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Preconditioning
Kinds of Preconditioning Terms modified by Preconditioning Selected AbstractsTHERMAL PRECONDITIONING PROTECTS THE HUMAN INTERNAL MAMMARY ARTERY FROM HYPOXIA/RE-OXYGENATION-INDUCED DAMAGECLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2006Angelika Hammerer-Lercher SUMMARY 1Preconditioning has been demonstrated to ameliorate ischaemia/reperfusion injury in several cells and tissues. Therefore, in the present study we investigated whether preconditioning of human bypass grafts, internal mammary artery (IMA) and saphenous vein (SV) induces heat shock protein (Hsp) expression and reduces apoptosis in response to subsequent hypoxia/re-oxygenation damage in both vessels. 2Internal mammary artery and SV rings, obtained from 30 patients (median age 66.5 years) undergoing coronary artery bypass grafting, were either incubated for 30 min at 42°C (preconditioned) or kept in a standard incubator at 37°C (not preconditioned). Six hours later, graft segments were exposed to 90 min hypoxia followed by a 30 min re-oxygenation period. Western blot, real-time quantative polymerase chain reaction analysis and apoptosis detection by the Terminal deoxyribonucleotidyl transferase-mediated dUTP,digoxigenin nick end-labelling method were performed. 3Heat-preconditioned IMA showed significantly increased protein expression of Hsp72 after hypoxia/re-oxygenation treatment compared with controls (median 9.1 vs 5.0 µg/mg total protein; P = 0.048). Expression of Hsp73 was weak and Hsp60 was not detectable in the IMA. 4In the SV, neither protein nor mRNA expression of Hsp were significantly different between preconditioned and not preconditioned veins. 5There were significantly fewer apoptotic cells in the intima of the preconditioned compared with not preconditioned IMA (P = 0.041) after hypoxia/re-oxygenation injury, whereas in the SV apoptosis was not significantly prevented by preconditioning. 6Mild heat preconditioning before hypoxia/re-oxygenation injury is a stimulus for Hsp72 protein expression and a reduction in apoptosis in the human IMA. [source] NEW INSIGHT INTO THE SIGNALLING PATHWAYS OF HEAT STRESS-INDUCED MYOCARDIAL PRECONDITIONING: PROTEIN KINASE C, TRANSLOCATION AND HEAT SHOCK PROTEIN 27 PHOSPHORYLATIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2004Claire Arnaud SUMMARY 1.,Heat stress (HS) is known to induce delayed preconditioning against myocardial infarction 24 h later, but the exact signalling pathway of this response remains to be elucidated. In previous studies, we have shown evidence for the implication of protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK) in the HS-induced reduction in infarct size. Furthermore, in their phosphorylated state, small heat shock proteins (Hsp27) seem to confer cytoskeletal protection. In the present study, we sought to determine the effect of HS on the subcellular distribution of PKC isoforms and on Hsp27 phosphorylation. 2.,Rats were subjected to either HS (42°C for 15 min; HS group) or sham anaesthesia (sham group) before their hearts were excised. Myocardial tissue extracts obtained 20 min or 24 h after HS were processed for western blot analysis. 3.,In the HS group, PKC, translocated from the cytosolic to the particulate fraction (4426 ± 128 vs 6258 ± 316 arbitrary units; P = 0.002). Chelerythrine (5 mg/kg, i.p.), a PKC inhibitor, abolished this translocation. Western blot analysis of Hsp27 24 h after HS showed a marked increase in protein expression and phosphorylation in the particulate fraction. 4.,In the present study, we have shown that HS induces the translocation of PKC, from the cytosolic to the particulate fraction. Along with our previous observation that PKC is a trigger of HS-induced myocardial preconditioning, the results of the present study suggest an important role of the , isoform of PKC in this cardioprotective mechanism. Furthermore, we have also demonstrated that the cytoprotective protein Hsp27 is phosphorylated following HS. Therefore, we can conclude that PKC and MAPK/Hsp27 are involved in the signalling pathway of HS-induced cardioprotection. [source] Enhancement of In Vitro Hair Shaft Elongation in Follicles Stored in Buffers That Prevent Follicle Cell ApoptosisDERMATOLOGIC SURGERY, Issue 1 2004Walter Krugluger MD Background. Viability and survival of stored micrografts during hair follicle transplantation are important limitations of micrograft transplantation procedures. In this study, we investigated the effect of different storage solutions and inhibitors of apoptotic cell death (ACD) on hair follicle cell viability by measuring in vitro hair shaft elongation (HSE) for 5 days. Methods. Micrografts from informed patients undergoing routine micrograft transplantation were stored for 5 hours at room temperature in phosphate-buffered salt solution (PBS) or HEPES-buffered Dulbecco's modified Eagle's medium (DMEM), containing different concentrations of the ACD-inhibitors aminoguanidine (AMG), hormones (insulin, hydrocortisone), 14,15-epoxy-eicosatrienoic acid (14,15-EET), or combinations of these. Results. In vitro, HSE was significantly increased in micrografts stored in DMEM compared with PBS (2.3%±0.6% vs. 28.4%±3.9%, P<0.0001). DMEM supplemented with AMG (10 ,g/mL) or 14,15-EET (1 ng/mL) further increased in vitro HSE (33.9%±7.1%, p=0.01, and 32.8%±6.1%, P=0.02, respectively). Evaluation of ACD in stored micrografts, performed by determination of cytoplasmic histone-associated DNA fragments, confirmed the results found by HSE. ACD was detectable after a 36-hour culture in serum-containing medium and was higher in micrografts stored in PBS compared with micrografts stored in DMEM (A405nm/A492nm: 1.63±0.21 vs. 1.42±0.07, respectively; P<0.01). The addition of AMG further decreased serum-induced ACD in the micrografts (DMEM 1.42±0.07 vs. DMEM/AMG 0.90±0.11, P<0.0001). Conclusion. Our study demonstrated an important role of ACD in micrograft transplantation surgery. Preconditioning of micrografts with storage buffers containing inhibitors of ACD could prevent serum-induced ACD after transplantation and might increase the viability of micrografts and the clinical outcome in micrograft transplantation. [source] Preconditioning and postconditioning: new strategies for cardioprotectionDIABETES OBESITY & METABOLISM, Issue 6 2008D. J. Hausenloy Despite optimal therapy, the morbidity and mortality of coronary heart disease (CHD) remains significant, particularly in patients with diabetes or the metabolic syndrome. New strategies for cardioprotection are therefore required to improve the clinical outcomes in patients with CHD. Ischaemic preconditioning (IPC) as a cardioprotective strategy has not fulfilled it clinical potential, primarily because of the need to intervene before the index ischaemic event, which is impossible to predict in patients presenting with an acute myocardial infarction (AMI). However, emerging studies suggest that IPC-induced protection is mediated in part by signalling transduction pathways recruited at time of myocardial reperfusion, creating the possibility of harnessing its cardioprotective potential by intervening at time of reperfusion. In this regard, the recently described phenomenon of ischaemic postconditioning (IPost) has attracted great interest, particularly as it represents an intervention, which can be applied at time of myocardial reperfusion for patients presenting with an AMI. Interestingly, the signal transduction pathways, which underlie its protection, are similar to those recruited by IPC, creating a potential common cardioprotective pathway, which can be recruited at time of myocardial reperfusion, through the use of appropriate pharmacological agents given as adjuvant therapy to current myocardial reperfusion strategies such as thrombolysis and primary percutaneous coronary intervention for patients presenting with an AMI. This article provides a brief overview of IPC and IPost and describes the common signal transduction pathway they both appear to recruit at time of myocardial reperfusion, the pharmacological manipulation of which has the potential to generate new strategies for cardioprotection. [source] Ischemic preconditioning affects interleukin release in fatty livers of rats undergoing ischemia/reperfusionHEPATOLOGY, Issue 3 2004Anna Serafín The present study evaluates the effect of ischemic preconditioning on interleukin-1 (IL-1) and interleukin-10 (IL-10) generation following hepatic ischemia/reperfusion (I/R) in normal and steatotic livers as well as the role of nitric oxide (NO) in this process. Increased IL-1, and IL-10 levels were observed in normal livers after I/R. Steatotic livers showed higher IL-1, levels than normal livers, and IL-10 at control levels. The injurious role of IL-1, and the benefits of IL-10 on hepatic I/R injury was shown with the use of IL-1 receptor antagonist (IL-1ra), anti-IL-10 polyclonal antibody against IL-10 (anti-IL-10) and exogenous IL-10. The effective dose of these treatments was different in both types of livers. Preconditioning prevented IL-1, release and increased IL-10 generation after I/R in normal and steatotic livers. IL-1, or anti-IL-10 pretreatments reversed the benefits of preconditioning. IL-1, action inhibition in a preconditioned group that was pretreated with anti-IL-10 did not modify the benefits of preconditioning. In addition, anti-IL-10 pretreatment in the preconditioned group resulted in IL-1, levels comparable to those observed after I/R. NO inhibition eliminated the benefits of preconditioning on IL-10 release, IL-1, levels, and hepatic injury. In conclusion, preconditioning, through IL-10 overproduction, inhibits IL-1, release and the ensuing hepatic I/R injury in normal and steatotic livers. IL-10 generation induced by preconditioning could be mediated by NO. (HEPATOLOGY 2004;39:688,698.) [source] Efficient preconditioning of the discrete adjoint equations for the incompressible Navier,Stokes equationsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 10-11 2005René Schneider Abstract Preconditioning of the discrete adjoint equations is closely related to preconditioning the linear systems arising in the Newton linearization of the discretized flow equations. We investigate the use of an optimal preconditioner for both problems on the example of a finite element discretization of the steady state incompressible Navier,Stokes equations. It is demonstrated that complications arising from the use of a zero mean pressure condition in the problem formulation can be overcome by modifying the preconditioner suitably. Copyright © 2005 John Wiley & Sons, Ltd. [source] Induction of hypoxia inducible factor-1 attenuates metabolic insults induced by 3-nitropropionic acid in rat C6 glioma cellsJOURNAL OF NEUROCHEMISTRY, Issue 3 2005Ya-Ting Yang Abstract Compromised mitochondrial function in neurons and glia has been observed in several neurodegenerative disorders, including Huntington's disease and Alzheimer's disease. Chemical/hypoxic preconditioning may afford protection against subsequently more severe oxidative damages. In this study, we tested whether induction of hypoxia inducible factor-1 (HIF-1) may exert cytoprotective effects against mitochondrial dysfunction caused by 3-nitropropionic acid (3-NP) in glial cells. Preconditioning of C6 astroglial cells with cobalt chloride, mimosine (MIM), and desferrioxamine (DFO), all of which known to activate HIF-1, significantly attenuated cytotoxicity induced by 3-NP, an irreversible inhibitor of mitochondrial complex II, and antimycin A, a mitochondrial complex III inhibitor. Application of cadmium chloride capable of neutralizing cobalt-induced HIF-1 activation, HIF-specific oligodeoxynucleotide (ODN) decoy, and antisense phosphorothioate ODN against HIF-1, abolished the protective effect mediated by preconditioning with cobalt chloride. Preloading of C6 cells with SN50, PD98059, or SB202190, the respective inhibitor of nuclear factor-,B (NF-,B), p44/p42 extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK), failed to affect the protection afforded by cobalt preconditioning. Taken together, these results suggest that HIF-1 induction secondary to preconditioning with cobalt chloride or iron chelators may mediate the protective effects against metabolic insult induced by the mitochondrial inhibitor 3-NP in C6 astroglial cells. [source] ,-Amino-3-hydroxy-5-methyl-4-isoxazole propionate attenuates glutamate-induced caspase-3 cleavage via regulation of glycogen synthase kinase 3,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2008Takaaki Nishimoto Abstract Preconditioning of sublethal ischemia exhibits neuroprotection against subsequent ischemia-induced neuronal death. It has been indicated that glutamate, an excitatory amino acid, is involved in the pathogenesis of ischemia-induced neuronal death or neurodegeneration. To elucidate whether prestimulation of glutamate receptor could counter ischemia-induced neuronal death or neurodegeneration, we examined the effect of ,-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), an ionotropic subtype of glutamate receptor, on excess glutamate-induced excitotoxicity using primary cortical neuronal cultures. We found that AMPA exerted a neuroprotective effect in a time- and concentration-dependent manner. A blocker of phosphatidylinositol-3 kinase (PI3K), LY294002 (10 ,M), significantly attenuated AMPA-induced protection. In addition, Ser473 of Akt/PKB, a downstream target of PI3K, was phosphorylated by AMPA administration (10 ,M). Glycogen synthase kinase 3, (GSK3,), which has been reported to be inactivated by Akt, was phosphorylated at Ser9 by AMPA. Ser9-phosphorylated GSK3, or inactivated form would be a key molecule for neuroprotection, insofar as lithium chloride (100 ,M) and SB216763 (10 ,M), inhibitors of GSK3,, also induced phosphorylation of GSK3, at Ser9 and exerted neuroprotection, respectively. Glutamate (100 ,M) increased cleaved caspase-3, an apoptosis-related cysteine protease, and caspase-3 inhibitor (Ac-DEVD-CHO; 1 ,M) blocked glutamate-induced excitotoxicity in our culture. AMPA (10 ,M, 24 hr) and SB216763 (10 ,M) prominently decreased glutamate-induced caspase-3 cleavage. These findings suggest that AMPA activates PI3K-Akt and subsequently inhibits GSK3, and that inactivated GSK3, attenuates glutamate-induced caspase-3 cleavage and neurotoxicity. © 2007 Wiley-Liss, Inc. [source] Preconditioning with thrombin can be protective or worsen damage after endothelin-1-induced focal ischemia in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2006Petra Henrich-Noack Abstract The serine protease thrombin has shown direct neuroprotective and neurotoxic effects on brain tissue in cerebral ischemia. Previous data suggested that thrombin-induced protection in vivo can be achieved by preconditioning rather than by acute treatment. In the current work, we used a model of mild ischemia to investigate the effects of preischemic intracerebral thrombin injection on neural damage. By intracerebral injection of endothelin-1 in freely moving animals, we achieved middle cerebral artery occlusion (MCAO), and 7 days postischemia we performed histological quantification of the infarct areas. Thrombin was injected as a preconditioning stimulus intracerebrally 7 days or 2 and 3 days before ischemia. For acute treatment, thrombin was injected 20 min before MCAO. Thrombin induced significant neuroprotection when given 7 days before endothelin-1-induced MCAO but was deleterious when given 2 and 3 days before the insult. The deleterious effect was not seen when thrombin was given acutely before ischemia. Our data demonstrate that preconditioning with thrombin can protect against damage or worsen ischemic damage. Its effect depended on the time interval between thrombin injection and insult. A low dose of thrombin did not induce a major deleterious effect in the acute phase of the infarct development after mild transient ischemia. © 2006 Wiley-Liss, Inc. [source] Mediators of rat ischemic hepatic preconditioning after cold preservation identified by microarray analysisLIVER TRANSPLANTATION, Issue 11 2006Àurea Navarro-Sabaté Hepatic ischemia-reperfusion injury associated with liver transplantation is an as yet unresolved problem in clinical practice. Preconditioning protects the liver against the deleterious effects of ischemia, although the mechanism underlying this preconditioning is still unclear. To profile gene expression patterns involved in hepatic ischemic preconditioning, we analyzed the changes in gene expression in rat livers by DNA microarray analysis. Approximately 116 genes were found to have altered gene expression after 8 hours of cold ischemia. Moreover, the expression of 218 genes was modified by classic preconditioning followed by the same ischemia process. Given the importance of the effects of ischemic preconditioning (IP) in minimizing the liver damage induced by sustained ischemia before reperfusion, this study analyzed the putative genes involved in the beneficial role of IP in liver grafts undergoing cold ischemia before its implantation in the recipient (IP+I). Great differences were found in the gene expression pattern of ischemic preconditioning + long cold ischemia (IP+I) group when compared with the long cold ischemia alone condition (I), which could explain the protective regulatory mechanisms that take place after preconditioning. Twenty-six genes that were downregulated in cold ischemia were found upregulated after preconditioning preceding a long cold ischemia period. These would be genes activated or maintained by preconditioning. Heat shock protein genes and 3-hydroxy-3-methylglutaryl-coenzyme A reductase are among the most markedly induced transcripts. Liver Transpl. 12:1615,1625, 2006. © 2006 AASLD. [source] Ischemic preconditioning attenuates the oxidant-dependent mechanisms of reperfusion cell damage and death in rat liverLIVER TRANSPLANTATION, Issue 11 2002Barbara Cavalieri In an in vivo rat model of liver ischemia followed by reperfusion a consistent appearance of necrosis and activation of biochemical pathways of apoptosis was reproduced and monitored after 30 minutes reperfusion. Preconditioning by application of a short cycle of ischemia-reperfusion (10 minutes + 10 minutes) positively conditioned recovery of the organ at reperfusion, attenuating both necrotic and apoptotic events. Preconditioning at least halved cell oxidative damage occurring early at reperfusion, and as a major consequence, the increase of cytolysis and apoptosis occurring at reperfusion was about 50% less. The attenuation of both pathways of cell death by preconditioning appeared at least partly related to its modulate action on H2O2 and 4-hydroxy-2,3-trans-nonenal production. The overall data point to a marked diminished oxidant generation and oxidative reactions as one major possible mechanism through which ischemic preconditioning exerts protection against necrotic and apoptotic insult to the postischemic liver. [source] Preconditioning protects the guinea-pig urinary bladder against ischaemic conditions in vitroNEUROUROLOGY AND URODYNAMICS, Issue 7 2003Bruno Lorenzi Abstract Aims To investigate the ability of ischaemic preconditioning (IPC) to protect guinea-pig detrusor from damage caused by a subsequent more prolonged exposure to ischaemic conditions. Materials and Methods Smooth muscle strips were mounted for tension recording in small organ baths continuously superfused with Krebs' solution at 37°C. Ischaemia was mimicked by removing oxygen and glucose from the superfusing solution. Contractile responses to electrical field stimulation (EFS) and carbachol were monitored. Three regimes of preconditioning were examined: 15, 10, and 5 min of ischaemic conditions followed by 15, 10, and 5 min of normal conditions, respectively. Results Without preconditioning, nerve-mediated responses were significantly and proportionally reduced by periods of ischaemic conditions lasting for 45, 60, and 90 min, but recovered fully after exposure to ischaemic conditions for 30 min. The recovery of the responses to EFS was significantly improved in preconditioned strips when the period of ischaemic conditions was 45 or 60 min. However, no significant differences were seen with preconditioning when the period of ischaemic conditions was 90 min. The recovery of responses to carbachol was much greater than for the responses to EFS, and no significant differences were found between control and preconditioned strips. Conclusions It is suggested that in vivo short periods of transient ischaemia may be able to protect the guinea-pig bladder from the impairment associated with longer periods of ischaemia and reperfusion, which might happen in obstructed micturition. Our results also indicate that the phenomenon affects mainly the intrinsic nerves, which are more susceptible to ischaemic damage than the smooth muscle. Neurourol. Urodynam. 22:687,692, 2003. © 2003 Wiley-Liss, Inc. [source] Preconditioning and a posteriori error estimates using h - and p -hierarchical finite elements with rectangular supportsNUMERICAL LINEAR ALGEBRA WITH APPLICATIONS, Issue 5 2009I. Pultarová Abstract We show some of the properties of the algebraic multilevel iterative methods when the hierarchical bases of finite elements (FEs) with rectangular supports are used for solving the elliptic boundary value problems. In particular, we study two types of hierarchies; the so-called h - and p -hierarchical FE spaces on a two-dimensional domain. We compute uniform estimates of the strengthened Cauchy,Bunyakowski,Schwarz inequality constants for these spaces. Moreover, for diagonal blocks of the stiffness matrices corresponding to the fine spaces, the optimal preconditioning matrices can be found, which have tri- or five-diagonal forms for h - or p -refinements, respectively, after a certain reordering of the elements. As another use of the hierarchical bases, the a posteriori error estimates can be computed. We compare them in test examples for h - and p -hierarchical FEs with rectangular supports. Copyright © 2008 John Wiley & Sons, Ltd. [source] Hypoxic preconditioning protects rat hearts against ischaemia,reperfusion injury: role of erythropoietin on progenitor cell mobilizationTHE JOURNAL OF PHYSIOLOGY, Issue 23 2008Jih-Shyong Lin Preconditioning, such as by brief hypoxic exposure, has been shown to protect hearts against severe ischaemia. Here we hypothesized that hypoxic preconditioning (HPC) protects injured hearts by mobilizing the circulating progenitor cells. Ischaemia,reperfusion (IR) injury was induced by left coronary ligation and release in rats kept in room air or preconditioned with 10% oxygen for 6 weeks. To study the role of erythropoietin (EPO), another HPC + IR group was given an EPO receptor (EPOR) antibody via a subcutaneous mini-osmotic pump 3 weeks before IR induction. HPC alone gradually increased haematocrit, cardiac and plasma EPO, and cardiac vascular endothelial growth factor (VEGF) only in the first two weeks. HPC improved heart contractility, reduced ischaemic injury, and maintained EPO and EPOR levels in the infarct tissues of IR hearts, but had no significant effect on VEGF. Interestingly, the number of CD34+CXCR4+ cells in the peripheral blood and their expression in HPC-treated hearts was higher than in control. Preconditioning up-regulated cardiac expression of stromal derived factor-1 (SDF-1) and prevented its IR-induced reduction. The EPOR antibody abolished HPC-mediated functional recovery, and reduced SDF-1, CXCR4 and CD34 expression in IR hearts, as well as the number of CD34+CXCR4+ cells in blood. The specificity of neutralizing antibody was confirmed in an H9c2 culture system. In conclusion, exposure of rats to moderate hypoxia leads to an increase in progenitor cells in the heart and circulation. This effect is dependent on EPO, which induces cell homing by increased SDF-1/CXCR4 and reduces the heart susceptibly to IR injury. [source] Preconditioning of skeletal muscle against contraction-induced damage: the role of adaptations to oxidants in miceTHE JOURNAL OF PHYSIOLOGY, Issue 1 2004F. McArdle Adaptations of skeletal muscle following exercise are accompanied by changes in gene expression, which can result in protection against subsequent potentially damaging exercise. One cellular signal activating these adaptations may be an increased production of reactive oxygen and nitrogen species (ROS). The aim of this study was to examine the effect of a short period of non-damaging contractions on the subsequent susceptibility of muscle to contraction-induced damage and to examine the changes in gene expression that occur following the initial contraction protocol. Comparisons with changes in gene expression in cultured myotubes following treatment with a non-damaging concentration of hydrogen peroxide (H2O2) were used to identify redox-sensitive genes whose expression may be modified by the increased ROS production during contractions. Hindlimb muscles of mice were subjected to a preconditioning, non-damaging isometric contraction protocol in vivo. After 4 or 12 h, extensor digitorum longus (EDL) and soleus muscles were removed and subjected to a (normally) damaging contraction protocol in vitro. Muscles were also analysed for changes in gene expression induced by the preconditioning protocol using cDNA expression techniques. In a parallel study, C2C12 myotubes were treated with a non-damaging concentration (100 ,m) of H2O2 and, at 4 and 12 h following treatment, myotubes were treated with a damaging concentration of H2O2 (2 mm). Myotubes were analysed for changes in gene expression at 4 h following treatment with 100 ,m H2O2 alone. Data demonstrate that a prior period of non-damaging contractile activity resulted in significant protection of EDL and soleus muscles against a normally damaging contraction protocol 4 h later. This protection was associated with significant changes in gene expression. Prior treatment of myotubes with a non-damaging concentration of H2O2 also resulted in significant protection against a damaging treatment, 4 and 12 h later. Comparison of changes in gene expression in both studies identified haem oxygenase-1 as the sole gene showing increased expression during adaptation in both instances suggesting that activation of this gene results from the increased ROS production during contractile activity and that it may play a role in protection of muscle cells against subsequent exposure to damaging activity. [source] Preconditioning protects the retinal pigment epithelium cells from oxidative stress-induced cell deathACTA OPHTHALMOLOGICA, Issue 1 2009Rajesh K. Sharma Abstract. Purpose:, The cytotoxic effects of oxidative stress, which play an important role in ocular diseases, are well known. In this study, we investigated the effect of non-lethal doses of oxidative stress on various cell functions, namely cell viability, cell attachment and cell migration in a widely used retinal pigment epithelium (RPE) cell line (ARPE-19). Methods:, A single exposure to various concentrations of hydrogen peroxide (H2O2) was used to establish a dose response for H2O2 -induced cell death. Other cellular responses, such as changes in cell attachment and migration, were monitored after exposure to increasing doses. Finally, the effects of preconditioning cells with increasing non-lethal doses of H2O2, with and without a subsequent exposure to lethal doses of H2O2, were determined. Results:, The optimum dose for inducing cell death in ARPE-19 cells was between 900 and 1000 ,m H2O2. Preconditioning the cells with 1, 10 and 50 ,m of H2O2 provided a dose-dependent protection against cell death induced by a lethal dose (900,1000 ,m) of H2O2. Preconditioning with higher doses caused cells to become more susceptible to the cytotoxic effects of the lethal dose. Although H2O2 increased cell attachment in lower doses, it induced a dose-dependent inhibition of cell attachment to the substrate in higher doses. H2O2 did not affect cell migration in sub-lethal doses. Conclusion:, Preconditioning RPE cells with limited exposure to non-lethal oxidative stress confers significant protection against subsequent H2O2 -induced cell death. It also affects cell attachment in a dose-specific manner. This finding may help in understanding the pathogenesis of diseases in which oxidative stress plays an important role and in determining the suitability of certain treatment strategies, in particular RPE transplantation in the treatment of age-related macular degeneration. [source] Java multithreading-based parallel approximate arrow-type inversesCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 10 2008George A. Gravvanis Abstract A new parallel shared memory Java multithreaded design and implementation of the explicit approximate inverse preconditioning, for efficiently solving arrow-type linear systems on symmetric multiprocessor systems (SMPs), is presented. A new parallel algorithm for computing a class of optimized approximate arrow-type inverse matrix is introduced. The performance on an SMP, using Java multithreading, is investigated by solving arrow-type linear systems and numerical results are given. The parallel performance of the construction of the optimized approximate inverse and the explicit preconditioned generalized conjugate gradient square scheme, using a dynamic workload scheduling, is also presented. Copyright © 2007 John Wiley & Sons, Ltd. [source] Ischaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at-risk myocardium: an experimental study in the pigACTA PHYSIOLOGICA, Issue 1 2010A. Waldenström Abstract Aim:, ,Pre-treatment' with short repetitive periods of ischaemia (ischaemic preconditioning) has proved to be a powerful mechanism for modification of the extent of myocardial damage following acute coronary artery occlusion. The exact mechanism of protection induced by ischaemic preconditioning is not known. We herewith put forward a contributing component for protection with preconditioning involving a shift in the adenylate kinase (AK) equilibrium reaction in favour of adenosine triphosphate (ATP) formation. Methods:, A coronary artery was occluded in anaesthetized thoracotomized pigs to induce ischaemic preconditioning as well as a longer period of ischaemia. Microdialysis probes were inserted in ischaemic and control myocardium and were infused with 14C- adenosine with two different specific activities. 14C-lactate was identified and measured in the effluent. Results:,14C-adenosine was taken up by non-preconditioned and preconditioned myocardium during ischaemia. Significantly increased levels of 14C-lactate were recovered in preconditioned myocardium. 14C-adenosine with high specific activity resulted in a specific activity of lactate that was 2.7 times higher than that of lactate after administration of 14C-adenosine with low specific activity. Mass spectrography verified the identity of 14C-lactate. Conclusions:, Preconditioning up-regulates a new metabolic pathway (starting with 5,-nucleotidase and ending up with lactate) resulting in ATP formation in the micromolar range on top of another effect terminating in a useful shift in the AK equilibrium reaction in favour of ATP generation in the millimolar range. Although the up-regulation of the purine nucleoside phosphorylase pathway is clearly demonstrated, its biological relevance remains to be proved. [source] Protective effects of exercise preconditioning on hindlimb unloading-induced atrophy of rat soleus muscleACTA PHYSIOLOGICA, Issue 1 2009H. Fujino Abstract Aim:, A chronic decrease in the activation and loading levels of skeletal muscles as occurs with hindlimb unloading (HU) results in a number of detrimental changes. Several proteolytic pathways are involved with an increase in myofibrillar protein degradation associated with HU. Exercise can be used to counter this increase in proteolytic activity and, thus, may be able to protect against some of the detrimental changes associated with chronic decreased use. The purpose of the present study was to determine the potential of a single bout of preconditioning endurance exercise in attenuating the effects of 2 weeks of HU on the mass, phenotype and force-related properties of the soleus muscle in adult rats. Methods:, Male Wistar rats were subjected to HU for 2 weeks. One half of the rats performed a single bout of treadmill exercise for 25 min immediately prior to the 2 weeks of HU. Results:, Soleus mass, maximum tetanic tension, myofibrillar protein content, fatigue resistance and percentage of type I (slow) myosin heavy chain were decreased in HU rats. In addition, markers for the cathepsin, calpain, caspase and ATP-ubiquitin-proteasome proteolytic pathways were increased. The preconditioning endurance exercise bout attenuated all of the detrimental changes associated with HU, and increased HSP72 mRNA expression and protein levels. Conclusion:, These findings indicate that exercise preconditioning may be an effective countermeasure to the detrimental effects of chronic decreases in activation and loading levels on skeletal muscles and that an elevation in HSP72 may be one of the mechanisms associated with these responses. [source] Pretreatment with insulin before ischaemia reduces infarct size in Langendorff-perfused rat heartsACTA PHYSIOLOGICA, Issue 2 2009B. N. Fuglesteg Abstract Aim:, To compare the possible role of Akt and mammalian target of rapamycin (mTOR) in mediating cardioprotection against ischaemia under three different conditions: (1) During ischaemic preconditioning (IPC), (2) when insulin was given as a pretreatment agent (InsPC) and (3) when insulin was given as a reperfusion cell survival agent (InsR). Methods:, Isolated perfused rat hearts were subjected to IPC (3 × 5 min) or InsPC (50 mU mL,1; 3 × 5 min), before 30 min of regional ischaemia followed by 120 min of reperfusion ± 1L-6-hydroxymethyl- chiro -inositol-2 - [(R)-2- O -methyl-3- O -octadecylcarbonate] (HIMO) (20 ,m; Akt inhibitor) or rapamycin (1 nm; mTOR inhibitor). In addition, insulin (3 mU mL,1) was given at the onset of reperfusion, ±HIMO or rapamycin. Risk zone (R) and infarct size (I) were determined with Evans blue and tetrazolium staining respectively. Western blot analysis was performed on tissue from Langendorff-perfused rat hearts and cell lysates from cultured HL1 cells. Results:, IPC, InsPC and InsR treatment resulted in a significant reduction in infarct size compared to controls (all P < 0.05). This protective effect of IPC and insulin was abolished by the inhibitors. However, the putative Akt inhibitor, although capable of abolishing cardioprotection induced by insulin, was not able to inhibit insulin-induced phosphorylation of Akt in Langendorff-perfused rat hearts and cultured HL1 cells. The target for this compound therefore remains to be determined. Conclusion:, IPC and insulin (either as InsPC or InsR) appear to activate mTOR, and this kinase seems to play an essential role in cardioprotection against ischaemia and reperfusion injury as rapamycin blocked the protection. [source] Preconditioning and postconditioning: new strategies for cardioprotectionDIABETES OBESITY & METABOLISM, Issue 6 2008D. J. Hausenloy Despite optimal therapy, the morbidity and mortality of coronary heart disease (CHD) remains significant, particularly in patients with diabetes or the metabolic syndrome. New strategies for cardioprotection are therefore required to improve the clinical outcomes in patients with CHD. Ischaemic preconditioning (IPC) as a cardioprotective strategy has not fulfilled it clinical potential, primarily because of the need to intervene before the index ischaemic event, which is impossible to predict in patients presenting with an acute myocardial infarction (AMI). However, emerging studies suggest that IPC-induced protection is mediated in part by signalling transduction pathways recruited at time of myocardial reperfusion, creating the possibility of harnessing its cardioprotective potential by intervening at time of reperfusion. In this regard, the recently described phenomenon of ischaemic postconditioning (IPost) has attracted great interest, particularly as it represents an intervention, which can be applied at time of myocardial reperfusion for patients presenting with an AMI. Interestingly, the signal transduction pathways, which underlie its protection, are similar to those recruited by IPC, creating a potential common cardioprotective pathway, which can be recruited at time of myocardial reperfusion, through the use of appropriate pharmacological agents given as adjuvant therapy to current myocardial reperfusion strategies such as thrombolysis and primary percutaneous coronary intervention for patients presenting with an AMI. This article provides a brief overview of IPC and IPost and describes the common signal transduction pathway they both appear to recruit at time of myocardial reperfusion, the pharmacological manipulation of which has the potential to generate new strategies for cardioprotection. [source] Mild peripheral neuropathy prevents both leg muscular ischaemia and activation of exercise-induced coagulation in Type 2 diabetic patients with peripheral artery diseaseDIABETIC MEDICINE, Issue 10 2007F. Piarulli Abstract Aim, To study the influence of peripheral neuropathy on intermittent claudication in patients with Type 2 diabetes (T2DM). Methods, Twenty-five patients with T2DM were grouped according to the ankle/brachial index (ABI): 10 with ABI > 0.9 without peripheral artery disease (PAD; group T2DM) and 15 with ABI < 0.9 with PAD (group T2DM + PAD). Twelve individuals without T2DM with PAD (group PAD without T2DM) were also enrolled. Tests for peripheral neuropathy were performed in all patients. ABI, rate pressure product, prothrombin fragments 1 + 2 (F1+2), thrombin-anti-thrombin complex (TAT), and d -dimer were measured before and after a treadmill test. During exercise both initial and absolute claudication distance and electrocardiogram readings were recorded. Results, We found mild peripheral neuropathy in 20% of group T2DM and 46.7% of group T2DM + PAD (P < 0.01). After exercise, the rate pressure product increased in each group; ABI fell in T2DM + PAD (P < 0.0001) and in PAD without T2DM (P = 0.0005); the fall was greater in the latter group. Initial and absolute claudication distances were similar in PAD patients. In group T2DM + PAD, absolute claudication distance was longer in the subgroup without peripheral neuropathy (P < 0.05), whereas ABI and rate pressure products were similar. F1+2 values at rest were higher in group T2DM + PAD. After exercise, F1+2 values and TAT increased only in group PAD without T2DM. Conclusion, Only group PAD without T2DM experienced muscular ischaemia, whereas group T2DM + PAD did not. Mild peripheral neuropathy may have prevented them from reaching the point of muscular ischaemia during the treadmill test, because they stopped exercising with the early onset of pain. Reaching a false absolute claudication distance may induce ischaemic preconditioning. These findings suggest a possible protective role of mild peripheral neuropathy in T2DM patients with intermittent claudication, by preventing further activation of coagulation during treadmill testing. [source] Fast derivatization of the non-protein amino acid ornithine with FITC using an ultrasound probe prior to enantiomeric determination in food supplements by EKCELECTROPHORESIS, Issue 6 2009Elena Domínguez-Vega Abstract An EKC method for the determination of ornithine (Orn) enantiomers has been developed after a fast pre-capillary derivatization with FITC. The derivatization step was needed to provide a chemical moiety to the Orn molecule, enabling a sensitive UV detection and the interaction with the CDs used as chiral selectors. To accelerate the derivatization reaction, an ultrasound probe was used. For the development of the chiral method, the influence of different experimental conditions (type and concentration of the chiral selector, temperature, and separation voltage) was investigated. Due to the anionic nature of the analyte (FITC-Orn), five neutral CDs were employed as chiral selectors. The native ,-CD showed the highest chiral separation power, observing that a low concentration of this CD (1,mM), using a working temperature of 25°C and a separation voltage of 20,kV, enabled to obtain the highest enantioresolution for Orn and its separation from other amino acids usually present in food supplements. After optimizing the method for the preconditioning of the capillary, the analytical characteristics of the chiral method were established. Linearity, LOD and LOQ, precision, and accuracy were evaluated previously to the determination of Orn enantiomers contained in ten commercial food supplements. No interferences from other amino acids present in these samples were observed. [source] Astrocyte-derived factors modulate the inhibitory effect of ethanol on dendritic developmentGLIA, Issue 4 2002Penelope A. Yanni Abstract Numerous studies in vivo and in vitro have demonstrated that ethanol disrupts neuromorphogenesis. However, it has not been determined what role, if any, is played by non-neuronal cells in mediating this effect. We recently reported that ethanol inhibits dendritic development in low-density cultures of fetal rat hippocampal pyramidal neurons (Yanni and Lindsley, 2000: Dev Brain Res 120:233,243). In this culture system, cortical astrocytes precondition neuronal culture media for 2 days before the addition of neurons, which then develop on a separate substrate in coculture with the astrocytes. To determine whether astrocyte response to ethanol mediates the effects of ethanol on neurons, the present study compared dendritic development of neurons after 6 days in medium containing 400 mg/dl ethanol in coculture with live astrocytes and in conditioned medium from astrocytes that were never exposed to ethanol. The same experiment was also performed with and without ethanol present during astrocyte preconditioning of the medium. The effects of ethanol differed depending on when it was added to the cultures relative to addition of newly dissociated neurons. However, the effects of ethanol were not related to whether neurons were cocultured with live astrocytes. When astrocytes preconditioned the medium normally, ethanol added at plating inhibited dendritic development of neurons regardless of whether they were maintained in coculture with live astrocytes or in conditioned medium. In surprising contrast, the presence of ethanol during astrocyte preconditioning of the media had a growth promoting effect on subsequent dendrite development despite the continued presence of ethanol in the medium. Thus, astrocytes release soluble factors in response to ethanol that can protect neurons from the inhibitory effects of ethanol on dendritic growth, but the timing of neuronal exposure to these factors, or their concentration, may influence their activity. GLIA 38:292,302, 2002. © 2002 Wiley-Liss, Inc. [source] Ischemic preconditioning of the murine liver protects through the Akt kinase pathway,HEPATOLOGY, Issue 3 2006Kunihiko Izuishi Hepatic ischemia-reperfusion (I/R) injury occurs in the settings of transplantation, trauma, and elective liver resection. Ischemic preconditioning has been used as a strategy to reduce inflammation and organ damage from I/R of the liver. However, the mechanisms involved in this process are poorly understood. We examined the role of the phosphatidylinositol 3 (PI3) kinase/Akt-signaling pathway during hepatic ischemic preconditioning (IPC). Prior to a prolonged warm ischemic insult, BALB/c mice were subjected to a 20-minute IPC period consisting of 10 minutes of ischemia and 10 minutes of reperfusion. Mice undergoing IPC demonstrated a significantly greater level and earlier activation of Akt in the liver compared with control animals. IPC also resulted in markedly less hepatocellular injury and improved survival compared with control animals. Akt activation associated with hepatic IPC suppressed the activity of several modulators of apoptosis, including Bad, glycogen synthase kinase ,, and caspase-3. In addition, IPC also inhibited the activities of c-Jun N -terminal kinase and nuclear factor ,B after I/R. Pretreatment of mice with PI3 kinase inhibitors completely abolished Akt phosphorylation and the protective effects seen with IPC. In conclusion, these results indicate that the PI3 kinase/Akt pathway plays an essential role in the protective effects of IPC in hepatic I/R injury. Modulation of this pathway may be a potential strategy in clinical settings of ischemic liver injury to decrease organ damage. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2006;44:573,580.) [source] Ischemic preconditioning affects interleukin release in fatty livers of rats undergoing ischemia/reperfusionHEPATOLOGY, Issue 3 2004Anna Serafín The present study evaluates the effect of ischemic preconditioning on interleukin-1 (IL-1) and interleukin-10 (IL-10) generation following hepatic ischemia/reperfusion (I/R) in normal and steatotic livers as well as the role of nitric oxide (NO) in this process. Increased IL-1, and IL-10 levels were observed in normal livers after I/R. Steatotic livers showed higher IL-1, levels than normal livers, and IL-10 at control levels. The injurious role of IL-1, and the benefits of IL-10 on hepatic I/R injury was shown with the use of IL-1 receptor antagonist (IL-1ra), anti-IL-10 polyclonal antibody against IL-10 (anti-IL-10) and exogenous IL-10. The effective dose of these treatments was different in both types of livers. Preconditioning prevented IL-1, release and increased IL-10 generation after I/R in normal and steatotic livers. IL-1, or anti-IL-10 pretreatments reversed the benefits of preconditioning. IL-1, action inhibition in a preconditioned group that was pretreated with anti-IL-10 did not modify the benefits of preconditioning. In addition, anti-IL-10 pretreatment in the preconditioned group resulted in IL-1, levels comparable to those observed after I/R. NO inhibition eliminated the benefits of preconditioning on IL-10 release, IL-1, levels, and hepatic injury. In conclusion, preconditioning, through IL-10 overproduction, inhibits IL-1, release and the ensuing hepatic I/R injury in normal and steatotic livers. IL-10 generation induced by preconditioning could be mediated by NO. (HEPATOLOGY 2004;39:688,698.) [source] Induction of cellular resistance against Kupffer cell,derived oxidant stress: A novel concept of hepatoprotection by ischemic preconditioningHEPATOLOGY, Issue 2 2003Rolf J. Schauer Ischemic preconditioning (IP) triggers protection of the liver from prolonged subsequent ischemia. However, the underlying protective mechanisms are largely unknown. We investigated whether and how IP protects the liver against reperfusion injury caused by Kupffer cell (KC)-derived oxidants. IP before 90 minutes of warm ischemia of rat livers in vivo significantly reduced serum alanine aminotransferase (AST) levels and leukocyte adherence to sinusoids and postsinusoidal venules during reperfusion. This protective effect was mimicked by postischemic intravenous infusion of glutathione (GSH), an antioxidative strategy against KC-derived H2O2. Interestingly, no additional protection was achieved by infusion of GSH to preconditioned animals. These findings and several additional experiments strongly suggest IP mediated antioxidative effects: IP prevented oxidant cell injury in isolated perfused rat livers after selective KC activation by zymosan. Moreover, IP prevented cell injury and pertubations of the intracellular GSH/GSSG redox system caused by direct infusion of H2O2 (0.5 mmol/L). IP-mediated resistance against H2O2 could neither be blocked by the adenosine A2a antagonist DMPX nor mimicked by A2a agonist CGS21680. In contrast, H2O2 resistance was abolished by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, but induced when p38 MAPK was directly activated by anisomycin. In conclusion, we propose a novel concept of hepatoprotection by IP: protection of liver cells by enhancing their resistance against KC-derived H2O2. Activation of p38 MAPK and preservation of the intracellular GSH/oxidized glutathione (GSSG) redox system, but not adenosine A2a receptor stimulation, seems to be pivotal for the development of H2O2 resistance in preconditioned livers. [source] Low-dose TNF-, protects against hepatic ischemia-reperfusion injury in mice: Implications for preconditioningHEPATOLOGY, Issue 1 2003Narci Teoh Tumor necrosis factor , (TNF-,) is implicated in the pathogenesis of hepatic ischemia reperfusion injury but can also prime hepatocytes to enter the cell cycle. Ischemic preconditioning protects against ischemia-reperfusion (IR) liver injury and is associated with activation of nuclear factor ,B (NF-,B) and cell cycle entry. We examined the pattern of TNF-, release during hepatic IR in the presence or absence of ischemic preconditioning, and we tested whether a single low-dose injection of TNF could mimic the biologic effects of ischemic preconditioning. In naïve mice, hepatic and plasma levels of TNF-, rose during hepatic ischemia, reaching high levels after 90 minutes; values remained elevated during reperfusion until 44 hours. Following the ischemic preconditioning stimulus, there was an early rise in hepatic and serum TNF-, levels, but, during a second prolonged ischemic interval peak, TNF-, values were lower than in naïve mice and declined to negligible levels by 2 hours reperfusion. An injection with 1 ,g or 5 ,g/kg body weight TNF-, 30 minutes prior to hepatic IR substantially reduced liver injury determined by liver histology and serum alanine aminotransferase (ALT) levels. As in ischemic preconditioning, TNF-, pretreatment activated NF-,B DNA binding, STAT3, cyclin D1, cyclin-dependent kinase 4 (cdk4) expression, and cell cycle entry, determined by proliferating cell nuclear antigen (PCNA) staining of hepatocyte nuclei. In conclusion, the hepatoprotective effects of "preconditioning" can be simulated by TNF-, injection, which has identical downstream effects on cell cycle entry. We propose that transient increases in TNF-, levels may substitute for, as well as, mediate the hepatoprotective effects of ischemic preconditioning against hepatic IR injury. [source] Current studies on therapeutic approaches for ischemia/reperfusion injury in steatotic liversHEPATOLOGY RESEARCH, Issue 9 2008Chengfu Xu Steatotic livers are particularly vulnerable to ischemia/reperfusion (I/R) injury, resulting in poor outcomes following liver surgery and transplantation. Therapeutic approaches for I/R injury in steatotic livers are currently under intensive investigation. This review summarizes and discusses the approaches developed during the last few years to prevent hepatic I/R injury in steatotic livers. Among the proposed approaches, ischemic preconditioning and intermittent clamping are the two most promising approaches that have been applied in some clinical centers for liver surgery and transplantation, but most of others have not reached clinical application yet. [source] Roles of nuclear factor-,B in postischemic liverHEPATOLOGY RESEARCH, Issue 5 2008Thomas Shin Hepatic ischemia/reperfusion (I/R) results in a chain of events that culminate in liver dysfunction and injury. I/R injury is characterized by early oxidant stress followed by an intense acute inflammatory response that involves the transcription factor nuclear factor (NF)-,B. In addition to being a primary regulator of pro-inflammatory gene expression, NF-,B may play other roles in the hepatic response to I/R, such as mediating the expression of anti-apoptotic genes, preventing the accumulation of damaging reactive oxygen species, facilitating liver regeneration, and mediating the protective effects of ischemic preconditioning. In the present study, we review the diverse functions of NF-,B during hepatic I/R injury. [source] | ||||||||||||||||||||||||||||||||||||||||||||||