a rat model of hypoxic-ischemic brain injury.

    PubMed

    Nayak, Prasanta K; Kerr, D Steven

    2015-07-10

    Global ischemia during cardiac surgery, brain surgery and stroke leads to lasting neuropsychological impairments. Previously we showed that low-dose GYKI-52466 preconditioning protects against kainic acid-induced seizures and unilateral hypoxic-ischemic (HI) damage in rats. Here, we evaluated low-dose GYKI-52466 on electrophysiological indices of hippocampal CA1 function after HI. Male Sprague-Dawley rats (26 days old) were administered saline or GYKI-52466 (3mg/kg, s.c.) 90min before left common carotid artery occlusion and allowed to recover 2h prior to placement in a hypoxia chamber (1h; 8% O2/92% N2). On days 14 and 90 post-HI, contralateral and, where possible, ipsilateral hippocampal slices were prepared and population spikes and field excitatory postsynaptic potentials (EPSPs) recorded at 30-32°C. Slices with population spikes ?3mV and/or field EPSPs ?1mV were accepted for long-term potentiation (LTP) and depression (LTD) studies. GYKI-52466 preconditioning prevented the stroke-induced suppression of population spikes and field EPSPs in both contralateral and ipsilateral hippocampi at 14 and 90 days. On days 14 and 90, both LTP and LTD were readily induced in both contralateral and ipsilateral hippocampi from sham-operated controls. After stroke, LTP was significantly impaired in contralateral and completely absent in ipsilateral hippocampi. In ischemic animals preconditioned with low-dose GYKI-52466, LTP was readily induced on both sides. Hippocampal LTD was unaffected by either HI or GYKI preconditioning on both days 14 and 90. The present results indicate that prophylactic low-dose GYKI-52466 preserves CA1 function and synaptic plasticity processes contralateral, and more importantly, ipsilateral to the site of damage. PMID:25869178

  19. Hyperglycemia abolishes the protective effect of ischemic preconditioning in glomerular endothelial cells in vitro

    PubMed Central

    Schenning, Katie J; Anderson, Sharon; Alkayed, Nabil J; Hutchens, Michael P

    2015-01-01

    In preclinical investigations, ischemic preconditioning (IPC) protects kidneys from ischemia/reperfusion injury. The direct effects of IPC on glomerular endothelial cells have not been studied in detail. Most investigations of IPC have focused on healthy cells and animals, and it remains unknown whether IPC is renoprotective in the setting of medical comorbidities such as diabetes. In this study, we determined the preventive potential of IPC in healthy glomerular endothelial cell monolayers, and compared these results to monolayers cultured under hyperglycemic conditions. We exposed glomerular endothelial monolayers to 1 h of IPC 24 h prior to oxygen–glucose deprivation (OGD), an in vitro model of ischemia/reperfusion injury. Glomerular endothelial monolayer integrity was assessed by measuring transendothelial electrical resistance, albumin flux, and cell survival. We found that IPC protected healthy but not hyperglycemic glomerular endothelial monolayers from ischemia/reperfusion injury. Furthermore, not only was the protective effect of IPC lost in the setting of hyperglycemia, but IPC was actually deleterious to the integrity of hyperglycemic glomerular endothelial cell monolayers. PMID:25804266

  20. Cardiac Phosphoproteomics during Remote Ischemic Preconditioning: A Role for the Sarcomeric Z-Disk Proteins

    PubMed Central

    Abdul-Ghani, Safa; Heesom, Kate J.; Angelini, Gianni D.; Suleiman, M-Saadeh

    2014-01-01

    Remote ischemic preconditioning (RIPC) induced by brief ischemia/reperfusion cycles of remote organ (e.g., limb) is cardioprotective. The myocardial cellular changes during RIPC responsible for this phenomenon are not currently known. The aim of this work was to identify the activation by phosphorylation of cardiac proteins following RIPC. To achieve our aim we used isobaric tandem mass tagging (TMT) and reverse phase nanoliquid chromatography tandem spectrometry using a Linear Trap Quadropole (LTQ) Orbitrap Velos mass spectrometer. Male C57/Bl6 mice were anesthetized by an intraperitoneal injection of Tribromoethanol. A cuff was placed around the hind limb and inflated at 200?mmHg to prevent blood flow as confirmed by Laser Doppler Flowmetry. RIPC was induced by 4 cycles of 5?min of limb ischemia followed by 5?min of reperfusion. Hearts were extracted for phosphoproteomics. We identified approximately 30 phosphoproteins that were differentially expressed in response to RIPC protocol. The levels of several phosphoproteins in the Z-disk of the sarcomere including phospho-myozenin-2 were significantly higher than control. This study describes and validates a novel approach to monitor the changes in the cardiac phosphoproteome following the cardioprotective intervention of RIPC and prior to index ischemia. The increased level of phosphorylated sarcomeric proteins suggests they may have a role in cardiac signaling during RIPC. PMID:24795895

  1. Cardiac phosphoproteomics during remote ischemic preconditioning: a role for the sarcomeric Z-disk proteins.

    PubMed

    Abdul-Ghani, Safa; Heesom, Kate J; Angelini, Gianni D; Suleiman, M-Saadeh

    2014-01-01

    Remote ischemic preconditioning (RIPC) induced by brief ischemia/reperfusion cycles of remote organ (e.g., limb) is cardioprotective. The myocardial cellular changes during RIPC responsible for this phenomenon are not currently known. The aim of this work was to identify the activation by phosphorylation of cardiac proteins following RIPC. To achieve our aim we used isobaric tandem mass tagging (TMT) and reverse phase nanoliquid chromatography tandem spectrometry using a Linear Trap Quadropole (LTQ) Orbitrap Velos mass spectrometer. Male C57/Bl6 mice were anesthetized by an intraperitoneal injection of Tribromoethanol. A cuff was placed around the hind limb and inflated at 200?mmHg to prevent blood flow as confirmed by Laser Doppler Flowmetry. RIPC was induced by 4 cycles of 5?min of limb ischemia followed by 5?min of reperfusion. Hearts were extracted for phosphoproteomics. We identified approximately 30 phosphoproteins that were differentially expressed in response to RIPC protocol. The levels of several phosphoproteins in the Z-disk of the sarcomere including phospho-myozenin-2 were significantly higher than control. This study describes and validates a novel approach to monitor the changes in the cardiac phosphoproteome following the cardioprotective intervention of RIPC and prior to index ischemia. The increased level of phosphorylated sarcomeric proteins suggests they may have a role in cardiac signaling during RIPC. PMID:24795895

  2. Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease

    PubMed Central

    Liang, Y.; Li, Y.P.; He, F.; Liu, X.Q.; Zhang, J.Y.

    2015-01-01

    Remote ischemic preconditioning (RIPre) can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG) surgery were assigned randomly to a RIPre group (n=20) or coronary heart disease (CHD) group (n=20). Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD), CD34+ monocyte count, and endothelial nitric oxide synthase (eNOS expression). Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.5±2.4 vs 4.9±4.2%, P<0.05) and significantly reduced troponin after CABG surgery (0.72±0.31 and 1.64±0.19, P<0.05). RIPre activated STAT-3 and increased CD34+ endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells. PMID:25923462

  3. Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart

    PubMed Central

    Jeremic, Nevena; Petkovic, Anica; Srejovic, Ivan; Zivkovic, Vladimir; Djuric, Dragan; Jakovljevic, Vladimir

    2015-01-01

    Objective The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion. Methods The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG) after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped) for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC) were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC) hearts first underwent preconditioning lasting 5 minutes with 100?M omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion. Results Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion. Conclusion Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible.

  4. Exercise preconditioning of myocardial infarct size in dogs is triggered by calcium.

    PubMed

    Parra, Víctor M; Macho, Pilar; Sánchez, Gina; Donoso, Paulina; Domenech, Raúl J

    2015-03-01

    We showed that exercise induces early and late myocardial preconditioning in dogs and that these effects are mediated through nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase activation. As the intracoronary administration of calcium induces preconditioning and exercise enhances the calcium inflow to the cell, we studied if this effect of exercise triggers exercise preconditioning independently of its hemodynamic effects. We analyzed in 81 dogs the effect of blocking sarcolemmal L-type Ca channels with a low dose of verapamil on early and late preconditioning by exercise, and in other 50 dogs, we studied the effect of verapamil on NADPH oxidase activation in early exercise preconditioning. Exercise reduced myocardial infarct size by 76% and 52% (early and late windows respectively; P < 0.001 both), and these effects were abolished by a single low dose of verapamil given before exercise. This dose of verapamil did not modify the effect of exercise on metabolic and hemodynamic parameters. In addition, verapamil blocked the activation of NADPH oxidase during early preconditioning. The protective effect of exercise preconditioning on myocardial infarct size is triggered, at least in part, by calcium inflow increase to the cell during exercise and, during the early window, is mediated by NADPH oxidase activation. PMID:25658459

  5. Clinical application of preconditioning and postconditioning to achieve neuroprotection.

    PubMed

    Dezfulian, Cameron; Garrett, Matthew; Gonzalez, Nestor R

    2013-02-01

    Ischemic conditioning is a form of endogenous protection induced by transient, subcritical ischemia in a tissue. Organs with high sensitivity to ischemia, such as the heart, the brain, and spinal cord, represent the most critical and potentially promising targets for potential therapeutic applications of ischemic conditioning. Numerous preclinical investigations have systematically studied the molecular pathways and potential benefits of both pre- and postconditioning with promising results. The purpose of this review is to summarize the present knowledge on cerebral pre- and postconditioning, with an emphasis in the clinical application of these forms of neuroprotection. A systematic MEDLINE search for the terms preconditioning and postconditioning was performed. Publications related to the nervous system and to human applications were selected and analyzed. Pre- and postconditioning appear to provide similar levels of neuroprotection. The preconditioning window of benefit can be subdivided into early and late effects, depending on whether the effect appears immediately after the sublethal stress or with a delay of days. In general, early effects have been associated posttranslational modification of critical proteins (membrane receptors, mitochondrial respiratory chain) while late effects are the result of gene up- or downregulation. Transient ischemic attacks appear to represent a form of clinically relevant preconditioning by inducing ischemic tolerance in the brain and reducing the severity of subsequent strokes. Remote forms of ischemic pre- and postconditioning have been more commonly used in clinical studies, as the remote application reduces the risk of injuring the target tissue for which protection is pursued. Limb transient ischemia is the preferred method of induction of remote conditioning with evidence supporting its safety. Clinical studies in a variety of populations at risk of central nervous damage including carotid disease, cervical myelopathy, and subarachnoid hemorrhage have shown improvement in surrogate markers of injury. Promising preclinical and early clinical studies noting improvement in surrogate markers of central nervous injury after the use of remote pre- and postconditioning treatments demand follow-up systematic investigations to address effectiveness. Challenges in the application of these techniques to pressing clinical cerebrovascular disease ought to be overcome through careful, well-designed, translational investigations. PMID:24323188

  6. Preconditioning and postconditioning: underlying mechanisms and clinical application.

    PubMed

    Hausenloy, Derek J; Yellon, Derek M

    2009-06-01

    Coronary heart disease (CHD) is the leading cause of death world-wide. Its major pathophysiological manifestation is acute myocardial ischaemia-reperfusion injury. Innovative treatment strategies for protecting the myocardium against the detrimental effects of this form of injury are required in order to improve clinical outcomes in patients with CHD. In this regard, harnessing the endogenous protection elicited by the heart's ability to 'condition' itself, has recently emerged as a powerful new strategy for limiting myocardial injury, preserving left ventricular systolic function and potentially improving morbidity and mortality in patients with CHD. 'Conditioning' the heart to tolerate the effects of acute ischaemia-reperfusion injury can be initiated through the application of several different mechanical and pharmacological strategies. Inducing brief non-lethal episodes of ischaemia and reperfusion to the heart either prior to, during, or even after an episode of sustained lethal myocardial ischaemia has the capacity to dramatically reduce myocardial injury--a phenomenon termed ischaemic preconditioning (IPC), preconditioning or postconditioning, respectively. Intriguingly, similar levels of cardioprotection can be achieved by applying the brief episodes of non-lethal ischaemia and reperfusion to an organ or tissue remote from the heart, thereby obviating the need to 'condition' the heart directly. This phenomenon has been termed remote ischaemic 'conditioning', and it can offer widespread systemic protection to other organs which are susceptible to acute ischaemia-reperfusion injury such as the brain, liver, intestine or kidney. Furthermore, the identification of the signalling pathways which underlie the effects of 'conditioning', has provided novel targets for pharmacological agents allowing one to recapitulate the benefits of these cardioprotective phenomena--so-termed pharmacological preconditioning and postconditioning. Initial clinical studies, reporting beneficial effects of 'conditioning' the heart to tolerate acute ischaemia-reperfusion injury, have been encouraging. Larger multi-centred randomised studies are now required to determine whether these 'conditioning' strategies are able to impact on clinical outcomes. In this article, we provide an overview of 'conditioning' in all its various forms, describe the underlying mechanisms and review the recent clinical application of this emerging cardioprotective strategy. PMID:19081095

  7. Eigenmode Analysis of Boundary Conditions for One-Dimensional Preconditioned Euler Equations

    NASA Technical Reports Server (NTRS)

    Darmofal, David L.

    1998-01-01

    An analysis of the effect of local preconditioning on boundary conditions for the subsonic, one-dimensional Euler equations is presented. Decay rates for the eigenmodes of the initial boundary value problem are determined for different boundary conditions. Riemann invariant boundary conditions based on the unpreconditioned Euler equations are shown to be reflective with preconditioning, and, at low Mach numbers, disturbances do not decay. Other boundary conditions are investigated which are non-reflective with preconditioning and numerical results are presented confirming the analysis.

  8. A frequency dependent preconditioned wavelet method for atmospheric tomography

    NASA Astrophysics Data System (ADS)

    Yudytskiy, Mykhaylo; Helin, Tapio; Ramlau, Ronny

    2013-12-01

    Atmospheric tomography, i.e. the reconstruction of the turbulence in the atmosphere, is a main task for the adaptive optics systems of the next generation telescopes. For extremely large telescopes, such as the European Extremely Large Telescope, this problem becomes overly complex and an efficient algorithm is needed to reduce numerical costs. Recently, a conjugate gradient method based on wavelet parametrization of turbulence layers was introduced [5]. An iterative algorithm can only be numerically efficient when the number of iterations required for a sufficient reconstruction is low. A way to achieve this is to design an efficient preconditioner. In this paper we propose a new frequency-dependent preconditioner for the wavelet method. In the context of a multi conjugate adaptive optics (MCAO) system simulated on the official end-to-end simulation tool OCTOPUS of the European Southern Observatory we demonstrate robustness and speed of the preconditioned algorithm. We show that three iterations are sufficient for a good reconstruction.

  9. Preconditioned Mixed Spectral Element Methods for Elasticity and Stokes Problems

    NASA Technical Reports Server (NTRS)

    Pavarino, Luca F.

    1996-01-01

    Preconditioned iterative methods for the indefinite systems obtained by discretizing the linear elasticity and Stokes problems with mixed spectral elements in three dimensions are introduced and analyzed. The resulting stiffness matrices have the structure of saddle point problems with a penalty term, which is associated with the Poisson ratio for elasticity problems or with stabilization techniques for Stokes problems. The main results of this paper show that the convergence rate of the resulting algorithms is independent of the penalty parameter, the number of spectral elements Nu and mildly dependent on the spectral degree eta via the inf-sup constant. The preconditioners proposed for the whole indefinite system are block-diagonal and block-triangular. Numerical experiments presented in the final section show that these algorithms are a practical and efficient strategy for the iterative solution of the indefinite problems arising from mixed spectral element discretizations of elliptic systems.

  10. Is There A Place For Cerebral Preconditioning In The Clinic?

    PubMed Central

    Keep, Richard F.; Wang, Michael M.; Xiang, Jianming; Hua, Ya; Xi, Guohua

    2010-01-01

    Preconditioning (PC) describes a phenomenon whereby a sub-injury inducing stress can protect against a later injurious stress. Great strides have been made in identifying the mechanisms of PC-induced protection in animal models of brain injury. While these may help elucidate potential therapeutic targets, there are questions over the clinical utility of cerebral PC, primarily because of questions over the need to give the PC stimulus prior to the injury, narrow therapeutic windows and safety. The object of this review is to address the question of whether there may indeed be a clinical use for cerebral PC and to discuss the deficiencies in our knowledge of PC that may hamper such clinical translation. PMID:20563278

  11. Iterated preconditioned LSQR method for inverse problems on unstructured grids

    NASA Astrophysics Data System (ADS)

    Arridge, S. R.; Betcke, M. M.; Harhanen, L.

    2014-06-01

    This article presents a method for solving large-scale linear inverse imaging problems regularized with a nonlinear, edge-preserving penalty term such as total variation or the Perona-Malik technique. Our method is aimed at problems defined on unstructured meshes, where such regularizers naturally arise in unfactorized form as a stiffness matrix of an anisotropic diffusion operator and factorization is prohibitively expensive. In the proposed scheme, the nonlinearity is handled with lagged diffusivity fixed point iteration, which involves solving a large-scale linear least squares problem in each iteration. Because the convergence of Krylov methods for problems with discontinuities is notoriously slow, we propose to accelerate it by means of priorconditioning (Bayesian preconditioning). priorconditioning is a technique that, through transformation to the standard form, embeds the information contained in the prior (Bayesian interpretation of a regularizer) directly into the forward operator and thence into the solution space. We derive a factorization-free preconditioned LSQR algorithm (MLSQR), allowing implicit application of the preconditioner through efficient schemes such as multigrid. The resulting method is also matrix-free i.e. the forward map can be defined through its action on a vector. We illustrate the performance of the method on two numerical examples. Simple 1D-deblurring problem serves to visualize the discussion throughout the paper. The effectiveness of the proposed numerical scheme is demonstrated on a three-dimensional problem in fluorescence diffuse optical tomography with total variation regularization derived algebraic multigrid preconditioner, which is the type of large scale, unstructured mesh problem, requiring matrix-free and factorization-free approaches that motivated the work here.

  12. Pharmacological preconditioning by diazoxide downregulates cardiac L-type Ca2+ channels

    PubMed Central

    González, G; Zaldívar, D; Carrillo, ED; Hernández, A; García, MC; Sánchez, JA

    2010-01-01

    BACKGROUND AND PURPOSE Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K+ (mitoKATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca2+ homeostasis during PPC, particularly changes in Ca2+ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca2+ channels. EXPERIMENTAL APPROACH PPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca2+ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the ?1c subunit of L-type channels in the cellular membrane were measured by Western blot. KEY RESULTS PPC was accompanied by a 50% reduction in ?1c subunit levels, and by a reversible fall in L-type current amplitude and Ca2+ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoKATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the ?1c subunit and Ca2+ channel function were prevented in part by the protease inhibitor leupeptin. CONCLUSIONS AND IMPLICATIONS PPC downregulated the ?1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca2+ channel, which in turn reduced Ca2+ influx, which may attenuate Ca2+ overload during reperfusion. PMID:20636393

  13. Hybrid preconditioning for iterative diagonalization of ill-conditioned generalized eigenvalue problems in electronic structure calculations

    SciTech Connect

    Cai, Yunfeng, E-mail: yfcai@math.pku.edu.cn [LMAM and School of Mathematical Sciences, Peking University, Beijing 100871 (China) [LMAM and School of Mathematical Sciences, Peking University, Beijing 100871 (China); Department of Computer Science, University of California, Davis 95616 (United States); Bai, Zhaojun, E-mail: bai@cs.ucdavis.edu [Department of Computer Science and Department of Mathematics, University of California, Davis 95616 (United States)] [Department of Computer Science and Department of Mathematics, University of California, Davis 95616 (United States); Pask, John E., E-mail: pask1@llnl.gov [Condensed Matter and Materials Division, Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Sukumar, N., E-mail: nsukumar@ucdavis.edu [Department of Civil and Environmental Engineering, University of California, Davis 95616 (United States)

    2013-12-15

    The iterative diagonalization of a sequence of large ill-conditioned generalized eigenvalue problems is a computational bottleneck in quantum mechanical methods employing a nonorthogonal basis for ab initio electronic structure calculations. We propose a hybrid preconditioning scheme to effectively combine global and locally accelerated preconditioners for rapid iterative diagonalization of such eigenvalue problems. In partition-of-unity finite-element (PUFE) pseudopotential density-functional calculations, employing a nonorthogonal basis, we show that the hybrid preconditioned block steepest descent method is a cost-effective eigensolver, outperforming current state-of-the-art global preconditioning schemes, and comparably efficient for the ill-conditioned generalized eigenvalue problems produced by PUFE as the locally optimal block preconditioned conjugate-gradient method for the well-conditioned standard eigenvalue problems produced by planewave methods.

  14. Preconditioning for Numerical Simulation of Low Mach Number Three-Dimensional Viscous Turbomachinery Flows

    NASA Technical Reports Server (NTRS)

    Tweedt, Daniel L.; Chima, Rodrick V.; Turkel, Eli

    1997-01-01

    A preconditioning scheme has been implemented into a three-dimensional viscous computational fluid dynamics code for turbomachine blade rows. The preconditioning allows the code, originally developed for simulating compressible flow fields, to be applied to nearly-incompressible, low Mach number flows. A brief description is given of the compressible Navier-Stokes equations for a rotating coordinate system, along with the preconditioning method employed. Details about the conservative formulation of artificial dissipation are provided, and different artificial dissipation schemes are discussed and compared. The preconditioned code was applied to a well-documented case involving the NASA large low-speed centrifugal compressor for which detailed experimental data are available for comparison. Performance and flow field data are compared for the near-design operating point of the compressor, with generally good agreement between computation and experiment. Further, significant differences between computational results for the different numerical implementations, revealing different levels of solution accuracy, are discussed.

  15. Preconditioned domain decomposition scheme for three-dimensional aerodynamic sensitivity analysis

    NASA Technical Reports Server (NTRS)

    Eleshaky, Mohammed E.; Baysal, Oktay

    1993-01-01

    A preconditioned domain decomposition scheme is introduced for the solution of the 3D aerodynamic sensitivity equation. This scheme uses the iterative GMRES procedure to solve the effective sensitivity equation of the boundary-interface cells in the sensitivity analysis domain-decomposition scheme. Excluding the dense matrices and the effect of cross terms between boundary-interfaces is found to produce an efficient preconditioning matrix.

  16. Rapid communication Genetic depletion of cardiac myocyte STAT3 abolishes classical preconditioning

    Microsoft Academic Search

    Robert M. Smith; Naushaad Suleman; Lydia Lacerda; Lionel H. Opie; Shizuo Akira; Kenneth R. Chien; Michael N. Sack

    Objective: To evaluate the functional requirement of signal transducer and activator of transcription-3 (STAT-3) in cardiac myocyte tolerance to ischemia (I) and in classical preconditioning. Methods: Cardiac myocyte STAT-3 was depleted in mice using Cre-lox p technology. Isolated cardiomyocytes from wild-type (WT) and STAT-3-deficient mice were evaluated for viability following simulated ischemia (SI; 26 h). Cardiomyocytes were then preconditioned by

  17. That Which Does Not Kill You Makes You Stronger: A Molecular Mechanism for Preconditioning

    NSDL National Science Digital Library

    Jonathan E. McDunn (Washington University School of Medicine; Cellular Injury and Adaptation Laboratory, Departments of Surgery and Genetics REV)

    2005-07-05

    Preconditioning by sublethal stress can protect a cell from subsequent injury and apoptosis through a mechanism that has been unclear. Many such stresses stimulate the formation of stress granules: transient cytoplasmic foci that contain heat shock protein as well as translationally stalled mRNA and various mRNA-binding proteins. Recent research suggests that sequestration in stress granules of TRAF2, an adaptor protein that is required for tumor necrosis factor receptor 1 signaling, may underlie preconditioning by sublethal stresses.

  18. Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats

    Microsoft Academic Search

    Petra Hartmann; Renáta Varga; Zsuzsanna Zobolyák; Júlia Héger; Blanka Cs?sz; István Németh; Zsolt Rázga; Csaba Vízler; Dénes Garab; Péter Sántha; Gábor Jancsó; Mihály Boros; Andrea Szabó

    2011-01-01

    We have shown that ischaemic preconditioning ameliorates both the local periosteal and the systemic leukocyte activation evoked\\u000a by limb ischaemia–reperfusion. We hypothesized that the activation of chemosensitive afferent nerves by transient ischaemia\\u000a contributes to the protective mechanisms of ischaemic preconditioning via a calcitonin gene-related peptide (CGRP)-dependent\\u000a mechanism. In Sprague–Dawley rats, 60-min complete limb ischaemia was followed by 180 min of reperfusion.

  19. Effect of cyclic preconditioning on the tensile properties of human quadriceps tendons and patellar ligaments

    Microsoft Academic Search

    L. Schatzmann; P. Brunner; H. U. Stäubli

    1998-01-01

    Preconditioning of soft tissues has become a common procedure in tensile testing to assess the history dependence of these viscoelastic materials. To our knowledge, this is the first study comparing tensile properties of soft tissues before and after cyclic preconditioning with high loads. Sixteen quadriceps tendon-bone (QT-B) complexes and 16 patellar ligament-bone (PL-B) complexes from a young population (mean age

  20. Development of Roe-type scheme for all-speed flows based on preconditioning method

    Microsoft Academic Search

    Xue-song Li; Chun-wei Gu; Jian-zhong Xu

    2009-01-01

    The problems of mixed low-speed\\/high-speed flows are not solved properly with existing compressible method. Based on preconditioning technology, a new scheme, All-Speed-Roe scheme, is proposed. Compared with Roe scheme, it decreases the effect of acoustic speed in its numerical dissipation when Mach numbers decrease. Compared with traditional preconditioned Roe scheme, it overcomes the limit of being cut-off by the global

  1. Thrombin Preconditioning Reduces Iron-Induced Brain Swelling and Brain Atrophy

    Microsoft Academic Search

    Shuijiang Song; Haitao Hu; Ya Hua; Jianan Wang; Guohua Xi

    \\u000a Cerebral preconditioning with a low dose of thrombin attenuates brain edema induced by intracerebral hemorrhage (ICH), a large\\u000a dose of thrombin or iron. This study examined whether or not thrombin preconditioning (TPC) reduces neuronal death and brain\\u000a atrophy caused by iron. The right hippocampus of rats was pretreated with or without thrombin, and iron was then injected\\u000a into the same

  2. Convergence Acceleration of the Navier-Stokes Equations Through Time-Derivative Preconditioning

    NASA Technical Reports Server (NTRS)

    Merkle, Charles L.; Venkateswaran, Sankaran; Deshpande, Manish

    1996-01-01

    Chorin's method of artificial compressibility is extended to both compressible and incompressible fluids by using physical arguments to define artificial fluid properties that make up a local preconditioning matrix. In particular, perturbation expansions are used to provide appropriate temporal derivatives for the equations of motion at both low speeds and low Reynolds numbers. These limiting forms are then combined into a single function that smoothly merges into the physical time derivatives at high speeds so that the equations are left unchanged at transonic, high Reynolds number conditions. The effectiveness of the resulting preconditioning procedures for the Navier-Stokes equations is demonstrated for a wide speed and Reynolds number ranges by means of stability results and computational solutions. Nevertheless, the preconditioned equations sometimes fail to provide a solution for applications for which the non-preconditioned equations converge. Often this is because the reduced dissipation in the preconditioned equations results in an unsteady solution while the more dissipative non-preconditioned equations result in a steady state. Problems of this type represent a computational challenge; it is important to distinguish between non-convergence of algorithms, and the non-existence of steady state solutions.

  3. Neuroprotective effect of ischemic preconditioning in focal cerebral infarction: relationship with upregulation of vascular endothelial growth factor

    PubMed Central

    Liu, Yong; Zhu, Suiqiang; Wang, Yunfu; Hu, Jingquan; Xu, Lili; Ding, Li; Liu, Guangjian

    2014-01-01

    Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic preconditioning in rats by simulating a transient ischemic attack twice (each a 20-minute occlusion of the middle cerebral artery) before inducing focal cerebral infarction (2 hour occlusion-reperfusion in the same artery). We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after occlusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascular endothelial growth factor. PMID:25206770

  4. Effects of the phlebotropic drug Daflon 500 mg on postischemic reperfusion injury in striated skin muscle: a histomorphologic study in the hamster.

    PubMed

    Pickelmann, S; Nolte, D; Leiderer, R; Möllmann, M; Schütze, E; Messmer, K

    1999-11-01

    The objective of this study was to investigate the effects of the purified, micronized, flavonoid fraction Daflon 500 mg (S 5682, 90% diosmin and 10% hesperidin) on tissue damage and leukocyte emigration in striated skin muscle after ischemia-reperfusion, as assessed by histomorphometric analysis. The experimental model used was the transparent dorsal skin fold chamber in the awake Syrian golden hamster. Sixty-four animals were randomly allotted to two treatment groups and time points of investigation. Animals were fed with 30 mg kg(-1) body weight Daflon 500 mg (n = 32) or its vehicle, 5% Arabic gum solution (n = 32), as control 8 hours before ischemia. Before induction of a tourniquet ischemia of 4 hours' duration and at 0.5, 2, and 24 hours of reperfusion, tissue sections were preserved for light and electron microscopic analysis (n = seven or eight animals per time point). The number of intravascular and extravascular leukocytes was determined by light microscopic analysis of esterase-positive leukocytes. For quantitative analysis of ischemia-induced endothelial cell damage, the endothelial thickness of capillaries was calculated by a computer-assisted imaging system, whereas the ischemic tissue damage was assessed by means of a score system (grade 0-3) by an independent investigator. The number of emigrated leukocytes was significantly reduced in Daflon 500 mg-treated animals compared with numbers found in control animals. The histomorphologic muscle fiber damage increased after reperfusion in both groups but was significantly reduced in the Daflon 500 mg-treated animals 2 and 24 hours after reperfusion. These results suggest that the emigration of leukocytes plays an important role in the development of postischemic reperfusion injury of striated skin muscle. PMID:10560948

  5. Isoflurane Preconditioning Confers Cardioprotection by Activation of ALDH2

    PubMed Central

    Lang, Xiao-E; Wang, Xiong; Zhang, Ke-Rang; Lv, Ji-Yuan; Jin, Jian-Hua; Li, Qing-Shan

    2013-01-01

    The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R) injury. Aldehyde dehydrogenase 2 (ALDH2) is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKC?) inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKC? inhibitor. Activation of ALDH2 by mitochondrial PKC? plays an important role in the cardioprotection of isoflurane in myocardium I/R injury. PMID:23468836

  6. Preconditioning of the Magnetosphere by Calms before the Storm

    NASA Astrophysics Data System (ADS)

    Borovsky, J. E.; Lavraud, B.; Denton, M. H.; Steinberg, J. T.

    2006-12-01

    Intervals of extreme geomagnetic calm occur just prior to 66% of all recurring high-speed-stream-driven storms and just prior to 38% of CME-driven storms. An interval of calm prior to the onset of a storm can precondition the magnetosphere, resulting in a change in the nature of the storm. We will focus on changes in the storms caused by the build up of a large plasmasphere and the build up of cool dense plasma sheet (CDPS) plasma in the magnetosphere. We argue that the built-up plasmasphere during the calm and the resulting plasmaspheric drainage plume during the storm leads to (1) mass loading of the dayside neutral line causing a reduction in solar-wind/magnetosphere coupling during the storm, (2) enhanced decay of the number density of relativistic electrons in the outer radiation belt prior to the storm, (3) a dumping of the outer electron radiation belt by the formation of a clumpy plasmaspheric drainage plume in the early phase of the storm, and (4) mass loading of convection in the inner magnetosphere. We argue that the build up of CDPS plasma in the magnetosphere during a calm provides a more efficient fuel for the production of ring current during the early phase of the storm.

  7. Remote ischemic preconditioning delays fatigue development during handgrip exercise.

    PubMed

    Barbosa, T C; Machado, A C; Braz, I D; Fernandes, I A; Vianna, L C; Nobrega, A C L; Silva, B M

    2015-06-01

    Ischemic preconditioning (IPC) of one or two limbs improves performance of exercise that recruits the same limb(s). However, it is unclear whether IPC application to another limb than that in exercise is also effective and which mechanisms are involved. We investigated the effect of remote IPC (RIPC) on muscle fatigue, time to task failure, forearm hemodynamics, and deoxygenation during handgrip exercise. Thirteen men underwent RIPC in the lower limbs or a control intervention (CON), in random order, and then performed a constant load rhythmic handgrip protocol until task failure. Rates of contraction and relaxation (?Force/?Time) were used as indices of fatigue. Brachial artery blood flow and conductance, besides forearm microvascular deoxygenation, were assessed during exercise. RIPC attenuated the slowing of contraction and relaxation throughout exercise (P??0.05). In conclusion, RIPC applied to the lower limbs delayed the development of fatigue during handgrip exercise, prolonged time to task failure, but was not accompanied by changes in forearm hemodynamics and deoxygenation. PMID:24731023

  8. Remote Limb Ischemic Preconditioning: A Neuroprotective Technique in Rodents.

    PubMed

    Brandli, Alice

    2015-01-01

    Sublethal ischemia protects tissues against subsequent, more severe ischemia through the upregulation of endogenous mechanisms in the affected tissue. Sublethal ischemia has also been shown to upregulate protective mechanisms in remote tissues. A brief period of ischemia (5-10 min) in the hind limb of mammals induces self-protective responses in the brain, lung, heart and retina. The effect is known as remote ischemic preconditioning (RIP). It is a therapeutically promising way of protecting vital organs, and is already under clinical trials for heart and brain injuries. This publication demonstrates a controlled, minimally invasive method of making a limb - specifically the hind limb of a rat - ischemic. A blood pressure cuff developed for use in human neonates is connected to a manual sphygmomanometer and used to apply 160 mmHg pressure around the upper part of the hind limb. A probe designed to detect skin temperature is used to verify the ischemia, by recording the drop in skin temperature caused by pressure-induced occlusion of the leg arteries, and the rise in temperature which follows release of the cuff. This method of RIP affords protection to the rat retina against bright light-induced damage and degeneration. PMID:26065365

  9. Positive Indian Ocean Dipole events precondition southeast Australia bushfires

    NASA Astrophysics Data System (ADS)

    Cai, W.; Cowan, T.; Raupach, M.

    2009-10-01

    The devastating “Black Saturday” bushfire inferno in the southeast Australian state of Victoria in early February 2009 and the “Ash Wednesday” bushfires in February 1983 were both preceded by a positive Indian Ocean Dipole (pIOD) event. Is there a systematic pIOD linkage beyond these two natural disasters? We show that out of 21 significant bushfires seasons since 1950, 11 were preceded by a pIOD. During Victoria's wet season, particularly spring, a pIOD contributes to lower rainfall and higher temperatures exacerbating the dry conditions and increasing the fuel load leading into summer. Consequently, pIODs are effective in preconditioning Victoria for bushfires, more so than El Niño events, as seen in the impact on soil moisture on interannual time scales and in multi-decadal changes since the 1950s. Given that the recent increase in pIOD occurrences is consistent with what is expected from global warming, an increased bushfire risk in the future is likely across southeast Australia.

  10. Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats.

    PubMed

    Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa

    2013-01-01

    Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-? levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity. PMID:22915786

  11. Comparison of in vitro preconditioning responses of isolated pig and rabbit cardiomyocytes: effects of a protein phosphatase inhibitor, fostriecin.

    PubMed

    Armstrong, S C; Kao, R; Gao, W; Shivell, L C; Downey, J M; Honkanen, R E; Ganote, C E

    1997-11-01

    Calcium tolerant pig and rabbit cardiomyocytes were isolated using retrograde aortic perfusion of nominally calcium-free collagenase. Preconditioning protocols used 1 or 3x10-min episodes of ischemic pelleting or pre-incubation with 100 micro M adenosine, followed by a 15-min post-incubation and 180-240-min ischemic pelleting. Control cells were incubated and washed in parallel with the experimental groups. Injury was assessed by determination of cell morphology, trypan blue permeability following osmotic swelling, lactate and HPLC analysis of adenine nucleotides. Preconditioned pig cardiomyocytes had a reduced rate of ischemic contracture, but protection occurred without conservation of ATP. Preconditioned rabbit cardiomyocytes were protected without significant changes in rates of ischemic contracture or ATP depletion. Incubation of ischemic cells with the protein phosphatase inhibitor, fostriecin, at PP2A-selective concentrations (0.1-10 micro M), mimicked preconditioning in both rabbit and pig cardiomyocytes. In rabbits, the KATP channel blocker, 5-hydroxydecanoate (5-HD), did not block preconditioning or fostriecin protection. In the pig, 5-HD blocked both preconditioning and fostriecin protection, with return of the rates of ischemic contracture to control. However, 5-HD was an effective blocker of protection only in early ischemia. Fostriecin mimicked preconditioning in the rabbit and the early responses of the preconditioned pig. Preconditioning appears associated with protein phosphorylation in both the rabbit and the pig, but major pathways leading to protection may differ in the two species. PMID:9405176

  12. Preconditioning diabetic mesenchymal stem cells with myogenic medium increases their ability to repair diabetic heart

    PubMed Central

    2013-01-01

    Introduction Mesenchymal stem cells (MSCs) have the potential for treatment of diabetic cardiomyopathy; however, the repair capability of MSCs declines with age and disease. MSCs from diabetic animals exhibit impaired survival, proliferation, and differentiation and therefore require a strategy to improve their function. The aim of the study was to develop a preconditioning strategy to augment the ability of MSCs from diabetes patients to repair the diabetic heart. Methods Diabetes was induced in C57BL/6 mice (6 to 8 weeks) with streptozotocin injections (55 mg/kg) for 5 consecutive days. MSCs isolated from diabetic animals were preconditioned with medium from cardiomyocytes exposed to oxidative stress and high glucose (HG/H-CCM). Results Gene expression of VEGF, ANG-1, GATA-4, NKx2.5 MEF2c, PCNA, and eNOS was upregulated after preconditioning with HG/H-CCM, as evidenced by reverse transcriptase/polymerase chain reaction (RT-PCR). Concurrently, increased AKT phosphorylation, proliferation, angiogenic ability, and reduced levels of apoptosis were observed in HG/H-CCM-preconditioned diabetic MSCs compared with nontreated controls. HG/H-CCM-preconditioned diabetic-mouse-derived MSCs (dmMSCs) were transplanted in diabetic animals and demonstrated increased homing concomitant with augmented heart function. Gene expression of angiogenic and cardiac markers was significantly upregulated in conjunction with paracrine factors (IGF-1, HGF, SDF-1, FGF-2) and, in addition, reduced fibrosis, apoptosis, and increased angiogenesis was observed in diabetic hearts 4 weeks after transplantation of preconditioned dmMSCs compared with hearts with nontreated diabetic MSCs. Conclusions Preconditioning with HG/H-CCM enhances survival, proliferation, and the angiogenic ability of dmMSCs, augmenting their ability to improve function in a diabetic heart. PMID:23706645

  13. Glycine transporters type 1 inhibitor promotes brain preconditioning against NMDA-induced excitotoxicity.

    PubMed

    Pinto, Mauro Cunha Xavier; Lima, Isabel Vieira de Assis; da Costa, Flávia Lage Pessoa; Rosa, Daniela Valadão; Mendes-Goulart, Vânia Aparecida; Resende, Rodrigo Ribeiro; Romano-Silva, Marco Aurélio; de Oliveira, Antônio Carlos Pinheiro; Gomez, Marcus Vinícius; Gomez, Renato Santiago

    2015-02-01

    Brain preconditioning is a protective mechanism, which can be activated by sub-lethal stimulation of the NMDA receptors (NMDAR) and be used to achieve neuroprotection against stroke and neurodegenerative diseases models. Inhibitors of glycine transporters type 1 modulate glutamatergic neurotransmission through NMDAR, suggesting an alternative therapeutic strategy of brain preconditioning. The aim of this work was to evaluate the effects of brain preconditioning induced by NFPS, a GlyT1 inhibitor, against NMDA-induced excitotoxicity in mice hippocampus, as well as to study its neurochemical mechanisms. C57BL/6 mice (male, 10-weeks-old) were preconditioned by intraperitoneal injection of NFPS at doses of 1.25, 2.5 or 5.0 mg/kg, 24 h before intrahippocampal injection of NMDA. Neuronal death was evaluated by fluoro jade C staining and neurochemical parameters were evaluated by gas chromatography-mass spectrometry, scintillation spectrometry and western blot. We observed that NFPS preconditioning reduced neuronal death in CA1 region of hippocampus submitted to NMDA-induced excitotoxicity. The amino acids (glycine and glutamate) uptake and content were increased in hippocampus of animals treated with NFPS 5.0 mg/kg, which were associated to an increased expression of type-2 glycine transporter (GlyT2) and glutamate transporters (EAAT1, EAAT2 and EAAT3). The expression of GlyT1 was reduced in animals treated with NFPS. Interestingly, the preconditioning reduced expression of GluN2B subunits of NMDAR, whereas did not change the expression of GluN1 or GluN2A in all tested doses. Our study suggests that NFPS preconditioning induces resistance against excitotoxicity, which is associated with neurochemical changes and reduction of GluN2B-containing NMDAR expression. PMID:25312280

  14. Lipopolysaccharide preconditioning facilitates M2 activation of resident microglia after spinal cord injury.

    PubMed

    Hayakawa, Kentaro; Okazaki, Rentaro; Morioka, Kazuhito; Nakamura, Kozo; Tanaka, Sakae; Ogata, Toru

    2014-12-01

    The inflammatory response following spinal cord injury (SCI) has both harmful and beneficial effects; however, it can be modulated for therapeutic benefit. Endotoxin/lipopolysaccharide (LPS) preconditioning, a well-established method for modifying the immune reaction, has been shown to attenuate damage induced by stroke and brain trauma in rodent models. Although such effects likely are conveyed by tissue-repairing functions of the inflammatory response, the mechanisms that control the effects have not yet been elucidated. The present study preconditioned C57BL6/J mice with 0.05 mg/kg of LPS 48 hr before inducing contusion SCI to investigate the effect of LPS preconditioning on the activation of macrophages/microglia. We found that LPS preconditioning promotes the polarization of M1/M2 macrophages/microglia toward an M2 phenotype in the injured spinal cord on quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analyses. Flow cytometric analyses reveal that LPS preconditioning facilitates M2 activation in resident microglia but not in infiltrating macrophages. Augmented M2 activation was accompanied by vascularization around the injured lesion, resulting in improvement in both tissue reorganization and functional recovery. Furthermore, we found that M2 activation induced by LPS preconditioning is regulated by interleukin-10 gene expression, which was preceded by the transcriptional activation of interferon regulatory factor (IRF)-3, as demonstrated by Western blotting and an IRF-3 binding assay. Altogether, our findings demonstrate that LPS preconditioning has a therapeutic effect on SCI through the modulation of M1/M2 polarization of resident microglia. The present study suggests that controlling M1/M2 polarization through endotoxin signal transduction could become a promising therapeutic strategy for various central nervous system diseases. © 2014 Wiley Periodicals, Inc. PMID:25044014

  15. Analysis of physics-based preconditioning for single-phase subchannel equations

    SciTech Connect

    Hansel, J. E.; Ragusa, J. C. [Department of Nuclear Engineering, Texas A and M University, College Station, TX 77840 (United States); Allu, S.; Berrill, M. A.; Clarno, K. T. [Oak Ridge National Laboratory, 1 Bethel Valley Rd, Oak Ridge, TN 37831 (United States)

    2013-07-01

    The (single-phase) subchannel approximations are used throughout nuclear engineering to provide an efficient flow simulation because the computational burden is much smaller than for computational fluid dynamics (CFD) simulations, and empirical relations have been developed and validated to provide accurate solutions in appropriate flow regimes. Here, the subchannel equations have been recast in a residual form suitable for a multi-physics framework. The Eigen spectrum of the Jacobian matrix, along with several potential physics-based preconditioning approaches, are evaluated, and the the potential for improved convergence from preconditioning is assessed. The physics-based preconditioner options include several forms of reduced equations that decouple the subchannels by neglecting crossflow, conduction, and/or both turbulent momentum and energy exchange between subchannels. Eigen-scopy analysis shows that preconditioning moves clusters of eigenvalues away from zero and toward one. A test problem is run with and without preconditioning. Without preconditioning, the solution failed to converge using GMRES, but application of any of the preconditioners allowed the solution to converge. (authors)

  16. Oleanolic Acid Enhances the Beneficial Effects of Preconditioning on PC12 Cells

    PubMed Central

    Daniels, Willie M. U.; Mabandla, Musa V.

    2014-01-01

    Preconditioning triggers endogenous protection against subsequent exposure to higher concentrations of a neurotoxin. In this study, we investigated whether exposure to oleanolic acid (OA) enhances the protective effects of preconditioning on PC12 cells exposed to 6-hydroxydopamine (6-OHDA). A concentration response curve was constructed using 6-OHDA (50, 150, 300, and 600??M). The experiment consisted of 6 groups: untreated, OA only, Group 1: cells treated with 6-OHDA (50??M) for 1 hour, Group 2: cells treated with 6-OHDA (150??M) for 1 hour, Group 3: cells treated with 6-OHDA (50??M) for 30 minutes followed 6 hours later by treatment with 6-OHDA (150??M) for 30 minutes, and Group 4: cells treated as in group 3 but also received OA immediately after the second 6-OHDA treatment. Cell viability and apoptotic ratio were assessed using the MTT and Annexin V staining tests, respectively. In preconditioned cells, we found that cell viability remained high following exposure to 6-OHDA (150??M). OA treatment enhanced the protective effects of preconditioning. Similarly, with the annexin V apoptosis test, preconditioning protected the cell and this was enhanced by OA. Therefore, preexposure of PC12 cells to low 6-OHDA concentration can protect against subsequent toxic insults of 6-OHDA and OA enhances this protection. PMID:25478286

  17. Super-low Dose Endotoxin Pre-conditioning Exacerbates Sepsis Mortality

    PubMed Central

    Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu

    2015-01-01

    Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditioning with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in contrast to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks. PMID:26029736

  18. Enhanced cell volume regulation: a key mechanism in local and remote ischemic preconditioning.

    PubMed

    Diaz, Roberto J; Harvey, Kordan; Boloorchi, Azadeh; Hossain, Taneya; Hinek, Alina; Backx, Peter H; Wilson, Gregory J

    2014-06-15

    We have previously shown that ischemic preconditioning (IPC) protection against necrosis in whole hearts and in both fresh and cultured cardiomyocytes, as well as the improved regulatory volume decrease to hypoosmotic swelling in cardiomyocytes, is abrogated through Cl(-) channel blockade, pointing to a role for enhanced cell volume regulation in IPC. To further define this cardioprotective mechanism, cultured rabbit ventricular cardiomyocytes were preconditioned either by 10-min simulated ischemia (SI) followed by 10-min simulated reperfusion (SR), by 10-min exposure/10-min washout of remote IPC (rIPC) plasma dialysate (from rabbits subjected to repetitive limb ischemia), or by adenoviral transfection with the constitutively active PKC-? gene. These interventions were done before cardiomyocytes were subjected to either 60- or 75-min SI/60-min SR to assess cell necrosis (by trypan blue staining), 30-min SI to assess ischemic cell swelling, or 30-min hypoosmotic (200 mosM) stress to assess cell volume regulation. Necrosis after SI/SR and both SI- and hypoosmotic stress-induced swelling was reduced in preconditioned cardiomyocytes compared with control cardiomyocytes (neither preconditioned nor transfected). These effects on necrosis and cell swelling were blocked by either Cl(-) channel blockade or dominant negative knockdown of inwardly rectifying K(+) channels with adenoviruses, suggesting that Cl(-) and K(+) movements across the sarcolemma are critical for cell volume regulation and, thereby, cell survival under hypoxic/ischemic conditions. Our results define enhanced cell volume regulation as a key common mechanism of cardioprotection by preconditioning in cardiomyocytes. PMID:24760980

  19. Postischemic Long-Term Treatment with Qiangli Tianma Duzhong Capsule Improves Brain Functional Recovery via the Improvement of Hemorrheology and the Inhibition of Platelet Aggregation in a Rat Model of Focal Cerebral Ischemia

    PubMed Central

    Hong, Li-Zhi; Gu, Wei-wei; Ni, Yong; Xu, Min; Yang, Lei; Liu, Yan-Li; Yang, Shi-Ling; Zhou, Qiang; Gao, Xiu-Mei; Zhang, Hui-Ling

    2013-01-01

    Qiangli Tianma Duzhong capsule (TMDZ), a Chinese herbal drug, is clinically used to improve functional outcome in patients with ischemic stroke in China. This study was conducted to establish whether postischemic long-term treatment with TMDZ could reduce the loss of injured hemisphere and confer the improvements of neurological outcome in chronic survival of rats with 2?h middle cerebral artery occlusion (MCAO)/reperfusion brain injury and its primary mechanisms. We found that TMDZ (44.5, 89, or 178?mg/kg), administered per os 6?h after the onset of ischemia and for 28 consecutive days, significantly improved the behavior deficits, beginning on day 7, and further improved later. TMDZ treatment also markedly reduced the tissue loss of the injured hemisphere and improved histopathology. In the meantime, TMDZ treatment could improve hemorrheology and inhibit platelet aggregation. These results provide the first evidence that post-ischemic long-term treatment with TMDZ confers the improvements of neurological outcome and the loss of injured hemisphere in an animal ischemic stroke model, and its mechanisms might be associated with the improvements of hemorrheology and the inhibition of platelet aggregation. PMID:24319485

  20. Postischemic Long-Term Treatment with Qiangli Tianma Duzhong Capsule Improves Brain Functional Recovery via the Improvement of Hemorrheology and the Inhibition of Platelet Aggregation in a Rat Model of Focal Cerebral Ischemia.

    PubMed

    Hong, Li-Zhi; Gu, Wei-Wei; Ni, Yong; Xu, Min; Yang, Lei; Liu, Yan-Li; Yang, Shi-Ling; Zhou, Qiang; Gao, Xiu-Mei; Zhang, Hui-Ling

    2013-01-01

    Qiangli Tianma Duzhong capsule (TMDZ), a Chinese herbal drug, is clinically used to improve functional outcome in patients with ischemic stroke in China. This study was conducted to establish whether postischemic long-term treatment with TMDZ could reduce the loss of injured hemisphere and confer the improvements of neurological outcome in chronic survival of rats with 2?h middle cerebral artery occlusion (MCAO)/reperfusion brain injury and its primary mechanisms. We found that TMDZ (44.5, 89, or 178?mg/kg), administered per os 6?h after the onset of ischemia and for 28 consecutive days, significantly improved the behavior deficits, beginning on day 7, and further improved later. TMDZ treatment also markedly reduced the tissue loss of the injured hemisphere and improved histopathology. In the meantime, TMDZ treatment could improve hemorrheology and inhibit platelet aggregation. These results provide the first evidence that post-ischemic long-term treatment with TMDZ confers the improvements of neurological outcome and the loss of injured hemisphere in an animal ischemic stroke model, and its mechanisms might be associated with the improvements of hemorrheology and the inhibition of platelet aggregation. PMID:24319485

  1. An overview of NSPCG: A nonsymmetric preconditioned conjugate gradient package

    NASA Astrophysics Data System (ADS)

    Oppe, Thomas C.; Joubert, Wayne D.; Kincaid, David R.

    1989-05-01

    The most recent research-oriented software package developed as part of the ITPACK Project is called "NSPCG" since it contains many nonsymmetric preconditioned conjugate gradient procedures. It is designed to solve large sparse systems of linear algebraic equations by a variety of different iterative methods. One of the main purposes for the development of the package is to provide a common modular structure for research on iterative methods for nonsymmetric matrices. Another purpose for the development of the package is to investigate the suitability of several iterative methods for vector computers. Since the vectorizability of an iterative method depends greatly on the matrix structure, NSPCG allows great flexibility in the operator representation. The coefficient matrix can be passed in one of several different matrix data storage schemes. These sparse data formats allow matrices with a wide range of structures from highly structured ones such as those with all nonzeros along a relatively small number of diagonals to completely unstructured sparse matrices. Alternatively, the package allows the user to call the accelerators directly with user-supplied routines for performing certain matrix operations. In this case, one can use the data format from an application program and not be required to copy the matrix into one of the package formats. This is particularly advantageous when memory space is limited. Some of the basic preconditioners that are available are point methods such as Jacobi, Incomplete LU Decomposition and Symmetric Successive Overrelaxation as well as block and multicolor preconditioners. The user can select from a large collection of accelerators such as Conjugate Gradient (CG), Chebyshev (SI, for semi-iterative), Generalized Minimal Residual (GMRES), Biconjugate Gradient Squared (BCGS) and many others. The package is modular so that almost any accelerator can be used with almost any preconditioner.

  2. Limb ischemic preconditioning attenuates cerebral ischemic injury in rat model.

    PubMed

    Wang, W; Yu, X D; Mo, X; Zhang, H B; Zhu, D M

    2014-05-01

    Ischemic brain injury is not uncommon after open-heart surgery with cardiopulmonary bypass and seriously undermines the patients' life quality. Therefore, potential protective effects of limb ischemic preconditioning (LIP) on subsequent ischemic injury of the brain were investigated by evaluating anti-inflammatory effects and apoptosis of pyramidal neurons in the CA1 hippocampus. One hundred and eight Sprague-Dawley rats were divided into the middle cerebral artery occlusion (MCAO) group (n=54) and the LIP group (n=54). A thread was used to occlude the middle cerebral artery in the MCAO group and the LIP group animals were pretreated with LIP followed by MCAO. In the two groups, nine samples were collected at each time-point of 0, 6, 12, 24, 48 and 72 h after MCAO to detect IL-6 and IL-17 and their mRNA levels. Neurological severity scores (NSS) were examined before the animals were sacrificed. Compared with the LIP group, cerebral histopathological changes in the MCAO group were most distinct and significantly more infiltrated inflammatory and apoptotic neuronal cells were observed at 24, 48 and 72 h post-surgery. IL-17 and IL-6 mRNA levels analyzed by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR) were significantly reduced in the LIP group compared with the MCAO group at the 12, 24 and 48 h time-points. A significant reduction in IL-17 expression level was determined by enzyme-linked immunosorbent assay (ELISA) in the LIP group at 12, 24 and 48 h, while IL-6 was significantly reduced at the 24 and 48 h time-points. The NSSs were not significantly different between the groups. Therefore, in a MCAO rat model, we have proved that LIP pretreatment can protect the brain from infarction after ischemic injury and induce ischemic tolerance, potentially, by reducing IL-17 to provide anti-inflammatory effects and attenuate apoptosis of hippocampal neuronal cells. PMID:24002779

  3. Simulation of conformational preconditioning strategies for electrophoretic stretching of DNA in a microcontraction

    PubMed Central

    Hsieh, Chih-Chen; Lin, Tsung-Hsien

    2011-01-01

    We have used Brownian dynamics-finite element method to examine two conformational preconditioning approaches for improving DNA stretching in a microcontraction for the purpose of direct gene analysis. The newly proposed “pre-stretching” strategy is found to significantly improve the degree of DNA extension at the exit of the contraction. On the other hand, applying an oscillating extensional field to DNA yields no preconditioning effect. Detailed analysis of the evolution of DNA extension and conformation reveals that the success of our “pre-stretching” strategy relies on the “non-local” effect that cannot be predicted using simple kinematics analysis. In other words, accurate prediction can only be obtained using detailed simulations. Comparing to the existing preconditioning strategies, our “pre-stretching” method is easy to implement while still providing a very good performance. We hope that the insight gained from this study can be useful for future design of biomicrofluidic devices for DNA manipulation. PMID:22662058

  4. Novel Genes Critical for Hypoxic Preconditioning in Zebrafish Are Regulators of Insulin and Glucose Metabolism

    PubMed Central

    Manchenkov, Tania; Pasillas, Martina P.; Haddad, Gabriel G.; Imam, Farhad B.

    2015-01-01

    Severe hypoxia is a common cause of major brain, heart, and kidney injury in adults, children, and newborns. However, mild hypoxia can be protective against later, more severe hypoxia exposure via “hypoxic preconditioning,” a phenomenon that is not yet fully understood. Accordingly, we have established and optimized an embryonic zebrafish model to study hypoxic preconditioning. Using a functional genomic approach, we used this zebrafish model to identify and validate five novel hypoxia-protective genes, including irs2, crtc3, and camk2g2, which have been previously implicated in metabolic regulation. These results extend our understanding of the mechanisms of hypoxic preconditioning and affirm the discovery potential of this novel vertebrate hypoxic stress model. PMID:25840431

  5. Incomplete Gaussian elimination as a preconditioning for generalized conjugate gradient acceleration

    SciTech Connect

    Wallis, J.R.

    1983-11-01

    This paper discusses the application of preconditioned generalized conjugate gradient acceleration to fully implicit thermal simulation. The preconditioning step utilizes incomplete Gaussian elimination (IGE) to form an approximate factorization of the Jacobian matrix. IGE preconditioning and its implementation is discussed with respect to five, seven, nine or eleven-point finite difference approximations and optional well constraint equations. Numerical results were obtained using a thermal model allowing any number N/SUB c/ of components. The model's implicit formulation requires the solution of a linear system of equations in which each grid block has N /SUB c/ + 1 unknowns. Test problems involved combustion, steam drive and cyclic steam stimulation processes, some of which exhibited ill-conditioning, negative transmissabilities and high transmissability ratios. Numerical results indicate how different grid block orderings, different levels of incomplete factorization and different acceleration procedures affect convergence, storage and work requirements.

  6. Peri-operative anaesthetic myocardial preconditioning and protection - cellular mechanisms and clinical relevance in cardiac anaesthesia.

    PubMed

    Kunst, G; Klein, A A

    2015-04-01

    Preconditioning has been shown to reduce myocardial damage caused by ischaemia-reperfusion injury peri-operatively. Volatile anaesthetic agents have the potential to provide myocardial protection by anaesthetic preconditioning and, in addition, they also mediate renal and cerebral protection. A number of proof-of-concept trials have confirmed that the experimental evidence can be translated into clinical practice with regard to postoperative markers of myocardial injury; however, this effect has not been ubiquitous. The clinical trials published to date have also been too small to investigate clinical outcome and mortality. Data from recent meta-analyses in cardiac anaesthesia are also not conclusive regarding intra-operative volatile anaesthesia. These inconclusive clinical results have led to great variability currently in the type of anaesthetic agent used during cardiac surgery. This review summarises experimentally proposed mechanisms of anaesthetic preconditioning, and assesses randomised controlled clinical trials in cardiac anaesthesia that have been aimed at translating experimental results into the clinical setting. PMID:25764404

  7. Efficient Multi-Stage Time Marching for Viscous Flows via Local Preconditioning

    NASA Technical Reports Server (NTRS)

    Kleb, William L.; Wood, William A.; vanLeer, Bram

    1999-01-01

    A new method has been developed to accelerate the convergence of explicit time-marching, laminar, Navier-Stokes codes through the combination of local preconditioning and multi-stage time marching optimization. Local preconditioning is a technique to modify the time-dependent equations so that all information moves or decays at nearly the same rate, thus relieving the stiffness for a system of equations. Multi-stage time marching can be optimized by modifying its coefficients to account for the presence of viscous terms, allowing larger time steps. We show it is possible to optimize the time marching scheme for a wide range of cell Reynolds numbers for the scalar advection-diffusion equation, and local preconditioning allows this optimization to be applied to the Navier-Stokes equations. Convergence acceleration of the new method is demonstrated through numerical experiments with circular advection and laminar boundary-layer flow over a flat plate.

  8. Exogenous low dose hydrogen peroxide increases hypoxia-inducible factor-1alpha protein expression and induces preconditioning protection against ischemia in primary cortical neurons

    Microsoft Academic Search

    Shengjun Chang; Xiangning Jiang; Chong Zhao; Christina Lee; Donna M. Ferriero

    2008-01-01

    HIF-1 is believed to play a critical role in hypoxia\\/ischemia (H\\/I) preconditioning protection in neonatal brain. Recently, it has been shown that hydrogen peroxide (H2O2) may contribute to H\\/I preconditioning in rat primary neurons. We hypothesize that H2O2 produced during H\\/I preconditioning may increase HIF-1? protein expression and contribute to H\\/I preconditioning protection in the immature brain. To test this

  9. The role of Tregs and CD11c(+) macrophages/dendritic cells in ischemic preconditioning of the kidney.

    PubMed

    Cho, Won Yong; Choi, Hye Min; Lee, So Young; Kim, Myung Gyu; Kim, Hyoung-Kyu; Jo, Sang-Kyung

    2010-11-01

    Dendritic cells have the potential to induce tolerance and here we attempted to identify their role in the tolerance seen in ischemic pre-conditioning. We induced bilateral renal ischemic preconditioning in mice and then challenged them with an ischemic insult 7 days later. Compared to sham-operated controls, preconditioned mice were found to have reduced injury with less inflammation, but had an increased number of regulatory T cells (Tregs) in their kidneys after the delayed insult. Splenocytes from these mice had more Tregs and mature CD11c(+) cells, but reduced proliferative and cytokine-secretory responses, suggesting a state of immunosuppression compared to control mice. Anti-CD25 depletion followed by adoptive transfer of Tregs partially mitigated and then restored the protective effect of preconditioning. Depletion of CD11c(+) cells with liposomes containing clodronate was associated with partial loss of preconditioning benefits. The increased numbers of Tregs or impaired immune response found in splenocytes from preconditioned mice were partially reversed in splenocytes from liposome clodronate-treated animals, suggesting that CD11c(+) cells contribute to immune cell-mediated ischemic preconditioning. Hence, our results show that ischemic preconditioning of the kidney provides a negative signal to the peripheral immune system, partially mediating the tissue-protective and anti-inflammatory effects of this maneuver. PMID:20686446

  10. The Role of SUMO-Conjugating Enzyme Ubc9 in the Neuroprotection of Isoflurane Preconditioning Against Ischemic Neuronal Injury.

    PubMed

    Tong, Li; Wu, Zhixin; Ran, Mingzi; Chen, Yu; Yang, Lujia; Zhang, Haopeng; Zhang, Lina; Dong, Hailong; Xiong, Lize

    2015-06-01

    Preconditioning with volatile anesthetics can create an ischemia tolerance against cerebral ischemia-reperfusion injury. We investigated whether ubiquitin conjugase 9 (Ubc9), the E2 conjugase for SUMOylation, is associated with neuroprotection induced by isoflurane preconditioning (IsoPC). In vitro, Ubc9 protein expression was evaluated at 4 and 24 h after reoxygenation. The role of Ubc9 in the neuroprotective effect was assessed in the presence or absence of Ubc9 small interfering RNA (siRNA). In vivo, rats were preconditionally exposed for 1 h to 2 % isoflurane for five consecutive days followed by middle cerebral artery occlusion. Neurobehavioral scores and infarction volume were determined at different times after reperfusion. The role of Ubc9 in ischemic tolerance was evaluated by intracerebroventricular microinjection with the Ubc9 siRNA. We showed that isoflurane preconditioning improved the cell viability of the SH-SY5Y cells that were challenged by oxygen-glucose deprivation. It also reduced brain infarct volumes and improved neurologic outcomes in the focal cerebral ischemic rat. The expression of Ubc9 was upregulated by isoflurane preconditioning. Knockdown of Ubc9 significantly attenuated the isoflurane preconditioning-induced neuroprotective effects. Isoflurane preconditioning-induced neuroprotection against ischemic injuries is mediated by Ubc9. These results suggest a novel mechanism for isoflurane preconditioning-induced tolerance to cerebral ischemia. PMID:24961570

  11. Mechanical preconditioning enables electrophysiologic coupling of skeletal myoblast cells to myocardium

    PubMed Central

    Treskes, Philipp; Cowan, Douglas B.; Stamm, Christof; Rubach, Martin; Adelmann, Roland; Wittwer, Thorsten; Wahlers, Thorsten

    2015-01-01

    Objective The effect of mechanical preconditioning on skeletal myoblasts in engineered tissue constructs was investigated to resolve issues associated with conduction block between skeletal myoblast cells and cardiomyocytes. Methods Murine skeletal myoblasts were used to generate engineered tissue constructs with or without application of mechanical strain. After in vitro myotube formation, engineered tissue constructs were co-cultured for 6 days with viable embryonic heart slices. With the use of sharp electrodes, electrical coupling between engineered tissue constructs and embryonic heart slices was assessed in the presence or absence of pharmacologic agents. Results The isolation and expansion procedure for skeletal myoblasts resulted in high yields of homogeneously desmin-positive (97.1% ± 0.1%) cells. Mechanical strain was exerted on myotubes within engineered tissue constructs during gelation of the matrix, generating preconditioned engineered tissue constructs. Electrical coupling between preconditioned engineered tissue constructs and embryonic heart slices was observed; however, no coupling was apparent when engineered tissue constructs were not subjected to mechanical strain. Coupling of cells from engineered tissue constructs to cells in embryonic heart slices showed slower conduction velocities than myocardial cells with the embryonic heart slices (preconditioned engineered tissue constructs vs embryonic heart slices: 0.04 ± 0.02 ms vs 0.10 ± 0.05 ms, P = .011), lower stimulation frequencies (preconditioned engineered tissue constructs vs maximum embryonic heart slices: 4.82 ± 1.42 Hz vs 10.58 ± 1.56 Hz; P = .0009), and higher sensitivities to the gap junction inhibitor (preconditioned engineered tissue constructs vs embryonic heart slices: 0.22 ± 0.07 mmol/L vs 0.93 ± 0.15 mmol/L; P = .0004). Conclusions We have generated skeletal myoblast–based transplantable grafts that electrically couple to myocardium. PMID:22980065

  12. Fluid Shear Stress Pre-Conditioning Promotes Endothelial Morphogenesis of Embryonic Stem Cells Within Embryoid Bodies

    PubMed Central

    Nsiah, Barbara A.; Ahsan, Tabassum; Griffiths, Sarah; Cooke, Marissa; Nerem, Robert M.

    2014-01-01

    Pluripotent embryonic stem cells (ESCs) are capable of differentiating into all mesoderm-derived cell lineages, including endothelial, hematopoietic, and cardiac cell types. Common strategies to direct mesoderm differentiation of ESCs rely on exposing the cells to a series of biochemical and biophysical cues at different stages of differentiation to promote maturation toward specific cell phenotypes. Shear forces that mimic cardiovascular physiological forces can evoke a myriad of responses in somatic and stem cell populations, and have, thus, been studied as a means to direct stem cell differentiation. However, elucidating the effects of shear pre-conditioning on the subsequent vascular differentiation and morphogenesis of ESCs has yet to be examined. In this study, ESC monolayers were subjected to physiological shear (5?dyn/cm2) or static conditions for 2 days on collagen IV-coated substrates before initiating embryoid body (EB) differentiation. Immediately after the pre-conditioning period, shear pre-conditioned and statically cultured ESCs exhibited similar morphologies and largely retained a pluripotent phenotype; however, ESCs exposed to fluid shear expressed increased levels of endothelial marker genes Flk-1 (?3-fold), VE-cadherin (?3-fold), and PECAM (?2-fold), compared with statically cultured ESCs. After 7 days of EB culture, ?70% of EBs formed from shear pre-conditioned ESCs expressed significantly higher levels of endothelial marker genes compared with EBs formed from statically cultured ESCs. Interestingly, unlike EBs formed from statically cultured ESCs, EBs formed from fluid shear stress pre-conditioned ESCs exhibited a centrally localized region of VE-cadherin+ cells that persisted for at least 10 days of differentiation. These results demonstrate that fluid shear stress pre-conditioning not only promotes ESC endothelial gene expression but also subsequently impacts the organization of endothelial cells within EBs. Together, these studies highlight a novel approach to promote in vitro morphogenesis of developmental vasculogenic models and potentially promote pre-vascularization of tissue-engineered constructs derived from pluripotent stem cells. PMID:24138406

  13. Ischemic Preconditioning Targets the Respiration of Synaptic Mitochondria via Protein Kinase C?

    PubMed Central

    Dave, Kunjan R.; DeFazio, R. Anthony; Raval, Ami P.; Torraco, Alessandra; Saul, Isabel; Barrientos, Antoni; Perez-Pinzon, Miguel A.

    2008-01-01

    In the brain, ischemic preconditioning (IPC) diminishes mitochondrial dysfunction after ischemia and confers neuroprotection. Activation of ? protein kinase C (?PKC) has been proposed to be a key neuroprotective pathway during IPC. We tested the hypothesis that IPC increases the levels of ?PKC in synaptosomes from rat hippocampus, resulting in improved synaptic mitochondrial respiration. Preconditioning significantly increased the level of hippocampal synaptosomal ?PKC to 152% of sham-operated animals at 2 d of reperfusion, the time of peak neuroprotection. We tested the effect of ?PKC activation on hippocampal synaptic mitochondrial respiration 2 d after preconditioning. Treatment with the specific ?PKC activating peptide, tat-??RACK (tat-??-receptor for activated C kinase), increased the rate of oxygen consumption in the presence of substrates for complexes I, II, and IV to 157, 153, and 131% of control (tat peptide alone). In parallel, we found that ?PKC activation in synaptosomes from preconditioned animals resulted in altered levels of phosphorylated mitochondrial respiratory chain proteins: increased serine and tyrosine phosphorylation of 18 kDa subunit of complex I, decreased serine phosphorylation of FeS protein in complex III, increased threonine phosphorylation of COX IV (cytochrome oxidase IV), increased mitochondrial membrane potential, and decreased H2O2 production. In brief, ischemic preconditioning promoted significant increases in the level of synaptosomal ?PKC. Activation of ?PKC increased synaptosomal mitochondrial respiration and phosphorylation of mitochondrial respiratory chain proteins. We propose that, at 48 h of reperfusion after ischemic preconditioning, ?PKC is poised at synaptic mitochondria to respond to ischemia either by direct phosphorylation or activation of the ?PKC signaling pathway. PMID:18417696

  14. Cyclooxygenase-2 Mediates Hyperbaric Oxygen Preconditioning in the Rat Model of Transient Global Cerebral Ischemia

    PubMed Central

    Cheng, Oumei; Ostrowski, Robert P.; Wu, Bihua; Liu, Wenwu; Chen, Chunhua; Zhang, John H.

    2010-01-01

    Background and Purpose Hyperbaric oxygen preconditioning (HBO-PC) affords brain protection against transient global ischemia. In the present study we hypothesize that the mechanism of HBO-PC involves the induction of cyclooxygenase-2 (COX-2) in cerebral tissues prior to ischemia, which leads to a suppression of COX-2 and its downstream targets after global ischemic insult. Methods One hundred twenty nine male Sprague Dawley (SD) rats (280–300g body weight) were allocated to the naïve control group, sham operation group, three groups of animals subjected to 15 min four-vessel occlusion (4VO): untreated, preconditioned with HBO 2.5 atmospheres absolutes (ATA) for 1 hour daily for 5 days, preconditioned as above and administered with COX-2 inhibitor, NS-398 (1 mg/kg bw i.p.) prior to each preconditioning session, as well as normal rats preconditioned with HBO without ischemia. The mortality, the incidence of seizures and T-maze scores were recorded. The quantitative cell count in Nissl stain and TUNEL was conducted on day 7 after ischemia. The brain expression of COX-2 was analyzed with Western blotting and immunofluorescence staining. Results HBO-PC increased the number of surviving neurons in the CA1, which was associated with the reduced COX-2 expression in the hippocampus and in the cerebral cortex at 1 and 3 days post-ischemia. HBO-PC improved functional performance and tended to decrease mortality and the frequency of seizures. These beneficial effects of HBO-PC were abolished by the COX-2 selective inhibitor, NS-398. Conclusions HBO-PC reduced COX-2 expression and provided brain protection after global ischemia. Administration of COX-2 inhibitor with HBO prior to ischemia, abolished preconditioning effect, thereby implicating COX-2 as a mediator of HBO-PC in the ischemic brain. PMID:21164135

  15. Preconditioned methods for solving the incompressible and low speed compressible equations

    NASA Technical Reports Server (NTRS)

    Turkel, E.

    1986-01-01

    Acceleration methods are presented for solving the steady state incompressible equations. These systems are preconditioned by introducing artificial time derivatives which allow for a faster convergence to the steady state. The compressible equations in conservation form with slow flow are also considered. Two arbitrary functions, alpha and beta, are introduced in the general preconditioning. An analysis of this system is presented and an optimal value for beta is determined given a constant, alpha. It is further shown that the resultant incompressible equations form a symmetric hyperbolic system and so are well posed. Several generalizations to the compressible equations are presented which generalize previous results.

  16. Preconditioning electromyographic data for an upper extremity model using neural networks

    NASA Technical Reports Server (NTRS)

    Roberson, D. J.; Fernjallah, M.; Barr, R. E.; Gonzalez, R. V.

    1994-01-01

    A back propagation neural network has been employed to precondition the electromyographic signal (EMG) that drives a computational model of the human upper extremity. This model is used to determine the complex relationship between EMG and muscle activation, and generates an optimal muscle activation scheme that simulates the actual activation. While the experimental and model predicted results of the ballistic muscle movement are very similar, the activation function between the start and the finish is not. This neural network preconditions the signal in an attempt to more closely model the actual activation function over the entire course of the muscle movement.

  17. Preconditioned Bi-conjugate Gradient Method for Radiative Transfer in Spherical Media

    NASA Astrophysics Data System (ADS)

    Anusha, L. S.; Nagendra, K. N.; Paletou, F.; Léger, L.

    2009-10-01

    A robust numerical method called the Preconditioned Bi-Conjugate Gradient (Pre-BiCG) method is proposed for the solution of the radiative transfer equation in spherical geometry. A variant of this method called Stabilized Preconditioned Bi-Conjugate Gradient (Pre-BiCG-STAB) is also presented. These are iterative methods based on the construction of a set of bi-orthogonal vectors. The application of the Pre-BiCG method in some benchmark tests shows that the method is quite versatile, and can handle difficult problems that may arise in astrophysical radiative transfer theory.

  18. Using Chebyshev polynomials and approximate inverse triangular factorizations for preconditioning the conjugate gradient method

    NASA Astrophysics Data System (ADS)

    Kaporin, I. E.

    2012-02-01

    In order to precondition a sparse symmetric positive definite matrix, its approximate inverse is examined, which is represented as the product of two sparse mutually adjoint triangular matrices. In this way, the solution of the corresponding system of linear algebraic equations (SLAE) by applying the preconditioned conjugate gradient method (CGM) is reduced to performing only elementary vector operations and calculating sparse matrix-vector products. A method for constructing the above preconditioner is described and analyzed. The triangular factor has a fixed sparsity pattern and is optimal in the sense that the preconditioned matrix has a minimum K-condition number. The use of polynomial preconditioning based on Chebyshev polynomials makes it possible to considerably reduce the amount of scalar product operations (at the cost of an insignificant increase in the total number of arithmetic operations). The possibility of an efficient massively parallel implementation of the resulting method for solving SLAEs is discussed. For a sequential version of this method, the results obtained by solving 56 test problems from the Florida sparse matrix collection (which are large-scale and ill-conditioned) are presented. These results show that the method is highly reliable and has low computational costs.

  19. A preconditioned Krylov subspace approach to a tightly coupled aeromechanical system

    NASA Astrophysics Data System (ADS)

    Kilpatrick, Kevin Larry

    A tightly coupled approach is attempted to compute a modest fluid-structure interaction for high subsonic flow through a converging nozzle with deformable walls. A globally convergent Newton statement and a matrix-free GMRES linear equation solver are used to linearize and solve the coupled system of equations without explicitly forming the left hand side jacobian matrix associated with the Newton method. A variable forcing function term is successfully incorporated into the Newton statement to balance inner (linear) and outer (nonlinear) iterations. The fluid-structure system is solved for comparison purposes using a loosely coupled approach. Residual convergence stagnated in the tightly coupled system approach but converged successfully in the loosely coupled approach using the same coding for domain calculations. A novel approach using time derivative preconditioning is incorporated to speed convergence of the GMRES linear equation solver. No algebraic preconditioning is used. The fluid flow equations showed significant improvements using the time derivative preconditioning method but the error term generated in the structural equations overwhelmed the physical solution increment. The Taylor Weak Statement derivation of the finite element form of the fluid flow equations with time derivative preconditioning shows a strong connection to the Streamwise Upwind Petrov Galerkin (SUPG) method. This connection is exploited to develop a theoretical basis for the damping term and the time scale parameter common to the SUPG method.

  20. Increased Hypoxic Tolerance by Chemical Inhibition of Oxidative Phosphorylation: “Chemical Preconditioning

    Microsoft Academic Search

    M. W. Riepe; F. Esclaire; K. Kasischke; S. Schreiber; H. Nakase; O. Kempski; A. C. Ludolph; U. Dirnagl; J. Hugon

    1997-01-01

    A short ischemic episode preceding sustained ischemia is known to increase tolerance against ischemic cell death. We report early-onset long-lasting neuroprotection against in vitro hypoxia by preceding selective chemical inhibition of oxidative phosphorylation: “chemical preconditioning.” The amplitude of CA1 population spikes (psap) in hippocampal slices prepared from control animals (control slices) was 31 ± 27% (mean ± SD) upon 45-min

  1. An M-step preconditioned conjugate gradient method for parallel computation

    NASA Technical Reports Server (NTRS)

    Adams, L.

    1983-01-01

    This paper describes a preconditioned conjugate gradient method that can be effectively implemented on both vector machines and parallel arrays to solve sparse symmetric and positive definite systems of linear equations. The implementation on the CYBER 203/205 and on the Finite Element Machine is discussed and results obtained using the method on these machines are given.

  2. Eigenmode Analysis of Boundary Conditions for the One-Dimensional Preconditioned Euler Equations

    Microsoft Academic Search

    David L. Darmofal; Pierre Moinier; Michael B. Giles

    2000-01-01

    The effect of local preconditioning on boundary conditions is analyzed for the subsonic, one-dimensional Euler equations. Decay rates for the eigenmodes of the initial boundary value problem are determined for different boundary conditions and different preconditioners whose intent is to accelerate low Mach number computations. Riemann invariant boundary conditions based on the unpreconditioned Euler equations are shown to be reflective

  3. AN ODYSSEY INTO LOCAL REFINEMENT AND MULTILEVEL PRECONDITIONING III: IMPLEMENTATION AND NUMERICAL

    E-print Network

    implementations are performed in both C and MATLAB using the Finite Element ToolKit (FEtk), an open source finite words. finite element methods, local mesh refinement, multilevel preconditioning, BPX, red and red element software package. We finish the paper with a sequence of numerical experiments illustrating

  4. Combustion of coal\\/water mixtures with thermal preconditioning. Final report

    Microsoft Academic Search

    M. Novack; G. Roffe; G. Miller

    1985-01-01

    Thermal preconditioning is a process in which coal\\/water mixtures are vaporized to produce coal\\/steam suspensions, and then superheated to allow the coal to devolatilize producing suspensions of char particles in hydrocarbon gases and steam. This final product of the process can be injected without atomization, and burned directly in a gas turbine combustor. This paper reports on the results of

  5. A Preconditioned Newton-Krylov Method for Computing Stationary Pulse Solutions of Mode-locked Lasers

    E-print Network

    Polz, Martin

    -locked Lasers Jonathan R. Birge and Franz X. Kärtner Research Laboratory of Electronics and Department-locked laser cavity using a preconditioned matrix-implicit Newton-Krylov solver. Solutions are obtained two: (000.4430) Numerical approximation and analysis; (320.7090) Ultrafast lasers 1. Overview The effective

  6. Progress Toward a Stabilization and Preconditioning Protocol for Polycrystalline Thin-Film Photovoltaic Modules

    SciTech Connect

    del Cueto, J. A.; Deline, C. A.; Rummel, S. R.; Anderberg, A.

    2010-08-01

    Cadmium telluride (CdTe) and copper indium gallium diselenide (CIGS) thin-film photovoltaic (PV) modules can exhibit substantial variation in measured performance depending on prior exposure history. This study examines the metastable performance changes in these PV modules with the goal of establishing standard preconditioning or stabilization exposure procedures to mitigate measured variations prior to current-voltage (IV) measurements.

  7. CaMeL: Learning Method Preconditions for HTN Planning Okhtay Ilghami and Dana S. Nau

    E-print Network

    Nau, Dana S.

    CaMeL: Learning Method Preconditions for HTN Planning Okhtay Ilghami and Dana S. Nau Department, and a supervised learning algorithm, named CaMeL, based on this formalism. We present theo- retical results about CaMeL's soundness, completeness, and convergence properties. We also report experimental results

  8. How to Heat Up From the Cold: Examining the Preconditions for (Unconscious) Mood Effects

    Microsoft Academic Search

    Kirsten I. Ruys; Diederik A. Stapel

    2008-01-01

    What are the necessary preconditions to make people feel good or bad? In this research, the authors aimed to uncover the bare essentials of mood induction. Several induction techniques exist, and most of these techniques demand a relatively high amount of cognitive capacity. Moreover, to be effective, most techniques require conscious awareness. The authors proposed that the common and defining

  9. Project: (version of January 17, 2012) Preconditioned Boundary Element Methods for Electromagnetic

    E-print Network

    Hiptmair, Ralf

    Project: (version of January 17, 2012) Preconditioned Boundary Element Methods for Electromagnetic in September 2008 The project targets the scattering of time-harmonic electromagnetic waves at dielectric materials with different electromagnetic properties. The goal is to design fast numerical simulation methods

  10. Algebraic Multigrid Methods and Preconditioned Conjugate Gradient Algorithm for Lattice Block Materials Models

    Microsoft Academic Search

    Shi Shu; Ivo Babuska; Jinchao Xu; Yingxiong Xiao; Ludmil Zikatanovk

    In this paper, we construct and analyze a block preconditioned conjugate gradient(BPCG) method and a class of algebraic multigrid(AMG) methods ap- plied to the discrete mathematical models for lattice block materials. Numerical experiments show that the constructed AMG methods converge uniformly with respect to the size of problem and also to some crucial parameters. Such a uni- form convergence of

  11. Restoration of rocky slopes based on planted gabions and use of drought-preconditioned woody species

    Microsoft Academic Search

    Barbara Beikircher; Florin Florineth; Stefan Mayr

    2010-01-01

    The restoration of steep rock faces with shrubs and trees is difficult due to extreme microclimatic and edaphic conditions. In this study, we tested the applicability of free-standing planted gabions to improve the landscape and achieve protection against rockfall, erosion and enhanced surface flow. Furthermore, we analyzed the effect of preconditioning on drought tolerance of several planted species (Ligustrum vulgare,

  12. Metacognition and metarepresentation: Is a self-directed theory of mind a precondition for metacognition?

    E-print Network

    Paris-Sud XI, Université de

    effort, in particular those that are regulated by explicit self reference. An interesting and debated1 1 Metacognition and metarepresentation: Is a self-directed theory of mind a precondition will be able to attain some cognitive goal (learn new material, retrieve a proper name within seconds, or make

  13. Cognitive Preconditions of Early Reading and Spelling: A Latent-Variable Approach with Longitudinal Data

    ERIC Educational Resources Information Center

    Preßler, Anna-Lena; Könen, Tanja; Hasselhorn, Marcus; Krajewski, Kristin

    2014-01-01

    The aim of the present study was to empirically disentangle the interdependencies of the impact of nonverbal intelligence, working memory capacities, and phonological processing skills on early reading decoding and spelling within a latent variable approach. In a sample of 127 children, these cognitive preconditions were assessed before the onset…

  14. Metaphors and the market: Consequences and preconditions of agent and object metaphors in stock market commentary

    E-print Network

    Qian, Ning

    ; Attribution; Prediction; Media; Trajectory Much recent research has sought clues about market behavior research takes this approach by focusing on metaphor in market commentary. We use the term ``metaphorMetaphors and the market: Consequences and preconditions of agent and object metaphors in stock

  15. Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart.

    PubMed

    Cai, Zheqing; Luo, Weibo; Zhan, Huiwang; Semenza, Gregg L

    2013-10-22

    Both preclinical and clinical studies suggest that brief cycles of ischemia and reperfusion in the arm or leg may protect the heart against injury following prolonged coronary artery occlusion and reperfusion, a phenomenon known as remote ischemic preconditioning. Recent studies in mice indicate that increased plasma interleukin-10 (IL-10) levels play an important role in remote ischemic preconditioning induced by clamping the femoral artery for 5 min followed by 5 min of reperfusion for a total of three cycles. In this study, we demonstrate that remote ischemic preconditioning increases plasma IL-10 levels and decreases myocardial infarct size in wild-type mice but not in littermates that are heterozygous for a knockout allele at the locus encoding hypoxia-inducible factor (HIF) 1?. Injection of a recombinant adenovirus encoding a constitutively active form of HIF-1? into mouse hind limb muscle was sufficient to increase plasma IL-10 levels and decrease myocardial infarct size. Exposure of C2C12 mouse myocytes to cyclic hypoxia and reoxygenation rapidly increased levels of IL-10 mRNA, which was blocked by administration of the HIF-1 inhibitor acriflavine or by expression of short hairpin RNA targeting HIF-1? or HIF-1?. Chromatin immunoprecipitation assays demonstrated that binding of HIF-1 to the Il10 gene was induced when myocytes were subjected to cyclic hypoxia and reoxygenation. Taken together, these data indicate that HIF-1 activates Il10 gene transcription and is required for remote ischemic preconditioning. PMID:24101519

  16. Renalase contributes to the renal protection of delayed ischaemic preconditioning via the regulation of hypoxia-inducible factor-1?

    PubMed Central

    Wang, Feng; Zhang, Guangyuan; Xing, Tao; Lu, Zeyuan; Li, Junhui; Peng, Cheng; Liu, Guohua; Wang, Niansong

    2015-01-01

    Ischaemic preconditioning (IPC) attenuates acute kidney injury (AKI) from renal ischaemia reperfusion. Renalase, an amine oxidase secreted by the proximal tubule, not only degrades circulating catecholamines but also protects against renal ischaemia reperfusion injury. Here, it has been suggested that the renoprotective effect of renal IPC is partly mediated by renalase. In a model of brief intermittent renal IPC, the increased cortex renalase expression was found to last for 48 hrs. IPC significantly reduced renal tubular inflammation, necrosis and oxidative stress following renal ischaemia reperfusion injury. Such effects were attenuated by blocking renalase with an anti-renalase monoclonal antibody. We further demonstrated that renalase expression was up-regulated by hypoxia in vitro via an hypoxia-inducible factor (HIF)-1? mechanism. The IPC-induced up-regulation of renalase in vivo was also reduced by pre-treatment with an HIF-1? inhibitor, 3-(5?-Hydroxymethyl-2?-furyl)-1-benzyl indazole. In summary, the renoprotective effect of IPC is partly dependent on the renalase expression, which may be triggered by hypoxia via an HIF-1? mechanism. Endogenous renalase shows potential as a therapeutic agent for the prevention and treatment of AKI. PMID:25781495

  17. Alpha 1-adrenoceptor activation mediates the infarct size-limiting effect of ischemic preconditioning through augmentation of 5'-nucleotidase activity.

    PubMed Central

    Kitakaze, M; Hori, M; Morioka, T; Minamino, T; Takashima, S; Sato, H; Shinozaki, Y; Chujo, M; Mori, H; Inoue, M

    1994-01-01

    We have reported that ischemic preconditioning may limit infarct size by increasing 5'-nucleotidase activity. The present study tested whether alpha 1-adrenoceptor stimulation in ischemic preconditioning mediates the infarct size-limiting effect through augmentation of 5'-nucleotidase activity. The coronary artery was occluded four times for 5 min separated by 5 min of reperfusion (ischemic preconditioning) in 82 dogs. Then the coronary artery was occluded for 90 min followed by 6 h of reperfusion. Infarct size normalized by risk area was smaller after ischemic preconditioning than in the control group (40.6 +/- 2.3 vs 6.7 +/- 2.0%, P < 0.001), even though no difference existed in endomyocardial collateral flow during ischemia (8.7 +/- 1.0 vs 8.9 +/- 1.0 ml/100 g per min). Ectosolic and cytosolic 5'-nucleotidase activity was increased after ischemic preconditioning. However, prazosin blunted the infarct size-limiting effect of ischemic preconditioning (infarct size: 42.8 +/- 3.7%). Intermittent alpha 1-adrenoceptor stimulation by methoxamine mimicked the increase in 5'-nucleotidase activity and the infarct size-limiting effect, which were abolished by alpha, beta,-methyleneadenosine 5'-diphosphate. Identical results were obtained in the conscious model (n = 20). Therefore, we conclude that increases in ectosolic 5'-nucleotidase activity due to alpha 1-adrenoceptor activation may contribute to the infarct size-limiting effect of ischemic preconditioning. Images PMID:8182151

  18. AMP-activated protein kinase (AMPK)-induced preconditioning in primary cortical neurons involves activation of MCL-1.

    PubMed

    Anilkumar, Ujval; Weisová, Petronela; Düssmann, Heiko; Concannon, Caoimhín G; König, Hans-Georg; Prehn, Jochen H M

    2013-03-01

    Neuronal preconditioning is a phenomenon where a previous exposure to a sub-lethal stress stimulus increases the resistance of neurons towards a second, normally lethal stress stimulus. Activation of the energy stress sensor, AMP-activated protein kinase (AMPK) has been shown to contribute to the protective effects of ischaemic and mitochondrial uncoupling-induced preconditioning in neurons, however, the molecular basis of AMPK-mediated preconditioning has been less well characterized. We investigated the effect of AMPK preconditioning using 5-aminoimidazole-4-carboxamide riboside (AICAR) in a model of NMDA-mediated excitotoxic injury in primary mouse cortical neurons. Activation of AMPK with low concentrations of AICAR (0.1 mM for 2 h) induced a transient increase in AMPK phosphorylation, protecting neurons against NMDA-induced excitotoxicity. Analysing potential targets of AMPK activation, demonstrated a marked increase in mRNA expression and protein levels of the anti-apoptotic BCL-2 family protein myeloid cell leukaemia sequence 1 (MCL-1) in AICAR-preconditioned neurons. Interestingly, over-expression of MCL-1 protected neurons against NMDA-induced excitotoxicity while MCL-1 gene silencing abolished the effect of AICAR preconditioning. Monitored intracellular Ca²? levels during NMDA excitation revealed that MCL-1 over-expressing neurons exhibited improved bioenergetics and markedly reduced Ca²? elevations, suggesting a potential mechanism through which MCL-1 confers neuroprotection. This study identifies MCL-1 as a key effector of AMPK-induced preconditioning in neurons. PMID:23199202

  19. Preconditioning’ with Low Dose Lipopolysaccharide Aggravates the Organ Injury / Dysfunction Caused by Hemorrhagic Shock in Rats

    PubMed Central

    Sordi, Regina; Chiazza, Fausto; Patel, Nimesh S. A.; Doyle, Rachel A.; Collino, Massimo; Thiemermann, Christoph

    2015-01-01

    Methods Male rats were ‘pretreated’ with phosphate-buffered saline (PBS; i.p.) or LPS (1 mg/kg; i.p.) 24 h prior to HS. Mean arterial pressure (MAP) was maintained at 30 ± 2 mmHg for 90 min or until 25% of the shed blood had to be re-injected to sustain MAP. This was followed by resuscitation with the remaining shed blood. Four hours after resuscitation, parameters of organ dysfunction and systemic inflammation were assessed. Results HS resulted in renal dysfunction, and liver and muscular injury. At a first glance, LPS preconditioning attenuated organ dysfunction. However, we discovered that HS-rats that had been preconditioned with LPS (a) were not able to sustain a MAP at 30 mmHg for more than 50 min and (b) the volume of blood withdrawn in these animals was significantly less than in the PBS-control group. This effect was associated with an enhanced formation of the nitric oxide (NO) derived from inducible NO synthase (iNOS). Thus, a further control group in which all animals were resuscitated after 50 min of hemorrhage was performed. Then, LPS preconditioning aggravated both circulatory failure and organ dysfunction. Most notably, HS-rats pretreated with LPS exhibited a dramatic increase in NF-?B activation and pro-inflammatory cytokines. Conclusion In conclusion, LPS preconditioning predisposed animals to an earlier vascular decompensation, which may be mediated by an excess of NO production secondary to induction of iNOS and activation of NF-?B. Moreover, LPS preconditioning increased the formation of pro-inflammatory cytokines, which is likely to have contributed to the observed aggravation of organ injury/dysfunction caused by HS. PMID:25830444

  20. Adenosine A1 receptor activation modulates N-methyl-d-aspartate (NMDA) preconditioning phenotype in the brain.

    PubMed

    Constantino, Leandra C; Pamplona, Fabrício A; Matheus, Filipe C; Ludka, Fabiana K; Gomez-Soler, Maricel; Ciruela, Francisco; Boeck, Carina R; Prediger, Rui D; Tasca, Carla I

    2015-04-01

    N-methyl-d-aspartate (NMDA) preconditioning is induced by subtoxic doses of NMDA and it promotes a transient state of resistance against subsequent lethal insults. Interestingly, this mechanism of neuroprotection depends on adenosine A1 receptors (A1R), since blockade of A1R precludes this phenomenon. In this study we evaluated the consequences of NMDA preconditioning on the hippocampal A1R biology (i.e. expression, binding properties and functionality). Accordingly, we measured A1R expression in NMDA preconditioned mice (75mg/kg, i.p.; 24h) and showed that neither the total amount of receptor, nor the A1R levels in the synaptic fraction was altered. In addition, the A1R binding affinity to the antagonist [(3)H] DPCPX was slightly increased in total membrane extracts of hippocampus from preconditioned mice. Next, we evaluated the impact of NMDA preconditioning on A1R functioning by measuring the A1R-mediated regulation of glutamate uptake into hippocampal slices and on behavioral responses in the open field and hot plate tests. NMDA preconditioning increased glutamate uptake into hippocampal slices without altering the expression of glutamate transporter GLT-1. Interestingly, NMDA preconditioning also induced antinociception in the hot plate test and both effects were reversed by post-activation of A1R with the agonist CCPA (0.2mg/kg, i.p.). NMDA preconditioning or A1R modulation did not alter locomotor activity in the open field. Overall, the results described herein provide new evidence that post-activation of A1R modulates NMDA preconditioning-mediated responses, pointing to the importance of the cross-talk between glutamatergic and adenosinergic systems to neuroprotection. PMID:25557798

  1. Protection against acetaminophen-induced liver injury by allopurinol is dependent on aldehyde oxidase-mediated liver preconditioning

    SciTech Connect

    Williams, C. David; McGill, Mitchell R.; Lebofsky, Margitta; Bajt, Mary Lynn; Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu

    2014-02-01

    Acetaminophen (APAP) overdose causes severe and occasionally fatal liver injury. Numerous drugs that attenuate APAP toxicity have been described. However these compounds frequently protect by cytochrome P450 inhibition, thereby preventing the initiating step of toxicity. We have previously shown that pretreatment with allopurinol can effectively protect against APAP toxicity, but the mechanism remains unclear. In the current study, C3HeB/FeJ mice were administered allopurinol 18 h or 1 h prior to an APAP overdose. Administration of allopurinol 18 h prior to APAP overdose resulted in an 88% reduction in liver injury (serum ALT) 6 h after APAP; however, 1 h pretreatment offered no protection. APAP-cysteine adducts and glutathione depletion kinetics were similar with or without allopurinol pretreatment. The phosphorylation and mitochondrial translocation of c-jun-N-terminal-kinase (JNK) have been implicated in the progression of APAP toxicity. In our study we showed equivalent early JNK activation (2 h) however late JNK activation (6 h) was attenuated in allopurinol treated mice, which suggests that later JNK activation is more critical for the toxicity. Additional mice were administered oxypurinol (primary metabolite of allopurinol) 18 h or 1 h pre-APAP, but neither treatment protected. This finding implicated an aldehyde oxidase (AO)-mediated metabolism of allopurinol, so mice were treated with hydralazine to inhibit AO prior to allopurinol/APAP administration, which eliminated the protective effects of allopurinol. We evaluated potential targets of AO-mediated preconditioning and found increased hepatic metallothionein 18 h post-allopurinol. These data show metabolism of allopurinol occurring independent of P450 isoenzymes preconditions the liver and renders the animal less susceptible to an APAP overdose. - Highlights: • 18 h allopurinol pretreatment protects against acetaminophen-induced liver injury. • 1 h allopurinol pretreatment does not protect from APAP-induced injury. • 18 h or 1 h oxypurinol pretreatment does not alter APAP-induced injury. • Inhibiting aldehyde oxidase eliminates protection from 18 h allopurinol pretreatment. • 18 h allopurinol induces metallothionein which protects the liver against APAP injury.

  2. S{sub 2}SA preconditioning for the S{sub n} equations with strictly non negative spatial discretization

    SciTech Connect

    Bruss, D. E.; Morel, J. E.; Ragusa, J. C. [Department of Nuclear Engineering, Texas A and M University, 3133 TAMU, College Station, TX 77843-3133 (United States)

    2013-07-01

    Preconditioners based upon sweeps and diffusion-synthetic acceleration have been constructed and applied to the zeroth and first spatial moments of the 1-D S{sub n} transport equation using a strictly non negative nonlinear spatial closure. Linear and nonlinear preconditioners have been analyzed. The effectiveness of various combinations of these preconditioners are compared. In one dimension, nonlinear sweep preconditioning is shown to be superior to linear sweep preconditioning, and DSA preconditioning using nonlinear sweeps in conjunction with a linear diffusion equation is found to be essentially equivalent to nonlinear sweeps in conjunction with a nonlinear diffusion equation. The ability to use a linear diffusion equation has important implications for preconditioning the S{sub n} equations with a strictly non negative spatial discretization in multiple dimensions. (authors)

  3. A preconditioned Newton-Krylov method for computing steady-state pulse solutions of mode-locked lasers

    E-print Network

    Birge, Jonathan R. (Jonathan Richards)

    2008-01-01

    We solve the periodic boundary value problem for a mode-locked laser cavity using a specially preconditioned matrix-implicit Newton-Krylov solver. Solutions are obtained at least an order of magnitude faster than with ...

  4. Remote renal preconditioning-induced cardioprotection: a key role of hypoxia inducible factor-prolyl 4-hydroxylases

    Microsoft Academic Search

    Ravi Kant; Vishal Diwan; Amteshwar Singh Jaggi; Nirmal Singh; Dhandeep Singh

    2008-01-01

    Remote preconditioning is a unique phenomenon in which brief episodes of ischemia and reperfusion to remote organ protect\\u000a the target organ against sustained ischemia–reperfusion (I\\/R)-induced injury. Protective effects of remote renal preconditioning\\u000a (RRPC) are well established in heart, but their mechanisms still remain to be elucidated. So, the present study was designed\\u000a to investigate the possible role of oxygen-sensing hypoxia

  5. Endothelial preconditioning by transient oxidative stress reduces inflammatory responses of cultured endothelial cells to TNF-a

    Microsoft Academic Search

    STEFAN ZAHLER; CHRISTIAN KUPATT; BERNHARD F. BECKER

    Brief episodes of ischemia can render an organ resistant to subsequent severe ischemia. This 'ischemic preconditioning' is ascribed to vari- ous mechanisms, including oxidative stress. We in- vestigated whether preconditioning exists on an en- dothelial level. Human umbilical vein endothelial cells (HUVECs) were transiently confronted with oxidative stress (1 mM H2O2, 5 min). Adhesion molecules ICAM-1 and E-selectin and release

  6. Hypoxic preconditioning induces stroke tolerance in mice via a cascading HIF, sphingosine kinase, and CCL2 signaling pathway

    PubMed Central

    Wacker, Bradley K.; Perfater, Jennifer L.; Gidday, Jeffrey M.

    2012-01-01

    The induction of ischemic tolerance by preconditioning provides a platform to elucidate endogenous mechanisms of stroke protection. In these studies, we characterize the relationship between hypoxia-inducible factor (HIF), sphingosine kinase 2 (SphK2), and CCL2 in models of hypoxic or pharmacological preconditioning-induced ischemic tolerance. A genetics-based approach using SphK2- and CCL2-null mice showed both SphK2 and CCL2 to be necessary for the induction of ischemic tolerance following preconditioning with hypoxia, the hypoxia-mimetic cobalt chloride, or the sphingosine-1-phosphate (S1P) agonist FTY720. A pharmacologic approach confirmed the necessity of HIF signaling for all three preconditioning stimuli, and showed the SphK/S1P pathway to transduce tolerance via the S1P1 receptor. Additionally, our data suggest significant cross-talk between HIF and SphK2-produced S1P signaling, which together act to upregulate CCL2 expression. Overall, HIF, SphK, S1P, and CCL2 participate in a signaling cascade to induce the gene expression responsible for the stroke-tolerant phenotype established by hypoxic and FTY720 preconditioning. The identification of these common molecular mediators involved in signaling the genomic response to multiple preconditioning stimuli provides several targets for therapeutic manipulation. PMID:23043544

  7. Activation of Nrf2-Regulated Glutathione Pathway Genes by Ischemic Preconditioning

    PubMed Central

    Bell, Karen F. S.; Fowler, Jill H.; Al-Mubarak, Bashayer; Horsburgh, Karen; Hardingham, Giles E.

    2011-01-01

    Prophylactic pharmacological activation of astrocytic gene expression driven by the transcription factor Nrf2 boosts antioxidant defences and protects against neuronal loss in ischemia and other disease models. However, the role of Nrf2 in mediating endogenous neuroprotective responses is less clear. We recently showed that Nrf2 is activated by mild oxidative stress in both rodent and human astrocytes. Moreover, brief exposure to ischemic conditions was found to activate Nrf2 both in vivo and in vitro, and this was found to contribute to neuroprotective ischemic preconditioning. Here we show that transient ischemic conditions in vitro and in vivo cause an increase in the expression of Nrf2 target genes associated with the glutathione pathway, including those involved in glutathione biosynthesis and cystine uptake. Taken together, these studies indicate that astrocytic Nrf2 may represent an important mediator of endogenous neuroprotective preconditioning pathways. PMID:21904646

  8. On linearization and preconditioning for radiation diffusion coupled to material thermal conduction equations

    SciTech Connect

    Feng, Tao, E-mail: fengtao2@mail.ustc.edu.cn [School of Mathematical Sciences, University of Science and Technology of China, Hefei 230052 (China) [School of Mathematical Sciences, University of Science and Technology of China, Hefei 230052 (China); Graduate School of China Academy Engineering Physics, Beijing 100083 (China); An, Hengbin, E-mail: an_hengbin@iapcm.ac.cn [National Key Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing 100094 (China)] [National Key Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing 100094 (China); Yu, Xijun, E-mail: yuxj@iapcm.ac.cn [National Key Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing 100094 (China)] [National Key Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing 100094 (China); Li, Qin, E-mail: liqin@lsec.cc.ac.cn [Chinese Academy of Mathematics and Systems Science, Beijing 100190 (China)] [Chinese Academy of Mathematics and Systems Science, Beijing 100190 (China); Zhang, Rongpei, E-mail: zhangrongpei@163.com [Graduate School of China Academy Engineering Physics, Beijing 100083 (China)] [Graduate School of China Academy Engineering Physics, Beijing 100083 (China)

    2013-03-01

    Jacobian-free Newton–Krylov (JFNK) method is an effective algorithm for solving large scale nonlinear equations. One of the most important advantages of JFNK method is that there is no necessity to form and store the Jacobian matrix of the nonlinear system when JFNK method is employed. However, an approximation of the Jacobian is needed for the purpose of preconditioning. In this paper, JFNK method is employed to solve a class of non-equilibrium radiation diffusion coupled to material thermal conduction equations, and two preconditioners are designed by linearizing the equations in two methods. Numerical results show that the two preconditioning methods can improve the convergence behavior and efficiency of JFNK method.

  9. Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice

    PubMed Central

    Mirrione, Martine M.; Konomos, Dorothy K.; Gravanis, Iordanis; Dewey, Stephen L.; Aguzzi, Adriano; Heppner, Frank L.; Tsirka, Stella E.

    2010-01-01

    Activated microglia have been associated with neurodegeneration in patients and in animal models of Temporal Lobe Epilepsy (TLE), however their precise functions as neurotoxic or neuroprotective is a topic of significant investigation. To explore this, we examined the effects of pilocarpine induced seizures in transgenic mice where microglia/macrophages were conditionally ablated. We found that unilateral ablation of microglia from the dorsal hippocampus did not alter acute seizure sensitivity. However, when this procedure was coupled with lipopolysaccharide (LPS) preconditioning (1 mg/kg given 24 hours prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activation in the ipsilateral hippocampus during acute seizures, and could be attributed to activity in the mossy fiber pathway. These findings reveal that preconditioning with LPS 24 hours prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation. PMID:20382223

  10. A Note on Substructuring Preconditioning for Nonconforming Finite Element Approximations of Second Order Elliptic Problems

    NASA Technical Reports Server (NTRS)

    Maliassov, Serguei

    1996-01-01

    In this paper an algebraic substructuring preconditioner is considered for nonconforming finite element approximations of second order elliptic problems in 3D domains with a piecewise constant diffusion coefficient. Using a substructuring idea and a block Gauss elimination, part of the unknowns is eliminated and the Schur complement obtained is preconditioned by a spectrally equivalent very sparse matrix. In the case of quasiuniform tetrahedral mesh an appropriate algebraic multigrid solver can be used to solve the problem with this matrix. Explicit estimates of condition numbers and implementation algorithms are established for the constructed preconditioner. It is shown that the condition number of the preconditioned matrix does not depend on either the mesh step size or the jump of the coefficient. Finally, numerical experiments are presented to illustrate the theory being developed.

  11. A comparison of element-by-element preconditioned iterative methods for solid and structural mechanics

    SciTech Connect

    Ferencz, R.M.

    1988-10-01

    Past work with element-by-element (EBE) preconditioned conjugate gradient iterative solution strategies has shown these techniques can be effective for large-scale, three-dimensional calculations in solid and structural mechanics. Significant gains over the profile storage direct solution method traditionally used in implicit finite element codes have been observed for a variety of real engineering analyses, especially in solid mechanics. Structural mechanics applications have proved less successful due to the ill-conditioned linear systems engendered by standard structural discretizations. This lack of robustness has recently motivated reconsideration of Lanczos-based algorithms as alternative iterative drivers. In this paper we compare the relative strengths of the conjugate gradient and Lanczos drivers when coupled with EBE preconditioning. The performance of the two methods is characterized, and compared with direct solution, using a model problem and a number of real engineering meshes. 26 refs., 14 figs., 2 tabs.

  12. Bradykinin preconditioning modulates aquaporin-4 expression after spinal cord ischemic injury in rats

    Microsoft Academic Search

    Xu Wei-bing; Gu Yan-ting; Wang Yan-feng; Lu Xu-hua; Jia Lian-shun; Lv Gang

    2008-01-01

    The study investigated whether bradykinin (BK) preconditioning could regulate the expression of aquaporin-4 (AQP4) using an in vivo transient spinal cord ischemia model in rats. BK was infused continuously via the left femoral artery with infusion pump for 15 min (10 µg\\/kg\\/min) then we induced ischemia for 20 min and reperfusion for 24 and 72 h respectively. The results demonstrated that the central part

  13. Novel Cellular Mechanisms for Neuroprotection in Ischemic Preconditioning: A View from Inside Organelles

    PubMed Central

    Sisalli, Maria Josè; Annunziato, Lucio; Scorziello, Antonella

    2015-01-01

    Ischemic preconditioning represents an important adaptation mechanism of CNS, which results in its increased tolerance to the lethal cerebral ischemia. The molecular mechanisms responsible for the induction and maintenance of ischemic tolerance in the brain are complex and not yet completely clarified. In the last 10?years, great attention has been devoted to unravel the intracellular pathways activated by preconditioning and responsible for the establishing of the tolerant phenotype. Indeed, recent papers have been published supporting the hypothesis that mitochondria might act as master regulators of preconditioning-triggered endogenous neuroprotection due to their ability to control cytosolic calcium homeostasis. More interestingly, the demonstration that functional alterations in the ability of mitochondria and endoplasmic reticulum (ER) managing calcium homeostasis during ischemia, opened a new line of research focused to the role played by mitochondria and ER cross-talk in the pathogenesis of cerebral ischemia in order to identify new molecular mechanisms involved in the ischemic tolerance. In line with these findings and considering that the expression of the three isoforms of the sodium calcium exchanger (NCX), NCX1, NCX2, and NCX3, mainly responsible for the regulation of Ca2+ homeostasis, was reduced during cerebral ischemia, it was investigated whether these proteins might play a role in neuroprotection induced by ischemic tolerance. In this review, evidence supporting the involvement of ER and mitochondria interaction within the preconditioning paradigm will be provided. In particular, the key role played by NCXs in the regulation of Ca2+-homeostasis at the different subcellular compartments will be discussed as new molecular mechanism proposed for the establishing of ischemic tolerant phenotype.

  14. Progress toward a stabilization and preconditioning protocol for polycrystalline thin-film photovoltaic modules

    Microsoft Academic Search

    Joseph A. del Cueto; Chris A. Deline; Steve R. Rummel; Allan Anderberg

    2010-01-01

    Cadmium telluride (CdTe) and copper indium gallium diselenide (CIGS) thin-film photovoltaic (PV) modules can exhibit substantial variation in measured performance depending on prior exposure history. We studied the metastable performance changes in these PV modules with the goal of establishing standard preconditioning or stabilization exposure procedures to mitigate measured variations prior to current-voltage (IV) measurements. We present the results of

  15. Large-numbered multicolor milu preconditioning on sx-3\\/14

    Microsoft Academic Search

    Shun Doi; Atsushi Hoshi

    1992-01-01

    This paper considers the vector implementation of preconditioned conjugate gradient (PCG) type methods in solving sparse linear systems of the 3D 7-point difference form. The modified incomplete LU (MILU) factorization is sought, where the system is numbered with respect to the multicolor ordering with a large number of colors (e.g. 75). The advantage in the usage of the large-numbered multicolor

  16. The role of the rat sarcoplasmic reticulum Ca 2+ ATPase promoter in myocardial ischemia-preconditioning

    Microsoft Academic Search

    Nengfeng Zhang; Baohua Zhu

    2010-01-01

    Intracellular calcium ion concentration ([Ca2+]i) is a key regulator of ischemia–reperfusion injury (IRI) and ischemic preconditioning (IPC), with myocardial sarcoplasmic\\u000a reticulum Ca2+-ATPase (SERCA2a) acting as the major regulatory protein in the control of [Ca2+]i. In this study, we examined the effect of the SERCA2a promoter in IRI and IPC. The SERCA2a promoter fragment was acquired\\u000a using PCR and molecular cloning

  17. Ischemia-Induced Mitochondrial Apoptosis is Significantly Attenuated by Ischemic Preconditioning

    Microsoft Academic Search

    Peter Racay; Maria Chomova; Zuzana Tatarkova; Peter Kaplan; Jozef Hatok; Dusan Dobrota

    2009-01-01

    Ischemic preconditioning (IPC) represents an important adaptation of CNS to sub-lethal ischemia, which results in increased\\u000a tolerance of CNS to the lethal ischemia. Ischemia-induced mitochondrial apoptosis is considered to be an important event leading\\u000a to neuronal cell death after cerebral blood flow arrest. In presented study, we have determined the effect of IPC on ischemia\\/reperfusion-induced\\u000a mitochondrial apoptosis. Global brain ischemia

  18. Electroacupuncture preconditioning reduces cerebral ischemic injury via BDNF and SDF-1? in mice

    PubMed Central

    2013-01-01

    Background This study was designed to determine if electroacupuncture (EA) preconditioning improves tissue outcome and functional outcome following experimentally induced cerebral ischemia in mice. In addition, we investigated whether the expression of brain-derived neurotrophic factor (BDNF) and stromal cell derived factor-1? (SDF-1?) and infarct volume were related with improvement in neurological and motor function by interventions in this study. Methods After treatment with EA at the acupoints ‘Baihui (GV20)’ and ‘Dazhui (GV14)’ for 20 min, BDNF was assessed in the cortical tissues based on Western blot and the SDF-1? and vascular endothelial growth factor (VEGF) levels in the plasma determined by ELISA. To assess the protective effects of EA against ischemic injury, the mice received once a day 20 min EA preconditioning for three days prior to the ischemic event. Focal cerebral ischemia was then induced by photothrombotic cortical ischemia. Infarct volumes, neurobehavioral deficit and motor deficit were evaluated 24 h after focal cerebral ischemia. Results The expression of BDNF protein increased significantly from 6 h, reaching a plateau at 12 h after the end of EA treatment in the cerebral cortex. Furthermore, SDF-1?, not VEGF, increased singnificantly from 12 h to 48 h after EA stimulation in the plasma. Moreover, EA preconditioning reduced the infarct volume by 43.5% when compared to control mice at 24 h after photothrombotic cortical ischemia. Consistent with a smaller infarct size, EA preconditioning showed prominent improvement of neurological function and motor function such as vestibule-motor function, sensori-motor function and asymmetric forelimb use. The expression of BDNF colocalized within neurons and SDF-1? colocalized within the cerebral vascular endothelium was observed throughout the ischemic cortex by EA. Conclusions Pretreatment with EA increased the production of BDNF and SDF-1?, which elicited protective effects against focal cerebral ischemia. These results suggest a novel mechanism of EA pretreatment-induced tolerance against cerebral ischemic injury. PMID:23356671

  19. Efficient large-scale power grid analysis based on preconditioned krylov-subspace iterative methods

    Microsoft Academic Search

    Tsung-Hao Chen; Charlie Chung-Ping Chen

    2001-01-01

    In this paper, we propose preconditioned Krylov-subspace iterative methods to perform efficient DC and transient simulations for large-scale linear circuits with an emphasis on power delivery circuits. We also prove that a circuit with inductors can be simplified from MNA to NA format, and the matrix becomes an s.p.d matrix. This property makes it suitable for the conjugate gradient with

  20. Heat-shock protein 70 is involved in hyperbaric oxygen preconditioning on decompression sickness in rats.

    PubMed

    Ni, Xiao-Xiao; Ni, Ming; Fan, Dan-Feng; Sun, Qiang; Kang, Zhi-Min; Cai, Zhi-Yu; Liu, Yun; Liu, Kan; Li, Run-Ping; Xu, Wei-Gang

    2013-01-01

    Decompression sickness (DCS) is a major concern in diving and space walk. Hyperbaric oxygen (HBO) preconditioning has been proved to enhance tolerance to DCS via nitric oxide. Heat-shock protein (HSP) 70 was also found to have protective effects against DCS. We hypothesized that the beneficial effects of HBO preconditioning on DCS was related to levels of elevated HSP70. HSPs (70, 27 and 90) expressed in tissues of spinal cord and lung in rats was detected at different time points following HBO exposure by Western blot. HSP27 and HSP90 showed a slight but not significant increase after HBO. HSP70 increased and reached highest at 18 h following exposure before decreasing. Then rats were exposed to HBO and subjected to simulated air dive and rapid decompression to induce DCS 18 h after HBO. The severity of DCS, along with levels of HSP70 expression, as well as the extent of oxidative and apoptotic parameters in the lung and spinal cord were compared among different groups of rats pretreated with HBO, HBO plus NG-nitro-l-arginine-methyl ester (l-NAME), HBO plus quercetin or normobaric air. HBO preconditioning significantly reduced the morbidity of DCS (from 66.7% to 36.7%), reduced levels of oxidation (malondialdehyde, 8-hydroxyguanine and hydrogen peroxide) and apoptosis (caspase-3 and -9 activities and the number of apoptotic cells). l-NAME or quercetin eliminated most of the beneficial effects of HBO on DCS, and counteracted the stimulation of HSP70 by HBO. Bubbles in pulmonary artery were detected using ultrasound imaging to observe the possible effect of HBO preconditioning on DCS bubble formation. The amounts of bubbles in rats pretreated with HBO or air showed no difference. These results suggest that HSP70 was involved in the beneficial effects of HBO on DCS in rats, suspected be by the antioxidation and antiapoptosis effects. PMID:23479759

  1. Endoplasmic reticulum stress-dependent activation of ATF3 mediates the late phase of ischemic preconditioning.

    PubMed

    Brooks, Alan C; Guo, Yiru; Singh, Mahavir; McCracken, James; Xuan, Yu-Ting; Srivastava, Sanjay; Bolli, Roberto; Bhatnagar, Aruni

    2014-11-01

    Ischemic preconditioning (PC) is an adaptive response to transient myocardial ischemia that protects the heart from subsequent ischemia/reperfusion (I/R) injury. However, the mechanisms underlying its cardioprotective effects remain unclear. Myocardium of adult male C57/BL6 mice, preconditioned by 6 cycles of 4 minute coronary occlusion and reperfusion, showed nuclear translocation of ATF3 and ATF6 and PERK phosphorylation 30 min after PC. The abundance of ER proteins, ATF3 and ATF4 was increased 24h after PC; however, there was no evidence of IRE-1 activation in WT or ER-stress activated indicator (ERAI) mice expressing XBP-1-Venus fusion protein. PC-induced nuclear translocation of ATF3 was attenuated in transgenic mice with cardiac-restricted overexpression of inducible ATF6. Ischemic PC increased the abundance of inducible nitric oxide synthase, cyclooxygenase-2, heme oxygenase-1 and aldose reductase to levels similar between WT and ATF3-null hearts; however, the increase in IL-6 and ICAM-1 was exaggerated in ATF3-null hearts. Genetic deletion of ATF3 did not increase infarct size in non-preconditioned hearts but abolished the cardioprotective effects of PC. Larger infarct size in preconditioned ATF3-null hearts was associated with greater neutrophil infiltration in the myocardium, but no ATF3-dependent changes in the total or relative abundance of inflammatory monocytes were observed. Ischemic PC activates the unfolded protein response (UPR) and the activation of ATF3 by ER stress is essential for the cardioprotective effects of late PC. PMID:25151953

  2. Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning

    Microsoft Academic Search

    K R Francis; L Wei

    2010-01-01

    Transplantation of neural progenitors derived from human embryonic stem cells (hESCs) provides a potential therapy for ischemic stroke. However, poor graft survival within the host environment has hampered the benefits and applications of cell-based therapies. The present investigation tested a preconditioning strategy to enhance hESC tolerance, thereby improving graft survival and the therapeutic potential of hESC transplantation. UC06 hESCs underwent

  3. A Principal Cognitive Precondition of Successful Child Computer Interactions in the Information Society

    Microsoft Academic Search

    Olga S. Fomichova

    2001-01-01

    A hypothesis about what is the principal cognitive precondition of successful systematic acquainting children with computers is put forward. For this, the notion of the Thought-Producing Self of the child is introduced. It is stated that the System of Emotional -Imaginative Teaching (EIT-system) based on the Theory of Dynamic Conceptual Mappings allows for realizing the Thought-Producing Self of each normal

  4. The role of remote ischemic preconditioning in the treatment of atherosclerotic diseases

    PubMed Central

    Vasdekis, Spyros N; Athanasiadis, Dimitrios; Lazaris, Andreas; Martikos, Georgios; Katsanos, Aristeidis H; Tsivgoulis, Georgios; Machairas, Anastasios; Liakakos, Theodoros

    2013-01-01

    Background Remote ischemic preconditioning (RIPC) is the application of a transient and brief ischemic stimulus to a distant site from the organ or tissue that is afterward exposed to injury ischemia, and has been found to reduce ischemia–reperfusion injury (IRI) in various animal models. RIPC appears to offer two distinct phases of endothelial IRI protection, which are presumably mediated through neuronal and humoral pathways. Methods We conducted a comprehensive literature review on the available published data about the potential effect of RIPC in patients undergoing IRI in one or more vital organs. Results Our search highlighted 24 randomized clinical trials about the effect of RIPC on variable clinical settings (abdominal aortic aneurysm repair, open heart surgery, percutaneous coronary intervention, living donor renal transplantation, coronary angiography, elective decompression surgery, carotid endarterectomy, recent stroke, or transient ischemic attack combined with intracranial carotid artery stenosis). Most of the trials focused on postoperative cardiac or renal function after RIPC with conflicting results. Preconditioning protocols, age limits, comorbidities, and concomitant drug use varied significantly across trials, and therefore no firm conclusions can be drawn using the available data. However, no severe local adverse events were observed in any patient undergoing limb or arm preconditioning. Conclusions RIPC is a safe and well-tolerated procedure that may constitute a potentially promising innovative treatment in atherosclerotic diseases. Large, multicenter, randomized clinical trials are required to determine an optimal protocol for the RIPC procedure, and to evaluate further the potential benefits of RIPC in human ischemic injury. PMID:24363964

  5. Lrg participates in lipopolysaccharide preconditioning-induced brain ischemia injury via TLR4 signaling pathway.

    PubMed

    Gong, Gu; Bai, Shurong; Wu, Wei; Hu, Ling; Liu, Yinghai; Niu, Jie; Dai, Xuemei; Yin, Liang; Wang, Xiaowu

    2014-09-01

    Lipopolysaccharide (LPS) preconditioning is a powerful neuroprotective phenomenon by which an injurious stimulus renders the brain resistant to a subsequent damaging ischemic insult. The LPS response gene (Lrg) is a recently identified gene in human dental pulp cells treated with LPS. However, the role and mechanism of Lrg in brain ischemia injury have not yet been demonstrated. Here, we sought to determine whether Lrg participates in LPS preconditioning-induced brain ischemia injury. The Lrg protein accumulates in brain tissue after middle cerebral artery occlusion (MCAO). Furthermore, knockdown of Lrg by small interfering RNA (siRNA) significantly increased the infarct size of brain injury. In addition, we investigated the mechanism of Lrg in brain ischemia injury. Lrg-siRNA could regulate inflammatory cytokine expression. Moreover, interleukin-1 receptor-associated kinase 1 (IRAK-1) and nuclear factor Kappa B (NF-?B) p65 protein levels were significantly increased by Lrg-siRNA in mice after MCAO. Conversely, interferon regulatory factor 3 (IRF3) protein level was decreased by Lrg-siRNA. Taken together, these results suggest that Lrg regulates the expression of inflammatory cytokines in LPS preconditioning-induced brain ischemia injury via the toll-like receptor 4 (TLR4) signaling pathway. Lrg may therefore serve as a novel therapeutic target for brain ischemia injury. PMID:24526448

  6. Prevent Shingles

    MedlinePLUS

    ... will develop chickenpox, not shingles. Disease of the Week App "Want to know more about shingles? Download CDC's mobile app now . See "Disease of the Week," highlighting disease facts and prevention tips. Find "Shingles" ...

  7. Preventing Suicide

    MedlinePLUS

    ... Health Features Media Sign up for Features Get Email Updates To receive email updates about this page, ... Prevention Features Media Sign up for Features Get Email Updates To receive email updates about this page, ...

  8. Preventing falls

    MedlinePLUS

    Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, Rowe BH. Interventions for preventing falls in older people living in the community. Cochrane Database of Systematic Reviews 2009, Issue ...

  9. Stroke Prevention

    Microsoft Academic Search

    Jörg Ederle; Martin M. Brown

    2008-01-01

    \\u000a Abstract\\u000a   Stroke is one of the leading causes of death and disability in the Western world and efforts should be made to prevent the\\u000a occurrence of stroke. Primary preventive measures are influenced by the patient's risk factor profile. A healthy lifestyle\\u000a should be encouraged. Hypertension as a major risk factor for stroke should be controlled either by lifestyle measures or,

  10. The natural olive constituent oleuropein induces nutritional cardioprotection in normal and cholesterol-fed rabbits: comparison with preconditioning.

    PubMed

    Andreadou, Ioanna; Benaki, Dimitra; Efentakis, Panagiotis; Bibli, Sofia-Iris; Milioni, Alkistis-Ioanna; Papachristodoulou, Anastasia; Zoga, Anastasia; Skaltsounis, Alexios-Leandros; Mikros, Emmanuel; Iliodromitis, Efstathios K

    2015-06-01

    Ischemic preconditioning, which is mediated by cell signaling molecules, protects the heart from ischemia-reperfusion injury by limiting the infarct size. Oleuropein, the main polyphenolic constituent of olives, reduced the infarct size in normal and cholesterol-fed rabbits when it was administered at a nutritional dose. The aim of the present study was to compare the effects of oleuropein and preconditioning in terms of the cell signaling and metabolism pathways underlying myocardial protection. Rabbits were randomly divided into six groups: the control group received 5?% dextrose for six weeks, the preconditioning group was subjected to two cycles of preconditioning with 5?min ischemia/10?min reperfusion, the O6 group was treated with oleuropein for six weeks, the Chol group was fed a cholesterol-enriched diet and 5?% dextrose for six weeks, and the CholO6 and CholO3 groups were treated with cholesterol and oleuropein for six and three weeks, respectively; oleuropein was dissolved in 5?% dextrose solution and was administered orally at a dose of 20?mg?×?kg(-1)?×?day(-1). All animals were subsequently subjected to 30?min myocardial ischemia followed by 10?min of reperfusion. At that time, myocardial biopsies were taken from the ischemic areas for the assessment of oxidative and nitrosative stress biomarkers (malondialdehyde and nitrotyrosine), and determination of phosphorylation of signaling molecules involved in the mechanism of preconditioning (PI3K, Akt, eNOS, AMPK, STAT3). The tissue extracts NMR metabolic profile was recorded and further analyzed by multivariate statistics. Oxidative biomarkers were significantly reduced in the O6, CholO6, and CholO3 groups compared to the control, preconditioning, and Chol groups. Considering the underlying signaling cascade, the phosphorylation of PI3K, Akt, eNOS, AMPK, and STAT-3 was significantly higher in the preconditioning and all oleuropein-treated groups compared to the control and Chol groups. The NMR-based metabonomic study, performed through the analysis of spectroscopic data, depicted differences in the metabolome of the various groups with significant alterations in purine metabolism. In conclusion, the addition of oleuropein to a normal or hypercholesterolemic diet results in a preconditioning-like intracellular effect, eliminating the deleterious consequences of ischemia and hypercholesterolemia, followed by a decrease of oxidative stress biomarkers. This effect is exerted through inducing preconditioning-involved signaling transduction. Nutritional preconditioning may support the low cardiovascular morbidity and mortality associated with the consumption of olive products. PMID:25473920

  11. Ischemic preconditioning ameliorates intestinal injury induced by ischemia-reperfusion in rats

    PubMed Central

    Ji, Yuan-Yuan; Wang, Zhi-Dong; Wang, Shu-Feng; Wang, Bao-Tai; Yang, Zheng-An; Zhou, Xiao-Rong; Lei, Ni-Na; Yue, Wei-Na

    2015-01-01

    AIM: To evaluate preventative effects of ischemic preconditioning (IP) in a rat model of intestinal injury induced by ischemia-reperfusion (IR). METHODS: Male Sprague-Dawley rats (250-300 g) were fasted for 24 h with free access to water prior to the operation. Eighteen rats were randomly divided into three experimental groups: S group (n = 6), rats were subjected to isolation of the superior mesenteric artery (SMA) for 40 min, then the abdomen was closed; IR group (n = 6), rats were subjected to clamping the SMA 40 min, and the abdomen was closed followed by a 4-h reperfusion; IP group (n = 6) rats underwent three cycles of 5 min ischemia and 5 min reperfusion, then clamping of the SMA for 40 min, then the abdomen was closed and a 4-h reperfusion followed. All animals were euthanized by barbiturate overdose (150 mg/kg pentobarbital sodium, i.v.) for tissue collection, and the SMA was isolated via median abdominal incision. Intestinal histologic injury was observed. Malondialdehyde (MDA), myeloperoxidase (MPO) and tumor necrosis factor (TNF)-? concentrations in intestinal tissue were measured. Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression, as well as nuclear factor (NF)-?B activity and expression in intestinal tissue were also determined. RESULTS: Compared with the IR group, IP reduced IR-induced histologic injury of the intestine in rats (2.00 ± 0.71 vs 3.60 ± 0.84, P < 0.05). IP significantly inhibited the increase in MDA content (5.6 ± 0.15 ?mol/L vs 6.84 ± 0.18 ?mol/L, P < 0.01), MPO activity (0.13 ± 0.01 U/L vs 0.24 ± 0.01 U/L, P < 0.01), and TNF-? levels (7.79 ± 2.35 pg/mL vs 10.87 ± 2.48 pg/mL, P < 0.05) in the intestinal tissue of rats. IP also markedly ameliorated the increase in ICAM-1 (204.67 ± 53.27 vs 353.33 ± 45.19, P < 0.05) and VCAM-1 (256.67 ± 58.59 vs 377.33 ± 41.42, P < 0.05) protein expression in the intestinal tissues. Additionally, IP remarkably decreased NF-?B activity (0.48 ± 0.16 vs 0.76 ± 0.22, P < 0.05) and protein expression (320.23 ± 38.16 vs 520.76 ± 40.53, P < 0.01) in rat intestinal tissue. CONCLUSION: IP may protect against IR-induced intestinal injury by attenuation of the neutrophil-endothelial adhesion cascade via reducing ICAM-1 and VCAM-1 expression and TNF-?-induced NF-?B signaling pathway activity. PMID:26185379

  12. Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair

    PubMed Central

    Wang, Lihan; Jiang, Zhi; Liu, Xianbao; Yu, Hong; Zhang, Zhaocai; Chen, Huiqiang; Chen, Han; Steinhoff, Gustav; Li, Jun; Jian’an Wang

    2013-01-01

    Background The therapeutic efficiency of bone marrow mononuclear cells (BMMNCs) autologous transplantation for myocardial infarction (MI) remains low. Here we developed a novel strategy to improve cardiac repair by preconditioning BMMNCs via angiotensin II type 2 receptor (AT2R) stimulation. Methods and Results Acute MI in rats led to a significant increase of AT2R expression in BMMNCs. Preconditioning of BMMNCs via AT2R stimulation directly with an AT2R agonist CGP42112A or indirectly with angiotensin II plus AT1R antagonist valsartan led to ERK activation and increased eNOS expression as well as subsequent nitric oxide generation, ultimately improved cardiomyocyte protection in vitro as measured by co-culture approach. Intramyocardial transplantation of BMMNCs preconditioned via AT2R stimulation improved survival of transplanted cells in ischemic region of heart tissue and reduced cardiomyocyte apoptosis and inflammation at 3 days after MI. At 4 weeks after transplantation, compared to DMEM and non-preconditioned BMMNCs group, AT2R stimulated BMMNCs group showed enhanced vessel density in peri-infarct region and attenuated infarct size, leading to global heart function improvement. Conclusions Preconditioning of BMMNCs via AT2R stimulation exerts protective effect against MI. Stimulation of AT2R in BMMNCs may provide a new strategy to improving therapeutic efficiency of stem cells for post MI cardiac repair. PMID:24340072

  13. Ischemic Preconditioning Protects against Spinal Cord Ischemia-Reperfusion Injury in Rabbits by Attenuating Blood Spinal Cord Barrier Disruption.

    PubMed

    Fang, Bo; Li, Xiao-Man; Sun, Xi-Jia; Bao, Na-Ren; Ren, Xiao-Yan; Lv, Huang-Wei; Ma, Hong

    2013-01-01

    Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood spinal cord barrier permeability was measured by Evan's Blue extravasation, spinal cord edema was evaluated using the wet-dry method, and spinal cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-? (TNF-?) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood spinal cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-? mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood spinal cord barrier permeability due to spinal cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-? expression. PMID:23685868

  14. Ischemic Preconditioning Protects against Spinal Cord Ischemia-Reperfusion Injury in Rabbits by Attenuating Blood Spinal Cord Barrier Disruption

    PubMed Central

    Fang, Bo; Li, Xiao-Man; Sun, Xi-Jia; Bao, Na-Ren; Ren, Xiao-Yan; Lv, Huang-Wei; Ma, Hong

    2013-01-01

    Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood spinal cord barrier permeability was measured by Evan’s Blue extravasation, spinal cord edema was evaluated using the wet-dry method, and spinal cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-? (TNF-?) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood spinal cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-? mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood spinal cord barrier permeability due to spinal cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-? expression. PMID:23685868

  15. Increased BDNF protein expression after ischemic or PKC epsilon preconditioning promotes electrophysiologic changes that lead to neuroprotection.

    PubMed

    Neumann, Jake T; Thompson, John W; Raval, Ami P; Cohan, Charles H; Koronowski, Kevin B; Perez-Pinzon, Miguel A

    2015-01-01

    Ischemic preconditioning (IPC) via protein kinase C epsilon (PKC?) activation induces neuroprotection against lethal ischemia. Brain-derived neurotrophic factor (BDNF) is a pro-survival signaling molecule that modulates synaptic plasticity and neurogenesis. Interestingly, BDNF mRNA expression increases after IPC. In this study, we investigated whether IPC or pharmacological preconditioning (PKC? activation) promoted BDNF-induced neuroprotection, if neuroprotection by IPC or PKC? activation altered neuronal excitability, and whether these changes were BDNF-mediated. We used both in vitro (hippocampal organotypic cultures and cortical neuronal-glial cocultures) and in vivo (acute hippocampal slices 48 hours after preconditioning) models of IPC or PKC? activation. BDNF protein expression increased 24 to 48 hours after preconditioning, where inhibition of the BDNF Trk receptors abolished neuroprotection against oxygen and glucose deprivation (OGD) in vitro. In addition, there was a significant decrease in neuronal firing frequency and increase in threshold potential 48 hours after preconditioning in vivo, where this threshold modulation was dependent on BDNF activation of Trk receptors in excitatory cortical neurons. In addition, 48 hours after PKC? activation in vivo, the onset of anoxic depolarization during OGD was significantly delayed in hippocampal slices. Overall, these results suggest that after IPC or PKC? activation, there are BDNF-dependent electrophysiologic modifications that lead to neuroprotection. PMID:25370861

  16. Cancer prevention.

    PubMed

    Tubiana, M

    1999-01-01

    Over 70% of human cancers are associated with lifestyle and about half of cancer deaths could be prevented by relatively simple individual actions: no smoking, moderate consumption of alcohol, increased consumption of fruit and vegetables, avoidance of sunbathing, obesity and a too high consumption of saturated lipids. Most of these efforts would also markedly decrease the incidence of cardiovascular and respiratory diseases. However, the concept of prevention is currently neither well accepted nor understood by the medical community and the general public. It is often felt that it restricts freedom, imposes a choice between pleasure and duty, and that passing judgement on lifestyle is a form of intolerance. The case of tobacco illustrates the difficulties encountered by prevention, notably among adolescents. The fight against smoking requires information, a societal approach (ban on advertising, increase in price), and a reduction of the example given by adult smoking (parents, peers, teachers, physicians, TV presenters, movie stars, have a great influence on adolescents), while tobacco cessation programs must be promoted. The various approaches should be integrated into a global program of health prevention, including health education at school from 5 to 12 years of age. The efficacy of each of the global program's components should be evaluated. Misconceptions such as overestimation of the impact of pollution on health should also be corrected. Health is created and experienced by people within the setting of their daily lives, in particular during childhood. Prevention is the responsibility of individual members of the community but also of the community as a whole. PMID:10522758

  17. Hypoxic preconditioning increases skin oxygenation and viability but does not alter VEGF expression or vascular density.

    PubMed

    Schlaudraff, Kai U; Pepper, Michael S; Tkatchouk, Elena N; Ehrenburg, Igor; Alizadeh, Navid; Montandon, Denys; Pittet, Brigitte

    2008-01-01

    Intermittent hypoxia is known to elicit adaptive changes that increase tissue oxygen delivery. We investigated the effects of intermittent hypoxic exposure (IHE) in normal skin (course study) and evaluated whether preoperative IHE-preconditioning alleviates acute ischemic injury in skin flaps (flap study). For 4 weeks, 55 rats were exposed to a daily IHE-session (6 hypoxic cycles, 9% O(2), 6 to 10 min) separated by 3 min of reoxygenation (20.9% O(2)). The time course of intracutaneous PO(2) was measured at weekly intervals. VEGF/VEGF-receptor-mRNA and vascular density were measured in normal skin before and after 1, 2, 3, and 4 weeks of the IHE course (20 rats). In 35 rats, skin flaps were elevated after IHE and similar studies were undertaken in samples from 3 flap areas at postoperative days 0.5, 2, and 4. Additionally, flap survival and cutaneous blood flow were quantitated. In normal skin, PO(2) was initially significantly decreased during the hypoxic cycles (PO(2) 4.1 +/- 1.5 mmHg). After 4 weeks of IHE, PO(2) (34.5 +/- 5.8 mmHg) was maintained even under hypoxic conditions. In flaps, IHE led to a 2.6-fold increase in PO(2), increased flap survival (+ 19.4%, day 7), and blood flow (+ 19.1%, day 10) (p < 0.01). In neither study did IHE-preconditioning increase VEGF/VEGF-receptor-mRNA expression or vascular density. We conclude that (1) IHE induces pronounced hypoxia in the skin, but progressive adaptation occurs within 4 weeks, (2) preoperative IHE-preconditioning leads to significantly higher PO(2), blood flow, and tissue survival in ischemic skin flaps, and (3) the transient hypoxia induced by IHE does not alter expression of VEGF or its receptors nor does it trigger angiogenesis. PMID:18331223

  18. A Randomized Pilot Trial of Remote Ischemic Preconditioning in Heart Failure with Reduced Ejection Fraction

    PubMed Central

    McDonald, Michael A.; Braga, Juarez R.; Li, Jing; Manlhiot, Cedric; Ross, Heather J.; Redington, Andrew N.

    2014-01-01

    Background Remote ischemic preconditioning (RIPC) induced by transient limb ischemia confers multi-organ protection and improves exercise performance in the setting of tissue hypoxia. We aimed to evaluate the effect of RIPC on exercise capacity in heart failure patients. Methods We performed a randomized crossover trial of RIPC (4×5-minutes limb ischemia) compared to sham control in heart failure patients undergoing exercise testing. Patients were randomly allocated to either RIPC or sham prior to exercise, then crossed over and completed the alternate intervention with repeat testing. The primary outcome was peak VO2, RIPC versus sham. A mechanistic substudy was performed using dialysate from study patient blood samples obtained after sham and RIPC. This dialysate was used to test for a protective effect of RIPC in a mouse heart Langendorff model of infarction. Mouse heart infarct size with RIPC or sham dialysate exposure was also compared with historical control data. Results Twenty patients completed the study. RIPC was not associated with improvements in peak VO2 (15.6+/?4.2 vs 15.3+/?4.6 mL/kg/min; p?=?0.53, sham and RIPC, respectively). In our Langendorff sub-study, infarct size was similar between RIPC and sham dialysate groups from our study patients, but was smaller than expected compared to healthy controls (29.0%, 27.9% [sham, RIPC] vs 51.2% [controls]. We observed less preconditioning among the subgroup of patients with increased exercise performance following RIPC (p<0.04). Conclusion In this pilot study of RIPC in heart failure patients, RIPC was not associated with improvements in exercise capacity overall. However, the degree of effect of RIPC may be inversely related to the degree of baseline preconditioning. These data provide the basis for a larger randomized trial to test the potential benefits of RIPC in patients with heart failure. Trial Registration ClinicalTrials.gov +++++NCT01128790 PMID:25181050

  19. Induction of systemic bone changes by preconditioning total body irradiation for bone marrow transplantation

    Microsoft Academic Search

    Osamu Miyazaki; Gen Nishimura; Reiko Okamoto; Hidekazu Masaki; Masaaki Kumagai; Yoko Shioda; Kumiko Nozawa; Hiroshi Kitoh

    2009-01-01

    Background  Preconditioning total body irradiation (TBI) prior to bone marrow transplantation (BMT) has been believed to be a safe procedure\\u000a that does not cause late morbidity; yet, a recent report raises the suspicion that TBI-induced chondroosseous abnormalities\\u000a do occur.\\u000a \\u000a \\u000a \\u000a Objective  To evaluate the radiological manifestations of TBI-induced skeletal alterations and their orthopaedic morbidity.\\u000a \\u000a \\u000a \\u000a Materials and methods  Subjects included 11 children with TBI-induced skeletal

  20. Results on the effect of orderings on SSOR and ILU preconditionings

    SciTech Connect

    Joubert, W.; Knill, E.

    1998-12-31

    It is known that for SSOR and ILU preconditionings for solving systems of linear equations, orderings can have an enormous impact on robustness, convergence rate and parallelism. Unfortunately, it has been observed that there is an inverse relation between the convergence rate and the parallelism of typical orderings used in practice. This paper presents some numerical experiments with simple matrices to illustrate this behavior as well as a new theoretical result which sheds some light on this phenomenon and also gives an upper bound on the convergence rate of a number of preconditioners in popular use.

  1. Application of preconditioned conjugate-gradient-like methods in reservoir simulation

    SciTech Connect

    Northrup, E.J.; Woo, P.T.

    1988-02-01

    Conjugate-gradient-like (CGL) methods were used to solve the matrix equations for several large-field and fine-grid models. The methods used incomplete LU (ILU) or modified incomplete LU (MILU) preconditioning coupled with orthomin acceleration. The CGL methods were applied to the original matrix or to a reduced system for red/black ordering. Test results from a black-oil model with fault throws, a fractured reservoir model, and three steamflood models are given. It was found that the CGL methods are effective for solving the matrix equations. A more powerful preconditioner improves reliability but may require more work. Guidelines for selecting the most effective method are provided.

  2. Application of preconditioned conjugate-gradient-like methods in reservoir simulation

    SciTech Connect

    Northrup, E.J.; Woo, P.T.

    1985-02-01

    Conjugate-gradient-like (CGL) methods were used to solve the matrix equations for several large field and fine grid models. The methods used ILU or MILU preconditioning coupled with Orthomin acceleration. The CGL methods were applied to the original matrix or to a reduced system from alternate diagonal ordering. Test results from a black oil model with fault throws, a fractured reservoir model, and three steamflood models are given. It was found that the CGL methods are effective for solving the matrix equations. A more powerful preconditioner improves reliability but may use more CPU time. Guidelines for selecting the most effective method are provided.

  3. Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest

    Microsoft Academic Search

    Matthias Thielmann; Eva Kottenberg; Kerstin Boengler; Christoph Raffelsieper; Markus Neuhaeuser; Jürgen Peters; Heinz Jakob; Gerd Heusch

    2010-01-01

    Remote ischemic preconditioning (RIPC) with transient upper limb ischemia reduces myocardial injury in patients undergoing\\u000a on-pump coronary artery bypass grafting (CABG) with cross-clamp fibrillation or blood cardioplegia for myocardial protection.\\u000a Whether or not such protection is still operative when standard crystalloid cardioplegic arrest is used is uncertain. Fifty-three\\u000a consecutive, non-diabetic patients with triple-vessel disease and 64 ± 12 years of age (mean ± SD), who

  4. Graph Embedding Techniques for Bounding Condition Numbers of Incomplete Factor Preconditioning

    NASA Technical Reports Server (NTRS)

    Guattery, Stephen

    1997-01-01

    We extend graph embedding techniques for bounding the spectral condition number of preconditioned systems involving symmetric, irreducibly diagonally dominant M-matrices to systems where the preconditioner is not diagonally dominant. In particular, this allows us to bound the spectral condition number when the preconditioner is based on an incomplete factorization. We provide a review of previous techniques, describe our extension, and give examples both of a bound for a model problem, and of ways in which our techniques give intuitive way of looking at incomplete factor preconditioners.

  5. A functional role of the cyclin-dependent kinase inhibitor 1 (p21WAF1/CIP1) for neuronal preconditioning

    PubMed Central

    Mergenthaler, Philipp; Muselmann, Claudia; Sünwoldt, Juliane; Isaev, Nickolay K; Wieloch, Tadeusz; Dirnagl, Ulrich; Meisel, Andreas; Ruscher, Karsten

    2013-01-01

    Hypoxic preconditioning is thought to rely on gene products regulated by hypoxia-inducible factor (HIF)-1. Here, we show that the HIF-1 target gene cyclin-dependent kinase inhibitor 1, p21WAF1/CIP1, is essential for neuroprotection by hypoxic/aglycemic or erythropoietin preconditioning using wild-type and p21WAF1/CIP1-deficient neurons. Furthermore, overexpression of wild-type p21WAF1/CIP1 or phospho-mutants significantly increased cell death after hypoxia/aglycemia. Moreover, deferoxamine-induced endogenous tolerance did not involve p21WAF1/CIP1 expression in cortical neurons. Our data suggest that balanced expression and potentially posttranslational regulation of p21WAF1/CIP1 is required for hypoxic preconditioning. PMID:23299246

  6. Evaluation of the effects of ischemic preconditioning on the hematological parameters of rats subjected to intestinal ischemia and reperfusion

    PubMed Central

    Tahir, Muhammad; Arshid, Samina; Heimbecker, Ana Maria C; Castro, Mariana S; de Souza Montero, Edna Frasson; Fontes, Belchor; Fontes, Wagner

    2015-01-01

    OBJECTIVES: Intestinal ischemia/reperfusion often leads to acute lung injury and multiple organ failure. Ischemic preconditioning is protective in nature and reduces tissue injuries in animal and human models. Although hematimetric parameters are widely used as diagnostic tools, there is no report of the influence of intestinal ischemia/reperfusion and ischemic preconditioning on such parameters. We evaluated the hematological changes during ischemia/reperfusion and preconditioning in rats. METHODS: Forty healthy rats were divided into four groups: control, laparotomy, intestinal ischemia/reperfusion and ischemic preconditioning. The intestinal ischemia/reperfusion group received 45 min of superior mesenteric artery occlusion, while the ischemic preconditioning group received 10 min of short ischemia and reperfusion before 45 min of prolonged occlusion. A cell counter was used to analyze blood obtained from rats before and after the surgical procedures and the hematological results were compared among the groups. RESULTS: The results showed significant differences in hematimetric parameters among the groups. The parameters that showed significant differences included lymphocyte, white blood cells and granulocyte counts; hematocrit; mean corpuscular hemoglobin concentration; red cell deviation width; platelet count; mean platelet volume; plateletcrit and platelet distribution width. CONCLUSION: The most remarkable parameters were those related to leukocytes and platelets. Some of the data, including the lymphocyte and granulocytes counts, suggest that ischemic preconditioning attenuates the effect of intestinal ischemia/reperfusion on circulating blood cells. Our work contributes to a better understanding of the hematological responses after intestinal ischemia/reperfusion and IPC, and the present findings may also be used as predictive values. PMID:25672431

  7. (S)-ZJM-289 preconditioning induces a late phase protection against nervous injury induced by transient cerebral ischemia and oxygen-glucose deprivation.

    PubMed

    Zhang, Chao; Zhang, Zhenzhen; Zhao, Qian; Wang, Xuliang; Ji, Hui; Zhang, Yihua

    2014-07-01

    (S)-ZJM-289, a novel nitric oxide (NO)-releasing derivative of 3-n-butylphthalide, induces the neuroprotection in a rat model of focal cerebral ischemia/reperfusion (I/R). However, much is unknown about the late phase effect in the neuroprotection of (S)-ZJM-289 preconditioning. The purpose of this study is to explore the late phase neuroprotection of (S)-ZJM-289 preconditioning, as well as underlying mechanisms involved. Preconditioning with 40-160 mg/kg, (S)-ZJM-289 significantly reduces brain damage after I/R. (S)-ZJM-289 preconditioning is effective when applied 1-3 days before I/R. Moreover, the degrees of neuroprotection offered by (S)-ZJM-289 preconditioning and ischemic preconditioning are virtually identical. (S)-ZJM-289 preconditioning also protects primary cultured cortical neurons against oxygen-glucose deprivation and recovery-induced cytotoxicity in vitro. (S)-ZJM-289 preconditioning significantly increases the generation of NO, but has no effect on the nitric oxide synthase activities. Additionally, (S)-ZJM-289 preconditioning promotes the dissociation between nuclear-factor-E2-related factor (Nrf2) and kelch-like ECH-associated protein 1, and induces Nrf2 nuclear localization. The neuroprotection of (S)-ZJM-289 preconditioning is blocked by Nrf2-siRNA in vitro. (S)-ZJM-289 preconditioning up-regulates antioxidant enzymes against nervous injury. (S)-ZJM-289 preconditioning significantly activates extracellular regulated protein kinases (ERK) and inhibits c-Jun N-terminal kinases signaling cascade. The neuroprotection is abolished by the ERK inhibitor PD98059 in vitro. Subsequently, (S)-ZJM-289 preconditioning increases the levels of anti-apoptotic protein B cell lymphoma 2 (Bcl-2) and inhibited the translocation of Bcl-2 associated X to the mitochondria, thus attenuating the release of cytochrome c from the mitochondria and the activation of downstream caspase. These results suggest that (S)-ZJM-289 preconditioning exerts the late phase protection against nervous injury induced by transient cerebral ischemia and oxygen-glucose deprivation. PMID:24277159

  8. Effect of ischemic and pharmacological preconditioning of lower limb muscle tissue on tissue oxygenation measured by near-infrared spectroscopy – a pilot study

    PubMed Central

    2014-01-01

    Background Ischemic or volatile anesthetic preconditioning is defined as tissue protection from impending ischemic cell damage by repetitive short periods of tissue exposure to ischemia or volatile anesthetics. Objective of this study was to elucidate, if ischemic preconditioning and pharmacological preconditioning with sevoflurane have effects on muscle tissue oxygen saturation in patients undergoing surgical revascularization of the lower limb. Methods In this prospective randomized pilot study ischemic and pharmacological (sevoflurane) preconditioning was performed in 40 patients with lower limb arterial occlusive disease undergoing surgical revascularization. Sevoflurane preconditioning was performed in one group (N?=?20) by repetitive application of sevoflurane for six minutes interspersed by six minutes of washout. Thereafter, ischemic preconditioning was performed in all patients (N?=?40) by repetitive clamping of the femoral artery for six minutes interspersed by six minutes of reperfusion. The effect of both procedures on leg muscle tissue oxygen saturation (rSO2) was measured by near-infrared spectroscopy during both procedures and during surgery and reperfusion (INVOS® 5100C Oxymeter with Small Adult SomaSensor® SAFB-SM, Somanetics, Troy, Michigan, USA). Results Repetitive clamping and reperfusion of the femoral artery resulted in significant cyclic decrease and increase of muscle rSO2 (p?preconditioning with sevoflurane resulted in a faster and higher increase of rSO2 during postoperative reperfusion (Maximal 111% baseline?±?20 versus 103% baseline?±?14, p?=?0.008) consistent with an additional effect of pharmacological preconditioning on leg perfusion. Conclusions Ischemic preconditioning of lower limb muscle tissue and pharmacological preconditioning with sevoflurane have an effect on tissue oxygenation in patients with lower limb occlusive arterial disease. Trial registration The trial has been registrated at http://www.ClinicalTrial.gov, Trial Number: NCT02038062 at 14 January 2014. PMID:25132803

  9. Effects of WEB 2086 on the protective role of preconditioning against arrhythmias in rats.

    PubMed

    Sariahmeto?lu, M; Cakici, I; Kanzik, I

    1998-09-01

    The purpose of the present study was to investigate a possible role of platelet activating factor (PAF) in ischaemic preconditioning (PC). Since both PC and PAF act through protein kinase C (PKC), PAF could play a role in PC. To test this hypothesis, anaesthetized, open-chest male rats were subjected to four different protocols. Group I was subjected to 30 min of left coronary artery occlusion. In Group II, WEB 2086 (10 mg kg-1 i.v. bolus+1 mg kg-1 h-1 i.v. infusion) a selective PAF antagonist was given to non-preconditioned rats 23 min before the 30-min occlusion period. In Group III and IV ischaemic PC was elicited by one cycle of 3 min occlusion and 5 min reperfusion and also in Group IV, WEB 2086 (10 mg kg-1 i.v. bolus+1 mg kg-1 h-1 i.v. infusion) was given 23 min before the 30 min occlusion period. Ventricular ectopic beats (VEB), ventricular tachycardia (VT), and ventricular fibrillation (VF) that occurred during 30 min occlusion were determined. WEB 2086 administration or PC reduced the VEBs significantly. Incidence of VT and VF were not affected by WEB 2086 compared with control values, although PC decreased the incidence of VT and VF. WEB 2086 administration did not attenuate PC-induced improvement of arrhythmia parameters. These data demonstrated that a specific PAF antagonist, WEB 2086 did not abolish PC-induced protection against arrhythmias. PMID:9782066

  10. Role of MicroRNAs in innate neuroprotection mechanisms due to preconditioning of the brain

    PubMed Central

    Jimenez-Mateos, Eva M.

    2015-01-01

    Insults to the brain that are sub-threshold for damage activate endogenous protective pathways, which can temporarily protect the brain against a subsequent harmful episode. This mechanism has been named as tolerance and its protective effects have been shown in experimental models of ischemia and epilepsy. The preconditioning-stimulus can be a short period of ischemia or mild seizures induced by low doses of convulsant drugs. Gene-array profiling has shown that both ischemic and epileptic tolerance feature large-scale gene down-regulation but the mechanism are unknown. MicroRNAs are a class of small non-coding RNAs of ~20–22 nucleotides length which regulate gene expression at a post-transcriptional level via mRNA degradation or inhibition of protein translation. MicroRNAs have been shown to be regulated after non-harmful and harmful stimuli in the brain and to contribute to neuroprotective mechanisms. This review focuses on the role of microRNAs in the development of tolerance following ischemic or epileptic preconditioning. PMID:25954143

  11. Magnetosphere preconditioning by the formation of a cold-dense plasma sheet under northward IMF

    NASA Astrophysics Data System (ADS)

    Lavraud, B.; Thomsen, M. F.; Jordanova, V. K.; Borovsky, J. E.; Denton, M. H.; Pulkkinen, T. I.

    2009-04-01

    Motivated by recent observations and simulations of the formation of a cold and dense plasma sheet in the tail of the magnetosphere under northward interplanetary magnetic field (IMF) and of the direct influence of the plasma sheet density on the ring current strength, this study aims at (1) highlighting how the coupling of these effects may lead to a preconditioning of the magnetosphere under northward IMF and (2) performing first tests of the validity of this hypothesis. We performed both parametric kinetic ring current simulation studies to investigate how the density and temperature of the plasma sheet affect the ring current strength during geomagnetic storms, and superposed epoch analysis of various parameters to investigate the response of the magnetosphere (as indicated by the Dst index) to the passage of Coronal Mass Ejections (CMEs) and Corotating Interaction Regions (CIRs). The results all suggest that solar wind structures may be more geoeffective if preceded by a northward IMF interval, and they are consistent with the hypothesis of a preconditioning by a cold, dense plasma sheet. A colder and denser plasma sheet may lead to a stronger ring current when that plasma is convected inward during the main phase of an ensuing storm.

  12. Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection

    PubMed Central

    Thiersch, Markus; Raffelsberger, Wolfgang; Frigg, Rico; Samardzija, Marijana; Wenzel, Andreas; Poch, Olivier; Grimm, Christian

    2008-01-01

    Background Retinal degeneration is a main cause of blindness in humans. Neuroprotective therapies may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1? in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration. To address the molecular mechanisms of the protection, we analyzed the transcriptome of the hypoxic retina using microarrays and real-time PCR. Results Hypoxic exposure induced a marked alteration in the retinal transcriptome with significantly different expression levels of 431 genes immediately after hypoxic exposure. The normal expression profile was restored within 16 hours of reoxygenation. Among the differentially regulated genes, several candidates for neuroprotection were identified like metallothionein-1 and -2, the HIF-1 target gene adrenomedullin and the gene encoding the antioxidative and cytoprotective enzyme paraoxonase 1 which was previously not known to be a hypoxia responsive gene in the retina. The strongly upregulated cyclin dependent kinase inhibitor p21 was excluded from being essential for neuroprotection. Conclusion Our data suggest that neuroprotection after hypoxic preconditioning is the result of the differential expression of a multitude of genes which may act in concert to protect visual cells against a toxic insult. PMID:18261226

  13. Remote ischemic preconditioning for myocardial protection: update on mechanisms and clinical relevance.

    PubMed

    Gill, Rabia; Kuriakose, Robin; Gertz, Zachary M; Salloum, Fadi N; Xi, Lei; Kukreja, Rakesh C

    2015-04-01

    Ischemic heart disease is the leading cause of death for both men and women worldwide, accruing 7.4 million deaths in 2012. There has been a continued search for better cardioprotective modalities that would reduce myocardial ischemia-reperfusion injury. Among these attempts, a more convenient model of ischemic preconditioning, known as remote ischemic preconditioning (RIPC) was first introduced in 1993 by Przyklenk and colleagues who reported that brief regional occlusion-reperfusion episodes in one vascular bed of the heart render protection to remote myocardial tissue. Subsequently, major advances in myocardial RIPC came with the use of skeletal muscle as the ischemic stimulus. To date, numerous studies have revealed that RIPC applied to the kidney, liver, mesentery, and skeletal muscle, have all exhibited cardioprotective effects. The main purpose of this review article is to summarize the new advances in understanding the molecular mechanisms of RIPC during the past 5 years, including those related to capsaicin-activated C sensory fibers, hypoxia-inducible factor 1?, connexin 43, extracellular vesicles, microRNA-144, microRNA-1, and nitrite. In addition, we have discussed results from several recent human clinical trials with RIPC. Taken together, the emerging clinical evidence supports the concept that the effectiveness of RIPC paired with its low-cost and non-invasive features makes it an ideal treatment before reperfusion after sustained ischemia. More carefully designed studies are warranted to fully exploit the clinical benefits of RIPC and its potential implications in patients with cardiovascular disease. PMID:25552250

  14. Anomalous rate dependence of the preconditioned response of soft tissue during load controlled deformation.

    PubMed

    Giles, Julie M; Black, Amanda E; Bischoff, Jeffrey E

    2007-01-01

    It has been observed in load controlled laboratory tests of myocardium and skin that the tissues can exhibit a decrease in nonlinear stiffness with an increase in loading rate: the faster a test is performed, the more compliant is the preconditioned material behavior. This response seems to conflict with what is generally expected of soft tissues based on stretch or strain controlled tests, in which an increased rate of deformation results in a stiffer material response. It is hypothesized that this anomalous behavior has not been observed previously due to the small number of cyclic load controlled mechanical characterization tests that are geared specifically towards viscoelastic tissue response. The goal of this paper is to examine the preconditioned response of soft tissue to load controlled deformation using nonlinear viscoelastic material models including quasi-linear viscoelasticity, and to determine under what conditions this anomalous behavior becomes apparent. Results from this study suggest that this behavior is a true phenomenon unique to load controlled deformations that results from the interplay of nonlinear effects and creep behavior. These results call for increased attention to experimental parameters when testing and modeling nonlinear viscoelastic material behavior. PMID:16730737

  15. The Role and Dynamics of ?-Catenin in Precondition Induced Neuroprotection after Traumatic Brain Injury

    PubMed Central

    Umschweif, Gali; Alexandrovich, Alexander G.; Trembovler, Victoria; Horowitz, Michal; Shohami, Esther

    2013-01-01

    Preconditioning via heat acclimation (34°C 30 d) results in neuroprotection from traumatic brain injury due to constitutive as well as dynamic changes triggered by the trauma. Among these changes is Akt phosphorylation, which decreases apoptosis and induces HIF1?. In the present study we investigated the Akt downstream GSK3?/? -catenin pathway and focused on post injury alternations of ? catenin and its impact on the cellular response in preconditioned heat acclimated mice. We found that the reduction in motor disability is accompanied with attenuation of depressive like behavior in heat acclimated mice that correlates with the GSK3? phosphorylation state. Concomitantly, a robust ? catenin phosphorylation is not followed by its degradation, or by reduced nuclear accumulation. Enhanced tyrosine phosphorylation of ? catenin in the injured area weakens the ? catenin-N cadherin complex. Membrane ? catenin is transiently reduced in heat acclimated mice and its recovery 7 days post TBI is accompanied by induction of the synaptic marker synaptophysin. We suggest a set of cellular events following traumatic brain injury in heat acclimated mice that causes ? catenin to participate in cell-cell adhesion alternations rather than in Wnt signaling. These events may contribute to synaptogenesis and the improved motor and cognitive abilities seen heat acclimated mice after traumatic brain injury. PMID:24124534

  16. Cardioprotective effect of remote preconditioning of trauma and remote ischemia preconditioning in a rat model of myocardial ischemia/reperfusion injury

    PubMed Central

    CHAI, QING; LIU, JIN; HU, YANG

    2015-01-01

    Remote ischemia preconditioning (RIPC) and remote preconditioning of trauma (RPCT) are two methods used to induce a cardioprotective function against ischemia/reperfusion injury (IRI). However, the underlying mechanisms of these two methods differ. The aim of the present study was to investigate the cardioprotective function of the two methods, and also observe whether combining RIPC with RPCT enhanced the protective effect. In total, 70 male Sprague Dawley rats were randomly divided into five groups, which included the sham, control, RIPC + RPCT, RPCT and RIPC groups. With the exception of the sham group, all the rats were subjected to myocardial IRI through the application of 30 min occlusion of the left coronary artery and 180 min reperfusion. Serum cardiac troponin I (cTnI) levels, myocardial infarct size (IS) and the cardiomyocyte apoptotic index (AI) were assessed. The levels of serum cTnI were lower in the experimental groups when compared with the control group (control, 58.59±12.50 pg/ml; RIPC + RPCT, 46.05±8.62 pg/ml; RPCT, 45.98±11.24 pg/ml; RIPC, 43.46±5.05 pg/ml; P<0.05, vs. control), and similar results were observed for the myocardial IS (control, 48.34±6.79%; RIPC + RPCT, 29.64±4.51%; RPCT, 29.05±8.51%; RIPC, 27.72±6.27%; P<0.05, vs. control) and the AI (control, 31.75±10.65%; RIPC + RPCT, 18.32±9.30%; RPCT, 18.51±9.26%; RIPC, 20.41±3.86%; P<0.05, vs. control). However, no statistically significant differences were observed among the three experimental groups (P>0.05). Therefore, RIPC and RPCT exhibit cardioprotective effects when used alone or in combination. However, a combination of RIPC and RPCT does not enhance the cardioprotective effect observed with the application of either single method. Therefore, for patients undergoing major abdominal surgery, RIPC was considered to be unnecessary, while for patients undergoing other types of non-cardiac major surgery and minimally invasive interventional surgery, RIPC may be useful. In addition, patients with embolism diseases are also liable to IRI when reperfusion treatment such as thrombolysis is conducted. Thus RIPC may also be beneficial for these patients.

  17. TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING

    EPA Science Inventory

    Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C. Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic Preconditioning Craig...

  18. Exercise preconditioning reduces ischemia reperfusion-induced focal cerebral infarct volume through up-regulating the expression of HIF-1?.

    PubMed

    Wang, Lu; Deng, Wenqian; Yuan, Qiongjia; Yang, Huijun

    2015-03-01

    To study the effect and mechanism of exercise preconditioning on focal cerebral ischemia reperfusion induced cerebral infarction via rat model; Sixty Sprague Dawley rats were divided into three groups at random: ischemia reperfusion group (IR, n=24), sham group (sham, n=12) and exercise preconditioning group (EP, n=24). Group EP carried out moderate exercise preconditioning for 4 weeks (swimming with non-weight bearing, 60 minutes/day, 6 days/week), Rats in Group EP and IR were established cerebral ischemia reperfusion injury model by Zea Longa's thread method. The cerebral infarct volume in rat of different group was evaluated after 2%TTC staining, expression of HIF-1? in rats' brain was detected by real-time RT-PCR, immunohistochmeistry method and western blot. No cerebral infarction and significant expression of HIF-1? in Group sham. Compared with Group IR, there was smaller infarct volume and stronger HIF-1? expression in Group EP (P<0.05). Moderate exercise preconditioning reduces ischemia reperfusion induced focal cerebral infarct volume through up-regulating the expression of HIF-1?. PMID:25796156

  19. Limb Ischemic Preconditioning Protects Endothelium from Oxidative Stress by Enhancing Nrf2 Translocation and Upregulating Expression of Antioxidases

    PubMed Central

    Chen, Min; Zhang, Mingsheng; Zhang, Xuanping; Li, Jie; Wang, Yan; Fan, Yanying; Shi, Ruizan

    2015-01-01

    Remote ischemic preconditioning is often performed by limb ischemic preconditioning (LIPC), which has been demonstrated to be beneficial to various cells, including endothelial cells. The mechanisms underlying the protection have not been well clarified. The present study was designed to observe the effects of sera derived from rats after LIPC on human umbilical vein endothelial cells (HUVECs) injured by hydrogen peroxide (H2O2) -induced oxidative stress and explore the involvement of redox state in the protection. Incubation with 1 mM H2O2 for 2 h induced a significant reduction in HUVECs’ viability with increased production of malondialdehyde (MDA) and reactive oxygen species (ROS). Preincubation with early preconditioning serum (EPS) or delayed preconditioning serum (DPS) derived from rats subjected to LIPC alleviated these changes. Both EPS and DPS increased the nuclear translocation of transcription factor nuclear factor E2-related factor 2 (Nrf2) and the expression of antioxidases. The protective effects of EPS and DPS were blocked neither by MEK/ERK inhibitors U0126 nor by PI3K/Akt inhibitors LY294002. In conclusion, the present study provides the evidence that LIPC protects the HUVECs from H2O2-induced injury by, at least partially, enhancement of Nrf2 translocation and upregulation of antioxidases via signaling pathways independent of MEK/ERK and PI3K/Akt. PMID:26029932

  20. Preconditioning with +Gz acceleration (head-to-foot inertial load) produces neuroprotection against transient focal cerebral ischemia in rats.

    PubMed

    Sang, Hanfei; Li, Jinsheng; Liu, Junle; Wang, Zhou; Huo, Tingting; Sun, Jing; Xiong, Lize

    2008-11-01

    Ischemic preconditioning is considered to be the most robust endogenous neuroprotectant. However, the conventional ischemic preconditioning protocol is both invasive and impractical to apply. The aim of the present study was to evaluate whether preconditioning with +Gz centrifuge acceleration (head-to-foot inertial load) which could induce brief episodes of sublethal ischemia in brain had neuroprotection against focal cerebral ischemic injury. A total of 85 male Sprague-Dawley rats were randomly assigned to five groups (n = 17 in each). The 2 Gz, 4 Gz, 6 Gz and 8 Gz groups were subjected to 3 min exposures at +2 Gz, +4 Gz, +6 Gz and +8 Gz, respectively for consecutive three times in animal centrifuge, with a 30-min rest period between each centrifuge run. The control group had no exposure to +Gz acceleration. Twenty-four hours after the last pretreatment, 12 rats in each groups were subjected to focal cerebral ischemia for 120 min and the other five rats in each group were sacrificed to measure the expression of heat shock protein 70(HSP70) in hippocampus by Western blot analysis. The results indicated that the 6 Gz and 8 Gz groups showed smaller infarct volume and lower neurologic deficit scores than the control group. The expression of HSP70 was significantly increased in 6 Gz and 8 Gz groups than those in the control group. Therefore, preconditioning with +Gz acceleration produced delayed neuroprotection against focal cerebral ischemia and that the neuroprotection may be related to the induction of HSP70. PMID:18778750

  1. Magnetosphere preconditioning under northward IMF: Evidence from the study of coronal mass ejection and corotating interaction region geoeffectiveness

    Microsoft Academic Search

    B. Lavraud; M. F. Thomsen; J. E. Borovsky; M. H. Denton; T. I. Pulkkinen

    2006-01-01

    Motivated by recent observations and simulations of the formation of a cold and dense plasma sheet in the tail of the magnetosphere under northward interplanetary magnetic field (IMF) and of the direct influence of the plasma sheet density on the ring current strength, this paper aims at (1) highlighting how the coupling of these effects may lead to a preconditioning

  2. Heat shock preconditioning protects against ER stress-induced apoptosis through the regulation of the BH3-only protein BIM.

    PubMed

    Kennedy, Donna; Mnich, Katarzyna; Samali, Afshin

    2014-01-01

    A mild heat shock (HS) preconditioning and acquisition of thermotolerance protects cells against a variety of cytotoxic agents that otherwise induce apoptosis. Here we tested whether there is a molecular link between HS preconditioning and endoplasmic reticulum (ER) stress-induced apoptosis. ER stress results from a loss of ER lumen homeostasis, culminating in an accumulation of unfolded/misfolded proteins in the ER and activation of unfolded protein response (UPR). Unresolved, ER stress leads to activation of BH3-only proteins, mitochondrial membrane permeabilization, caspase activation and apoptotic cell death. HS preconditioning (1 h at 42 °C) induced a rapid increase in HSPA1 (HSP70) levels which remained elevated for at least 48 h post-HS. HS preconditioning significantly reduced BAX, caspase activation and apoptosis in cell cultures treated with the ER stress-inducing agents thapsigargin (TG) and tunicamycin (TM). HS-mediated protection was found to be due to regulation of the BH3-only protein BIM. Further, overexpression of HSPA1 could not mimic the effect of HS on BIM expression, suggesting that other HS factors may play a role in inhibiting ER stress-induced apoptosis by regulating BIM. PMID:25349785

  3. Two examples of the impact of partitioning with Chaco and Metis on the convergence of additive Schwarz-preconditioned FGMRES

    SciTech Connect

    DeLong, M.

    1997-09-29

    Algebraic graph partitioning packages that require no geometric or physical information are often used to partition sparse linear systems for solution on parallel computers using Krylov-space iterative methods with domain decomposition-type preconditioning methods. The authors show through a couple of examples that this can have a substantial impact on the convergence of the iterative methods.

  4. Human bone marrow-derived mesenchymal stem cells display enhanced clonogenicity but impaired differentiation with hypoxic preconditioning.

    PubMed

    Boyette, Lisa B; Creasey, Olivia A; Guzik, Lynda; Lozito, Thomas; Tuan, Rocky S

    2014-02-01

    Stem cells are promising candidate cells for regenerative applications because they possess high proliferative capacity and the potential to differentiate into other cell types. Mesenchymal stem cells (MSCs) are easily sourced but do not retain their proliferative and multilineage differentiative capabilities after prolonged ex vivo propagation. We investigated the use of hypoxia as a preconditioning agent and in differentiating cultures to enhance MSC function. Culture in 5% ambient O(2) consistently enhanced clonogenic potential of primary MSCs from all donors tested. We determined that enhanced clonogenicity was attributable to increased proliferation, increased vascular endothelial growth factor secretion, and increased matrix turnover. Hypoxia did not impact the incidence of cell death. Application of hypoxia to osteogenic cultures resulted in enhanced total mineral deposition, although this effect was detected only in MSCs preconditioned in normoxic conditions. Osteogenesis-associated genes were upregulated in hypoxia, and alkaline phosphatase activity was enhanced. Adipogenic differentiation was inhibited by exposure to hypoxia during differentiation. Chondrogenesis in three-dimensional pellet cultures was inhibited by preconditioning with hypoxia. However, in cultures expanded under normoxia, hypoxia applied during subsequent pellet culture enhanced chondrogenesis. Whereas hypoxic preconditioning appears to be an excellent way to expand a highly clonogenic progenitor pool, our findings suggest that it may blunt the differentiation potential of MSCs, compromising their utility for regenerative tissue engineering. Exposure to hypoxia during differentiation (post-normoxic expansion), however, appears to result in a greater quantity of functional osteoblasts and chondrocytes and ultimately a larger quantity of high-quality differentiated tissue. PMID:24436440

  5. IEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION, VOL. 52, NO. 9, SEPTEMBER 2004 2277 Sparse Inverse Preconditioning of Multilevel Fast

    E-print Network

    Zhang, Jun

    ) preconditioning. I. INTRODUCTION THE solution to electromagnetic wave interaction with ma- terial coated objects an- tenna analysis [16], [31], [34]. In three-dimensional (3-D) elec- tromagnetic wave scatteringIEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION, VOL. 52, NO. 9, SEPTEMBER 2004 2277 Sparse Inverse

  6. Lung Cancer Prevention

    MedlinePLUS

    ... Cancer Prevention Lung Cancer Screening Lung Cancer Research Lung Cancer Prevention (PDQ®) What is prevention? Cancer prevention is ... to keep cancer from starting. General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  7. Role of the parasympathetic nervous system in cardioprotection by remote hindlimb ischaemic preconditioning.

    PubMed

    Donato, Martín; Buchholz, Bruno; Rodríguez, Manuel; Pérez, Virginia; Inserte, Javier; García-Dorado, David; Gelpi, Ricardo J

    2013-02-01

    This investigation was designed to determine the participation of the vagus nerve and muscarinic receptors in the remote ischaemic preconditioning (rIPC) mechanism. New Zealand rabbits were anaesthetized, and the femoral artery was dissected. After 30 min of monitoring, the hearts were isolated and subjected to 30 min of global no-flow ischaemia and 180 min of reperfusion (non-rIPC group). The ventricular function was evaluated, considering the left ventricular developed pressure and the left ventricular end-diastolic pressure. In the rIPC group, the rabbits were subjected to three cycles of hindlimb ischaemia (5 min) and reperfusion (5 min), and the same protocol as that used in non-rIPC group was then repeated. In order to evaluate the afferent neural pathway during the rIPC protocol we used two groups, one in which the femoral and sciatic nerves were sectioned and the other in which the spinal cord was sectioned (T9-T10 level). To study the efferent neural pathway during the rIPC protocol, the vagus nerve was sectioned and, in another group, atropine was administered. The effect of vagal stimulation was also evaluated. An infarct size of 40.8 ± 3.1% was obtained in the non-rIPC group, whereas in rIPC group the infarct size decreased to 16.4 ± 3.5% (P < 0.05). During the preconditioning protocol, the vagus nerve section and the atropine administration each abolished the effect of rIPC on infarct size. Vagal stimulation mimicked the effect of rIPC, decreasing infarct size to 15.2 ± 4.7% (P < 0.05). Decreases in infarct size were accompanied by improved left ventricular function. We demonstrated the presence of a neural afferent pathway, because the spinal cord section completely abolished the effect of rIPC on infarct size. In conclusion, rIPC activates a neural afferent pathway, the cardioprotective signal reaches the heart through the vagus nerve (efferent pathway), and acetylcholine activates the ischaemic preconditioning phenomenon when acting on the muscarinic receptors. PMID:22872660

  8. A preliminary biomechanical study of cyclic preconditioning effects on canine cadaveric whole femurs.

    PubMed

    Zdero, Rad; Gallimore, Chris H; McConnell, Alison J; Patel, Harshita; Nisenbaum, Rosane; Morshed, Golam; Koo, Henry; McKee, Michael D; Schemitsch, Emil H; Bougherara, Habiba

    2012-09-01

    Biomechanical preconditioning of biological specimens by cyclic loading is routinely done presumably to stabilize properties prior to the main phase of a study. However, no prior studies have actually measured these effects for whole bone of any kind. The aim of this study, therefore, was to quantify these effects for whole bones. Fourteen matched pairs of fresh-frozen intact cadaveric canine femurs were sinusoidally loaded in 4-point bending from 50 N to 300 N at 1 Hz for 25 cycles. All femurs were tested in both anteroposterior (AP) and mediolateral (ML) bending planes. Bending stiffness (i.e., slope of the force-vs-displacement curve) and linearity R(2) (i.e., coefficient of determination) of each loading cycle were measured and compared statistically to determine the effect of limb side, cycle number, and bending plane. Stiffnesses rose from 809.7 to 867.7 N/mm (AP, left), 847.3 to 915.6 N/mm (AP, right), 829.2 to 892.5 N/mm (AP, combined), 538.7 to 580.4 N/mm (ML, left), 568.9 to 613.8 N/mm (ML, right), and 553.8 to 597.1 N/mm (ML, combined). Linearity R(2) rose from 0.96 to 0.99 (AP, left), 0.97 to 0.99 (AP, right), 0.96 to 0.99 (AP, combined), 0.95 to 0.98 (ML, left), 0.94 to 0.98 (ML, right), and 0.95 to 0.98 (ML, combined). Stiffness and linearity R(2) versus cycle number were well-described by exponential curves whose values leveled off, respectively, starting at 12 and 5 cycles. For stiffness, there were no statistical differences for left versus right femurs (p?=?0.166), but there were effects due to cycle number (p?preconditioning cycles was needed to fully stabilize both the stiffness and linearity of the canine femurs. This is the first study to measure the effects of mechanical preconditioning on whole bones, having some practical implications on research practices. PMID:22938376

  9. Identical MicroRNAs Regulate Liver Protection during Anaesthetic and Ischemic Preconditioning in Rats: An animal study

    PubMed Central

    Morita, Tomonori; Ishikawa, Masashi; Sakamoto, Atsuhiro

    2015-01-01

    Anaesthetic preconditioning (APC) and ischemic preconditioning (IPC) ameliorate liver ischemia–reperfusion (I/R) injury and are important for regulating hepatic I/R injury. MicroRNAs (miRNAs) are short, noncoding RNA molecules of 21–23 nucleotides in length, and are currently under intensive investigation regarding their ability to regulate gene expression in a wide range of species. miRNA activity is involved in controlling a wide range of biological functions and processes. We evaluated whether APC and IPC are mediated by the same miRNAs by performing comprehensive miRNA screening experiments in a rat model of hepatic I/R injury. Twenty-one rats were randomly divided into three groups (n = 7/group): control (mock preconditioning), APC, and IPC. Control rats were subjected to 60 min of hepatic ischemia followed by 4 h of reperfusion, whereas the APC and IPC groups were preconditioned with 2% sevoflurane and hepatic ischemia for 10 min prior to ischemia-reperfusion, respectively. Liver samples were collected to measure miRNA levels after 3 h of reperfusion, and gene networks and canonical pathways were identified using Ingenuity Pathway Analysis (IPA). Blood samples were collected to measure the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Although haemodynamic parameters did not vary among the groups, AST and ALT levels were significantly higher in the control group than in the APC and IPC groups. Comprehensive miRNA screening experiments revealed that most miRNAs altered in the APC group were common to those in the IPC group. IPA identified five miRNAs related to the Akt–glycogen synthase kinase-3? (GSK-3?)–cyclin D1 pathway that were significantly affected by both preconditioning strategies. The application of either APC or IPC to ameliorate hepatic I/R injury results in expression of several common miRNAs that are related to the Akt–GSK–cyclin D1 pathway. PMID:25974021

  10. Retinal neuroprotection by hypoxic preconditioning is independent of hypoxia-inducible factor-1 alpha expression in photoreceptors.

    PubMed

    Thiersch, Markus; Lange, Christina; Joly, Sandrine; Heynen, Severin; Le, Yun Zheng; Samardzija, Marijana; Grimm, Christian

    2009-06-01

    Hypoxic preconditioning stabilizes hypoxia-inducible factor (HIF) 1 alpha in the retina and protects photoreceptors against light-induced cell death. HIF-1 alpha is one of the major transcription factors responding to low oxygen tension and can differentially regulate a large number of target genes. To analyse whether photoreceptor-specific expression of HIF-1 alpha is essential to protect photoreceptors by hypoxic preconditioning, we knocked down expression of HIF-1 alpha specifically in photoreceptor cells, using the cyclization recombinase (Cre)-lox system. The Cre-mediated knockdown caused a 20-fold reduced expression of Hif-1 alpha in the photoreceptor cell layer. In the total retina, RNA expression was reduced by 65%, and hypoxic preconditioning led to only a small increase in HIF-1 alpha protein levels. Accordingly, HIF-1 target gene expression after hypoxia was significantly diminished. Retinas of Hif-1 alpha knockdown animals did not show any pathological alterations, and tolerated hypoxic exposure in a comparable way to wild-type retinas. Importantly, the strong neuroprotective effect of hypoxic preconditioning against light-induced photoreceptor degeneration persisted in knockdown mice, suggesting that hypoxia-mediated survival of light exposure does not depend on an autocrine action of HIF-1 alpha in photoreceptor cells. Hypoxia-mediated stabilization of HIF-2 alpha and phosphorylation of signal transducer and activator of transcription 3 (STAT 3) were not affected in the retinas of Hif-1 alpha knockdown mice. Thus, these factors are candidates for regulating the resistance of photoreceptors to light damage after hypoxic preconditioning, along with several potentially neuroprotective genes that were similarly induced in hypoxic knockdown and control mice. PMID:19508692

  11. Second window of preconditioning normalizes palmitate use for oxidation and improves function during low-flow ischaemia

    PubMed Central

    Kudej, Raymond K.; Fasano, Mathew; Zhao, Xin; Lopaschuk, Gary D.; Fischer, Susan K.; Vatner, Dorothy E.; Vatner, Stephen F.; Lewandowski, E. Douglas

    2011-01-01

    Aims Although a major mechanism for cardioprotection is altered metabolism, little is known regarding metabolic changes in ischaemic preconditioning and subsequent ischaemia. Our objective was to examine the effects of the second window of preconditioning (SWOP), the delayed phase of preconditioning against infarction and stunning, on long-chain free fatty acid (LCFA) oxidation during ischaemia in chronically instrumented, conscious pigs. Methods and results We studied three groups: (i) normal baseline perfusion (n = 5); (ii) coronary artery stenosis (CAS; n = 5); (iii) CAS 24 h following 2 × 10 min coronary occlusions and 10 min reperfusion (n = 7). Ischaemia was induced by a left anterior descending (LAD) stenosis (40% flow reduction) for 90 min, dropping systolic wall thickening by 72%. LCFA oxidation was assessed following LAD infusion of 13C palmitate, i.e. during control or stenosis, by in vitro nuclear magnetic resonance of the sampled myocardium. Stenosis reduced subendocardial blood flow subendocardially, but not subepicardial, yet induced transmural reductions in LCFA oxidation and increased non-oxidative glycolysis. During stenosis, preconditioned hearts showed normalized contributions of LCFA to oxidative ATP synthesis, despite increased lactate accumulation. SWOP induced a shift towards LCFA oxidation during stenosis, despite increased malonyl-CoA, and marked protection of contractile function with a significant improvement in systolic wall thickening. Conclusion Thus, the second window of preconditioning normalized oxidative metabolism of LCFA during subsequent ischaemia despite elevated non-oxidative glycolysis and malonyl-CoA and was linked to protection of regional contractile function resulting in improved mechanical performance. Interestingly, the metabolic responses occurred transmurally while ischaemia was restricted solely to the subendocardium. PMID:21835931

  12. Sevoflurane preconditioning improving cerebral focal ischemia-reperfusion damage in a rat model via PI3K/Akt signaling pathway.

    PubMed

    Zhang, Yan; Tian, Shou-Yuan; Li, Yan-Wei; Zhang, Ling; Yu, Jian-Bo; Li, Jing; Chen, Yi-Yang; Wang, Ya-Xin; Liang, Yu; Zhang, Xiu-Shan; Wang, Wen-Sheng; Liu, Hai-Gen

    2015-09-10

    In this study, we aimed to assess the neuroprotective effect of sevoflurane preconditioning in a cerebral focal ischemia-reperfusion rat model. Sixty Sprague Dawley rats were divided into six groups: sham operated group, cerebral focal ischemia-reperfusion (CIR) group, CIR+sevoflurane preconditioning (SP) (2%) group, CIR+sevoflurane preconditioning (2.5%) group, CIR+sevoflurane preconditioning (3%) group, and CIR+sevoflurane preconditioning (3.5%) group. All subjects were euthanized 2days post-surgery and their hippocampus tissues were removed. Tissue malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were measured and hippocampus tissue samples were examined histopathologically. Results showed that significant difference in antioxidant, immunity indexes, and apoptosis-related protein expression was detected in hippocampus tissue between sham-operated control and CIR groups. Sevoflurane preconditioning significantly dose-dependently reduced MDA, IL-1?, IL-6, IL-10 and TNF-? levels and enhanced antioxidant enzyme activities in hippocampus tissue of CIR+SP groups compared to CIR group. In addition, sevoflurane preconditioning significantly dose-dependently upregulated PI3K, p-Akt and Bcl-2 levels and downregulated caspase-3 and Bax levels in hippocampus tissue of CIR+SP groups compared to CIR group. It can be concluded that sevoflurane preconditioning demonstrates a strong and ameliorative effect on cerebral I/R damage in rats. The neuroprotective mechanisms of sevoflurane preconditioning are associated with its properties of anti-apoptosis and anti-oxidation as well as regulation of PI3K and p-Akt signal activation. PMID:25979673

  13. [Axis I "illness experience and treatment preconditions" of operational psychodynamic diagnosis (OPD). Experiences in clinical practice].

    PubMed

    Schneider, W; Klauer, T; Freyberger, H J; Hake, K; von Wietersheim, J

    2000-12-01

    In a selective survey, results on psychometric properties and aspects of application of the axis I, "illness experience and treatment preconditions" of the Operational Psychodynamic Diagnoses (OPD) are described. Following remarks on the role of defense and coping theories in the conceptualisation of the axis, its structure and contents are outlined. After a brief summary of findings on its interrater reliability, several aspects of validity are discussed. Results on discriminative validity show that axis I items are useful in the statistical discrimination of subsamples differing in age, clinical diagnoses, and diagnostic setting (psychotherapy outpatient vs. psychosomatic consultation-liasion services). The contribution of axis I items to prediction of treatment outcomes, moreover, reveals high degree of predictive or treatment validity. After an integrative discussion of these findings, implications of patient personality and coping behaviour for axis I ratings are highlighted as important objectives for future OPD research. PMID:11199108

  14. Conceptual preconditions of overcoming of relativistic intentions in modern philosophy of science

    E-print Network

    Kulikov, Sergey

    2014-01-01

    The paper defends the thesis that it's possible to maintain some conceptual preconditions of overcoming of relativistic intentions in modern philosophy of science ("there are no any general foundations in philosophy of science"). We found two general foundations in philosophy of science as a minimum. From the first side it's realistic to reveal on the base of special understanding of time the value of time not only in natural thought (especially in theory of gravity) but also in humanitarian knowledge. That's why philosophy of science has independent position in epistemology and ontology corresponding to interpretation of time as a general category of scientific thinking. The nature of time has internally inconsistent (paradoxical) character. Time is phenomenon which existing and not existing at the same time. This phenomenon is identified with imaginary movement and also ideal (formal) process of formation of the nature. The general understanding of time is connected with its "mathematical" meaning as calcul...

  15. Matrix multiplication operations with data pre-conditioning in a high performance computing architecture

    DOEpatents

    Eichenberger, Alexandre E; Gschwind, Michael K; Gunnels, John A

    2013-11-05

    Mechanisms for performing matrix multiplication operations with data pre-conditioning in a high performance computing architecture are provided. A vector load operation is performed to load a first vector operand of the matrix multiplication operation to a first target vector register. A load and splat operation is performed to load an element of a second vector operand and replicating the element to each of a plurality of elements of a second target vector register. A multiply add operation is performed on elements of the first target vector register and elements of the second target vector register to generate a partial product of the matrix multiplication operation. The partial product of the matrix multiplication operation is accumulated with other partial products of the matrix multiplication operation.

  16. Effects of diabetes on myocardial infarct size and cardioprotection by preconditioning and postconditioning

    PubMed Central

    2012-01-01

    In spite of the current optimal therapy, the mortality of patients with ischemic heart disease (IHD) remains high, particularly in cases with diabetes mellitus (DM) as a co-morbidity. Myocardial infarct size is a major determinant of prognosis in IHD patients, and development of a novel strategy to limit infarction is of great clinical importance. Ischemic preconditioning (PC), postconditioning (PostC) and their mimetic agents have been shown to reduce infarct size in experiments using healthy animals. However, a variety of pharmacological agents have failed to demonstrate infarct size limitation in clinical trials. One of the possible reasons for the discrepancy between the results of animal experiments and clinical trials is that co-morbidities, including DM, modified myocardial responses to ischemia/reperfusion and to cardioprotective agents. Here we summarize observations of the effects of DM on myocardial infarct size and ischemic PC and PostC and discuss perspectives for protection of DM hearts. PMID:22694800

  17. Comparison of nested factorization, constrained pressure residual, and incomplete factorization preconditionings

    SciTech Connect

    Behie, A.

    1985-02-01

    Two recently developed methods for the solution of the sparse block-banded linear equation sets generated by fully implicit reservoir simulators are investigated. Nested factorization is a new approach to forming an incomplete factorization of the linear system. Comparisons are made of the nested factorization approach and the incomplete LU factorization (ILU) approach. Tests are done on both model problems and on problems generated by reservoir simulators. The nested factorization was no better than the best ILU method on both types of problems in most cases. In some cases it was considerably worse. Constrained pressure residual preconditioning (CPR) is a variant of the COMBINATIVE method. These two methods are compared on problems generated by black oil and steam simulators. CPR gives small improvements in convergence rates in some cases.

  18. Efficient preconditioning of the electronic structure problem in large scale ab initio molecular dynamics simulations.

    PubMed

    Schiffmann, Florian; VandeVondele, Joost

    2015-06-28

    We present an improved preconditioning scheme for electronic structure calculations based on the orbital transformation method. First, a preconditioner is developed which includes information from the full Kohn-Sham matrix but avoids computationally demanding diagonalisation steps in its construction. This reduces the computational cost of its construction, eliminating a bottleneck in large scale simulations, while maintaining rapid convergence. In addition, a modified form of Hotelling's iterative inversion is introduced to replace the exact inversion of the preconditioner matrix. This method is highly effective during molecular dynamics (MD), as the solution obtained in earlier MD steps is a suitable initial guess. Filtering small elements during sparse matrix multiplication leads to linear scaling inversion, while retaining robustness, already for relatively small systems. For system sizes ranging from a few hundred to a few thousand atoms, which are typical for many practical applications, the improvements to the algorithm lead to a 2-5 fold speedup per MD step. PMID:26133420

  19. Some Experiences with Nonoverlapping Schur Complement Parallel Preconditioning for CFD Calculations

    NASA Technical Reports Server (NTRS)

    Barth, Timothy J.; Chan, Tony F.; Tang, Wei-Pai; Kwak, Dochan (Technical Monitor)

    1996-01-01

    In this work we consider solving matrices which arise from the discretization of advection-diffusion field equations on arbitrary triangulated domains using stabilized numerical methods. The talk will discuss several candidate matrix preconditioning algorithms based on the 2 x 2 block factorization induced by an apriori partitioning of the triangulated domain. Application of the 2 x 2 block preconditioner requires the formation and inversion of the Schur complement submatrix. We consider several strategies for simplifying this task: incomplete Schur complement factorizations, drop tolerance element filling, Schur complement probing, and localized Schur complement inversion. Numerical results will be shown comparing performance and efficiency of these approximations. The matrix preconditioner has also been embedded into a Newton algorithm for solving the nonlinear Euler and Navier-Stokes equations governing compressible flow. The remainder of the talk will show numerous examples in CFD to demonstrate the efficiency and robustness of the techniques.

  20. Identification of Dynamic Processes Responsible for Preconditioning the Atmosphere for Severe Convective Outbreaks in Midlatitudes

    NASA Astrophysics Data System (ADS)

    Agard, J. V.; Emanuel, K.

    2014-12-01

    Budgets of the tendency of convective available potential energy (CAPE) are calculated using reanalysis data in case studies of several North American severe weather outbreaks from the years 2012 and 2013. These budgets separate the tendency of CAPE into terms arising from diabatic heating of the subcloud boundary layer, radiative cooling of the free troposphere, and advection of air in the free troposphere relative to the motion of a parcel to be lifted. It is found that in most cases, the CAPE tendency budget is dominated by the term representing diabatic heating of the subcloud layer, which establishes high CAPE values in advance of thunderstorm development. This result suggests the relative importance of surface entropy fluxes in supporting midlatitude severe local storms through atmospheric preconditioning (CAPE buildup). By extension, this result warrants further investigation into the roles of environmental land surface properties as controls on the climatology of midlatitude severe convecton, as such properties play important roles in modulating surface entropy fluxes.

  1. Heme Oxygenase 1 Is Associated with Ischemic Preconditioning-Induced Protection Against Brain Ischemia

    PubMed Central

    Zeynalov, Emil; Shah, Zahoor A.; Li, Rung-chi; Doré, Sylvain

    2009-01-01

    Ischemic preconditioning (IPC) protects brain against ischemic injury by activating specific mechanisms. Our goal was to determine if the inducible heme oxygenase 1 (HO1) is required for such protection. IPC before transient or permanent ischemia reduced cortical infarct volumes by 57.4% and 33.9%, respectively at 48 h in wildtype adult mice. Interestingly, IPC failed to protect the HO1 gene deleted mice against permanent ischemic brain injury. IPC also resulted in a significant increase in HO1 protein levels in the brain and correlated with reduced neurological deficits after permanent and transient brain ischemia. Our study demonstrates that neuroprotective effects of IPC are at least partially mediated via HO1. Elucidating the physiological/cellular role by which HO1 is protective against brain ischemia may aid the development of selective drugs to treat stroke and its associated neurological disorders. PMID:19465127

  2. Krylov methods preconditioned with incompletely factored matrices on the CM-2

    NASA Technical Reports Server (NTRS)

    Berryman, Harry; Saltz, Joel; Gropp, William; Mirchandaney, Ravi

    1989-01-01

    The performance is measured of the components of the key interative kernel of a preconditioned Krylov space interative linear system solver. In some sense, these numbers can be regarded as best case timings for these kernels. Sweeps were timed over meshes, sparse triangular solves, and inner products on a large 3-D model problem over a cube shaped domain discretized with a seven point template. The performance of the CM-2 is highly dependent on the use of very specialized programs. These programs mapped a regular problem domain onto the processor topology in a careful manner and used the optimized local NEWS communications network. The rather dramatic deterioration in performance was documented when these ideal conditions no longer apply. A synthetic workload generator was developed to produce and solve a parameterized family of increasingly irregular problems.

  3. Fluid preconditioning for Newton-Krylov-based, fully implicit, electrostatic particle-in-cell simulations

    E-print Network

    Chen, Guangye; Leibs, Christopher A; Knoll, Dana A; Taitano, William

    2013-01-01

    A recent proof-of-principle study proposes an energy- and charge-conserving, nonlinearly implicit electrostatic particle-in-cell (PIC) algorithm in one dimension [Chen et al, J. Comput. Phys., 230 (2011) 7018]. The algorithm in the reference employs an unpreconditioned Jacobian-free Newton-Krylov method, which ensures nonlinear convergence at every timestep (resolving the dynamical timescale of interest). Kinetic enslavement, which is one key component of the algorithm, not only enables fully implicit PIC a practical approach, but also allows preconditioning the kinetic solver with a fluid approximation. This study proposes such a preconditioner, in which the linearized moment equations are closed with moments computed from particles. Effective acceleration of the linear GMRES solve is demonstrated, on both uniform and non-uniform meshes. The algorithm performance is largely insensitive to the electron-ion mass ratio. Numerical experiments are performed on a 1D multi-scale ion acoustic wave test problem.

  4. Fluid preconditioning for Newton–Krylov-based, fully implicit, electrostatic particle-in-cell simulations

    SciTech Connect

    Chen, G., E-mail: gchen@lanl.gov [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Chacón, L. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)] [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Leibs, C.A. [University of Colorado Boulder, Boulder, CO 80309 (United States)] [University of Colorado Boulder, Boulder, CO 80309 (United States); Knoll, D.A. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)] [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Taitano, W. [University of New Mexico, Albuquerque, NM 87131 (United States)] [University of New Mexico, Albuquerque, NM 87131 (United States)

    2014-02-01

    A recent proof-of-principle study proposes an energy- and charge-conserving, nonlinearly implicit electrostatic particle-in-cell (PIC) algorithm in one dimension [9]. The algorithm in the reference employs an unpreconditioned Jacobian-free Newton–Krylov method, which ensures nonlinear convergence at every timestep (resolving the dynamical timescale of interest). Kinetic enslavement, which is one key component of the algorithm, not only enables fully implicit PIC as a practical approach, but also allows preconditioning the kinetic solver with a fluid approximation. This study proposes such a preconditioner, in which the linearized moment equations are closed with moments computed from particles. Effective acceleration of the linear GMRES solve is demonstrated, on both uniform and non-uniform meshes. The algorithm performance is largely insensitive to the electron–ion mass ratio. Numerical experiments are performed on a 1D multi-scale ion acoustic wave test problem.

  5. A projected preconditioned conjugate gradient algorithm for computing many extreme eigenpairs of a Hermitian matrix

    NASA Astrophysics Data System (ADS)

    Vecharynski, Eugene; Yang, Chao; Pask, John E.

    2015-06-01

    We present an iterative algorithm for computing an invariant subspace associated with the algebraically smallest eigenvalues of a large sparse or structured Hermitian matrix A. We are interested in the case in which the dimension of the invariant subspace is large (e.g., over several hundreds or thousands) even though it may still be small relative to the dimension of A. These problems arise from, for example, density functional theory (DFT) based electronic structure calculations for complex materials. The key feature of our algorithm is that it performs fewer Rayleigh-Ritz calculations compared to existing algorithms such as the locally optimal block preconditioned conjugate gradient or the Davidson algorithm. It is a block algorithm, and hence can take advantage of efficient BLAS3 operations and be implemented with multiple levels of concurrency. We discuss a number of practical issues that must be addressed in order to implement the algorithm efficiently on a high performance computer.

  6. Effect of a prior bout of preconditioning exercise on muscle damage from downhill walking.

    PubMed

    Maeo, Sumiaki; Ochi, Yusuke; Yamamoto, Masayoshi; Kanehisa, Hiroaki; Nosaka, Kazunori

    2015-03-01

    This study investigated whether reduced-duration downhill walking (DW) would confer a protective effect against muscle damage induced by a subsequent bout of longer duration DW performed 1 week or 4 weeks later. Healthy young adults were allocated to a control or one of the preconditioning exercise (PRE-1wk or PRE-4wk) groups (10 men and 4 women per group). PRE-1wk and PRE-4wk groups performed 20-min DW (-28% slope, 5 km/h, 10% body mass added to a backpack) 1 week and 4 weeks before 40-min DW, respectively, and the control group performed 40-min DW only. Maximal voluntary contraction (MVC) knee extension torque, plasma creatine kinase (CK) activity, and muscle soreness (100-mm visual analog scale) were measured before, immediately after, and 24, 48, and 72 h after DW, and the changes in these variables were compared among groups. The control group showed symptoms of muscle damage (e.g., prolonged decrease in MVC: -14% ± 10% at 48 h post-DW) after 40-min DW. Changes in all variables after 40-min DW of PRE-1wk and PRE-4wk groups were 54%-61% smaller (P < 0.05) than the control group, without significant differences between PRE-1wk and PRE-4wk groups for MVC and plasma CK activity. Importantly, changes after the preconditioning exercise (20-min DW) were 67%-69% smaller (P < 0.05) than those after the 40-min DW of the control group. These findings suggest that 20-min DW resulting in minor muscle damage conferred a protective effect against subsequent 40-min DW, and its effect could last for more than 4 weeks. PMID:25693898

  7. Elbe floods: An interaction of hydrological and meteorological (pre-)conditions

    NASA Astrophysics Data System (ADS)

    Nied, M.; Pardowitz, T.; Nissen, K.; Hundecha, Y.; Merz, B.; Ulbrich, U.

    2012-04-01

    The genesis of a river flood is triggered by the interaction of various elements. Key factors are the hydrological pre-conditions (e.g. soil saturation, snow cover) and the meteorological situation (e.g. amount and spatial distribution of precipitation). For the analysis of those key factors, we propose to classify the hydrological and meteorological (pre-)conditions of the Elbe river catchment and to identify flood favouring patterns. The meteorological classification is based on ERA 40 reanalysis data by Simulated Annealing clustering of mean sea level pressure, surface temperature and tropospheric humidity content. We find a good representation of typical winter and summer patterns, when using 40 classes. For each class its seasonality and probability to occur in connection with river flooding is determined. Two main types of patterns are found to be associated with Elbe river flooding: During summer, the most distinct pattern shows a cyclone over Southern Europe, which transports moist air from the Mediterranean towards central Europe, a situation also known as Vb. During winter, the patterns occurring prior to the floods mostly show a strong zonal flow, carrying moist air from the North East Atlantic. The hydrological classification is based on soil moisture as a representative of the initial catchment state. Soil moisture is simulated using a semi-distributed conceptual rainfall-runoff model that is calibrated using a Monte Carlo scheme with an objective function emphasizing high flows. Principal component analysis and cluster analysis are applied successively to identify patterns explaining most of the variability of the soil moisture dynamics and to identify days of similar soil moisture patterns. Independently of the number of clusters finally chosen, flood prone soil moisture clusters are detected. In a subsequent step, this pattern analysis will serve as the basis to estimate joint probabilities of the occurrence of hydro-meteorological pattern combinations that are flood prone. In addition, frequency changes of these pattern combinations under climate change will be examined.

  8. Loss of cardioprotection with ischemic preconditioning in aging hearts: role of sirtuin 1?

    PubMed

    Adam, Tasneem; Sharp, Stephanie; Opie, Lionel H; Lecour, Sandrine

    2013-01-01

    The effectiveness of ischemic preconditioning (IPC) to protect the heart against ischemia/reperfusion injury (IRI) declines with age. The deacetylase protein sirtuin 1 (Sirt 1) confers myriad functions including longevity and cardioprotection against IRI. As such, Sirt 1 may be a potential candidate to explain the protective effect of IPC. We aim to explore the role of Sirt 1 in the loss of the cardioprotective effect of IPC with age. Isolated hearts from young (9 weeks) and older (12-18 months) Long-Evans rats were subjected to 30 minutes of global ischemia and 60 minutes of reperfusion. Preconditioning stimuli were applied with either 2 cycles of 5-minute ischemia/reperfusion or with the potent Sirt 1 agonist resveratrol (RSV, 10 µmol/L) for 15 minutes followed by a 10-minute washout before the sustained ischemia. Both IPC and RSV significantly enhanced the functional recovery of young hearts by 168% (P < .001 vs control) and 65% (P < .01 vs control), respectively, and concomitantly reduced the infarct size by 65% and 45%, but the effect was blunted in older hearts. Administration of the selective Sirt 1 inhibitor III to young hearts did not alter the protective effect of IPC. Following ischemia/reperfusion, higher Sirt 1 deacetylase activity was detected in older hearts compared to young hearts (0.48 ± 0.13 arbitrary units [AU] vs 0.17 ± 0.03 AU, P < .01) and IPC did not alter Sirt 1 deacetylase activity. In conclusion, although Sirt 1 deacetylase activity is increased with age during ischemia/reperfusion, our data suggest that the loss of the cardioprotective effect of IPC in older animals is likely to be independent of Sirt 1. PMID:22960148

  9. Design and synthesis of nitrate esters of aromatic heterocyclic compounds as pharmacological preconditioning agents.

    PubMed

    Fotopoulou, Theano; Iliodromitis, Efstathios K; Koufaki, Maria; Tsotinis, Andrew; Zoga, Anastasia; Gizas, Vassilis; Pyriochou, Anastasia; Papapetropoulos, Andreas; Andreadou, Ioanna; Kremastinos, Dimitrios Th

    2008-04-15

    Ischemic preconditioning (IPC) constitutes an endogenous protective mechanism in which one or more brief periods of myocardial ischemia and reperfusion render the myocardium resistant to a subsequent more-sustained ischemic insult. Pharmacological preconditioning represents an ideal alternative of IPC. We now describe the design and synthesis of indole, quinoline, and purine systems with an attached pharmacophoric nitrate ester group. The indole and quinoline derivatives 4 and 5 possess structural features of the nitrate containing K(ATP) channel openers. Purine analogues 11 and 12, substituted at the position 6 by a piperidine moiety and at position 9 by an alkyl nitrate, could combine the effects of the nitrate containing K(ATP) channel openers and those of adenosine. Compound 13 bears the nicotinamide moiety of nicorandil instead of nitrate ester. Compounds 4, 5, and 11 reduced infarction and the levels of malondialdehyde (MDA) at reperfusion in anesthetized rabbits. Compounds 12 and 13 did not significantly reduce the infarct size. Analogues 4 and 5 increased cGMP and MDA during ischemia, while combined analogue 4 and mitoK(ATP) blocker 5-hydroxydecanoic acid (5-HD) abrogated this benefit suggesting an action through mitoK(ATP) channel opening. Treatment with derivative 11 combined with 5-HD as well as treatment with 11 and adenosine receptor blocker 8-(p-sulfophenyl)theophylline (SPT) did not abrogate cardioprotection. Compound 11 is a lead molecule for the synthesis of novel analogues possessing a dual mode of action through cGMP-mitoK(ATP) channel opening-free radicals and through adenosine receptors. PMID:18328715

  10. Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models

    PubMed Central

    Alamo, Patricia; Gallardo, Alberto; Pavón, Miguel A.; Casanova, Isolda; Trias, Manuel; Mangues, Maria A.; Vázquez, Esther; Villaverde, Antonio; Mangues, Ramon; Céspedes, Maria V.

    2014-01-01

    Mouse colorectal cancer (CRC) models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, haematological and transcoelomic spread but generate low metastatic efficiency. Our aim was to develop a new strategy that could increase the metastatic efficiency of these models. We used subcutaneous implantation of the human CRC cell lines HCT116 or SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT). This subcutaneous preconditioning significantly enhanced metastatic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung, liver and peritoneum, whereas, in the SW48 model, it induced a shift from non-metastatic to metastatic. In both models the number of apoptotic bodies in the primary tumour in the SC+ORT group was significantly reduced compared with that in the direct orthotopic injection (ORT) group. Moreover, in HCT116 tumours the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumour model, we observed a trend towards a higher number of tumour buds and single cells in the SC+ORT group but this did not reach statistical significance. At a molecular level, the enhanced metastatic efficiency observed in the HCT116 SC+ORT model was associated with an increase in AKT activation, VEGF-A overexpression and downregulation of ?1 integrin in primary tumour tissue, whereas, in SW48 SC+ORT mice, the level of expression of these proteins remained unchanged. In summary, subcutaneous preconditioning increased the metastatic dissemination of both orthotopic CRC models by increasing tumour cell survival and invasion at the tumour invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate anti-metastatic drugs against CRC. PMID:24487410

  11. Preconditioning of skeletal myoblast-based engineered tissue constructs enables functional coupling to myocardium in vivo

    PubMed Central

    Treskes, Philipp; Neef, Klaus; Srinivasan, Sureshkumar Perumal; Halbach, Marcel; Stamm, Christof; Cowan, Douglas; Scherner, Maximilian; Madershahian, Navid; Wittwer, Thorsten; Hescheler, Jürgen; Wahlers, Thorsten; Choi, Yeong-Hoon

    2015-01-01

    Objective Skeletal myoblasts fuse to form functional syncytial myotubes as an integral part of the skeletal muscle. During this differentiation process, expression of proteins for mechanical and electrical integration is seized, which is a major drawback for the application of skeletal myoblasts in cardiac regenerative cell therapy, because global heart function depends on intercellular communication. Methods Mechanically preconditioned engineered tissue constructs containing neonatal mouse skeletal myoblasts were transplanted epicardially. A Y-chromosomal specific polymerase chain reaction (PCR) was undertaken up to 10 weeks after transplantation to confirm the presence of grafted cells. Histologic and electrophysiologic analyses were carried out 1 week after transplantation. Results Cells within the grafted construct expressed connexin 43 at the interface to the host myocardium, indicating electrical coupling, confirmed by sharp electrode recordings. Analyses of the maximum stimulation frequency (5.65 ± 0.37 Hz), conduction velocity (0.087 ± 0.011 m/s) and sensitivity for pharmacologic conduction block (0.736 ± 0.080 mM 1-heptanol) revealed effective electrophysiologic coupling between graft and host cells, although significantly less robust than in native myocardial tissue (maximum stimulation frequency, 11.616 ± 0.238 Hz, P<.001; conduction velocity, 0.300 ± 0.057 m/s, P<.01; conduction block, 1.983 ± 0.077 mM 1-heptanol, P<.001). Conclusions Although untreated skeletal myoblasts cannot couple to cardiomyocytes, we confirm that mechanical preconditioning enables transplanted skeletal myoblasts to functionally interact with cardio-myocytes in vivo and, thus, reinvigorate the concept of skeletal myoblast-based cardiac cell therapy. PMID:25439779

  12. Glutamate transporter type 3 mediates isoflurane preconditioning-induced acute phase of neuroprotection in mice

    PubMed Central

    Li, Liaoliao; Deng, Jiao; Zuo, Zhiyi

    2013-01-01

    A pre-exposure to isoflurane reduces ischemic brain injury in rodents (isoflurane preconditioning). This neuroprotection has acute and delayed phases. Our previous in vitro studies suggest that the acute phase may involve excitatory amino acid transporters (EAAT). We determine whether this protection involves EAAT3, the major neuronal EAAT. Adult male EAAT3 knockout mice and their wild-type littermates were exposed or were not exposed to 1.5% isoflurane for 30 min. Sixty minutes later, they were subjected to a 90- or 60-min middle cerebral arterial occlusion (MCAO). Their neurological outcomes were evaluated 24 h after the MCAO. In another experiment, cerebral cortex was harvested for Western blotting at 30 min after animals were exposed to 1.5% isoflurane for 30 min. Here, we showed that isoflurane reduced brain infarct volumes and improved neurological functions of wild-type mice after a 90-min MCAO. However, isoflurane pre-exposure did not change the neurological outcome of EAAT3 knockout mice no matter whether the MCAO was for 90 min or 60 min. Isoflurane increased phospho-Akt, a survival-promoting protein, in the wild-type mice but not in the EAAT3 knockout mice. The isoflurane-induced neuroprotection in the wild-type mice was abolished by LY294004, an Akt activation inhibitor. LY294004 alone did not affect the neurological outcome of the wild-type or EAAT3 knockout mice after focal brain ischemia. These results suggest that the isoflurane preconditioning-induced acute phase of neuroprotection involves EAAT3. The downstream event includes Akt activation. PMID:23827345

  13. Quantification of neurovascular protection following repetitive hypoxic preconditioning and transient middle cerebral artery occlusion in mice.

    PubMed

    Poinsatte, Katherine; Selvaraj, Uma Maheswari; Ortega, Sterling B; Plautz, Erik J; Kong, Xiangmei; Gidday, Jeffrey M; Stowe, Ann M

    2015-01-01

    Experimental animal models of stroke are invaluable tools for understanding stroke pathology and developing more effective treatment strategies. A 2 week protocol for repetitive hypoxic preconditioning (RHP) induces long-term protection against central nervous system (CNS) injury in a mouse model of focal ischemic stroke. RHP consists of 9 stochastic exposures to hypoxia that vary in both duration (2 or 4 hr) and intensity (8% and 11% O2). RHP reduces infarct volumes, blood-brain barrier (BBB) disruption, and the post-stroke inflammatory response for weeks following the last exposure to hypoxia, suggesting a long-term induction of an endogenous CNS-protective phenotype. The methodology for the dual quantification of infarct volume and BBB disruption is effective in assessing neurovascular protection in mice with RHP or other putative neuroprotectants. Adult male Swiss Webster mice were preconditioned by RHP or duration-equivalent exposures to 21% O2 (i.e. room air). A 60 min transient middle cerebral artery occlusion (tMCAo) was induced 2 weeks following the last hypoxic exposure. Both the occlusion and reperfusion were confirmed by transcranial laser Doppler flowmetry. Twenty-two hr after reperfusion, Evans Blue (EB) was intravenously administered through a tail vein injection. 2 hr later, animals were sacrificed by isoflurane overdose and brain sections were stained with 2,3,5- triphenyltetrazolium chloride (TTC). Infarcts volumes were then quantified. Next, EB was extracted from the tissue over 48 hr to determine BBB disruption after tMCAo. In summary, RHP is a simple protocol that can be replicated, with minimal cost, to induce long-term endogenous neurovascular protection from stroke injury in mice, with the translational potential for other CNS-based and systemic pro-inflammatory disease states. PMID:25993394

  14. Skin Cancer Prevention

    MedlinePLUS

    ... Cancer Skin Cancer Screening Skin Cancer Research Skin Cancer Prevention (PDQ®) What is prevention? Cancer prevention is ... keep cancer from starting. General Information About Skin Cancer Key Points Skin cancer is a disease in ...

  15. National Diabetes Prevention Program

    MedlinePLUS

    ... please visit this page: About CDC.gov . National Diabetes Prevention Program Prevent Diabetes STAT: Get Involved Program Video: ... CDC/AMA Call to Action For Healthcare Providers Diabetes Prevention Recognition Program Program Topics About the Program Learn ...

  16. Preconditioning-induced protection of photoreceptors requires activation of the signal-transducing receptor gp130 in photoreceptors

    PubMed Central

    Ueki, Yumi; Le, Yun-Zheng; Chollangi, Srinivas; Muller, Werner; Ash, John D.

    2009-01-01

    Retinal degenerations are a class of neurodegenerative disorders that ultimately lead to blindness due to the death of retinal photoreceptors. In most cases, death is the result of long-term exposure to environmental, inflammatory, and genetic insults. In age-related macular degeneration, significant vision loss may take up to 70–80 years to develop. The protracted time to develop blindness suggests that retinal neurons have an endogenous mechanism for protection from chronic injury. Previous studies have shown that endogenous protective mechanisms can be induced by preconditioning animals with sublethal bright cyclic light. Such preconditioning can protect photoreceptors from a subsequent damaging insult and is thought to be accomplished through induced expression of protective factors. Some of the factors shown to be associated with protection bind and activate the signal transducing receptor gp130. To determine whether stress-induced endogenous protection of photoreceptors requires gp130, we generated conditional gp130 knockout (KO) mice with the Cre/lox system and used light-preconditioning to induce neuroprotection in these mice. Functional and morphological analyses demonstrated that the retina-specific gp130 KO impaired preconditioning-induced endogenous protection. Photoreceptor-specific gp130 KO mice had reduced protection, although the Müller cell KO mice did not, thus gp130-induced protection was restricted to photoreceptors. Using an animal model of retinitis pigmentosa, we found that the photoreceptor-specific gp130 KO increased sensitivity to genetically induced photoreceptor cell death, demonstrating that gp130 activation in photoreceptors had a general protective role independent of whether stress was caused by light or genetic mutations. PMID:19948961

  17. ILUBCG2-11: Solution of 11-banded nonsymmetric linear equation systems by a preconditioned biconjugate gradient routine

    NASA Astrophysics Data System (ADS)

    Chen, Y.-M.; Koniges, A. E.; Anderson, D. V.

    1989-10-01

    The biconjugate gradient method (BCG) provides an attractive alternative to the usual conjugate gradient algorithms for the solution of sparse systems of linear equations with nonsymmetric and indefinite matrix operators. A preconditioned algorithm is given, whose form resembles the incomplete L-U conjugate gradient scheme (ILUCG2) previously presented. Although the BCG scheme requires the storage of two additional vectors, it converges in a significantly lesser number of iterations (often half), while the number of calculations per iteration remains essentially the same.

  18. Chemical composition and physical quality characteristics of Ghanaian cocoa beans as affected by pulp pre-conditioning and fermentation

    Microsoft Academic Search

    Emmanuel Ohene Afoakwa; Jennifer Quao; Jemmy Takrama; Agnes Simpson Budu; Firibu Kwesi Saalia

    Investigations were conducted to evaluate the effects of pod storage (as a means of pulp preconditioning) and fermentation\\u000a on the chemical composition and physical characteristics of Ghanaian cocoa beans. A 4?×?2 full factorial design with factors\\u000a as pod storage (0, 7, 14, 21 days) and cocoa treatment (fermented and unfermented) were conducted. Samples were analyzed for\\u000a their chemical composition (moisture, crude

  19. Comparison of In Vitro Preconditioning Responses of Isolated Pig and Rabbit Cardiomyocytes: Effects of a Protein Phosphatase Inhibitor, Fostriecin

    Microsoft Academic Search

    S. C. Armstrong; R. Kao; W. Gao; L. C. Shivell; J. M. Downey; R. E. Honkanen; C. E. Ganote

    1997-01-01

    Calcium tolerant pig and rabbit cardiomyocytes were isolated using retrograde aortic perfusion of nominally calcium-free collagenase. Preconditioning protocols used 1 or 3×10-min episodes of ischemic pelleting or pre-incubation with 100?madenosine, followed by a 15-min post-incubation and 180–240-min ischemic pelleting. Control cells were incubated and washed in parallel with the experimental groups. Injury was assessed by determination of cell morphology, trypan

  20. Bradykinin preconditioning affects the number of degenerated neurons and the level of antioxidant enzymes in spinal cord ischemia in rabbits.

    PubMed

    Mechírová, Eva; Danielisová, Viera; Domoráková, Iveta; Danková, Marianna; Stebnický, Milan; Mi?ková, Helena; Burda, Jozef

    2014-01-01

    Bradykinin preconditioning has been used for acquisition of tolerance after spinal cord ischemia. Rabbits were preconditioned intraperitoneally with bradykinin 48 h prior to 20 min of abdominal aorta ligation followed by 24 and 48 h of reperfusion. The activities of SOD and catalase were measured and Fluoro Jade B (FJB)-positive degenerated neurons were evaluated. The outcomes of Tarlov scoring system used to assess neurological functions showed significant improvement in bradykinin groups compared to the ischemic group. The number of FJB-positive degenerated neurons was decreased in ventral horns of both bradykinin groups. Significantly decreased activities of total SOD and mitochondrial Mn-SOD were also detected in both bradykinin groups versus ischemic group while CuZn-SOD and catalase activities were significantly decreased only in the bradykinin group after 24h of reperfusion versus ischemic group. These findings suggest that one of the possibilities of the neuroprotective effect of delayed bradykinin preconditioning against spinal cord ischemic injury could be realized by mitochondrial protection and decreased synthesis of Mn-SOD as well as by promotion of neuronal survival. PMID:23981244

  1. H({div}) preconditioning for a mixed finite element formulation of the diffusion problem with random data

    NASA Astrophysics Data System (ADS)

    Elman, Howard C.; Furnival, Darran G.; Powell, Catherine E.

    2010-04-01

    We study H({div}) preconditioning for the saddle-point systems that arise in a stochastic Galerkin mixed formulation of the steady-state diffusion problem with random data. The key ingredient is a multigrid V-cycle for an H({div}) operator with random weight function acting on a certain tensor product space of random fields with finite variance. We build on the Arnold-Falk-Winther multigrid algorithm presented in 1997 by varying the spatial discretization from grid to grid whilst keeping the stochastic discretization fixed. We extend the deterministic analysis to accommodate the modified H({div}) operator and establish spectral equivalence bounds with a new multigrid V-cycle operator that are independent of the spatial and stochastic discretization parameters. We implement multigrid within a block-diagonal preconditioner for the full saddle-point problem, derive eigenvalue bounds for the preconditioned system matrices and investigate the impact of all the discretization parameters on the convergence rate of preconditioned MINRES.

  2. A Three Year Field Study of Preconditioning Native Illinois Beef Calves Sold Through a Cooperative Marketing Association — 1969 to 1971

    PubMed Central

    Woods, G. T.; Pickard, J. R.; Cowsert, C.

    1973-01-01

    During the fall of 1969, 1970 and 1971, Central Illinois practitioners preconditioned (PC) 1,576 beef calves at a cost range of $3.02 to $4.72. The PC program included weaning calves 30 days before sale, having calves eating grain from a bunk and drinking from a tank, vaccinated against blackleg, malignant edema, infectious bovine rhinotracheitis (IBR) and bovine parainfluenza virus (PI3). Calves were tagged in the right ear with the green certified preconditioned for health (CPH) tag of the American Association of Bovine Practitioners. Bovine virus diarrhea (BVD) vaccine was added to the program in 1970 and 1971 since clinical cases of the disease occurred in PC calves not receiving the vaccine in 1969. Intranasal PI3 vaccine and Pasteurella hemolytica and multocida bacterin was added to the 1971 program to attempt better immunization. In 1969, more PC than non-preconditioned (NPC) calves were treated for acute respiratory disease after sale. The 1970 study showed that fewer PC than NPC calves were treated for acute respiratory tract disease. The 1971 finding showed the greatest differences. A comparison of 389 PC and 227 NPC calves sold at auction in 1971 and moved into the same feedlots showed a statistically significant reduction in number of cases of acute respiratory tract disease treated in PC calves. Generally, PC calves sold at a higher price than NPC calves. PMID:4270429

  3. Differential proteomic profiling to study the mechanism of cardiac pharmacological preconditioning by resveratrol

    PubMed Central

    Bezstarosti, Karel; Das, Samarjit; Lamers, Jos M J; Das, Dipak K

    2006-01-01

    Recent studies demonstrated that resveratrol, a grape-derived polyphenolic phytoalexin, provides pharmacological preconditioning of the heart through a NO-dependent mechanism. To further explore the molecular mechanisms involved in resveratrol-mediated cardioprotection, we monitored the effects of resveratrol treatment after ischemia-reperfusion on the protein profile by implementation of proteomic analysis. Two groups of rats were studied; one group of animals was fed resveratrol for 7 days, while the other group was given vehicle only. The rats were sacrificed for the isolated working heart preparation and for isolation of cytoplasmic fraction from left ventricle homogenates to carry out the proteomic as well as immunoblot at baseline and at the end of 30 min ischemia/2-h perfusion. The results demonstrate significant cardiopro-tection with resveratrol evidenced by improved ventricular recovery and reduced infarct size and cardiomyocyte apopto-sis. The left ventricular cytoplasmic fractions were separated by two-dimensional electrophoresis (2-DE). Differentially regulated proteins were detected with quantitative computer analysis of the Coomassie blue stained 2-DE images and identified by MALDI-TOF (MS) and nanoLC-ESI-Q-TOF mass spectrometry (MS/MS). Five redox-regulated and precondi-tioning-related proteins were identified that were all upregulated by resveratrol: MAPKK, two different aB-crystallin species, HSP 27 and PE binding protein. Another HSP27 species and aldose reductase were downregulated and peroxire-doxin-2 remained constant. The results of the immunoblot analysis of phosphorylated MAPKK, -HSP27 and -aB-crys-tallin and PE binding protein were consistent with the proteomic findings, but not with peroxiredoxin-2. The proteomic analysis showed also downregulation of some proteins in the mitochondrial respiratory chain and matrix and the myofila-ment regulating protein MLC kinase-2. The results of the present study demonstrate that proteomic profiling enables the identification of resveratrol induced preconditioning-associated proteins which reflects not only changes in their expression level but also isoforms, post-translational modifications and regulating binding or activating partner proteins. PMID:17125593

  4. Think Detection. Think Prevention.

    E-print Network

    Calgary, University of

    Think Detection. Think Prevention. Think Activity. Office Ergonomics: #12;The Case of Mr. Z Mr. Z..........................................................................................7 Think Prevention. Ergonomics .............................................................11 What is office ergonomics?................................................................11 Making Your

  5. Comparison of the responses to hypoxia, ischaemia and ischaemic preconditioning in wild marmot and laboratory rabbit hearts.

    PubMed

    McKean, T; Mendenhall, W

    1996-03-01

    Marmots (Marmota flaviventris) are burrowing mammals that may be subjected to low levels of oxygen and high levels of carbon dioxide in their underground environment. Since marmots successfully deal with this physiological challenge, we hypothesized that the isolated perfused marmot heart would be damaged less and recover better from a bout of induced hypoxia or ischaemia than would the heart of a comparison animal, the New Zealand laboratory rabbit (Oryctolagus cuniculus). Isolated marmot and rabbit hearts were made hypoxic by a 30 min perfusion with an oxygen-deficient buffer. The hearts were then perfused with an oxygen-replete buffer and measurements of heart rate, left ventricular pressure and lactate dehydrogenase (LDH) release (an indicator of cell damage) were made over 5 or 10 min intervals for 30 min of hypoxia and 30 min of recovery. There were no species differences in the responses, except that the heart rate in marmots was about 50% of the rate in rabbits during the hypoxia part of the experiment. There was no evidence that the marmot hearts were damaged less or recovered better from hypoxia and reoxgenation than the rabbit hearts. Marmot and rabbit hearts were also subjected to 30 min of total ischaemia; measurements of heart rate, left ventricular pressure and LDH release were obtained during 30 min of reperfusion and compared with the pre-ischaemia values for these variables. There were no significant species differences. When the 30 min ischaemic period was preceded by a 5 min period of ischaemia and a 10 min reperfusion period (preconditioning), the rabbit hearts were protected by this brief ischaemic insult and recovered better than the hearts that had not been subjected to the preconditioning ischaemia. This was not true in the marmot hearts, however, as the preconditioning ischaemia did not promote a greater recovery over that in its absence. When preconditioned marmots hearts were compared with preconditioned rabbit hearts, there were no statistical differences in the responses. The hypothesis that marmot hearts would be damaged less and recover better from hypoxia and ischaemia was not supported by the experimental data. PMID:8867278

  6. Protein Misfolding Induces Hypoxic Preconditioning via a Subset of the Unfolded Protein Response Machinery?

    PubMed Central

    Mao, Xianrong R.; Crowder, C. Michael

    2010-01-01

    Prolonged cellular hypoxia results in energy failure and ultimately cell death. However, less-severe hypoxia can induce a cytoprotective response termed hypoxic preconditioning (HP). The unfolded protein response pathway (UPR) has been known for some time to respond to hypoxia and regulate hypoxic sensitivity; however, the role of the UPR, if any, in HP essentially has been unexplored. We have shown previously that a sublethal hypoxic exposure of the nematode Caenorhabditis elegans induces a protein chaperone component of the UPR (L. L. Anderson, X. Mao, B. A. Scott, and C. M. Crowder, Science 323:630-633, 2009). Here, we show that HP induces the UPR and that the pharmacological induction of misfolded proteins is itself sufficient to stimulate a delayed protective response to hypoxic injury that requires the UPR pathway proteins IRE-1, XBP-1, and ATF-6. HP also required IRE-1 but not XBP-1 or ATF-6; instead, GCN-2, which is known to suppress translation and induce an adaptive transcriptional response under conditions of UPR activation or amino acid deprivation, was required for HP. The phosphorylation of the translation factor eIF2?, an established mechanism of GCN-2-mediated translational suppression, was not necessary for HP. These data suggest a model where hypoxia-induced misfolded proteins trigger the activation of IRE-1, which along with GCN-2 controls an adaptive response that is essential to HP. PMID:20733002

  7. Mitochondrial Dihydrolipoamide Dehydrogenase Is Upregulated in Response to Intermittent Hypoxic Preconditioning

    PubMed Central

    Li, Rongrong; Luo, Xiaoting; Wu, Jinzi; Thangthaeng, Nopporn; Jung, Marianna E.; Jing, Siqun; Li, Linya; Ellis, Dorette Z.; Liu, Li; Ding, Zhengnian; Forster, Michael J.; Yan, Liang-Jun

    2015-01-01

    Intermittent hypoxia preconditioning (IHP) has been shown to protect neurons against ischemic stroke injury. Studying how proteins respond to IHP may identify targets that can help fight stroke. The objective of the present study was to investigate whether mitochondrial dihydrolipoamide dehydrogenase (DLDH) would respond to IHP and if so, whether such a response could be linked to neuroprotection in ischemic stroke injury. To do this, we subjected male rats to IHP for 20 days and measured the content and activity of DLDH as well as the three ?-keto acid dehydrogenase complexes that contain DLDH. We also measured mitochondrial electron transport chain enzyme activities. Results show that DLDH content was indeed upregulated by IHP and this upregulation did not alter the activities of the three ?-keto acid dehydrogenase complexes. Results also show that the activities of the five mitochondrial complexes (I-V) were not altered either by IHP. To investigate whether IHP-induced DLDH upregulation is linked to neuroprotection against ischemic stroke injury, we subjected both DLDH deficient mouse and DLDH transgenic mouse to stroke surgery followed by measurement of brain infarction volume. Results indicate that while mouse deficient in DLDH had exacerbated brain injury after stroke, mouse overexpressing human DLDH also showed increased brain injury after stroke. Therefore, the physiological significance of IHP-induced DLDH upregulation remains to be further investigated.

  8. Preconditioning and Acute Effects of Flavonoids in Protecting Cardiomyocytes from Oxidative Cell Death

    PubMed Central

    Akhlaghi, Masoumeh; Bandy, Brian

    2012-01-01

    While flavonoids can reportedly protect against cardiac ischemia-reperfusion injury, the relative effectiveness of different flavonoids and the mechanisms involved are unclear. We compared protection by different flavonoids using rat embryonic ventricular H9c2 cells subjected to simulated ischemia-reperfusion (IR) and to tert-butyl hydroperoxide (t-buOOH). Characterization of the IR model showed the relative contributions of glucose, serum, and oxygen deprivation to cell death. With long-term (2-3 day) pretreatment before IR the best protection was given by catechin, epigallocatechin gallate, proanthocyanidins, and ascorbate, which protected at all doses. Quercetin protected (34%) at 5??M but was cytotoxic at higher doses. Cyanidin protected mildly (10–15%) at 5 and 20??M, while delphinidin had no effect at 5??M and was cytotoxic at higher doses. Comparing long-term and acute protection by catechin, a higher concentration was needed for benefit with acute (1?hr) pretreatment. With a pure oxidative stress (t-buOOH) only quercetin significantly protected with 3-day pretreatment, while with short-term (1?h) pretreatments protection was best with quercetin and epigallocatechin gallate. The results suggest catechins to be especially useful as IR preconditioning agents, while quercetin and epigallocatechin gallate may be the most protective acutely in situations of oxidative stress. PMID:22829963

  9. Hyperbaric oxygen preconditioning attenuates hemorrhagic transformation through increasing PPAR? in hyperglycemic MCAO rats.

    PubMed

    Bian, Hetao; Hu, Qin; Liang, Xiping; Chen, Di; Li, Bo; Tang, Jiping; Zhang, John H

    2015-03-01

    Hyperbaric oxygen preconditioning (HBO-PC) has been demonstrated to attenuate hemorrhagic transformation (HT) after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. However, the mechanisms remain to be illustrated. Recently, HBO-PC has been shown to activate peroxisome proliferator-activated receptor-gamma (PPAR?) by increasing 15d-PGJ2 in primary cultured neurons. We hypothesize that HBO-PC reduces HT by suppressing inflammation through increasing 15d-PGJ2 and activating PPAR? in hyperglycemic MCAO rats. HBO (2.5ATA) was administered for 1h daily for 5 consecutive days. The PPAR? inhibitor GW9662 was administered intraperitoneally to designated animals. Infarction volume, hemorrhage volume, neurological scores and mortality were analyzed. The levels of 15d-PGJ2, PPAR?, TNF-? and IL-1?, tight junction proteins as well as the activity of MMP-2 and MMP-9 were evaluated 24h after MCAO. HBO-PC reduced HT, improved neurological function, down-regulated inflammatory molecules and inhibited the activation of MMP-9 by increasing 15d-PGJ2 and PPAR? at 24h after MCAO. The results suggested that HBO-PC might be an alternative measure to decrease HT in ischemic stroke. PMID:25542160

  10. A preconditioning technique for Schur complement systems arising in stochastic optimization

    SciTech Connect

    Petra, C. G.; Anitescu, M. (Mathematics and Computer Science)

    2012-01-01

    Deterministic sample average approximations of stochastic programming problems with recourse are suitable for a scenario-based parallelization. In this paper the parallelization is obtained by using an interior-point method and a Schur complement mechanism for the interior-point linear systems. However, the direct linear solves involving the dense Schur complement matrix are expensive, and adversely affect the scalability of this approach. We address this issue by proposing a stochastic preconditioner for the Schur complement matrix and by using Krylov iterative methods for the solution of the dense linear systems. The stochastic preconditioner is built based on a subset of existing scenarios and can be assembled and factorized on a separate process before the computation of the Schur complement matrix finishes on the remaining processes. The expensive factorization of the Schur complement is removed from the parallel execution flow and the scaling of the optimization solver is considerably improved with this approach. The spectral analysis indicates an exponentially fast convergence in probability to 1 of the eigenvalues of the preconditioned matrix with the number of scenarios incorporated in the preconditioner. Numerical experiments performed on the relaxation of a unit commitment problem show good performance, in terms of both the accuracy of the solution and the execution time.

  11. Mitochondrial Dihydrolipoamide Dehydrogenase is Upregulated in Response to Intermittent Hypoxic Preconditioning.

    PubMed

    Li, Rongrong; Luo, Xiaoting; Wu, Jinzi; Thangthaeng, Nopporn; Jung, Marianna E; Jing, Siqun; Li, Linya; Ellis, Dorette Z; Liu, Li; Ding, Zhengnian; Forster, Michael J; Yan, Liang-Jun

    2015-01-01

    Intermittent hypoxia preconditioning (IHP) has been shown to protect neurons against ischemic stroke injury. Studying how proteins respond to IHP may identify targets that can help fight stroke. The objective of the present study was to investigate whether mitochondrial dihydrolipoamide dehydrogenase (DLDH) would respond to IHP and if so, whether such a response could be linked to neuroprotection in ischemic stroke injury. To do this, we subjected male rats to IHP for 20 days and measured the content and activity of DLDH as well as the three ?-keto acid dehydrogenase complexes that contain DLDH. We also measured mitochondrial electron transport chain enzyme activities. Results show that DLDH content was indeed upregulated by IHP and this upregulation did not alter the activities of the three ?-keto acid dehydrogenase complexes. Results also show that the activities of the five mitochondrial complexes (I-V) were not altered either by IHP. To investigate whether IHP-induced DLDH upregulation is linked to neuroprotection against ischemic stroke injury, we subjected both DLDH deficient mouse and DLDH transgenic mouse to stroke surgery followed by measurement of brain infarction volume. Results indicate that while mouse deficient in DLDH had exacerbated brain injury after stroke, mouse overexpressing human DLDH also showed increased brain injury after stroke. Therefore, the physiological significance of IHP-induced DLDH upregulation remains to be further investigated. PMID:26078703

  12. Preconditioned iterative methods applied to singularly perturbed elliptic boundary value problems: Volume 2

    SciTech Connect

    Goldstein, C.I.

    1987-01-01

    It is the purpose of this report to modify and extend results in a previous report, concerning a class of multigrid preconditioners developed for use in the iterative solution of singularly perturbed elliptic boundary value problems. Typically, the low order derivative terms are multiplied by a large parameter, K. The preconditioner was based on a ''partial'' multigrid V cycle applied to the discrete LaPlacian, -..delta../sup h/, where h is the grid size. By this, we mean that the coarse grid residual problem is not solved. At most, one or a few relaxation sweeps are applied on this grid level. The multigrid preconditioner is now extended to include the W cycle applied to -..delta../sup h/ as well as -..delta../sup h/ + K/sup 2/. It is shown how to choose the coarsest grid size as a function of K, h, and the type of multigrid cycle in order to obtain optimal convergence of the preconditioned iterative method. It is proved that the low frequency subspace is scaled by 0(K/sup -2/) for both the V and W cycles. For the W cycle, it is proved that the multigrid preconditioner is norm equivalent to (-..delta../sup h/ + K/sup 2/)/sup -1/, uniformly in both K and h. The results are proved using Fourier analysis.

  13. Preconditioned iterative methods applied to singularly perturbed elliptic boundary value problems

    SciTech Connect

    Goldstein, C.I.

    1985-01-01

    A class of multigrid preconditioners is developed, analyzed, and tested in connection with the iterative solution of multi-dimensional boundary value problems for which the magnitude of the coefficients of the lower order terms are large compared to the coefficients of the highest order terms. In particular, this occurs in connection with singularly perturbed elliptic boundary value problems, where the coefficients are characterized by a parameter, epsilon, that varies over a specified parameter range. Conjugate gradient type iterative methods are applied to the large, sparse system of linear equations arising from a finite element or finite difference discretization. It is proved for variable coefficient partial differential operators that the condition number of the preconditioned matrix is uniformly bounded for all epsilon, provided the number of grid levels in a ''partial'' multigrid cycle is suitably chosen as a function of epsilon. The multigrid cycle is applied to the five-point scheme for the Dirichlet problem, even when more complicated differential operators and higher order discretizations are considered. This preconditioner is well suited for implementation on vector and parallel computers.

  14. The impact of experimental preconditioning using vascular endothelial growth factor in stroke and subarachnoid hemorrhage.

    PubMed

    Eicker, Sven Oliver; Hoppe, Moritz; Etminan, Nima; Macht, Stephan; Perrin, Jason; Steiger, Hans-Jakob; Hänggi, Daniel

    2013-01-01

    Vascular endothelial growth factor (VEGF) stimulating angiogenesis was shown to be a potential novel therapeutic approach for the treatment of ischemic vascular diseases. The goal of the present study was to examine whether transfection of VEGF before occurrence of major stroke (part I) and cerebral vasospasm after experimental subarachnoid hemorrhage (SAH; part II) develops neuroprotective qualities. A total of 25 (part I) and 26 (part II) brains were analyzed, respectively. In part one, a significant reduction of infarct volume in the VEGF-treated stroke animals (43% reduction, P < 0.05) could be detected. In part two, significant vasospasm was induced in all hemorrhage groups (P < 0.02). Analyzing microperfusion, a significant higher amount of perfused vessels could be detected (P < 0.01), whereas no significant effect could be detected towards macroperfusion. Histologically, no infarctions were observed in the VEGF-treated SAH group and the sham-operated group. Minor infarction in terms of vasospasm-induced small lesions could be detected in the control vector transduced group (P = 0.05) and saline-treated group (P = 0.09). The present study demonstrates the preconditioning impact of systemic intramuscular VEGF injection in animals after major stroke and induced severe vasospasm after SAH. PMID:23634319

  15. Low G preconditioning reduces liver injury induced by high +Gz exposure in rats

    PubMed Central

    Shi, Bin; Feng, Zhi-Qiang; Li, Wen-Bing; Zhang, Hong-Yi

    2015-01-01

    AIM: To investigate the effect of repeated lower +Gz exposure on liver injury induced by high +Gz exposure in rats. METHODS: Sixty male Wister rats were randomly divided into a blank control group, a low G preconditioning group (LG) (exposed to +4 Gz/5 min per day for 3 d before +10 Gz/5 min exposure), and a +10 Gz/5 min group (10G) (n = 20 in each group). Blood specimens and liver tissue were harvested at 0 h and 6 h after +10 Gz/5 min exposure. Liver function was analyzed by measuring serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and liver injury was further assessed by histopathological observation. Malondialdehyde (MDA), superoxide dismutase (SOD) and Na+-K+-ATPase were determined in hepatic tissue. RESULTS: The group LG had lower ALT, AST, and MDA values at 0 h after exposure than those in group 10G. SOD values and Na+-K+-ATPase activity in the LG group were higher than in group 10G 0 h post-exposure. Hepatocyte injury was significantly less in group LG than in group 10G on histopathological evaluation. CONCLUSION: It is suggested that repeated low +Gz exposure shows a protective effect on liver injury induced by high +Gz exposure in rats.

  16. The effect of warm liver ischaemia & reperfusion injury on circulating plasma lipid levels & lipolytic enzyme activity in rat & the impact of ischaemic preconditioning

    PubMed Central

    Lanitis, Sophocles; Lolis, Evangelos; Dafnios, Nikolaos; Sgourakis, George; Voros, Dionysios C.; Vassiliou, Ioannis

    2012-01-01

    Background & objectives: Ischaemia/reperfusion (I/R) associated with major liver surgery compromises liver function. Ischaemic preconditioning (IPC) may be effective in minimizing hepatic I/R injury. This study aimed to investigate the impact of liver ischaemic manipulations on lipid metabolism in rat during the process of liver recovery after liver surgery. Methods: Sixty three male Wistar rats were assigned to three groups: the sham group, the I/R group which underwent warm ischaemia and reperfusion (I/R), and the IPC group. The animals were subdivided in 3 groups [1st, 3rdand 7th postoperative day (PO)]. Hepatic lipase (HL) and total lipase (TL) activity and the levels of aspartate and alanine transaminases (AST, ALT), triglycerides, HDL and cholesterol were measured in plasma. Results: There was no significant difference in the activity of HL and TL between the groups. Significant higher levels of HDL (P<0.0001) were observed in the IPC group when compared to the other groups on the 3rd PO day. Triglycerides (P<0.0001) and HDL (P=0.003) in the IPC group were higher than the sham group on the 7th PO day while HDL was also higher in the I/R group. Significantly higher cholesterol levels were found in the I/R and IPC groups on the 7th PO day, which were not observed in the sham group. There was a similar curve for triglycerides in the sham and IPC groups while there were significantly higher levels of triglycerides on day 7 for the I/R group. The levels of HDL in the IPC group were higher on the 3rd and 7th PO day, compared to day 1. Interpretation & conclusion: Warm ischaemia and I/R injury do not seem to affect lipolytic enzyme activity after the 1st PO day despite the effects on plasma lipids. IPC seems to prevent accumulation of triglycerides and cholesterol in plasma. PMID:22960895

  17. The Mechanism of Sevoflurane Preconditioning-Induced Protections against Small Intestinal Ischemia Reperfusion Injury Is Independent of Mast Cell in Rats

    PubMed Central

    Su, Guangjie; Zhao, Weicheng; Huang, Pinjie; Luo, Gangjian; Hei, Ziqing

    2013-01-01

    The study aimed to investigate whether sevoflurane preconditioning can protect against small intestinal ischemia reperfusion (IIR) injury and to explore whether mast cell (MC) is involved in the protections provided by sevoflurane preconditioning. Sprague-Dawley rats exposed to sevoflurane or treated with MC stabilizer cromolyn sodium (CS) were subjected to 75-minute superior mesenteric artery occlusion followed by 2-hour reperfusion in the presence or absence of MC degranulator compound 48/80 (CP). Small intestinal ischemia reperfusion resulted in severe intestinal injury as demonstrated by significant elevations in intestinal injury scores and p47phox and gp91phox, ICAM-1 protein expressions and malondialdehyde and IL-6 contents, and MPO activities as well as significant reductions in SOD activities, accompanied with concomitant increases in mast cell degranulation evidenced by significant increases in MC counts, tryptase expression, and ?-hexosaminidase concentrations, and those alterations were further upregulated in the presence of CP. Sevoflurane preconditioning dramatically attenuated the previous IIR-induced alterations except MC counts, tryptase, and ?-hexosaminidase which were significantly reduced by CS treatment. Furthermore, CP exacerbated IIR injury was abrogated by CS but not by sevoflurane preconditioning. The data collectively indicate that sevoflurane preconditioning confers protections against IIR injury, and MC is not involved in the protective process. PMID:24369442

  18. The U.S. Geological Survey Modular Ground-Water Model - PCGN: A Preconditioned Conjugate Gradient Solver with Improved Nonlinear Control

    USGS Publications Warehouse

    Naff, Richard L.; Banta, Edward R.

    2008-01-01

    The preconditioned conjugate gradient with improved nonlinear control (PCGN) package provides addi-tional means by which the solution of nonlinear ground-water flow problems can be controlled as compared to existing solver packages for MODFLOW. Picard iteration is used to solve nonlinear ground-water flow equations by iteratively solving a linear approximation of the nonlinear equations. The linear solution is provided by means of the preconditioned conjugate gradient algorithm where preconditioning is provided by the modi-fied incomplete Cholesky algorithm. The incomplete Cholesky scheme incorporates two levels of fill, 0 and 1, in which the pivots can be modified so that the row sums of the preconditioning matrix and the original matrix are approximately equal. A relaxation factor is used to implement the modified pivots, which determines the degree of modification allowed. The effects of fill level and degree of pivot modification are briefly explored by means of a synthetic, heterogeneous finite-difference matrix; results are reported in the final section of this report. The preconditioned conjugate gradient method is coupled with Picard iteration so as to efficiently solve the nonlinear equations associated with many ground-water flow problems. The description of this coupling of the linear solver with Picard iteration is a primary concern of this document.

  19. Remote ischemic preconditioning delays the onset of acute mountain sickness in normobaric hypoxia

    PubMed Central

    Berger, Marc M; Köhne, Hannah; Hotz, Lorenz; Hammer, Moritz; Schommer, Kai; Bärtsch, Peter; Mairbäurl, Heimo

    2015-01-01

    Acute mountain sickness (AMS) is a neurological disorder occurring when ascending too fast, too high. Remote ischemic preconditioning (RIPC) is a noninvasive intervention protecting remote organs from subsequent hypoxic damage. We hypothesized that RIPC protects against AMS and that this effect is related to reduced oxidative stress. Fourteen subjects were exposed to 18 hours of normoxia (21% oxygen) and 18 h of normobaric hypoxia (12% oxygen, equivalent to 4500 m) on different days in a blinded, randomized order. RIPC consisted of four cycles of lower limb ischemia (5 min) and 5 min of reperfusion, and was performed immediately before the study room was entered. A control group was exposed to hypoxia (12% oxygen, n = 14) without RIPC. AMS was evaluated by the Lake Louise score (LLS) and the AMS-C score of the Environmental Symptom Questionnaire. Plasma concentrations of ascorbate radicals, oxidized sulfhydryl (SH) groups, and electron paramagnetic resonance (EPR) signal intensity were measured as biomarkers of oxidative stress. RIPC reduced AMS scores (LLS: 1.9 ± 0.4 vs. 3.2 ± 0.5; AMS-C score: 0.4 ± 0.1 vs. 0.8 ± 0.2), ascorbate radicals (27 ± 7 vs. 65 ± 18 nmol/L), oxidized SH groups (3.9 ± 1.4 vs. 14.3 ± 4.6 ?mol/L), and EPR signal intensity (0.6 ± 0.2 vs. 1.5 ± 0.4 × 106) after 5 h in hypoxia (all P < 0.05). After 18 hours in hypoxia there was no difference in AMS and oxidative stress between RIPC and control. AMS and plasma markers of oxidative stress did not correlate. This study demonstrates that RIPC transiently reduces symptoms of AMS and that this effect is not associated with reduced plasma levels of reactive oxygen species. PMID:25742960

  20. The Mechanism of Helium-Induced Preconditioning: A Direct Role for Nitric Oxide in Rabbits

    PubMed Central

    Pagel, Paul S.; Krolikowski, John G.; Pratt, Phillip F.; Shim, Yon Hee; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

    2008-01-01

    BACKGROUND Helium produces preconditioning against myocardial infarction by activating prosurvival signaling, but whether nitric oxide (NO) generated by endothelial NO synthase plays a role in this phenomenon is unknown. We tested the hypothesis that NO mediates helium-induced cardioprotection in vivo. METHODS Rabbits (n = 62) instrumented for hemodynamic measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3 h reperfusion, and received 0.9% saline (control) or three cycles of 70% helium–30% oxygen administered for 5 min interspersed with 5 min of an air–oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of pretreatment with the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg), the selective inducible NOS inhibitor aminoguanidine hydrochloride (AG; 300 mg/kg), or selective neuronal NOS inhibitor 7-nitroindazole (7-NI; 50 mg/kg). In additional rabbits, the fluorescent probe 4,5-diaminofluroscein diacetate (DAF-2DA) and confocal laser microscopy were used to detect NO production in the absence or presence of helium with or without L-NAME pretreatment. RESULTS Helium reduced (P < 0.05) infarct size (24% ± 4% of the left ventricular area at risk; mean ± sd) compared with control (46% ± 3%). L-NAME, AG, and 7-NI did not alter myocardial infarct size when administered alone. L-NAME, but not 7-NI or AG, abolished helium-induced cardioprotection. Helium enhanced DAF-2DA fluorescence compared with control (26 ± 8 vs 15 ± 5 U, respectively). Pretreatment with L-NAME abolished these helium-induced increases in DAF-2DA fluorescence. CONCLUSIONS The results indicate that cardioprotection by helium is mediated by NO that is probably generated by endothelial NOS in vivo. PMID:18713880

  1. Delayed Tolerance With Repetitive Transient Focal Ischemic Preconditioning in the Mouse

    PubMed Central

    Zhang, Jian; Yang, Zeng-Jin; Klaus, Judith A.; Koehler, Raymond C.; Huang, Judy

    2008-01-01

    Background and Purpose Transient ischemic attacks have long been regarded as a risk factor for the incidence of stroke but may reduce the severity of stroke by inducing ischemic tolerance. The present objective was to develop an ischemic preconditioning (IPC) model of delayed tolerance in the mouse based on repetitive, transient middle cerebral artery occlusion (MCAO). Methods Mice anesthetized with halothane or isoflurane underwent IPC, which consisted of repetitive MCAO at 45-minute intervals by the intraluminal filament technique. A 90-minute test MCAO was performed 24 to 96 hours later. Results Using an IPC of 2 5-minute MCAO episodes, the reduction in infarct volume from the test MCAO was maximal with a 72-hour delay in striatum (70%) and cerebral cortex (64%) when halothane was used for surgical anesthesia. With isoflurane anesthesia, the reduction in infarct volume was less prominent in striatum (34%) and not significant in cortex (9%) despite similar levels of arterial pressure and decreases in cortical perfusion. Neuronal cell death was rare 6 days after this IPC stimulus alone with halothane or isoflurane. Increasing the severity of IPC to 3 5-minute bouts or 1 15-minute bout of MCAO in the presence of isoflurane anesthesia augmented the reduction in infarct volume in striatum and cortex, but it also augmented selective neuronal cell death in striatum after the IPC stimulus alone. Conclusions These data demonstrate that a repetitive focal IPC stimulus can be titrated to induce delayed tolerance in both striatum and cortex of the mouse without inducing neuronal death by itself. PMID:18239169

  2. Impact of ischemic preconditioning on functional sympatholysis during handgrip exercise in humans.

    PubMed

    Horiuchi, Masahiro; Endo, Junko; Thijssen, Dick H J

    2015-02-01

    Repeated bouts of ischemia followed by reperfusion, known as ischemic preconditioning (IPC), is found to improve exercise performance. As redistribution of blood from the inactive areas to active skeletal muscles during exercise (i.e., functional sympatholysis) is important for exercise performance, we examined the hypothesis that IPC improves functional sympatholysis in healthy, young humans. In a randomized study, 15 healthy young men performed a 10-min resting period, dynamic handgrip exercise at 10% maximal voluntary contraction (MVC), and 25% MVC. This protocol was preceded by IPC (IPC; 4 × 5-min 220-mmHg unilateral occlusion) or a sham intervention (CON; 4 × 5-min 20-mmHg unilateral occlusion). Near-infrared spectroscopy was used to assess changes in oxygenated hemoglobin and myoglobin in skeletal muscle (HbO2 + MbO2) in response to sympathetic activation (via cold pressor test (CPT)) at baseline and during handgrip exercise (at 10% and 25%). In resting conditions, HbO2 + MbO2 significantly decreased during CPT (-11.0 ± 1.0%), which was significantly larger during the IPC-trial (-13.8 ± 1.2%, P = 0.006). During handgrip exercise at 10% MVC, changes in HbO2 + MbO2 in response to the CPT were blunted after IPC (-8.8 ± 1.5%) and CON (-8.3 ± 0.4%, P = 0.593). During handgrip exercise at 25% MVC, HbO2 + MbO2 in response to the CPT increased (2.0 ± 0.4%), whereas this response was significantly larger when preceded by IPC (4.2 ± 0.6%, P = 0.027). Collectively, these results indicate that IPC-induced different vascular changes at rest and during moderate exercise in response to sympathetic activation. This suggests that, in healthy volunteers, exposure to IPC may alter tissue oxygenation during sympathetic stimulation at rest and during exercise. PMID:25713329

  3. Mitochondrial nitroalkene formation and mild uncoupling in ischaemic preconditioning: implications for cardioprotection

    PubMed Central

    Nadtochiy, Sergiy M.; Baker, Paul R.S.; Freeman, Bruce A.; Brookes, Paul S.

    2009-01-01

    Aims Both mitochondria and nitric oxide (NO•) contribute to cardioprotection by ischaemic preconditioning (IPC). IPC causes mild uncoupling of mitochondria via uncoupling proteins (UCPs) and the adenine nucleotide translocase (ANT), and mild uncoupling per se is cardioprotective. Although electrophilic lipids are known to activate mitochondrial uncoupling, the role of such species in IPC-induced uncoupling and cardioprotection is unclear. We hypothesized that endogenous formation of NO•-derived electrophilic lipids (nitroalkenes such as nitro-linoleate, LNO2) during IPC may stimulate mitochondrial uncoupling via post-translational modification of UCPs and ANT, thus affording cardioprotection. Methods Hearts from male Sprague-Dawley rats were Langendorff-perfused and subjected to IPC. Nitroalkene formation was measured by HPLC-ESI-MS/MS. The effects of exogenous LNO2 and biotin-tagged LNO2 on isolated heart mitochondria and cardiomyocytes were also investigated. Results Nitroalkenes including LNO2 were endogenously generated in mitochondria of IPC hearts. Synthetic LNO2 (<1 µM) activated mild uncoupling, an effect blocked by UCP and ANT inhibitors. LNO2 (<1 µM) also protected cardiomyocytes against simulated ischaemia–reperfusion injury. Biotinylated LNO2 covalently modified ANT thiols and possibly UCP-2. No effects of LNO2 were attributable to NO• release, cGMP signalling, mitochondrial KATP channels, or protective kinase signalling. Conclusion Components of a novel signalling pathway are inferred, wherein nitroalkenes formed by IPC-stimulated nitration reactions may induce mild mitochondrial uncoupling via post-translational modification of ANT and UCP-2, subsequently conferring resistance to ischaemia–reperfusion injury. PMID:19050010

  4. An adenosine agonist and preconditioning shift the distribution of myocardial blood flow in conscious pigs.

    PubMed

    Huang, C H; Kim, S J; Ghaleh, B; Kudej, R K; Shen, Y T; Bishop, S P; Vatner, S F

    1999-02-01

    The goal of this study was to determine whether the cardioprotective effects of an A1-receptor agonist and ischemic preconditioning (IPC) involve a shift in the pre-coronary artery occlusion (CAO) spatial distribution of myocardial blood flow, which might shed light on the mechanism of IPC and explain its heterogeneous effects. Accordingly, 60 min of CAO followed by 72 h of coronary artery reperfusion (CAR) was examined in three groups of conscious pigs 10-14 days after instrumentation with aortic and left atrial catheters and coronary artery occluders. Myocardial infarct size, expressed as a fraction of the area at risk (AAR), was reduced significantly (P < 0.05) by infusion of the A1 agonist (27.1 +/- 6.6%) and to a greater extent (P < 0.05) by IPC (11.6 +/- 5.1%) compared with infarct size in vehicle-treated animals (55.1 +/- 2.9%). Transmural myocardial blood flow (radioactive microspheres) in the AAR shifted toward lower levels after infusion of the A1 agonist (1.27 +/- 0.19 vs. 0.74 +/- 0.10 ml. min-1. g-1) or IPC (1.27 +/- 0.11 vs. 0.96 +/- 0.09 ml. min-1. g-1) but not after infusion of the vehicle (1.20 +/- 0.10 vs. 1.23 +/- 0.09 ml. min-1. g-1). This study demonstrated that both pretreatment with an adenosine A1 agonist and also IPC altered the spatial distribution of pre-CAO myocardial blood flow, which might reflect a downregulation of metabolic state and thus play a role in the cardioprotective effects of IPC. PMID:9950835

  5. The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats

    PubMed Central

    Min, Seon Ok; Kim, Sung Hoon; Lee, Sang Woo; Cho, Jin A

    2011-01-01

    Background/Aims Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats. Methods To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (TC), IP, and intermittent clamping (IC). Ischemic injury was induced by clamping the left portal pedicle including the portal vein and hepatic artery. Liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to assess liver damage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining for apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell replication were also performed. Results Day-1 ALT and AST were highest in IP, however, levels in NC and IC were comparably low on days 1-7. There was no significant correlation of AST or ALT with experimental groups (P=0.615 and P=0.186). On TUNEL, numbers of apoptotic cells at 100× magnification (cells/field) were 31.8±24.2 in NC, 69.0±72.3 in TC, 80.2±63.1 in IP, and 21.2±20.8 in IC (P<0.05). When regeneration capacity was assessed by PCNA staining, PCNA-positive cells (cells/field) at 400× were 3.4±6.0 in NC, 16.9±69 in TC, 17.0±7.8 in IP and 7.4±7.6 in IC (P<0.05). Conclusions Although regeneration capacity in IP is higher than IC, the liver is vulnerable to ischemic damage in cirrhotic rats. Careful consideration is needed in applying IP in the clinical setting. PMID:21757985

  6. Mitogen-activated Protein Kinase p38? and Retinal Ischemic Preconditioning

    PubMed Central

    Dreixler, John C.; Barone, Frank C.; Shaikh, Afzhal R.; Du, Eugenie; Roth, Steven

    2009-01-01

    In previous studies, inhibition of mitogen activated protein kinase (MAP) p38 significantly improved recovery and attenuated apoptosis after retinal ischemia in rats. Yet, ischemic preconditioning (IPC) attenuated the ischemia-induced increase in p38 expression. We hypothesized that p38 was required for induction of ischemic tolerance by IPC. We examined the mechanisms of involvement of p38 in IPC neuroprotection. IPC or ischemia was induced in rat retina in vivo. Recovery after ischemia performed 24 h after IPC was assessed functionally (electroretinography) and histologically at 7 days after ischemia in the presence or absence of inhibition of p38. We examined the role of p38? in the mimicking of IPC produced by opening mitochondrial KATP channels using diazoxide, or stimulation of p38 activation by anisomycin. The importance of adenosine receptors in p38 activation after IPC was assessed using specific blockers of adenosine A1 and A2a receptors. Interfering RNA (siRNA) or SB203580 were used to block p38?. Phosphorylated p38 levels were measured. Phosphorylated p38 protein increased with IPC. Interfering RNA (siRNA) to p38? prior to IPC, or inhibiting p38 activation with SB203580, with ischemia following 24 h later, significantly attenuated the neuroprotective effect of IPC. Anisomycin administered to increase p38 mimicked IPC, an effect blocked by SB203580. IPC mimicking with diazoxide, an opener of mitochondrial KATP channels, was diminished with p38? siRNA. Adenosine receptor blockade did not decrease the elevated levels of phosphorylated p38 after IPC. Specific inhibition of p38? suggests that this MAPK is involved in the protective effects of IPC, and that p38 is downstream of mitochondrial KATP channels, but not adenosine receptors, in this neuroprotection. PMID:19631642

  7. Exploring the Human Plasma Proteome for Humoral Mediators of Remote Ischemic Preconditioning - A Word of Caution

    PubMed Central

    Helgeland, Erik; Breivik, Lars Ertesvåg; Vaudel, Marc; Svendsen, Øyvind Sverre; Garberg, Hilde; Nordrehaug, Jan Erik; Berven, Frode Steingrimsen; Jonassen, Anne Kristine

    2014-01-01

    Despite major advances in early revascularization techniques, cardiovascular diseases are still the leading cause of death worldwide, and myocardial infarctions contribute heavily to this. Over the past decades, it has become apparent that reperfusion of blood to a previously ischemic area of the heart causes damage in and of itself, and that this ischemia reperfusion induced injury can be reduced by up to 50% by mechanical manipulation of the blood flow to the heart. The recent discovery of remote ischemic preconditioning (RIPC) provides a non-invasive approach of inducing this cardioprotection at a distance. Finding its endogenous mediators and their operative mode is an important step toward increasing the ischemic tolerance. The release of humoral factor(s) upon RIPC was recently demonstrated and several candidate proteins were published as possible mediators of the cardioprotection. Before clinical applicability, these potential biomarkers and their efficiency must be validated, a task made challenging by the large heterogeneity in reported data and results. Here, in an attempt to reproduce and provide more experimental data on these mediators, we conducted an unbiased in-depth analysis of the human plasma proteome before and after RIPC. From the 68 protein markers reported in the literature, only 28 could be mapped to manually reviewed (Swiss-Prot) protein sequences. 23 of them were monitored in our untargeted experiment. However, their significant regulation could not be reproducibly estimated. In fact, among the 394 plasma proteins we accurately quantified, no significant regulation could be confidently and reproducibly assessed. This indicates that it is difficult to both monitor and reproduce published data from experiments exploring for RIPC induced plasma proteomic regulations, and suggests that further work should be directed towards small humoral factors. To simplify this task, we made our proteomic dataset available via ProteomeXchange, where scientists can mine for novel potential targets. PMID:25333471

  8. Reactive Oxygen Species and Mitochondrial KATP Channels Mediate Helium-Induced Preconditioning Against Myocardial Infarction In Vivo

    PubMed Central

    Pagel, Paul S.; Krolikowski, John G.; Pratt, Phillip F.; Shim, Yon Hee; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

    2008-01-01

    Objectives Helium produces preconditioning by activating prosurvival kinases, but the roles of reactive oxygen species (ROS) or mitochondrial KATP channels in this process are unknown. We tested the hypothesis that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. Design Randomized, prospective study. Setting University research laboratory. Participants Male New Zealand white rabbits. Interventions Rabbits (n=64) were instrumented for measurement of systemic hemodynamics and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion. In separate experimental groups, rabbits (n=7 or 8 per group) were randomly assigned to receive 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before LAD occlusion with or without the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptoproprionyl glycine (2-MPG; 75 mg/kg), or the mitochondrial KATP antagonist 5-hydroxydecanoate (5-HD; 5 mg/kg). Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni's modification of Student's t test. Measurements and Main Results Myocardial infarct size was determined using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium significantly (P<0.05) reduced infarct size (23±4% of the area at risk; mean±SD) compared with control (46±3%). NAC, 2-MPG, and 5-HD did not affect irreversible ischemic injury when administered alone (49±5, 45±6, and 45±3%), but these drugs blocked reductions in infarct size produced by helium (45±4, 45±2, and 44±3%). Conclusions The results suggest that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. PMID:18662630

  9. Effect of Preconditioning by Light Load Eccentric Exercise Versus Heat on Markers of Muscle Damage in Collegiate Males

    PubMed Central

    Zaheer, Sumbul; Moiz, Jamal Ali; Shareef, Mohammad Yaqoob; Hussain, Ejaz

    2014-01-01

    Background: Delayed onset muscle soreness (DOMS) occurs following unaccustomed or intense bouts of exercise. Previous research has demonstrated that that preconditioning with low load exercise or heat relieves muscle soreness. However, actively warming up the muscles with exercise may be an effective alternative. Objectives: This study compared preconditioning effect of light load eccentric exercise and heat using microwave diathermy on markers of muscle damage in collegiate males. Patients and Methods: Thirty six sedentary collegiate males were randomly assigned into two experimental groups: 10% Eccentric exercise group (10% ECC group) and Microwave diathermy group (MWD group). Both the groups performed 30 repetitions of maximal eccentric exercise (Max-ECC) of the elbow flexors. The 10% ECC group performed light load eccentric exercise (10% ECC), five sets, six repetitions using a dumbbell set at 10% of maximal voluntary isometric contraction strength (MVC), 2 days prior to Max-ECC. The MWD group received heat using microwave diathermy (150 watts, 20 minutes) one day prior to Max-ECC. Changes in MVC, range of motion (ROM), upper arm circumference, soreness, were assessed before and 24-72 hours after whereas serum creatine kinase activity and lactate dehydrogenase (LDH) activity up to 48 hours following the Max-ECC were compared between groups by a mixed model ANOVA. Results: No significant difference (P > 0.05) were found between the groups for changes in all variables post Max-ECC, except for LDH activity showing significant interaction effect (P = 0.04). Conclusions: Preconditioning with light load eccentric exercise and heat using microwave diathermy treatment did not differ in their effects on muscle damage markers after Max-ECC. However, with time their effects on LDH activity were found to be different. PMID:25520766

  10. Computational Modeling of Free Convection Between Coaxial Cylinders on the Basis of a Preconditioned Form of Navier-Stokes Equations

    NASA Astrophysics Data System (ADS)

    Volkov, K. N.; Karpenko, A. G.

    2014-07-01

    We have performed computational modeling of the free-convective fl ow in the gap between two coaxial cylinders on the basis of complete Navier-Stokes equations from the viewpoint of the compressible gas model. To stabilize numerical calculations of the viscous compressible gas at small Mach numbers, we used the preconditioning method based on the application of physical variables and the dual time stepping method. We have investigated the fl ow structure in the gap between the cylinders and the heat-transfer characteristics on the surface of the outer and inner cylinders at various Rayleigh numbers.

  11. Morphine reduces the threshold of helium preconditioning against myocardial infarction: the role of opioid receptors in rabbits

    PubMed Central

    Pagel, Paul S.; Krolikowski, John G.; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

    2015-01-01

    Objectives Brief, repetitive administration of helium before prolonged coronary artery occlusion and reperfusion protects myocardium against infarction. Opioid receptors mediate the cardioprotective effects of ischemic pre- and postconditioning, but whether these receptors also play a role in helium preconditioning is unknown. We tested the hypotheses that opioid receptors mediate helium preconditioning and that morphine (a ?1-opioid receptor agonist with ?1-opioid agonist properties) lowers the threshold of cardioprotection produced by helium in vivo. Design Randomized, prospective study. Setting University research laboratory. Participants Male New Zealand white rabbits. Interventions Rabbits (n=56) were instrumented for measurement of systemic hemodynamics and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion. In separate experimental groups, rabbits (n=6 or 7 per group) received 0.9% saline (control), one or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture, morphine (0.1 mg/kg, i.v.), or the nonselective opioid antagonist naloxone (6 mg/kg, i.v.) before LAD occlusion. Other groups of rabbits received three cycles of helium or one cycle of helium plus morphine (0.1 mg/kg) in the absence or presence of naloxone (6 mg/kg) before ischemia and reperfusion. Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni’s modification of Student’s t test. Measurements and Main Results Myocardial infarct size was determined using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium reduced myocardial infarct size in an exposure-related manner [36±6 (P>0.05) and 25±4% (P<0.05 versus control) for one and three cycles of helium, respectively; data are mean±SD] compared with control (44±7%). Morphine and naloxone alone did not affect infarct size (45±2 and 40±8%, respectively). The combination of one cycle of helium and morphine reduced infarct size (24±5%, P<0.05 versus control) to an equivalent degree as three cycles of helium. Naloxone pretreatment abolished cardioprotection produced by three cycles of helium (47±2%) and the combination of one cycle of helium plus morphine (45±4%). Conclusions The results indicate that morphine lowers the threshold of helium preconditioning. Opioid receptors mediate helium preconditioning and its augmentation by morphine in vivo. PMID:19231239

  12. Child Maltreatment Prevention

    MedlinePLUS

    ... Initiatives Dating Matters® Domestic Violence Prevention Enhancements and Leadership Through Alliances, Focusing on Outcomes for Communities United ... VETOViolence) Previously Funded Domestic Violence Prevention Enhancement and ... Through Alliances (DELTA) States Public Health Leadership Initiative ( ...

  13. Preventing HIV with Medicine

    MedlinePLUS

    ... information in Spanish ( en español ) Preventing HIV with medicine Get medicine right after you are exposed to ... to top More information on Preventing HIV with medicine Explore other publications and websites National HIV and ...

  14. Lead Poisoning Prevention Tips

    MedlinePLUS

    ... can become contaminated from household dust or exterior soil. Both are known lead sources. Regularly wet-mop ... entering the house to prevent bringing lead-contaminated soil in from outside. Prevent children from playing in ...

  15. Preventing High Blood Pressure

    MedlinePLUS

    ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

  16. High Blood Cholesterol Prevention

    MedlinePLUS

    ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

  17. ATP-sensitive potassium channels mediate the anti-ischemic properties of ischemic and pharmacologic preconditioning in rat random-pattern skin flap.

    PubMed

    Beheshtian, Azadeh; Demehri, Shadpour; Kiumehr, Saman; Salmasi, Amirali Hassanzadeh; Nezami, Behtash Ghazi; Ghazinezami, Behtash; Rahimpour, Sina; Amanpour, Saeed; Rabbani, Shahram; Mohagheghi, Mohammad Ali; Dehpour, Ahmad Reza

    2006-07-01

    Ischemic preconditioning (IPC) and pharmacologic preconditioning by morphine and adenosine may significantly decrease the amount of necrosis in rat random pattern skin flaps. We examined the role of ATP-sensitive potassium channels (K(ATP) channels) in mediating these protective phenomenon by using glibenclamide a nonspecific blocker of these channels. We also investigated whether administration of diazoxide an opener of the K(ATP) channels could mimic the same protective effect. Ninety male Sprague-Dawley rats were randomly divided into either control or treatment groups (n = 6 each). Bipedicled dorsal skin flaps (2 x 8 cm) were elevated at the midline. In pharmacologic preconditioning groups, 1 mL of morphine (5 mg/flap), adenosine (0.5 mg/flap), or different doses of diazoxide (0.5, 1, 5, and 15 mg/flap) were administered locally in the cranial half of the flap, respectively. One milliliter of saline was locally injected in the control group. In the IPC group, 1 hour after local saline injection the cranial pedicle was clamped for 20 minutes, and then 40 minutes' reperfusion was performed. In another experiment, 0.3 mg/kg of glibenclamide was injected intraperitoneally 30 minutes before local administration of saline or drug in ischemic or pharmacologic preconditioning groups. Regardless of the group, all flaps were cut at the cranial side 2 hours after elevation and were sutured back. Flap survival area was evaluated on the seventh postoperative day. IPC and pharmacologic preconditioning with morphine, adenosine, and diazoxide (in higher doses; 1, 5, and 15 mg/flap) improved survival area compared with the control group. Glibenclamide abolished their protective effect. K(ATP) channels may have a key role in anti-ischemic properties of IPC and pharmacologic preconditioning. PMID:16799317

  18. FACILITY POLLUTION PREVENTION GUIDE

    EPA Science Inventory

    The U.S. Environmental Protection Agency (U.S. EPA) has developed the Facility Pollution Prevention Guide for those who are interested in and responsible for pollution prevention in industrial or service facilities. t summarizes the benefits of a company-wide pollution prevention...

  19. Holiday Crime Prevention Tips

    E-print Network

    Hardy, Christopher R.

    Holiday Crime Prevention Tips presented by: #12;Holiday Crime Prevention Tips 'Tis the season grinches. #12;Holiday Crime Prevention Tips Nothing can ruin the Christmas spirit faster than becoming secured. #12;Protecting Your Home Dont post your family name on your mailbox or on your house. A burglar

  20. Obesity Prevention During Adulthood

    Microsoft Academic Search

    Suzanne Phelan; Meghan Butryn; Rena R. Wing

    The weight distribution of the U.S. population has been shifting upwards, and overweight and obesity have increased steadily across all ages. As discussed in Chapters 18 through 20, it is important that obesity prevention efforts begin during childhood. However, the importance of obesity prevention in children should not overshadow the need and potential for prevention of excess weight gain in

  1. Child Povertyy Prevention Council

    E-print Network

    Harms, Kyle E.

    Child Povertyy Prevention Council for Louisianafor Louisiana Implementation Plan February 2009eb ua In response to ACT 559 of the 2008 Regular Session of the Louisiana Legislature #12;Child Poverty Prevention Council for Louisiana Implementation Plan ­ 2009 #12;Child Poverty Prevention Council for Louisiana 3

  2. Prevention of Food Poisoning.

    ERIC Educational Resources Information Center

    Army Quartermaster School, Ft. Lee, VA.

    The programed text provides a single lesson, four-hour, correspondence subcourse on the prevention of food poisoning. It covers the following areas: a definition of food poisoning; chemical food poisoning; biological food poisoning; causes and prevention of trichinosis; six factors controlling bacteria growth; bacterial infection; prevention of…

  3. Suicide Prevention Triangle.

    ERIC Educational Resources Information Center

    Cutter, Fred

    This manual provides resource tools and strategies to enhance the suicide prevention capabilities of health professionals and the health care setting in which care is provided. In the first section, terms are defined and the suicide prevention triangle model is described. Applications of the model and good practices for suicide prevention in any…

  4. Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart

    PubMed Central

    2011-01-01

    Background Nitric oxide (NO) has been noted to produce ischemic preconditioning (IPC)-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS) by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM). The present study was designed to investigate the involvement of caveolin in attenuation of the cardioprotective effect of IPC during DM in rat. Methods Experimental DM was induced by single dose of streptozotocin (50 mg/Kg, i.p,) and animals were used for experiments four weeks later. Isolated heart was mounted on Langendorff's apparatus, and was subjected to 30 min of global ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Kreb's-Henseleit solution (K-H). Extent of injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC) staining, and release of lactate dehydrogenase (LDH) and creatin kinase-MB (CK-MB) in coronary effluent. The cardiac release of NO was noted by measuring the level of nitrite in coronary effluent. Results IPC- induced cardioprotection and release of NO was significantly decreased in diabetic rat heart. Pre-treatment of diabetic rat with daidzein (DDZ) a caveolin inhibitor (0.2 mg/Kg/s.c), for one week, significantly increased the release of NO and restored the attenuated cardioprotective effect of IPC. Also perfusion of sodium nitrite (10 ?M/L), a precursor of NO, significantly restored the lost effect of IPC, similar to daidzein in diabetic rat. Administration of 5-hydroxy deaconate (5-HD), a mito KATP channel blocker, significantly abolished the observed IPC-induced cardioprotection in normal rat or daidzein and sodium nitrite perfused diabetic rat heart alone or in combination. Conclusions Thus, it is suggested that attenuation of the cardioprotection in diabetic heart may be due to decrease the IPC mediated release of NO in the diabetic myocardium, which may be due to up -regulation of caveolin and subsequently decreased activity of eNOS. PMID:21745415

  5. INJURY & ILLNESS PREVENTION PLAN (IIPP)

    E-print Network

    Reed, Christopher A.

    INJURY & ILLNESS PREVENTION PLAN (IIPP) University of California Riverside (UCR) Injury & Illness Prevention Plan (IIPP) describes specific 2. Written Documents Document Location Injury and Illness Prevention Plan

  6. Aging-related Decrease of Human ASC Angiogenic Potential Is Reversed by Hypoxia Preconditioning Through ROS Production

    PubMed Central

    Barros, Sandra De; Dehez, Stéphanie; Arnaud, Emmanuelle; Barreau, Corinne; Cazavet, Alexandre; Perez, Guillaume; Galinier, Anne; Casteilla, Louis; Planat-Bénard, Valérie

    2013-01-01

    Adipose stroma/stem cells (ASC) represent an ideal source of autologous cells for cell-based therapy. Their transplantation enhances neovascularization after experimental ischemic injury. Aging is associated with a progressive decrease in the regenerative potential of mesenchymal stem cells (MSCs) from bone marrow. This work aims to determine the aging effect on human ASC capacities. First, we show that aging impairs angiogenic capacities of human ASC (hASC) in a mouse ischemic hindlimb model. Although no change in hASC number, phenotype, and proliferation was observed with aging, several mechanisms involved in the adverse effects of aging have been identified in vitro combining a concomitant decrease in (i) ASC ability to differentiate towards endothelial cells, (ii) secretion of proangiogenic and pro-survival factors, and (iii) oxidative stress. These effects were counteracted by a hypoxic preconditioning that improved in vivo angiogenic capacities of hASC from older donors, while hASC from young donors that have a strong ability to manage hypoxic stress were not. Finally, we identified reactive oxygen species (ROS) generation as a key signal of hypoxia on hASC angiogenic capacities. This study demonstrates for the first time that age of donor impaired angiogenic capacities of hASC in ischemic muscle and change in ROS generation by hypoxic preconditioning reverse the adverse effect of aging. PMID:23070114

  7. Pre-conditioning the epigenetic response to high vapor pressure deficit increases the drought tolerance of Arabidopsis thaliana

    PubMed Central

    Tricker, Penny J; Rodríguez López, Carlos M; Hadley, P; Wagstaff, C; Wilkinson, Mike J

    2013-01-01

    Epigenetic modification of the genome via cytosine methylation is a dynamic process that responds to changes in the growing environment. This modification can also be heritable. The combination of both properties means that there is the potential for the life experiences of the parental generation to modify the methylation profiles of their offspring and so potentially to “pre-condition” them to better accommodate abiotic conditions encountered by their parents. We recently identified high vapor pressure deficit (vpd)-induced DNA methylation at 2 gene loci in the stomatal development pathway and an associated reduction in leaf stomatal frequency.1 Here, we test whether this epigenetic modification pre-conditioned parents and their offspring to the more severe water stress of periodic drought. We found that 3 generations of high vpd-grown plants were better able to withstand periodic drought stress over 2 generations. This resistance was not directly associated with de novo methylation of the target stomata genes, but was associated with the cmt3 mutant’s inability to maintain asymmetric sequence context methylation. If our finding applies widely, it could have significant implications for evolutionary biology and breeding for stressful environments. PMID:24270688

  8. Pre-conditioning the epigenetic response to high vapor pressure deficit increases the drought tolerance of Arabidopsis thaliana.

    PubMed

    Tricker, Penny; Rodríguez López, Carlos; Hadley, Paul; Wagstaff, Carol; Wilkinson, Mike

    2013-10-01

    Epigenetic modification of the genome via cytosine methylation is a dynamic process that responds to changes in the growing environment. This modification can also be heritable. The combination of both properties means that there is the potential for the life experiences of the parental generation to modify the methylation profiles of their offspring and so potentially to "pre-condition" them to better accommodate abiotic conditions encountered by their parents. We recently identified high vapor pressure deficit (vpd)-induced DNA methylation at 2 gene loci in the stomatal development pathway and an associated reduction in leaf stomatal frequency. (1) Here, we test whether this epigenetic modification pre-conditioned parents and their offspring to the more severe water stress of periodic drought. We found that 3 generations of high vpd-grown plants were better able to withstand periodic drought stress over 2 generations. This resistance was not directly associated with de novo methylation of the target stomata genes, but was associated with the cmt3 mutant's inability to maintain asymmetric sequence context methylation. If our finding applies widely, it could have significant implications for evolutionary biology and breeding for stressful environments. PMID:24270688

  9. Giving rheumatology patients online home access to their electronic medical record (EMR): advantages, drawbacks and preconditions according to care providers.

    PubMed

    van der Vaart, Rosalie; Drossaert, Constance H C; Taal, Erik; van de Laar, Mart A F J

    2013-09-01

    Technology enables patients home access to their electronic medical record (EMR), via a patient portal. This study aims to analyse (dis)advantages, preconditions and suitable content for this service, according to rheumatology health professionals. A two-phase policy Delphi study was conducted. First, interviews were performed with nurses/nurse practitioners (n = 9) and rheumatologists (n = 13). Subsequently, collected responses were quantified, using a questionnaire among the interviewees. The following advantages of patient home access to the EMR were reported: (1) enhancement of patient participation in treatment, (2) increased knowledge and self-management, (3) improved patient-provider interaction, (4) increased patient safety, and (5) better communication with others. Foreseen disadvantages of the service included: (1) problems with interpretation of data, (2) extra workload, (3) a change in consultation content, and (4) disturbing the patient-provider interaction. Also, the following preconditions emerged from the data: (1) optimal security, (2) no extra record, but a patient-accessible section, (3) no access to clinical notes, and (4) a lag time on the release of lab data. Most respondents reported that data on diagnosis, medication, treatment plan and consultations could be released to patients. On releasing more complex data, such as bodily examinations, lab results and radiological images the opinions differed considerably. Providing patients home access to their medical record might be a valuable next step into patient empowerment and in service towards the patient, provided that security is optimal and content and presentation of data are carefully considered. PMID:22453527

  10. Transcriptional signature of human adipose tissue-derived stem cells (hASCs) preconditioned for chondrogenesis in hypoxic conditions

    SciTech Connect

    Pilgaard, L.; Lund, P.; Duroux, M. [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark)] [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark); Lockstone, H.; Taylor, J. [Bioinformatics and Statistical Genetics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom)] [Bioinformatics and Statistical Genetics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom); Emmersen, J.; Fink, T. [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark)] [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark); Ragoussis, J. [Genomics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom)] [Genomics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom); Zachar, V., E-mail: vlaz@hst.aau.dk [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark)

    2009-07-01

    Hypoxia is an important factor involved in the control of stem cells. To obtain a better insight into the phenotypical changes brought about by hypoxic preconditioning prior to chondrogenic differentiation; we have investigated growth, colony-forming and chondrogenic capacity, and global transcriptional responses of six adipose tissue-derived stem cell lines expanded at oxygen concentrations ranging from ambient to 1%. The assessment of cell proliferation and colony-forming potential revealed that the hypoxic conditions corresponding to 1% oxygen played a major role. The chondrogenic inducibility, examined by high-density pellet model, however, did not improve on hypoxic preconditioning. While the microarray analysis revealed a distinctive inter-donor variability, the exposure to 1% hypoxia superseded the biological variability and produced a specific expression profile with 2581 significantly regulated genes and substantial functional enrichment in the pathways of cell proliferation and apoptosis. Additionally, exposure to 1% oxygen resulted in upregulation of factors related to angiogenesis and cell growth. In particular, leptin (LEP), the key regulator of body weight and food intake was found to be highly upregulated. In conclusion, the results of this investigation demonstrate the significance of donor demographics and the importance of further studies into the use of regulated oxygen tension as a tool for preparation of ASCs in order to exploit their full potential.

  11. REACTIVE TRANSPORT MODELING USING A PARALLEL FULLY-COUPLED SIMULATOR BASED ON PRECONDITIONED JACOBIAN-FREE NEWTON-KRYLOV

    SciTech Connect

    Luanjing Guo; Chuan Lu; Hai Huang; Derek R. Gaston

    2012-06-01

    Systems of multicomponent reactive transport in porous media that are large, highly nonlinear, and tightly coupled due to complex nonlinear reactions and strong solution-media interactions are often described by a system of coupled nonlinear partial differential algebraic equations (PDAEs). A preconditioned Jacobian-Free Newton-Krylov (JFNK) solution approach is applied to solve the PDAEs in a fully coupled, fully implicit manner. The advantage of the JFNK method is that it avoids explicitly computing and storing the Jacobian matrix during Newton nonlinear iterations for computational efficiency considerations. This solution approach is also enhanced by physics-based blocking preconditioning and multigrid algorithm for efficient inversion of preconditioners. Based on the solution approach, we have developed a reactive transport simulator named RAT. Numerical results are presented to demonstrate the efficiency and massive scalability of the simulator for reactive transport problems involving strong solution-mineral interactions and fast kinetics. It has been applied to study the highly nonlinearly coupled reactive transport system of a promising in situ environmental remediation that involves urea hydrolysis and calcium carbonate precipitation.

  12. Development of the IM147: an alternative inspection/maintenance mass-emission transient test to address vehicle preconditioning concerns.

    PubMed

    Joy, Richard W; Heirigs, Philip L; Torgerson, Garrett D; St Denis, Michael; Austin, Thomas C; Gordon, Jay; Tefft, Bob; Lindner, Jim

    2004-03-01

    A series of studies was performed to develop an alternative to the U.S. Environmental Protection Agency's gold standard IM240 mass-based emission test. The new IM147 test was based on the second phase of the IM240 that consists of 147 sec of transient vehicle operation. Paired IM240/IM147 tests were conducted on vehicles ranging from 1981 to 1996 to determine IM147 cutpoints and excess emissions were identified. Additionally, an optimized test procedure was developed that combined possible triplicate IM147s with improved drive trace quality control, fast-pass, and retest methods. The optimized procedure was found to provide improved vehicle preconditioning with a relatively minor decrease in excess emissions identification. Resulting identification rates ranged from 96 to 100% for hydrocarbons (HC), 93-100% for CO, and 93-100% for NOx, depending on cutpoint selection, while false failures caused by lack of vehicle preconditioning were reduced to essentially zero. Significant vehicle throughput improvements were achieved through the development of software algorithms involving modal fast-pass and retest procedures. Modal drive trace variation limits also were developed to improve test accuracy. The combination of the algorithms reduced average IM147 test times by nearly 60%. PMID:15061610

  13. Identifying hydrological pre-conditions and rainfall triggers of slope failures for 2014 storm events in the Ialomita Subcarpathians, Romania

    NASA Astrophysics Data System (ADS)

    Chitu, Zenaida; Bogaard, Thom; Busuioc, Aristita; Burcea, Sorin; Adler, Mary-Jeanne; Sandric, Ionut

    2015-04-01

    Like in many parts of the world, in Romania, landslides represent recurrent phenomena that produce numerous damages to infrastructure every few years. Various studies on landslide occurrence in the Curvature Subcarpathians reveal that rainfall represents the most important triggering factor for landslides. Depending on rainfall characteristics and environmental factors different types of landslides were recorded in the Ialomita Subcarpathians: slumps, earthflows and complex landslides. This area, located in the western part of Curvature Subcarpathians, is characterized by a very complex geology whose main features are represented by the nappes system, the post tectonic covers, the diapirism phenomena and vertical faults. This work aims to investigate hydrological pre-conditions and rainfall characteristics which triggered slope failures in 2014 in the Ialomita Subcarpathians, Romania. Hydrological pre-conditions were investigated by means of water balance analysis and low flow techniques, while spatial and temporal patterns of rainfalls were estimated using radar data and six rain gauges. Additionally, six soil moisture stations that are fitted with volumetric soil moisture sensors and temperature soil sensors were used to estimate the antecedent soil moisture conditions.

  14. Detailed qualitative dynamic knowledge representation using a BioNetGen model of TLR-4 signaling and preconditioning

    PubMed Central

    An, Gary C.; Faeder, James R.

    2009-01-01

    Introduction Intracellular signaling/synthetic pathways are being increasingly extensively characterized. However, while these pathways can be displayed in static diagrams, in reality they exist with a degree of dynamic complexity that is responsible for heterogeneous cellular behavior. Multiple parallel pathways exist and interact concurrently, limiting the ability to integrate the various identified mechanisms into a cohesive whole. Computational methods have been suggested as a means of concatenating this knowledge to aid in the understanding of overall system dynamics. Since the eventual goal of biomedical research is the identification and development of therapeutic modalities, computational representation must have sufficient detail to facilitate this “engineering” process. Adding to the challenge, this type of representation must occur in a perpetual state of incomplete knowledge. We present a modeling approach to address this challenge that is both detailed and qualitative. This approach is termed “dynamic knowledge representation,” and is intended to be an integrated component of the iterative cycle of scientific discovery. Methods BioNetGen (BNG), a software platform for modeling intracellular signaling pathways, was used to model the toll-like receptor 4 (TLR-4) signal transduction cascade. The informational basis of the model was a series of reference papers on modulation of (TLR-4) signaling, and some specific primary research papers to aid in the characterization of specific mechanistic steps in the pathway. This model was detailed with respect to the components of the pathway represented, but qualitative with respect to the specific reaction coefficients utilized to execute the reactions. Responsiveness to simulated lipopolysaccharide (LPS) administration was measured by tumor necrosis factor (TNF) production. Simulation runs included evaluation of initial dose-dependent response to LPS administration at 10, 100, 1000, and 10000, and a subsequent examination of preconditioning behavior with increasing LPS at 10, 100, 1000 and 10000 and a secondary dose of LPS at 10000 administered at ?27 h of simulated time. Simulations of “knockout” versions of the model allowed further examination of the interactions within the signaling cascade. Results The model demonstrated a dose-dependent TNF response curve to increasing stimulus by LPS. Preconditioning simulations demonstrated a similar dose-dependency of preconditioning doses leading to attenuation of response to subsequent LPS challenge—a “tolerance” dynamic. These responses match dynamics reported in the literature. Furthermore, the simulated “knockout” results suggested the existence and need for dual negative feedback control mechanisms, represented by the zinc ring-finger protein A20 and inhibitor kappa B proteins (I?B), in order for both effective attenuation of the initial stimulus signal and subsequent preconditioned “tolerant” behavior. Conclusions We present an example of detailed, qualitative dynamic knowledge representation using the TLR-4 signaling pathway, its control mechanisms and overall behavior with respect to preconditioning. The intent of this approach is to demonstrate a method of translating the extensive mechanistic knowledge being generated at the basic science level into an executable framework that can provide a means of “conceptual model verification.” This allows for both the “checking” of the dynamic consequences of a mechanistic hypothesis and the creation of a modular component of an overall model directed at the engineering goal of biomedical research. It is hoped that this paper will increase the use of knowledge representation and communication in this fashion, and facilitate the concatenation and integration of community-wide knowledge. PMID:18835283

  15. Facility pollution prevention planning

    SciTech Connect

    Evers, D.P. [Battelle Memorial Inst., Columbus, OH (United States)

    1995-09-01

    Pollution prevention planning is a comprehensive and continual evaluation of business operations. The results pollution prevention program affects many functional areas within a company, such as the production line, accounting practices, and management. It has much in common with the planning already conducted for other aspects of business operations, but it looks at the facility as an integrated whole instead of as a series of disjoint parts or operations. A flowchart is presented illustrating the major elements in the pollution prevention program. This section describes the elements of pollution prevention program planning and design. These elements include building support for pollution prevention throughout the company, organizing the program, setting goals and objectives, performing a preliminary assessment of pollution prevention opportunities, and identifying potential problems and their solutions.

  16. [Prevention of psychic disorders].

    PubMed

    Siepmann, M

    2012-06-01

    Prevention aims to avoid the occurrence of psychiatric illness and disability caused by psychic disorders. The relevant interventions refer to the individual, the family context and other environmental factors. Universal and primary prevention target the entire population or a part of this (i. e. students). Secondary and selective intervention should prevent the manifestation of psychiatric disorders in vulnerable individuals (i. e. children with behavioral problems). Tertiary measures aim at preventing the worsening or recurrence of symptoms in individuals who already suffer from mental illness. Within the past 25 years protective and risk factors that reduce or increase the probability of occurrence of mental disorders have increasingly been identified. This results in improved prevention. The present article gives an overview of preventive measures against the most common mental disorders in the light of the current evidence base. PMID:22644494

  17. HSP70.1 AND -70.3 ARE REQUIRED FOR LATE-PHASE PROTECTION INDUCED BY ISCHEMIC PRECONDITIONING OF MOUSE HEARTS

    EPA Science Inventory

    Heat-Shock Proteins 70.1 and 70.3 Are Required for Late-phase Protection Induced by Ischemic Preconditioning of the Mouse Heart Craig R. Hampton 1 , Akira Shimamoto 1 , Christine L. Rothnie 1 , Jeaneatte Griscavage-Ennis 1 , Albert Chong 1 , David J. Dix 2 , Edward D. Ve...

  18. Rapid pacing-induced preconditioning is recaptured by farnesol treatment in hearts of cholesterol-fed rats: Role of polyprenyl derivatives and nitric oxide

    Microsoft Academic Search

    Peter Ferdinandy; Csaba Csonka; Tamás Csont; Zoltán Szilvássy; László Dux

    1998-01-01

    We have previously shown that hypercholesterolemia leads to the loss of pacing-induced preconditioning (PC), possibly due to the impairment of cardiac nitric oxide (NO) synthesis. It has been shown that excess exogenous cholesterol inhibits formation of several polyprenyl derivatives involved in signal transduction. In the present study, we examined whether PC and cardiac NO synthesis are restored by treatment with

  19. Remote preconditioning by infrarenal aortic occlusion is operative via y1-opioid receptors and free radicals in vivo in the rat heart

    Microsoft Academic Search

    Christof Weinbrenner; Falk Schulze; Ruth H. Strasser

    Background: Ischemic preconditioning (PC) is a powerful mechanism in reducing infarct size of the heart. Protection can be performed either by an ischemic stimulus of the heart itself or by ischemia of an organ distant to the heart (remote PC). We have previously shown that remote PC by infrarenal occlusion of the aorta (IOA) in the rat is as powerful

  20. sb203580 preconditioning recharges matrix-expanded human adult stem cells for chondrogenesis in an inflammatory environment - A feasible approach for autologous stem cell based osteoarthritic cartilage repair.

    PubMed

    Zhang, Ying; Pizzute, Tyler; Li, Jingting; He, Fan; Pei, Ming

    2015-09-01

    Autologous stem cells are a promising cell source for cartilage regeneration; however, cell replicative senescence and joint posttraumatic inflammation provide challenges in bringing this treatment modality to fruition. In this study, we hypothesized that preconditioning with p38 MAPK inhibitor (sb203580) would recharge decellularized extracellular matrix (dECM) expanded human synovium-derived stem cell (hSDSC) chondrogenesis in an inflammatory environment. We found that preconditioning with sb203580 greatly enhanced dECM expanded hSDSC proliferation and chondrogenic potential while supplementation with sb203580 in an induction medium dramatically retarded hSDSC chondrogenic differentiation, even for dECM expanded cells. We also found that sb203580 preconditioning enhanced matrix-expanded hSDSC chondrogenic capacity even in an interleukin-1 (IL-1) induced inflammatory environment. Non-detectable expression of HLA-DR in the hSDSCs grown on allogeneic dECM indicates the feasibility of commercial preparation of these dECMs from healthy, young donors for patients who need autologous transplantation. Our study indicated that p38 MAPK inhibitor has a distinctive priming effect on dECM mediated stem cell cartilage regeneration. Combined rejuvenation with sb203580 and dECM expansion can precondition hSDSCs' resurfacing capacity for osteoarthritic patients with cartilage defects. PMID:26122165

  1. Angina-Induced Protection Against Myocardial Infarction in Adult and Elderly Patients: A Loss of Preconditioning Mechanism in the Aging Heart?

    Microsoft Academic Search

    Pasquale Abete; Nicola Ferrara; Francesco Cacciatore; Alfredo Madrid; Sabatino Bianco; Claudio Calabrese; Claudio Napoli; Paola Scognamiglio; Ornella Bollella; Angelo Cioppa; Giancarlo Longobardi; Franco Rengo

    1997-01-01

    Objectives. The present study examined whether angina 48 h before myocardial infarction provides protection in adult and elderly patients.Background. The mortality rate for coronary artery disease is greater in elderly than in young patients. In experimental studies, ischemic preconditioning affords an endogenous form of protection against ischemia–reperfusion injury in adult but not in senescent hearts. Angina before myocardial infarction, a

  2. Facility Pollution Prevention Guide

    SciTech Connect

    Not Available

    1992-05-01

    The U.S. Environmental Protection Agency (U.S. EPA) has developed the Facility Pollution Prevention Guide for those who are interested in and responsible for pollution prevention in industrial or service facilities. It summarizes the benefits of a company-wide pollution prevention program and suggests ways to incorporate pollution prevention in company policies and practices. The Guide describes how to establish a company-wide pollution prevention program. It outlines procedures for conducting a preliminary assessment to identify opportunities for waste reduction or elimination. Then, it describes how to use the results of the preassessment to prioritize areas for detailed assessment, how to use the detailed assessment to develop pollution prevention options, and how to implement those options that withstand feasibility analysis. Methods of evaluating, adjusting, and maintaining the program are described. Later chapters deal with cost analysis for pollution prevention projects and with the roles of product design and energy conservation in pollution prevention. Appendices consist of materials that will support the pollution prevention effort: assessment worksheets, sources of additional information, examples of evaluative methods, and a glossary.

  3. Using pan-Arctic, springtime, surface radiation observations to quantify atmospheric preconditioning processes that impact the sea ice melt season

    NASA Astrophysics Data System (ADS)

    Cox, Christopher; Uttal, Taneil; Starkweather, Sandy; Intrieri, Janet; Maturilli, Marion; Kustov, Vasily; Konopleva, Elena; Crepinsek, Sara; Long, Chuck

    2015-04-01

    Accurate, seasonal-scale forecasts of sea ice extent and distribution are critical for weather forecasting, transportation, the energy industry and local Arctic communities. Current forecasting methods capture an overall trend of decreasing sea ice on decadal scales, but do not reliably predict inter-annual variability. Recent work using satellite observations identified a relationship between spring-time, cloud modulated, shortwave radiation, and late season sea-ice extent; this relationship suggested an atmospheric preconditioning process that modulates the ice-albedo feedback and sets the stage for the melt season. Due to a general lack of emphasis on the role of the atmosphere on the evolution of the summer sea-ice, compounded by biases in cloud properties within models, this preconditioning process is poorly represented in current forecasting methods. Longwave and shortwave radiation data collected at the surface from stations surrounding the Arctic Basin as part of the Baseline Surface Radiation Network (BSRN) provide high-quality, continuous observations of the surface radiation budget. This includes downwelling fluxes and surface-cloud radiative interactions which cannot be directly acquired by satellites. These BSRN data are used to investigate the role of the atmosphere and clouds in seasonal scale variability of sea ice conditions, and the potential for improving predictability by incorporating these atmospheric observations into prediction strategies. We find that the downwelling fluxes measured at the land stations in spring are well correlated with sea ice conditions in September, especially in regions of the Arctic Ocean where late summer sea ice concentration has large inter-annual variability. Using observations of the total radiative flux (longwave + shortwave) at the surface, it is possible to make a seasonal sea-ice extent forecast that is within the range of uncertainty of forecasts currently incorporated into the Sea Ice Prediction Network (SIPN). Cloud variability and associated shortwave modulation of the ice-albedo feedback are found to be important, but the shortwave anomaly alone is insufficient unless combined with the longwave anomaly, which dominates and is opposite in sign in the presence of clouds. The amount of open water in the Western Arctic in September and October then controls cloud cover during the autumn freeze-up, potentially revealing a preconditioning mechanism that persists into the following melt season.

  4. Dropout Prevention Strategies.

    ERIC Educational Resources Information Center

    Peck, Nancy L.; Eberhard, Raymond G.

    1988-01-01

    Dropout prevention is emerging as the most important new issue in education. Broad demographic trends predict a continuing growth in the population of at-risk youth, those most likely to drop out of school. The overall goal of any dropout prevention activity is to reduce the number of at-risk students. This issue is devoted to what research and…

  5. DIABETES PREVENTION PROGRAM

    EPA Science Inventory

    The Diabetes Prevention Program (DPP) was a major clinical trial, or research study, aimed at discovering whether either diet and exercise or the oral diabetes drug metformin (Glucophage) could prevent or delay the onset of type 2 diabetes in people with impaired glucose toleranc...

  6. Fire Prevention Inspection Procedures.

    ERIC Educational Resources Information Center

    Pribyl, Paul F.

    Lesson plans are provided for a fire prevention inspection course of the Wisconsin Fire Service Training program. Objectives for the course are to enable students to describe and conduct fire prevention inspections, to identify and correct hazards common to most occupancies, to understand the types of building construction and occupancy, and to…

  7. Creating a Preventive School.

    ERIC Educational Resources Information Center

    Dickel, C. Timothy; And Others

    This document notes that counselors are increasingly called upon to develop activities intended to prevent rather than remediate. It describes a model by which counselors can systematically develop, implement, and then evaluate a preventive intervention, and it suggests that the most beneficial approach is group planning with the involvement of…

  8. National Osteoporosis Prevention Month

    E-print Network

    MAY National Osteoporosis Prevention Month JUNE National Dairy Month Texas AgriLife Extension - Bone Health Power Point # P4-1 Eat Smart for Bone Health # P4-2 Osteoporosis Disease Statistics # P4-3 Osteoporosis = Porous Bones # P4-4 Risk Factors # P4-5 Risk Factors (continued) # P4-6 Steps to Prevention # P4

  9. LEAD POISONING PREVENTION INFORMATION

    E-print Network

    Families AreForever LEAD POISONING PREVENTION INFORMATION FOR PARENTS & PROSPECTIVE-lead levels There is no safe level of lead in the body. Often, symptoms are not obvious, so lead poisoning's medical examination in the U.S. or contact your state or local Childhood Lead Poisoning Prevention Program

  10. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework

    SciTech Connect

    Calabrese, Edward J. [School of Public Health, Morrill I, N344, Univ. of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu; Bachmann, Kenneth A. [Univ. of Toledo, OH 43606 (United States); Bailer, A. John [Miami Univ., FL 33124 (United States); Bolger, P. Michael [US Food and Drug Administration, MD 20857 (United States); Borak, Jonathan [Yale Univ., CT 06520 (United States); Cai, Lu [Univ. of Louisville School of Medicine, KY 40292 (United States); Cedergreen, Nina [The Royal Veterinary and Agricultural Univ. (KVL) (Denmark); Cherian, M. George [Univ. of Western Ontario (Canada); Chiueh, Chuang C. [Taipei Medical Univ., Taipei, Taiwan (China); Clarkson, Thomas W. [Univ. of Rochester, NY 14627 (United States); Cook, Ralph R. [RRC Consulting, LLC, TX 78727 (United States); Diamond, David M. [Univ. of South Florida, FL 33620 (United States); Doolittle, David J. [RJR Tobacco Company, NC 27101 (United States); Dorato, Michael A. [Eli Lilly and Company, IN 46285 (United States); Duke, Stephen O. [ARS, USDA, MD 20857 (United States); Feinendegen, Ludwig [Heinrich-Heine-Univ. Duesseldorf (Germany); Gardner, Donald E. [Inhalation Toxicology Associates, DC 20006 (United States); Hart, Ronald W. [NCTR, US Food and Drug Administration (Retired), MD 20857 (United States); Hastings, Kenneth L. [US Food and Drug Administration, MD 20857 (United States); Hayes, A. Wallace [Harvard Univ., MA 02114 (United States); Hoffmann, George R. [College of the Holy Cross, MA 01610 (United States); Ives, John A. [Samueli Institute for Information Biology, VA 22314 (United States); Jaworowski, Zbigniew [Central Lab for Radiological Protection, Warszawa (Poland); Johnson, Thomas E. [Univ. of Colorado, CO 80309 (United States); Jonas, Wayne B. [Samueli Institute for Information Biology, VA 22314 (United States); Kaminski, Norbert E. [Michigan State Univ., MI 48824 (United States)] [and others

    2007-07-01

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

  11. Hyperbaric oxygen preconditioning protects lung against hyperoxic acute lung injury in rats via heme oxygenase-1 induction.

    PubMed

    Feng, Ying; Zhang, Zinan; Li, Qiang; Li, Weihao; Xu, Jing; Cao, Huifang

    2015-01-01

    Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. Previous studies have shown hyperbaric oxygen preconditioning (HBO-PC) had a protective effect on oxidative injury. In the present study, we investigated the effect of HBO-PC on HALI in rats. The results demonstrated that HBO-PC ameliorated the lung biochemical and histological alterations induced by hyperoxia, decreased oxidative products but increased antioxidant enzymes. Furthermore, HBO-PC up-regulated heme oxygenase-1 (HO-1) mRNA and activity in lung tissues. The administration of HO-1 inhibitor, Zinc protoporphyrin IX, abolished its protective effects. The data showed that HBO-PC could protect rats against HALI and the anti-oxidative effect may be related to the up-regulation of HO-1. PMID:25264201

  12. Preconditions for sensitivity in measuring change: visual analogue scales compared to rating scales in a Likert format.

    PubMed

    Pfennings, L; Cohen, L; van der Ploeg, H

    1995-10-01

    In a study of preconditions of responsiveness, we examined the variances obtained by two different ways of responding to questionnaire items. Subjects were 168 first-year medical students. They all completed a questionnaire of nine items. The original Likert-like scoring was (partially) replaced by visual analogue scoring in three quarters of the questionnaires. For three items the analogue form had a significantly greater variance than the discrete form, but no discrete item had a significantly greater variance than its analogue counterpart. Assuming that a greater variance was indicative for a greater responsiveness, our findings provide some support for the preferred use of analogue scales over discrete response categories in the measurement of changes over time. PMID:8559872

  13. Combined Analysis of Thruster Plume Behavior in Rarefied Region by Preconditioned Navier-Stokes and DSMC Methods

    NASA Astrophysics Data System (ADS)

    Lee, Kyun Ho; Lee, Sung Nam; Yu, Myoung Jong; Kim, Su Kyum; Baek, Seung Wook

    Satellite attitude is usually controlled by plume exhaust from thrusters into the vacuum of space. To study the plume effects in the highly rarefied region, the Direct Simulation Monte Carlo (DSMC) method is usually used, because the plume flow field contains the entire range of flow regime from the near-continuum near the nozzle exit through the transitional state to free molecular state at the far field region from the nozzle. The purpose of this study is to investigate the behavior of a small monopropellant thruster plume in the vacuum region numerically by using the DSMC method. To obtain more accurate results, the preconditioned Navier-Stokes algorithm is introduced to calculate continuum flow fields inside the thruster to predict nozzle exit properties, which are used for inlet conditions of DSMC method. As a result, the plume characteristics in the highly rarefied flow, such as strong nonequilibrium near nozzle exit, large back flow region, etc., are investigated.

  14. Measuring waste prevention.

    PubMed

    Zorpas, Antonis A; Lasaridi, Katia

    2013-05-01

    The Waste Framework Directive (WFD-2008/98/EC) has set clear waste prevention procedures, including reporting, reviewing, monitoring and evaluating. Based on the WFD, the European Commission and will offer support to Member States on how to develop waste prevention programmes through guidelines and information sharing on best practices. Monitoring and evaluating waste prevention activities are critical, as they constitute the main tools to enable policy makers, at the national and local level, to build their strategic plans and ensure that waste prevention initiatives are effective and deliver behaviour change. However, how one can measure something that is not there, remains an important and unresolved research question. The paper reviews and attempts to evaluate the methods that are being used for measuring waste prevention and the impact of relevant implemented activities at the household level, as the available data is still limited. PMID:23453356

  15. Magnetosphere preconditioning under northward IMF: Evidence from the study of coronal mass ejection and corotating interaction region geoeffectiveness

    NASA Astrophysics Data System (ADS)

    Lavraud, B.; Thomsen, M. F.; Borovsky, J. E.; Denton, M. H.; Pulkkinen, T. I.

    2006-09-01

    Motivated by recent observations and simulations of the formation of a cold and dense plasma sheet in the tail of the magnetosphere under northward interplanetary magnetic field (IMF) and of the direct influence of the plasma sheet density on the ring current strength, this paper aims at (1) highlighting how the coupling of these effects may lead to a preconditioning of the magnetosphere under northward IMF and (2) performing first tests of the validity of this hypothesis. We have analyzed superposed epoch time series of various parameters to investigate the response of the magnetosphere (as indicated by the Dst index) to the passage of coronal mass ejections (CMEs) and corotating interaction regions (CIRs). We first focused on the difference between the measured Dst signature and that predicted by a semiempirical Dst model. For both CME- and CIR-driven storms the superposed epoch results show that the model Dst predictions tend to underestimate the actual storm strength (by up to 10-30%) for events that are preceded by a substantial interval of northward IMF, as opposed to those with no such preceding northward IMF. We also analyzed Los Alamos geosynchronous spacecraft data for these events. The average density and temperature measured at storm onset are substantially higher and slightly lower, respectively, for the cases with preceding northward IMF intervals. These results suggest that solar wind structures may be more geoeffective if preceded by a northward IMF interval and they are consistent with the hypothesis of a preconditioning by a cold, dense plasma sheet. A colder and denser plasma sheet may lead to a stronger ring current when that plasma is convected inward during the main phase of an ensuing storm.

  16. Hypoxia Precondition Promotes Adipose-Derived Mesenchymal Stem Cells Based Repair of Diabetic Erectile Dysfunction via Augmenting Angiogenesis and Neuroprotection

    PubMed Central

    Li, ShaoDan; Xu, Yong; Chen, Ping; Liu, Yi; Ding, Qiang; Wahafu, Wasilijiang; Hong, BaoFa; Yang, MingHui

    2015-01-01

    The aim of the present study was to examine whether hypoxia preconditioning could improve therapeutic effects of adipose derived mesenchymal stem cells (AMSCs) for diabetes induced erectile dysfunction (DED). AMSCs were pretreated with normoxia (20% O2, N-AMSCs) or sub-lethal hypoxia (1% O2, H-AMSCs). The hypoxia exposure up-regulated the expression of several angiogenesis and neuroprotection related cytokines in AMSCs, including vascular endothelial growth factor (VEGF) and its receptor FIK-1, angiotensin (Ang-1), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), stromal derived factor-1 (SDF-1) and its CXC chemokine receptor 4 (CXCR4). DED rats were induced via intraperitoneal injection of streptozotocin (60 mg/kg) and were randomly divided into three groups—Saline group: intracavernous injection with phosphate buffer saline; N-AMSCs group: N-AMSCs injection; H-AMSCs group: H-AMSCs injection. Ten rats without any treatment were used as normal control. Four weeks after injection, the mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured. The contents of endothelial, smooth muscle, dorsal nerve in cavernoursal tissue were assessed. Compared with N-AMSCs and saline, intracavernosum injection of H-AMSCs significantly raised ICP and ICP/MAP (p<0.05). Immunofluorescent staining analysis demonstrated that improved erectile function by MSCs was significantly associated with increased expression of endothelial markers (CD31 and vWF) (p<0.01) and smooth muscle markers (?-SMA) (p<0.01). Meanwhile, the expression of nNOS was also significantly higher in rats receiving H-AMSCs injection than those receiving N-AMSCs or saline injection. The results suggested that hypoxic preconditioning of MSCs was an effective approach to enhance their therapeutic effect for DED, which may be due to their augmented angiogenesis and neuroprotection. PMID:25790284

  17. Hypoxic Preconditioning Differentially Affects GABAergic and Glutamatergic Neuronal Cells in the Injured Cerebellum of the Neonatal Rat

    PubMed Central

    Patterson, Sean I.; Muñoz, Estela M.; Seltzer, Alicia M.

    2014-01-01

    In this study we examined cerebellar alterations in a neonatal rat model of hypoxic-ischemic brain injury with or without hypoxic preconditioning (Pc). Between postnatal days 7 and 15, the cerebellum is still undergoing intense cellular proliferation, differentiation and migration, dendritogenesis and synaptogenesis. The expression of glutamate decarboxylase 1 (GAD67) and the differentiation factor NeuroD1 were examined as markers of Purkinje and granule cells, respectively. We applied quantitative immunohistochemistry to sagittal cerebellar slices, and Western blot analysis of whole cerebella obtained from control (C) rats and rats submitted to Pc, hypoxia-ischemia (L) and a combination of both treatments (PcL). We found that either hypoxia-ischemia or Pc perturbed the granule cells in the posterior lobes, affecting their migration and final placement in the internal granular layer. These effects were partially attenuated when the Pc was delivered prior to the hypoxia-ischemia. Interestingly, whole nuclear NeuroD1 levels in Pc animals were comparable to those in the C rats. However, a subset of Purkinje cells that were severely affected by the hypoxic-ischemic insult—showing signs of neuronal distress at the levels of the nucleus, cytoplasm and dendritic arborization—were not protected by Pc. A monoclonal antibody specific for GAD67 revealed a three-band pattern in cytoplasmic extracts from whole P15 cerebella. A ?110 kDa band, interpreted as a potential homodimer of a truncated form of GAD67, was reduced in Pc and L groups while its levels were close to the control animals in PcL rats. Additionally we demonstrated differential glial responses depending on the treatment, including astrogliosis in hypoxiated cerebella and a selective effect of hypoxia-ischemia on the vimentin-immunolabeled intermediate filaments of the Bergmann glia. Thus, while both glutamatergic and GABAergic cerebellar neurons are compromised by the hypoxic-ischemic insult, the former are protected by a preconditioning hypoxia while the latter are not. PMID:25032984

  18. Hypoxic preconditioning differentially affects GABAergic and glutamatergic neuronal cells in the injured cerebellum of the neonatal rat.

    PubMed

    Benitez, Sergio G; Castro, Analía E; Patterson, Sean I; Muñoz, Estela M; Seltzer, Alicia M

    2014-01-01

    In this study we examined cerebellar alterations in a neonatal rat model of hypoxic-ischemic brain injury with or without hypoxic preconditioning (Pc). Between postnatal days 7 and 15, the cerebellum is still undergoing intense cellular proliferation, differentiation and migration, dendritogenesis and synaptogenesis. The expression of glutamate decarboxylase 1 (GAD67) and the differentiation factor NeuroD1 were examined as markers of Purkinje and granule cells, respectively. We applied quantitative immunohistochemistry to sagittal cerebellar slices, and Western blot analysis of whole cerebella obtained from control (C) rats and rats submitted to Pc, hypoxia-ischemia (L) and a combination of both treatments (PcL). We found that either hypoxia-ischemia or Pc perturbed the granule cells in the posterior lobes, affecting their migration and final placement in the internal granular layer. These effects were partially attenuated when the Pc was delivered prior to the hypoxia-ischemia. Interestingly, whole nuclear NeuroD1 levels in Pc animals were comparable to those in the C rats. However, a subset of Purkinje cells that were severely affected by the hypoxic-ischemic insult--showing signs of neuronal distress at the levels of the nucleus, cytoplasm and dendritic arborization--were not protected by Pc. A monoclonal antibody specific for GAD67 revealed a three-band pattern in cytoplasmic extracts from whole P15 cerebella. A ?110 kDa band, interpreted as a potential homodimer of a truncated form of GAD67, was reduced in Pc and L groups while its levels were close to the control animals in PcL rats. Additionally we demonstrated differential glial responses depending on the treatment, including astrogliosis in hypoxiated cerebella and a selective effect of hypoxia-ischemia on the vimentin-immunolabeled intermediate filaments of the Bergmann glia. Thus, while both glutamatergic and GABAergic cerebellar neurons are compromised by the hypoxic-ischemic insult, the former are protected by a preconditioning hypoxia while the latter are not. PMID:25032984

  19. Role of adaptor protein MyD88 in TLR-mediated preconditioning and neuroprotection after acute excitotoxicity.

    PubMed

    Larochelle, Antoine; Bellavance, Marc-André; Rivest, Serge

    2015-05-01

    Excitotoxic cell death is a crucial mechanism through which neurodegeneration occurs in numerous pathologies of the central nervous system (CNS), such as Alzheimer's disease, stroke and spinal cord injury. Toll-like receptors (TLRs) are strongly expressed on microglial cells and are key regulators of the innate immune response to neuronal damage. However, it is still unclear whether their stimulation is protective or harmful in excitotoxic contexts. In this study, we demonstrate that systemic administration of lipopolysaccharide (LPS) or Pam3CSK4 24h prior to an intrastriatal injection of kainic acid (KA) significantly protected cortical neurons in the acute phase of injury. Protection could not be detected with the TLR3 ligand poly-IC. Histological analyses revealed that microglia of LPS and Pam3CSK4 pre-conditioned group were primed to react to injury and exhibited a stronger expression of Tnf and Tlr2 mRNA. We also found that mice deficient for MyD88, a critical adaptor protein for most TLR, were more vulnerable than WT mice to KA-induced excitotoxicity at early (12h and 24h) and late (10days) time points. Finally, bone-marrow chimeric mice revealed that MyD88 signaling in CNS resident cells, but not in cells of hematopoietic origin, mediates the protective effect. This study unravels the potential of TLR2 and TLR4 agonists to induce a protective state of preconditioning against KA-mediated excitotoxicity and further highlights the beneficial role of cerebral MyD88 signaling in this context. PMID:25733102

  20. What’s preventing more prevention?

    Microsoft Academic Search

    Lawrence K. Gottlieb; Halsted R. Holman

    1992-01-01

    Objective:To determine the views of leaders in academic medicine concerning the need for programs in preventive medicine (PM) and the\\u000a prevailing barriers to program development.\\u000a \\u000a Design:Structured interviews.\\u000a \\u000a \\u000a \\u000a Setting:Medical schools of the United States.\\u000a \\u000a \\u000a \\u000a Patients\\/participants:90% of deans and chairpersons of departments of medicine and preventive medicine.\\u000a \\u000a \\u000a \\u000a Interventions:None.\\u000a \\u000a \\u000a \\u000a Measurements and main results:91% considered academic PM underdeveloped and 100% considered their own programs

  1. Ischemic Stroke Prevention.

    PubMed

    Chaturvedi; Hickenbottom; Levine

    1999-05-01

    More than 700,000 strokes occur annually in the United States--one every 40 to 50 seconds. Although stroke is one of the nation's most expensive diseases to treat, costing $41 billion per year, most strokes (perhaps as many as two thirds) are preventable. Twenty percent of the United States population will have 80% of all strokes; this estimate is based on five established, major risk factors for stroke: hypertension, diabetes mellitus, cigarette smoking, hyperlipidemia, and heart disease. Therefore, stroke is not random but is generally predictable. It is an ideal target for effective prevention strategies that are simple and inexpensive. Ischemic stroke prevention has been shown to be effective in several scenarios: primary prevention, prevention after a transient ischemic attack (TIA), and secondary prevention. Dietary, lifestyle, and risk factor modification; use of aspirin, ticlopidine, clopidogrel, and warfarin; and carotid endarterectomy all have a role in stroke prevention in selected persons. Emerging therapies include the use of vitamins, cerebral arterial angioplasty, and stenting. Annual risk assessment, screening, and intervention should be part of a concerted national effort to reduce the incidence of the third leading cause of death and the number one cause of adult disability in the United States. PMID:11096701

  2. Pollution prevention research strategy

    SciTech Connect

    Herrmann, J.

    1998-09-01

    ORD developed a Pollution Prevention Research Strategy that elaborates on the directions in the strategic plan and provides a framework to guide investments in pollution prevention research and development over the next five years. The strategy contains four chapters: Chapter 1 sets the context; Chapter 2 outlines a strategic pollution prevention rationale; Chapter 3 describes four long-term goals and accompanying strategic objectives to be addressed and includes activities to be pursued as part of the research strategy; and Chapter 4 describes the implementation approach for the goals and objectives presented in Chapter 3.

  3. In Vivo Analysis of Laser Preconditioning in Incisional Wound Healing of Wild-Type and HSP70 Knockout Mice With Raman Spectroscopy

    PubMed Central

    Makowski, Alexander J.; Davidson, Jeffrey M.; Mahadevan-Jansen, Anita; Jansen, E. Duco

    2013-01-01

    Background and Objective Laser preconditioning augments incisional wound healing by reducing scar tissue and increasing maximum tensile load of the healed wound [.Wilmink et al. (2009) J Invest Dermatol 129(1): 205–216]. Recent studies have optimized treatments or confirmed results using HSP70 as a biomarker. Under the hypothesis that HSP70 plays a role in reported results and to better understand the downstream effects of laser preconditioning, this study utilized a probe-based Raman spectroscopy (RS) system to achieve an in vivo, spatiotemporal biochemical profile of murine skin incisional wounds as a function of laser preconditioning and the presence of HSP70. Study Design/Materials and Methods A total of 19 wild-type (WT) and HSP70 knockout (HSP70?/?) C57BL/ 6 mice underwent normal and laser preconditioned incisional wounds. Laser thermal preconditioning was conducted via previously established protocol (? = 1.85 µm, H0 =7.64 mJ/cm2 per pulse, spot diameter = 5 mm, Rep. rate = 50 Hz, ?p = 2 milliseconds, exposure time = 10 minutes) with an Aculight Renoir diode laser, with tissue temperature confirmed by real-time infrared camera measurements. Wound-healing progression was quantified by daily collection of a spatial distribution of Raman spectra. The results of RS findings were then qualified using standard histology and polarization microscopy. Results Raman spectra yielded significant differences (t-test; ? =0.05) in several known biochemical peaks between WT and HSP70 (?/?) mice on wounds and in adjacent tissue early in the wound-healing process. Analysis of peak ratios implied (i) an increase in protein configuration in and surrounding the wound in WT mice, and (ii) an increased cellular trend in WT mice that was prolonged due to laser treatment. Polarization microscopy confirmed that laser treated WT mice showed increased heterogeneity in collagen orientation. Conclusions The data herein supports the theory that HSP70 is involved in normal skin protein configuration and the cellularity of early wound healing. Laser preconditioning extends cellular trends in the presence of HSP70. Despite study limitations, RS provided a non-invasive method for quantifying temporal trends in altered wound healing, narrowing candidates and design for future studies with clinically applicable instrumentation. PMID:22275297

  4. [Primary prevention of osteopenia].

    PubMed

    Falkenbach, A

    1992-11-01

    In industrialized countries the clinical and socioeconomic importance of osteoporosis has been well recognized in recent years. Various treatments have been introduced for secondary prevention in established osteoporosis. There is, however, a deficit in the primary prevention of osteopenia. In every age group physical exercise stimulates mineralization of the bone. With regular training adolescents can achieve a higher peak bone mass. In old age the physiologic decrease of bone mass can be retarded by physical exercise. A diet rich in calcium has positive effects on mineralization of the bone. Estrogens have proved efficacious in the prevention of osteoporosis in postmenopausal women. Abstinence from nicotine and alcohol contributes to the prevention of osteopenia. PMID:1439691

  5. Help prevent hospital errors

    MedlinePLUS

    ... prevent medical errors when you are in the hospital. ... Share your health information with health care providers in the hospital. DO NOT think they already know it. Know what tests are being done. Ask what the test is for, ...

  6. Household Safety: Preventing Choking

    MedlinePLUS

    ... a child, it's a good idea to: Learn cardiopulmonary resuscitation (CPR) and the Heimlich maneuver. Keep the following numbers ... Childproofing and Preventing Household Accidents Choosing Safe Toys CPR First-Aid Kit Getting Help: Know the Numbers ...

  7. Diabetes Prevention Program (DPP)

    MedlinePLUS

    ... Recruiting Patients & Families Consortia, Networks & Centers Reports & Planning Diabetes Prevention Program (DPP) Page Content On this page: ... increased risk of developing diabetes. [ Top ] Type 2 Diabetes and Prediabetes Type 2 diabetes is a disorder ...

  8. Scabies: Prevention and Control

    MedlinePLUS

    ... message, please visit this page: About CDC.gov . Parasites - Scabies Parasites Home Share Compartir Prevention & Control When a person ... Cases Publications Information For: Institutions Travelers Related Links Parasites A-Z Index Parasites Glossary Neglected Tropical Diseases ...

  9. Brain Basics: Preventing Stroke

    MedlinePLUS

    Brain Basics: Preventing Stroke Request free mailed brochure Table of Contents Introduction What is a Stroke? What ... Americans are protecting their most important asset—their brain. Are you? Stroke ranks as the fourth leading ...

  10. Preventability of Cancer

    PubMed Central

    Colditz, Graham A.; Wei, Esther K.

    2013-01-01

    Whereas models of cancer disparities and variation in cancer burden within population groups now specify multiple levels of action from biologic processes to individual risk factors and social and physical contextual factors, approaches to estimating the preventable proportion of cancer use more traditional direct models often from single exposures to cancer at specific organ sites. These approaches are reviewed, and the strengths and limitations are presented. The need for additional multilevel data and approaches to estimation of preventability are identified. International or regional variation in cancer may offer the most integrated exposure assessment over the life course. For the four leading cancers, which account for 50% of incidence and mortality, biologic, social, and physical environments play differing roles in etiology and potential prevention. Better understanding of the interactions and contributions across these levels will help refine prevention strategies. PMID:22224878

  11. Preventing Eye Injuries

    MedlinePLUS

    ... the Sun Eye Health News Consumer Alerts Preventing Eye Injuries Tweet Protecting your eyes from injury is ... as possible, even if the injury seems minor. Eye Injury Facts and Myths Men are more likely ...

  12. Preventing Weight Gain

    MedlinePLUS

    ... proportion of fat increases. This shift slows their metabolism, making it easier to gain weight. In addition, ... Disease Control and Prevention 1600 Clifton Rd Atlanta, GA 30333 800-CDC-INFO (800-232-4636) TTY: ( ...

  13. Pollution prevention through chemistry

    SciTech Connect

    Breen, J.J.; Anastas, P.T.; Hassur, S.M.; Tobin, P.S. [Environmental Protection Agency, Washington, DC (United States). Office of Pollution Prevention and Toxics

    1995-09-01

    Prosperity without pollution, and the consideration of how to achieve this economic and environmental imperative, has become the fundamental environmental theme of the 1990s. The new strategy--pollution prevention--will serve s the keystone of federal, state, and local environmental policy. The challenge is to switch from two decades of environmental policy based on pollution controls and government-mandated regulations to a future environmental policy based on pollution prevention, source reduction, recycling, and waste minimization. To make this change will require a new social compact among environmental, industrial, and regulatory interests. This chapter focuses on the role of chemistry and the contributions of synthetic and process analytical chemists. It also describes the implementation of pollution prevention concepts into the premanufacturing notice review process mandated by Section 5 of the Toxic Substances Control Act (TSCA) and discusses the implications of pollution prevention for chemical safety. 55 refs.

  14. Preventing Pressure Sores

    MedlinePLUS Videos and Cool Tools

    ... Injury 101 The Basics of Spinal Cord Injury Rehabilitation Preventing Pressure Sores Transition from Hospital to Home ... Cord Injury 101 The Basics of Pediatric SCI Rehabilitation Transitions for Children with Spinal Cord Injury What ...

  15. IS SUICIDE PREVENTABLE?

    PubMed Central

    Elias, Ralph B.

    1959-01-01

    Among 500 cases of suicide analyzed in Stockholm, fewer than a third were associated with depression. Most forms of psychiatric disease were represented. Nevertheless, most persons give some warning before attempting suicide, and these warnings should be the signal for preventive action. Centers with trained personnel could prevent many suicides, if the potential victims were recognized and referred early enough. Laymen too should be educated to recognize potential suicide and help avert it. PMID:13629348

  16. Preventing tap water burns.

    PubMed Central

    Baptiste, M S; Feck, G

    1980-01-01

    Based on a 1974-1975 survey of hospital records in upstate New York, we estimate that 347 tap water burns will require inpatient treatment annually, with children and the elderly at increased risk. The number and severity of burns from tap water makes them an important prevention priority. Reducing the temperature of household hot water supplies could be a practical and effective prevention measure. PMID:7386711

  17. Spinal Cord Injury Prevention Tips

    MedlinePLUS

    Spinal Cord Injury Prevention Tips Preventing SCI Biking prevention tips While many cycling injuries are head injuries, the ... NeurosurgeryToday.org Every year, an estimated 11,000 spinal cord injury (SCI) accidents occur in the United States. ...

  18. Pneumocystis Pneumonia Risk and Prevention

    MedlinePLUS

    ... Diseases Share Compartir Risk & Prevention Who gets pneumocystis pneumonia (PCP)? PCP is extremely rare in healthy people. ... chronic lung diseases How can I prevent pneumocystis pneumonia (PCP)? There is no vaccine to prevent PCP. ...

  19. Preventive interventions among children exposed to trauma of armed conflict: a literature review.

    PubMed

    Peltonen, Kirsi; Punamäki, Raija-Leena

    2010-01-01

    Increasing research is available on the preconditions for child mental health and optimal development in traumatic conditions, whereas less is known how to translate the findings into effective interventions to help traumatized children. This literature review analyses the effectiveness of psychosocial preventive interventions and treatments and their theoretical bases among children traumatized in the context of armed conflicts (war, military violence, terrorism and refugee). The first aim is to evaluate the effectiveness of preventive interventions in preventing emotional distress and impairment and promoting optimal emotional-cognitive and social development. The second task is to analyze the nature of the underlying mechanisms for the success of preventive interventions, and the theoretical premises of the choice of intervention techniques, procedures and tools. We found 16 relevant published studies, but an examination of them revealed that only four of them had experimental designs strong enough that they could be included in the meta-analysis. While the subjective reports of the researchers suggested that systematic preventive interventions were effective in decreasing PTSD and depressive symptoms among children traumatized due to armed conflict, the more objective results of the meta-analysis and the weaknesses in designs uncovered during the meta-analysis undermine such a conclusion. Additionally, a majority of the reported preventive interventions focused only on children's biased cognitive processes and negative emotions, while only a few aimed at influencing multiple domains of child development and improving developmental functioning on emotional, social and psychophysiological levels. It is concluded that substantial additional work needs to be done in developing effective preventive interventions and treatments for children traumatized by exposure to war and violence. PMID:19998393

  20. Help Prevent Diabetes with Exercise

    NSDL National Science Digital Library

    WGBH Educational Foundation

    2011-07-01

    This animated video segment adapted from the Centers for Disease Control and Prevention, featuring American Indian characters, explains how children can help prevent diabetes through regular physical activity.

  1. Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C2H2 zinc finger protein.

    PubMed

    Han, D; Zhang, C; Fan, W J; Pan, W J; Feng, D M; Qu, S L; Jiang, Z S

    2015-01-01

    Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C2H2 motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element. PMID:25493376

  2. Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C2H2 zinc finger protein.

    PubMed

    Han, D; Zhang, C; Fan, W J; Pan, W J; Feng, D M; Qu, S L; Jiang, Z S

    2014-10-31

    Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C2H2 motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element. PMID:25372717

  3. CPDES2: A preconditioned conjugate gradient solver for linear asymmetric matrix equations arising from coupled partial differential equations in two dimensions

    NASA Astrophysics Data System (ADS)

    Anderson, D. V.; Koniges, A. E.; Shumaker, D. E.

    1988-11-01

    Many physical problems require the solution of coupled partial differential equations on two-dimensional domains. When the time scales of interest dictate an implicit discretization of the equations a rather complicated global matrix system needs solution. The exact form of the matrix depends on the choice of spatial grids and on the finite element or finite difference approximations employed. CPDES2 allows each spatial operator to have 5 or 9 point stencils and allows for general couplings between all of the component PDE's and it automatically generates the matrix structures needed to perform the algorithm. The resulting sparse matrix equation is solved by either the preconditioned conjugate gradient (CG) method or by the preconditioned biconjugate gradient (BCG) algorithm. An arbitrary number of component equations are permitted only limited by available memory. In the sub-band representation used, we generate an algorithm that is written compactly in terms of indirect indices which is vectorizable on some of the newer scientific computers.

  4. Use of the preconditioned conjugate gradient algorithm as a generic solver for mixed-model equations in animal breeding applications1

    Microsoft Academic Search

    S. Tsuruta; I. Misztal; I. Stranden

    Utility of the preconditioned conjugate gradient algorithm with a diagonal preconditioner for solving mixed-model equations in animal breeding ap- plications was evaluated with 16 test problems. The problems included single- and multiple-trait analyses, with data on beef, dairy, and swine ranging from small examples to national data sets. Multiple-trait models considered low and high genetic correlations. Conver- gence was based

  5. Pharmacologic preconditioning of random-pattern skin flap in rats using local cyclosporine and FK-506: interaction with nitric oxide system.

    PubMed

    Nezami, Behtash Ghazi; Ghazinezami, Behtash; Rahimpour, Sina; Gholipour, Taha; Ghasemi, Mehdi; Sadeghipour, Hamed; Mehr, Shahram Ejtemaie; Emami-Razavi, Seyed Hassan; Dehpour, Ahmad Reza

    2007-10-01

    It has been suggested that immunophilin ligands such as cyclosporine and FK-506 (tacrolimus) affect the survival of ischemic tissues. Our objective was to show an acute effect of local cyclosporin-A (CsA) and FK-506 on ischemic protection in a random-pattern skin-flap model in rats and investigate the effect of nitric oxide (NO) pathways as a modulator of protection of these agents. Ninety male Sprague-Dawley rats were randomly assigned to treatment groups. Bipedicled dorsal flaps (2 x 8 cm) were elevated at midline. Prior to cutting the cranial pedicle to induce permanent ischemia, pharmacologic preconditioning groups received local injection of CsA (0.3, 1, or 3 nmol/flap) or FK-506 (0.01, 0.03, or 0.1 pmol/flap), and the ischemic preconditioning (IPC) group underwent temporary clamping of the cranial pedicle. At the seventh day postoperatively, the survival of the flaps was measured. In other groups, nitric oxide synthase inhibitor N omega-nitro-l-arginine methyl ester hydrochloride (L-NAME) was administered with effective CsA and FK-506, and ischemic preconditioning. Nitric oxide precursor L-arginine doses were also studied, and a systemic subeffective dose (100 mg/kg) was coadministered with subeffective CsA and FK-506. Significant increase in flap survival was obtained with CsA (1 nmol/flap), FK-506 (0.1 pmol/flap), and IPC. These protections were abolished by systemic administration of L-NAME (10 mg/kg). Coadministration of subeffective doses of CsA (0.3 nmol/flap) and FK-506 (0.03 pmol/flap), with subeffective systemic l-arginine, significantly improved flap survival.Pharmacologic preconditioning with local, single, low doses of CsA or FK-506 is shown to be even more effective than IPC. Administration of the NOS substrate l-arginine potentiates these effects. PMID:17901737

  6. Hypoxia-preconditioned adipose tissue-derived mesenchymal stem cell increase the survival and gene expression of engineered neural stem cells in a spinal cord injury model

    Microsoft Academic Search

    Jin Soo Oh; Yoon Ha; Sung Su An; Momin Khan; William A. Pennant; Hyo Jin Kim; Do Heum Yoon; Minhyung Lee; Keung Nyun Kim

    2010-01-01

    Hypoxic preconditioning (HP) is a novel strategy to make stem cells resistant to the ischemic environment they encounter after transplantation into injured tissue; this strategy improves survival of both the transplanted cells and the host cells at the injury site. Using both in vitro and in vivo injury models, we confirmed that HP-treated adipose tissue-derived mesenchymal stem cells (HP-AT-MSCs) increased

  7. Inositol 1,4,5-triphosphate receptors and NAD(P)H mediate Ca 2+ signaling required for hypoxic preconditioning of hippocampal neurons

    Microsoft Academic Search

    P. E. Bickler; C. S. Fahlman; J. Gray; W. McKleroy

    2009-01-01

    Exposure of neurons to a non-lethal hypoxic stress greatly reduces cell death during subsequent severe ischemia (hypoxic preconditioning, HPC). In organotypic cultures of rat hippocampus, we demonstrate that HPC requires inositol triphosphate (IP3) receptor-dependent Ca2+ release from the endoplasmic reticulum (ER) triggered by increased cytosolic NAD(P)H. Ca2+ chelation with intracellular BAPTA, ER Ca2+ store depletion with thapsigargin, IP3 receptor block

  8. A Parallel, Fully Coupled, Fully Implicit Solution to Reactive Transport in Porous Media Using the Preconditioned Jacobian-Free Newton-Krylov Method

    SciTech Connect

    Luanjing Guo; Hai Huang; Derek Gaston; Cody Permann; David Andrs; George Redden; Chuan Lu; Don Fox; Yoshiko Fujita

    2013-03-01

    Modeling large multicomponent reactive transport systems in porous media is particularly challenging when the governing partial differential algebraic equations (PDAEs) are highly nonlinear and tightly coupled due to complex nonlinear reactions and strong solution-media interactions. Here we present a preconditioned Jacobian-Free Newton-Krylov (JFNK) solution approach to solve the governing PDAEs in a fully coupled and fully implicit manner. A well-known advantage of the JFNK method is that it does not require explicitly computing and storing the Jacobian matrix during Newton nonlinear iterations. Our approach further enhances the JFNK method by utilizing physics-based, block preconditioning and a multigrid algorithm for efficient inversion of the preconditioner. This preconditioning strategy accounts for self- and optionally, cross-coupling between primary variables using diagonal and off-diagonal blocks of an approximate Jacobian, respectively. Numerical results are presented demonstrating the efficiency and massive scalability of the solution strategy for reactive transport problems involving strong solution-mineral interactions and fast kinetics. We found that the physics-based, block preconditioner significantly decreases the number of linear iterations, directly reducing computational cost; and the strongly scalable algebraic multigrid algorithm for approximate inversion of the preconditioner leads to excellent parallel scaling performance.

  9. Downregulation of MiR-199a Derepresses Hypoxia-Inducible Factor-1? and Sirtuin 1 and Recapitulates Hypoxia Preconditioning in Cardiac Myocytes

    PubMed Central

    Rane, Shweta; He, Minzhen; Sayed, Danish; Vashistha, Himanshu; Malhotra, Ashwani; Sadoshima, Junichi; Vatner, Dorothy E.; Vatner, Stephen F.; Abdellatif, Maha

    2012-01-01

    MicroRNAs are posttranscriptional gene regulators that are differentially expressed during various diseases and have been implicated in the underlying pathogenesis. We report here that miR-199a is acutely downregulated in cardiac myocytes on a decline in oxygen tension. This reduction is required for the rapid upregulation of its target, hypoxia-inducible factor (Hif)-1?. Replenishing miR-199a during hypoxia inhibits Hif-1? expression and its stabilization of p53 and, thus, reduces apoptosis. On the other hand, knockdown of miR-199a during normoxia results in the upregulation of Hif-1? and Sirtuin (Sirt)1 and reproduces hypoxia preconditioning. Sirt1 is also a direct target of miR-199a and is responsible for downregulating prolyl hydroxylase 2, required for stabilization of Hif-1?. Thus, we conclude that miR-199a is a master regulator of a hypoxia-triggered pathway and can be exploited for preconditioning cells against hypoxic damage. In addition, the data demonstrate a functional link between 2 key molecules that regulate hypoxia preconditioning and longevity. PMID:19265035

  10. Gender-Based Violence Prevention. Issues in Prevention

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012

    2012-01-01

    This issue of "Issues in Prevention" focuses on gender-based violence prevention. This issue contains the following articles: (1) Preventing Gender-Based Violence: An Overview (Linda Langford); (2) Q&A With Amelia Cobb; (3) Denim Day at HBCUs; (4) Dear Colleague Letter; (5) ED Grants for Violence Prevention; and (6) Higher Education Center…

  11. Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation.

    PubMed

    Cahova, Monika; Palenickova, Eliska; Dankova, Helena; Sticova, Eva; Burian, Martin; Drahota, Zdenek; Cervinkova, Zuzana; Kucera, Otto; Gladkova, Christina; Stopka, Pavel; Krizova, Jana; Papackova, Zuzana; Oliyarnyk, Olena; Kazdova, Ludmila

    2015-07-15

    Nonalcoholic fatty liver disease is associated with chronic oxidative stress. In our study, we explored the antioxidant effect of antidiabetic metformin on chronic [high-fat diet (HFD)-induced] and acute oxidative stress induced by short-term warm partial ischemia-reperfusion (I/R) or on a combination of both in the liver. Wistar rats were fed a standard diet (SD) or HFD for 10 wk, half of them being administered metformin (150 mg·kg body wt(-1)·day(-1)). Metformin treatment prevented acute stress-induced necroinflammatory reaction, reduced alanine aminotransferase and aspartate aminotransferase serum activity, and diminished lipoperoxidation. The effect was more pronounced in the HFD than in the SD group. The metformin-treated groups exhibited less severe mitochondrial damage (markers: cytochrome c release, citrate synthase activity, mtDNA copy number, mitochondrial respiration) and apoptosis (caspase 9 and caspase 3 activation). Metformin-treated HFD-fed rats subjected to I/R exhibited increased antioxidant enzyme activity as well as attenuated mitochondrial respiratory capacity and ATP resynthesis. The exposure to I/R significantly increased NADH- and succinate-related reactive oxygen species (ROS) mitochondrial production in vitro. The effect of I/R was significantly alleviated by previous metformin treatment. Metformin downregulated the I/R-induced expression of proinflammatory (TNF-?, TLR4, IL-1?, Ccr2) and infiltrating monocyte (Ly6c) and macrophage (CD11b) markers. Our data indicate that metformin reduces mitochondrial performance but concomitantly protects the liver from I/R-induced injury. We propose that the beneficial effect of metformin action is based on a combination of three contributory mechanisms: increased antioxidant enzyme activity, lower mitochondrial ROS production, and reduction of postischemic inflammation. PMID:26045616

  12. Transferred inter-cell ischemic preconditioning-induced neuroprotection may be mediated by adenosine A1 receptors.

    PubMed

    Yun, Jungyeon; Li, Jun; Zuo, Zhiyi

    2014-04-01

    Ischemic preconditioning-induced neuroprotection is a well-known phenomenon. We hypothesize that this form of neuroprotection is transferable among the same type of cells. To test this hypothesis, human neuroblastoma SH-SY5Y cells were induced to become neuron-like cells. Primary rat cortical neuronal cultures were also used. These cells were subjected to various lengths of short oxygen-glucose deprivation (OGD, an in vitro simulation of ischemia) and then 1-h OGD. Some cells that were not exposed to a short episode of ischemia were incubated with culture medium from the cells that had 3- or 5-min OGD. Those cells were subjected to OGD for 1h at 1 or 24h after they were exposed to the medium. Cell injury was evaluated at 24h after the 1-h OGD by lactate dehydrogenase release assay. In another experiment, cells subjected to a 3-min OGD or exposed to the medium from cells that had a 3-min OGD were harvested at 30min after the OGD or the medium exposure for Western blotting of Akt, a prosurvival protein. Our study showed that a prior episode of ischemia lasting from 3 to 10min significantly reduced the 1-h OGD-induced cell injury. Medium from cells subjected to a 3-min OGD also induced acute and delayed phases of neuroprotection in OGD-naïve human neuron-like cells and primary rat cortical neuronal cultures. Cells subjected to a 3-min OGD or incubated with the medium from cells exposed to a 3-min OGD had increased phosphorylated/activated Akt. The increased phosphorylated Akt and neuroprotection induced by medium transferring were inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 receptor inhibitor. The 3-min OGD-induced neuroprotection was inhibited by LY294002, an Akt activation inhibitor. These results suggest that ischemic preconditioning-induced neuroprotection is transferable among the cells. Small molecules, such as adenosine, may mediate this effect. PMID:24613761

  13. On acoustic waveform tomography of wide-angle OBS data—strategies for pre-conditioning and inversion

    NASA Astrophysics Data System (ADS)

    Kamei, R.; Pratt, R. G.; Tsuji, T.

    2013-08-01

    We successfully apply the acoustic Laplace-Fourier waveform tomography method to delineate P-wave velocity structures of the mega-splay fault system in the central part of the seismogenic Nankai subduction zone offshore Japan, using densely sampled wide-angle ocean bottom seismograph (OBS) data originally acquired in 2004. Our success is due to new and carefully designed data preconditioning and inversion strategies to mitigate (i) the well-known non-linearity of waveform inversion, (ii) the challenges arising from crustal-scale survey designs (e.g. undersampling of the OBSs), and (iii) modelling errors due to the use of the acoustic assumption. We identify a sixfold set of key components that together lead to the success of the high-resolution waveform tomography image: (i) Availability of low-frequency components (starting at 2.25 Hz) reducing the non-linearity, and access to large offset data (up to 55 km) increasing the depth of illumination and the recovery of low wavenumber components. (ii) A highly accurate traveltime tomography result (with an rms error of approximately 60 ms) that further mitigates the non-linearity. (iii) A hierarchical inversion approach in which phase spectra are inverted first to reduce artefacts from the acoustic assumption, and amplitude information is only incorporated in the final stages. (iv) A Laplace-Fourier domain approach that facilitates a multiscale approach to mitigate non-linearity by restricting the inversion to the low frequency components and early arrivals first, and sequentially including higher frequencies and later arrivals. (v) A pre-conditioning strategy for eliminating undesirable high wavenumber components from the the gradient. (vi) A strategy for source estimation that reduce the influence of the instrumental design. In the OBS case study used for illustration purposes, Laplace-Fourier waveform tomography retrieves velocity anomalies as small as 700 m (horizontally) and 350 m (vertically) above the top of the Philippine Sea Plate. The resulting velocity structures include low-velocity zones and thrust structures which have not been previously identified clearly. The velocity models are validated by scrutiny of synthetic and observed waveforms, by evaluating the coherency of source estimates, and by comparison with 3-D pre-stack migrated (PreSDM) images. Chequerboard tests and point-scatter tests demonstrate both the reliability and the limitations of the acoustic implementation.

  14. Ray-parameter based stacking and enhanced pre-conditioning for stable inversion of receiver function data

    NASA Astrophysics Data System (ADS)

    Chen, Youlin; Niu, Fenglin

    2013-09-01

    While inversion of seismic velocity from receiver function data could be instable due to its intrinsic non-linearity and non-uniqueness, improper stacking of receiver function could also introduce significant biases to the resulting velocity structure. In a distance section of receiver functions, the Moho Ps conversion and the two reverberations possess a positive and negative moveout, respectively. Stacking receiver functions without moveout correction could significantly reduce and distort the amplitude and waveform of these phases. Inversion with these incorrectly stacked receiver functions will thus inevitably introduce artefacts to the resulting velocity structure. In this study, we have improved the inversion procedure in two ways. First, we introduce a ray-parameter based (RPB) stacking method to correctly construct receiver function data for inversion. Specifically we develop a `four-pin' method that accounts for the moveout effect of the converted and reverberated phases in stacking individual receiver functions recorded at various distances. Secondly, we divide the receiver function trace into conversion and reverberation windows and assign different weights between the two windows in the inversion. More weight is given to the Ps conversion window in resolving the shallow structure, which can be nearly fixed in the successive inversion of deeper structure. We also employ other pre-conditioning proposed by previous studies, such as balancing the receiver function data being filtered with different Gaussian filters, smoothing the velocity model and further regulating the model based on existing information. We compute synthetic receiver functions at distances between 30° and 90° from a target model and then use the RPB stacking method to generate the input data for various inversions (iterative linear) with different initial models. Our inversions with enhanced pre-conditioning and RPB stacked data demonstrate a good capability in recovering the target model from generally more stable iterations. Applying these techniques to two broad-band stations in China indicates that the improvements on data stacking and inversion can eliminate potential stacking-induced artefacts, and yield models more consistent with surface geology.

  15. PREVENT Cancer Preclinical Drug Development Program (PREVENT) | Division of Cancer Prevention

    Cancer.gov

    The PREVENT Cancer Drug Development Program is a National Cancer Institute-supported pipeline to bring new cancer PREVENTing interventions and biomarkers through preclinical development towards clinical trials.

  16. Prevention of Eye Injuries

    PubMed Central

    Pashby, Tom

    1981-01-01

    In Canada 30,000 people are registered as blind; in one third of these, blindness might have been avoided. Prevention is the key to reducing the number of eye injuries and blind eyes. The role of the family physician in early identification of treatable conditions and in the education of patients is discussed, but responsibility for prevention belongs to all physicians. The success of prevention is seen in the great reduction in eye injuries in industry and sports since eye protectors have been commonly used. However, many dangers to the eyes are either not recognized or are not taken seriously enough. This paper discusses some of the common causes of serious eye injuries in the home, in sports and in industry. Imagesp464-aFig. 1Fig. 2Fig. 3Fig. 4 PMID:21289691

  17. Keloids: prevention and management.

    PubMed

    Sidle, Douglas M; Kim, Haena

    2011-08-01

    Keloids result from an abnormal wound-healing process in which the normal regulatory pathways during tissue regeneration and scar remodeling are disrupted. While the pathogenesis of keloids continues to be investigated, numerous treatment options exist. Although prevention of keloid formation is the best management, early recognition of keloid formation is integral in treatment and prevention of recurrence. Surgical resection with adjuvant silicone gel sheeting or triamcinolone injection is common, but can still result in recurrence. New treatments include chemotherapeutics such as 5-fluorouracil, bleomycin, and mitomycin C. Although further clinical investigation is required for newer treatments, initial results are promising. PMID:21856538

  18. Preconditioning L6 Muscle Cells with Naringin Ameliorates Oxidative Stress and Increases Glucose Uptake

    PubMed Central

    Dhanya, R.; Arun, K. B.; Nisha, V. M.; Syama, H. P.; Nisha, P.; Santhosh Kumar, T. R.; Jayamurthy, P.

    2015-01-01

    Enhanced oxidative stress contributes to pathological changes in diabetes and its complications. Thus, strategies to reduce oxidative stress may alleviate these pathogenic processes. Herein, we have investigated Naringin mediated regulation of glutathione (GSH) & intracellular free radical levels and modulation of glucose uptake under oxidative stress in L6 cell lines. The results from the study demonstrated a marked decrease in glutathione with a subsequent increase in free radical levels, which was reversed by the pretreatment of Naringin. We also observed that the increased malondialdehyde level, the marker of lipid peroxidation on induction of oxidative stress was retrieved on Naringin pretreatment. Addition of Naringin (100 ?M) showed approximately 40% reduction in protein glycation in vitro. Furthermore, we observed a twofold increase in uptake of fluorescent labeled glucose namely 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2 - NBDG) on Naringin treatment in differentiated L6 myoblast. The increased uptake of 2-NBDG by L6 myotubes may be attributed due to the enhanced translocation of GLUT4. Our results demonstrate that Naringin activate GSH synthesis through a novel antioxidant defense mechanism against excessive Reactive Oxygen Species (ROS) production, contributing to the prevention of oxidative damage in addition to its effect on glycemic control. PMID:26147673

  19. Isoflurane preconditioning provides neuroprotection against stroke by regulating the expression of the TLR4 signalling pathway to alleviate microglial activation

    PubMed Central

    Sun, Meiyan; Deng, Bin; Zhao, Xiaoyong; Gao, Changjun; Yang, Lu; Zhao, Hui; Yu, Daihua; Zhang, Feng; Xu, Lixian; Chen, Lei; Sun, Xude

    2015-01-01

    Excessive microglial activation often contributes to inflammation-mediated neurotoxicity in the ischemic penumbra during the acute stage of ischemic stroke. Toll-like receptor 4 (TLR4) has been reported to induce microglial activation via the NF-?B pathway. Isoflurane preconditioning (IP) can provide neuroprotection and inhibit microglial activation. In this study, we investigated the roles of the TLR4 signalling pathway in IP to exert neuroprotection following ischemic stroke in vivo and in vitro. The results showed that 2% IP alleviated neurological deficits, reduced the infarct volume, attenuated apoptosis and weakened microglial activation in the ischemic penumbra. Furthermore, IP down-regulated the expression of HSP 60, TLR4 and MyD88 and up-regulated inhibitor of I?B-? expression compared with I/R group in vivo. In vitro, 2% IP and a specific inhibitor of TLR4, CLI-095, down-regulated the expression of TLR4, MyD88, IL-1?, TNF-? and Bax, and up-regulated I?B-? and Bcl-2 expression compared with OGD group. Moreover, IP and CLI-095 attenuated microglial activation-induced neuronal apoptosis, and overexpression of the TLR4 gene reversed the neuroprotective effects of IP. In conclusion, IP provided neuroprotection by regulating TLR4 expression directly, alleviating microglial activation and neuroinflammation. Thus, inhibiting the activation of microglial activation via TLR4 may be a new avenue for stroke treatment. PMID:26086415

  20. Adenosine decreases post-ischaemic cardiac TNF-alpha production: anti-inflammatory implications for preconditioning and transplantation.

    PubMed Central

    Meldrum, D R; Cain, B S; Cleveland, J C; Meng, X; Ayala, A; Banerjee, A; Harken, A H

    1997-01-01

    Tumour necrosis factor-alpha (TNF-alpha) is an autocrine contributor to myocardial dysfunction and cardiomyocyte death in ischaemia-reperfusion injury (I/R), sepsis, chronic heart failure and cardiac allograft rejection. Cardiac resident macrophages, infiltrating leucocytes, and cardiomyocytes themselves produce TNF-alpha. Although adenosine reduces macrophage TNF-alpha production and protects myocardium against I/R, it remains unknown whether I/R induces an increase in cardiac TNF-alpha in a crystalloid-perfused model (in the absence of blood), and, whether adenosine decreases cardiac TNF-alpha and protects function after I/R. To study this, isolated rat hearts were crystalloid-perfused using the Langendorff method and subjected to I/R, with or without adenosine pretreatment. Post-ischaemic cardiac TNF-alpha (enzyme-linked immunosorbent assay and bioassay) and function were determined (Langendorff). I/R increased cardiac TNF-alpha and impaired myocardial function. Adenosine decreased cardiac TNF-alpha and improved post-ischaemic functional recovery. This study demonstrates that: first, I/R induces an increase in cardiac tissue TNF-alpha in a crystalloid-perfused model: second, adenosine decreases cardiac TNF-alpha and improves post-ischaemic myocardial function; third, decreased cardiac TNF-alpha may represent a mechanism by which adenosine protects myocardium; and fourth, adenosine-induced suppression of cardiac TNF-alpha may provide an anti-inflammatory link to preconditioning and have implications for cardiac allograft preservation. PMID:9497488