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Sample records for ischemic preconditioning ip

  1. Ischemic preconditioning protects against ischemic brain injury

    PubMed Central

    Ma, Xiao-meng; Liu, Mei; Liu, Ying-ying; Ma, Li-li; Jiang, Ying; Chen, Xiao-hong

    2016-01-01

    In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia. PMID:27335560

  2. The Influence of Diabetes Mellitus in Myocardial Ischemic Preconditioning

    PubMed Central

    Rezende, Paulo Cury; Rahmi, Rosa Maria

    2016-01-01

    Ischemic preconditioning (IP) is a powerful mechanism of protection discovered in the heart in which ischemia paradoxically protects the myocardium against other ischemic insults. Many factors such as diseases and medications may influence IP expression. Although diabetes poses higher cardiovascular risk, the physiopathology underlying this condition is uncertain. Moreover, although diabetes is believed to alter intracellular pathways related to myocardial protective mechanisms, it is still controversial whether diabetes may interfere with ischemic preconditioning and whether this might influence clinical outcomes. This review article looks at published reports with animal models and humans that tried to evaluate the possible influence of diabetes in myocardial ischemic preconditioning.

  3. The Influence of Diabetes Mellitus in Myocardial Ischemic Preconditioning

    PubMed Central

    Rezende, Paulo Cury; Rahmi, Rosa Maria

    2016-01-01

    Ischemic preconditioning (IP) is a powerful mechanism of protection discovered in the heart in which ischemia paradoxically protects the myocardium against other ischemic insults. Many factors such as diseases and medications may influence IP expression. Although diabetes poses higher cardiovascular risk, the physiopathology underlying this condition is uncertain. Moreover, although diabetes is believed to alter intracellular pathways related to myocardial protective mechanisms, it is still controversial whether diabetes may interfere with ischemic preconditioning and whether this might influence clinical outcomes. This review article looks at published reports with animal models and humans that tried to evaluate the possible influence of diabetes in myocardial ischemic preconditioning. PMID:27656659

  4. Ischemic preconditioning and clinical scenarios

    PubMed Central

    Narayanan, Srinivasan V.; Dave, Kunjan R.; Perez-Pinzon, Miguel A.

    2013-01-01

    Purpose of review Ischemic preconditioning (IPC) is gaining attention as a novel neuroprotective therapy and could provide an improved mechanistic understanding of tolerance to cerebral ischemia. The purpose of this article is to review the recent work in the field of IPC and its applications to clinical scenarios. Recent findings The cellular signaling pathways that are activated following IPC are now better understood and have enabled investigators to identify several IPC mimetics. Most of these studies were performed in rodents, and efficacy of these mimetics remains to be evaluated in human patients. Additionally, remote ischemic preconditioning (RIPC) may have higher translational value than IPC. Repeated cycles of temporary ischemia in a remote organ can activate protective pathways in the target organ, including the heart and brain. Clinical trials are underway to test the efficacy of RIPC in protecting brain against subarachnoid hemorrhage. Summary IPC, RIPC, and IPC mimetics have the potential to be therapeutic in various clinical scenarios. Further understanding of IPC-induced neuroprotection pathways and utilization of clinically relevant animal models are necessary to increase the translational potential of IPC in the near future. PMID:23197083

  5. Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats

    PubMed Central

    XUE, TONG-MIN; TAO, LI-DE; ZHANG, JIE; ZHANG, PEI-JIAN; LIU, XIA; CHEN, GUO-FENG; ZHU, YI-JIA

    2016-01-01

    The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF-κBp65 expression levels, with reduced expression of Bcl-2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF-α and IL-1 were significantly reduced in the IP group. Immunohistochemistry for Bcl-2 and Bax indicated that Bcl-2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro-inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury. PMID:26821057

  6. Cardioprotection acquired through exercise: the role of ischemic preconditioning.

    PubMed

    Marongiu, Elisabetta; Crisafulli, Antonio

    2014-11-01

    A great bulk of evidence supports the concept that regular exercise training can reduce the incidence of coronary events and increase survival chances after myocardial infarction. These exercise-induced beneficial effects on the myocardium are reached by means of the reduction of several risk factors relating to cardiovascular disease, such as high cholesterol, hypertension, obesity etc. Furthermore, it has been demonstrated that exercise can reproduce the "ischemic preconditioning" (IP), which refers to the capacity of short periods of ischemia to render the myocardium more resistant to subsequent ischemic insult and to limit infarct size during prolonged ischemia. However, IP is a complex phenomenon which, along with infarct size reduction, can also provide protection against arrhythmia and myocardial stunning due to ischemia-reperfusion. Several clues demonstrate that preconditioning may be directly induced by exercise, thus inducing a protective phenotype at the heart level without the necessity of causing ischemia. Exercise appears to act as a physiological stress that induces beneficial myocardial adaptive responses at cellular level. The purpose of the present paper is to review the latest data on the role played by exercise in triggering myocardial preconditioning.

  7. Cardioprotection Acquired Through Exercise: The Role of Ischemic Preconditioning

    PubMed Central

    Marongiu, Elisabetta; Crisafulli, Antonio

    2014-01-01

    A great bulk of evidence supports the concept that regular exercise training can reduce the incidence of coronary events and increase survival chances after myocardial infarction. These exercise-induced beneficial effects on the myocardium are reached by means of the reduction of several risk factors relating to cardiovascular disease, such as high cholesterol, hypertension, obesity etc. Furthermore, it has been demonstrated that exercise can reproduce the “ischemic preconditioning” (IP), which refers to the capacity of short periods of ischemia to render the myocardium more resistant to subsequent ischemic insult and to limit infarct size during prolonged ischemia. However, IP is a complex phenomenon which, along with infarct size reduction, can also provide protection against arrhythmia and myocardial stunning due to ischemia-reperfusion. Several clues demonstrate that preconditioning may be directly induced by exercise, thus inducing a protective phenotype at the heart level without the necessity of causing ischemia. Exercise appears to act as a physiological stress that induces beneficial myocardial adaptive responses at cellular level. The purpose of the present paper is to review the latest data on the role played by exercise in triggering myocardial preconditioning. PMID:24720421

  8. Heat shock proteins, end effectors of myocardium ischemic preconditioning?

    PubMed Central

    Guisasola, María Concepcion; Desco, Maria del Mar; Gonzalez, Fernanda Silvana; Asensio, Fernando; Dulin, Elena; Suarez, Antonio; Garcia Barreno, Pedro

    2006-01-01

    The purpose of this study was to investigate (1) whether ischemia-reperfusion increased the content of heat shock protein 72 (Hsp72) transcripts and (2) whether myocardial content of Hsp72 is increased by ischemic preconditioning so that they can be considered as end effectors of preconditioning. Twelve male minipigs (8 protocol, 4 sham) were used, with the following ischemic preconditioning protocol: 3 ischemia and reperfusion 5-minute alternative cycles and last reperfusion cycle of 3 hours. Initial and final transmural biopsies (both in healthy and ischemic areas) were taken in all animals. Heat shock protein 72 messenger ribonucleic acid (mRNA) expression was measured by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method using complementary DNA normalized against the housekeeping gene cyclophilin. The identification of heat shock protein 72 was performed by immunoblot. In our “classic” preconditioning model, we found no changes in mRNA hsp72 levels or heat shock protein 72 content in the myocardium after 3 hours of reperfusion. Our experimental model is valid and the experimental techniques are appropriate, but the induction of heat shock proteins 72 as end effectors of cardioprotection in ischemic preconditioning does not occur in the first hours after ischemia, but probably at least 24 hours after it, in the so-called “second protection window.” PMID:17009598

  9. Ischemic preconditioning for cell-based therapy and tissue engineering.

    PubMed

    Hsiao, Sarah T; Dilley, Rodney J; Dusting, Gregory J; Lim, Shiang Y

    2014-05-01

    Cell- and tissue-based therapies are innovative strategies to repair and regenerate injured hearts. Despite major advances achieved in optimizing these strategies in terms of cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. The non-genetic approach of ischemic/hypoxic preconditioning to enhance cell- and tissue-based therapies has received much attention in recent years due to its non-invasive drug-free application. Here we discuss the current development of hypoxic/ischemic preconditioning to enhance stem cell-based cardiac repair and regeneration.

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

    PubMed

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

    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 ischemia-reperfusion injury in isolated hearts from adult (A, 6 months old), sedentary 'ad libitum' fed (SL), trained ad libitum fed (TL), sedentary food-restricted (SR), trained- and food-restricted senescent rats (TR) (24 months old) were investigated. Norepinephrine release in coronary effluent was determined by high performance liquid cromatography. IP significantly improved final recovery of percent developed pressure in hearts from A (p<0.01) but not in those from SL (p=NS) vs unconditioned controls. Developed pressure recovery was partial in hearts from TL and SR (64.3 and 67.3%, respectively; p<0.05 vs controls) but it was total in those from TR (82.3%, p=NS vs A; p<0.05 vs hearts from TL and SR). Similarly, IP determined a similar increase of norepinephrine release in A (p<0.001) and in TR (p<0.001, p=NS vs adult). IP was abolished by depletion of myocardial norepinephrine stores by reserpine in all groups. Thus, IP reduces post-ischemic dysfunction in A but not in SL. Moreover, IP was preserved partially in TR and SR and totally in TR. Complete IP maybe due to full restoration of norepinephrine release in response to IP stimulus.

  11. [Myocardial serotonin metabolism after local ischemia and ischemic precondition].

    PubMed

    Naumenko, S E; Latysheva, T V; Gilinskiĭ, M A

    2014-07-01

    To determine the effect of ischemic preconditioning upon myocardial serotonin and 5-hydroxyindolacetic acid (5-HIAA) dynamic in myocardial ischemia and reperfusion. 28 male Wistar rats anesthetized with urethane were randomly divided into 2 groups. In the control group (n = 13) rats were subjected to 30 min coronary occlusion and subsequent 120 min reperfusion. In the ex- perimental group (n = 15) ischemic preconditioning (3 x 3 min ischemia + 3 x 3 min reperfusion) before prolonged ischemia was used. Myocardial interstitial serotonin and 5-HIAA were measured using a microdialysis technique. Myocardial serotonin and 5-HIAA significantly increased af- ter ischemic preconditioning (p = 0.00298; p = 0.00187). In prolonged ischemia interstitial serotonin level was lower in the experimental group vs. control up to 20 min of ischemia (p < 0.05). We conclude that ischemic preconditioning increases interstitial myocardial serotonin, but inhibit serotonin increase in subsequent prolonged myocardial ischemia. After 20 minutes of reperfusion the lack of correlation between serotonin and 5-HIAA levels appeared which may be the evidence of serotonin uptake activation.

  12. Remote ischemic preconditioning improves post resuscitation cerebral function via overexpressing neuroglobin after cardiac arrest in rats.

    PubMed

    Fan, Ran; Yu, Tao; Lin, Jia-Li; Ren, Guang-Dong; Li, Yi; Liao, Xiao-Xing; Huang, Zi-Tong; Jiang, Chong-Hui

    2016-10-01

    In this study, we investigated the effects of remote ischemic preconditioning on post resuscitation cerebral function in a rat model of cardiac arrest and resuscitation. The animals were randomized into six groups: 1) sham operation, 2) lateral ventricle injection and sham operation, 3) cardiac arrest induced by ventricular fibrillation, 4) lateral ventricle injection and cardiac arrest, 5) remote ischemic preconditioning initiated 90min before induction of ventricular fibrillation, and 6) lateral ventricle injection and remote ischemic preconditioning before cardiac arrest. Reagent of Lateral ventricle injection is neuroglobin antisense oligodeoxynucleotides which initiated 24h before sham operation, cardiac arrest or remote ischemic preconditioning. Remote ischemic preconditioning was induced by four cycles of 5min of limb ischemia, followed by 5min of reperfusion. Ventricular fibrillation was induced by current and lasted for 6min. Defibrillation was attempted after 6min of cardiopulmonary resuscitation. The animals were then monitored for 2h and observed for an additionally maximum 70h. Post resuscitation cerebral function was evaluated by neurologic deficit score at 72h after return of spontaneous circulation. Results showed that remote ischemic preconditioning increased neurologic deficit scores. To investigate the neuroprotective effects of remote ischemic preconditioning, we observed neuronal injury at 48 and 72h after return of spontaneous circulation and found that remote ischemic preconditioning significantly decreased the occurrence of neuronal apoptosis and necrosis. To further comprehend mechanism of neuroprotection induced by remote ischemic preconditioning, we found expression of neuroglobin at 24h after return of spontaneous circulation was enhanced. Furthermore, administration of neuroglobin antisense oligodeoxynucleotides before induction of remote ischemic preconditioning showed that the level of neuroglobin was decreased then partly abrogated

  13. Investigation of Reperfusion Injury and Ischemic Preconditioning in Microsurgry

    PubMed Central

    Wang, Wei Zhong

    2008-01-01

    Ischemia/reperfusion (I/R) is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive surgeries in the extremities. Salvage of a prolonged ischemic extremity or flap still remains a challenge for the microvascular surgeon. One of the common complications after microsurgery is I/R-induced tissue death or I/R injury. Twenty years after the discovery, ischemic preconditioning (IPC) has emerged as a powerful method for attenuating I/R injury in a variety of organs or tissues. However, its therapeutic expectations still need to be fulfilled. In this article, the author reviews some important experimental evidences of I/R injury as well as preconditioning-induced protection in the fields relevant to microsurgery. PMID:18946882

  14. Role of thioredoxin-1 in ischemic preconditioning, postconditioning and aged ischemic hearts.

    PubMed

    D'Annunzio, Veronica; Perez, Virginia; Boveris, Alberto; Gelpi, Ricardo J; Poderoso, Juan J

    2016-07-01

    Thioredoxin is one of the most important cellular antioxidant systems known to date, and is responsible of maintaining the reduced state of the intracellular space. Trx-1 is a small cytosolic protein whose transcription is induced by stress. Therefore it is possible that this antioxidant plays a protective role against the oxidative stress caused by an increase of reactive oxygen species concentration, as occurs during the reperfusion after an ischemic episode. However, in addition to its antioxidant properties, it is able to activate other cytoplasmic and nuclear mediators that confer cardioprotection. It is remarkable that Trx-1 also participates in myocardial protection mechanisms such as ischemic preconditioning and postconditioning, activating proteins related to cellular survival. In this sense, it has been shown that Trx-1 inhibition abolished the preconditioning cardioprotective effect, evidenced through apoptosis and infarct size. Furthermore, ischemic postconditioning preserves Trx-1 content at reperfusion, after ischemia. However, comorbidities such as aging can modify this powerful cellular defense leading to decrease cardioprotection. Even ischemic preconditioning and postconditioning protocols performed in aged animal models failed to decrease infarct size. Therefore, the lack of success of antioxidants therapies to treat ischemic heart disease could be solved, at least in part, avoiding the damage of Trx system. PMID:26987940

  15. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

    SciTech Connect

    Li, Zhao; Jin, Zhu-Qiu

    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

  16. Effects of ischemic preconditioning on ischemia/reperfusion-induced arrhythmias by upregulatation of connexin 43 expression

    PubMed Central

    2011-01-01

    Background The susceptibility of hypertrophied myocardium to ischemia-reperfusion injury is associated with increased risk of postoperative arrhythmias. We investigate the effects of ischemic preconditioning (IP) on post-ischemic reperfusion arrhythmias in hypertrophic rabbit hearts. Methods Thirty-three rabbit models of myocardial hypertrophy were randomly divided into three groups of 11 each: non-ischemia-reperfusion group (group A), ischemia-reperfusion group (group B), and ischemic preconditioning group (group C). Another ten healthy rabbits with normal myocardium served as the healthy control group. Rabbit models of myocardial hypertrophy were induced by abdominal aortic banding. Surface electrocardiogram (ECG) was recorded and Curtis-Ravingerova score was used for arrhythmia quantification. Connexin 43 (Cx43) expression was assessed by immunohistochemistry. Results Ratios of heart weight to body weight and left ventricular weight to body weight increase significantly in the three groups compared with the healthy control group (p < 0.05). Arrhythmia incidence in group C is significantly lower than group B (p < 0.05). Curtis-Ravingerova score in group C is lower than group B (p < 0.05). Cx43 expression area in group A is smaller by comparison with the healthy control group (p < 0.05). Cx43 expression area and fluorescence intensity in group B are reduced by 60.9% and 23.9%, respectively, compared with group A (p < 0.05). In group C, Cx43 expression area increases by 32.5% compared with group B (p < 0.05), and decreases by 54.8% compared with group A (p < 0.05). Conclusions The incidence of ischemia/reperfusion-induced arrhythmias in hypertrophic rabbit hearts decreases after IP, which plays an important protecting role on the electrophysiology of hypertrophied myocardium by up-regulating the expression of Cx43. PMID:21635761

  17. Nitrite as a mediator of ischemic preconditioning and cytoprotection

    PubMed Central

    Murillo, Daniel; Kamga, Christelle; Mo, Li; Shiva, Sruti

    2011-01-01

    Ischemia/reperfusion (IR) injury is a central component in the pathogenesis of several diseases and is a leading cause of morbidity and mortality in the western world. Subcellularly, mitochondrial dysfunction, characterized by depletion of ATP, calcium-induced opening of the mitochondrial permeability transition pore, and exacerbated reactive oxygen species (ROS) formation, plays an integral role in the progression of IR injury. Nitric oxide (NO) and more recently nitrite (NO2-) are known to modulate mitochondrial function, mediate cytoprotection after IR and have been implicated in the signaling of the highly protective ischemic preconditioning (IPC) program. Here, we review what is known about the role of NO and nitrite in cytoprotection after IR and consider the putative role of nitrite in IPC. Focus is placed on the potential cytoprotective mechanisms involving NO and nitrite-dependent modulation of mitochondrial function. PMID:21277988

  18. Can anaerobic performance be improved by remote ischemic preconditioning?

    PubMed

    Lalonde, François; Curnier, Daniel Y

    2015-01-01

    Remote ischemic preconditioning (RIPC) provides a substantial benefit for heart protection during surgery. Recent literature on RIPC reveals the potential to benefit the enhancement of sports performance as well. The aim of this study was to investigate the effect of RIPC on anaerobic performance. Seventeen healthy participants who practice regular physical activity participated in the project (9 women and 8 men, mean age 28 ± 8 years). The participants were randomly assigned to an RIPC intervention (four 5-minute cycles of ischemia reperfusion, followed by 5 minutes using a pressure cuff) or a SHAM intervention in a crossover design. After the intervention, the participants were tested for alactic anaerobic performance (6 seconds of effort) followed by a Wingate test (lactic system) on an electromagnetic cycle ergometer. The following parameters were evaluated: average power, peak power, the scale of perceived exertion, fatigue index (in watt per second), peak power (in Watt), time to reach peak power (in seconds), minimum power (in Watt), the average power-to-weight ratio (in watt per kilogram), and the maximum power-to-weight ratio (in watt per kilogram). The peak power for the Wingate test is 794 W for RIPC and 777 W for the control group (p = 0.208). The average power is 529 W (RIPC) vs. 520 W for controls (p = 0.079). Perceived effort for RIPC is 9/10 on the Borg scale vs. 10/10 for the control group (p = 0.123). Remote ischemic preconditioning does not offer any significant benefits for anaerobic performance.

  19. Possible involvement of ubiquitin proteasome system and other proteases in acute and delayed aspects of ischemic preconditioning of brain in mice.

    PubMed

    Rehni, Ashish Kumar; Singh, Thakur Gurjeet; Behl, Nidhi; Arora, Sandeep

    2010-01-01

    The present study has been designed to investigate the potential role of ubiquitin proteasome system and other proteases in acute as well as delayed aspects of ischemic preconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24 h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min (ischemic preconditioning) both immediately before (for acute preconditioning) and 24 h before (for delayed preconditioning) global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. Z-Leu-Leu-Phe-Chinese hamster ovary (CHO) (2 mg/kg, intraperitoneally (i.p.)), an inhibitor of ubiquitin proteasome system and other proteases attenuated the neuroprotective effect of both the acute as well as delayed ischemic preconditioning. It is concluded that the neuroprotective effect of both the acute as well as delayed phases of ischemic preconditioning may be due to the activation of ubiquitin proteasome system and other proteases.

  20. Protective effects of remote ischemic preconditioning in isolated rat hearts

    PubMed Central

    Teng, Xiao; Yuan, Xin; Tang, Yue; Shi, Jingqian

    2015-01-01

    To use Langendorff model to investigate whether remote ischemic preconditioning (RIPC) attenuates post-ischemic mechanical dysfunction on isolated rat heart and to explore possible mechanisms. SD rats were randomly divided into RIPC group, RIPC + norepinephrine (NE) depletion group, RIPC + pertussis toxin (PTX) pretreatment group, ischemia/reperfusion group without treatment (ischemia group) and time control (TC) group. RIPC was achieved through interrupted occlusion of anterior mesenteric artery. Then, Langendorff model was established using routine methods. Heart function was tested; immunohistochemistry and ELISA methods were used to detect various indices related to myocardial injury. Compared with ischemia group in which the hemodynamic parameters deteriorated significantly, heart function recovered to a certain degree among the RIPC, RIPC + NE depletion, and RIPC + PTX groups (P<0.05). More apoptotic nuclei were observed in ischemia group than in the other three groups (P<0.05); more apoptotic nuclei were detected in NE depletion and PTX groups than in RIPC group (P<0.05). While, there was no significant difference between NE depletion and PTX groups. In conclusion, RIPC protection on I/R myocardium extends to the period after hearts are isolated. NE and PTX-sensitive inhibitory G protein might have a role in the protection process. PMID:26550168

  1. Conditional Knockout of Myocyte Focal Adhesion Kinase Abrogates Ischemic Preconditioning in Adult Murine Hearts

    PubMed Central

    Perricone, Adam J.; Bivona, Benjamin J.; Jackson, Fannie R.; Vander Heide, Richard S.

    2013-01-01

    Background Our laboratory has previously demonstrated the importance of a cytoskeletal‐based survival signaling pathway using in vitro models of ischemia/reperfusion (IR). However, the importance of this pathway in mediating stress‐elicited survival signaling in vivo is unknown. Methods and Results The essential cytoskeletal signaling pathway member focal adhesion kinase (FAK) was selectively deleted in adult cardiac myocytes using a tamoxifen‐inducible Cre‐Lox system (α‐MHC‐MerCreMer). Polymerase chain reaction (PCR) and Western blot were performed to confirm FAK knockout (KO). All mice were subjected to a 40‐minute coronary occlusion followed by 24 hours of reperfusion. Ischemic preconditioning (IP) was performed using a standard protocol. Control groups included wild‐type (WT) and tamoxifen‐treated α‐MHC‐MerCreMer+/−/FAKWT/WT (experimental control) mice. Infarct size was expressed as a percentage of the risk region. In WT mice IP significantly enhanced the expression of activated/phosphorylated FAK by 36.3% compared to WT mice subjected to a sham experimental protocol (P≤0.05; n=6 hearts [sham], n=4 hearts [IP]). IP significantly reduced infarct size in both WT and experimental control mice (43.7% versus 19.8%; P≤0.001; 44.7% versus 17.5%; P≤0.001, respectively). No difference in infarct size was observed between preconditioned FAK KO and nonpreconditioned controls (37.1% versus 43.7% versus 44.7%; FAK KO versus WT versus experimental control; P=NS). IP elicited a 67.2%/88.8% increase in activated phosphatidylinositol‐3‐kinase (PI3K) p85/activated Akt expression in WT mice, but failed to enhance the expression of either in preconditioned FAK KO mice. Conclusions Our results indicate that FAK is an essential mediator of IP‐elicited cardioprotection and provide further support for the hypothesis that cytoskeletal‐based signaling is an important component of stress‐elicited survival signaling. PMID:24080910

  2. Effects of ischemic preconditioning on short-duration cycling performance.

    PubMed

    Cruz, Rogério Santos de Oliveira; de Aguiar, Rafael Alves; Turnes, Tiago; Salvador, Amadeo Félix; Caputo, Fabrizio

    2016-08-01

    It has been demonstrated that ischemic preconditioning (IPC) improves endurance performance. However, the potential benefits during anaerobic events and the mechanism(s) underlying these benefits remain unclear. Fifteen recreational cyclists were assessed to evaluate the effects of IPC of the upper thighs on anaerobic performance, skeletal muscle activation, and metabolic responses during a 60-s sprint performance. After an incremental test and a familiarization visit, subjects were randomly submitted in visits 3 and 4 to a performance protocol preceded by intermittent bilateral cuff inflation (4 × (5 min of blood flow restriction + 5 min reperfusion)) at either 220 mm Hg (IPC) or 20 mm Hg (control). To increase data reliability, each intervention was replicated, which was also in a random manner. In addition to the mean power output, the pulmonary oxygen uptake, blood lactate kinetics, and quadriceps electromyograms (EMGs) were analyzed during performance and throughout 45 min of passive recovery. After IPC, performance was improved by 2.1% compared with control (95% confidence intervals of 0.8% to 3.3%, P = 0.001), followed by increases in (i) the accumulated oxygen deficit, (ii) the amplitude of blood lactate kinetics, (iii) the total amount of oxygen consumed during recovery, and (iv) the overall EMG amplitude (P < 0.05). In addition, the ratio between EMG and power output was higher during the final third of performance after IPC (P < 0.05). These results suggest an increased skeletal muscle activation and a higher anaerobic contribution as the ultimate responses of IPC on short-term exercise performance.

  3. Remote ischemic preconditioning in hemodialysis: a pilot study.

    PubMed

    Park, Jongha; Ann, Soe Hee; Chung, Hyun Chul; Lee, Jong Soo; Kim, Shin-Jae; Garg, Scot; Shin, Eun-Seok

    2014-01-01

    Hemodialysis (HD)-induced myocardial ischemia is associated with an elevated cardiac troponin T, and is common in asymptomatic patients undergoing conventional HD. Remote ischemic preconditioning (RIPC) has a protective effect against myocardial ischemia-reperfusion injury. We hypothesized that RIPC also has a protective effect on HD-induced myocardial injury. Chronic HD patients were randomized to the control group or the RIPC group. RIPC was induced by transient occlusion of blood flow to the arm with a blood-pressure cuff for 5 min, followed by 5 min of deflation. Three cycles of inflation and deflation were undertaken before every HD session for 1 month (total 12 times). The primary outcome was the change in cardiac troponin T (cTnT) level at day 28 from baseline. Demographic and baseline laboratory values were not different between the control (n = 17) and the RIPC groups (n = 17). cTnT levels tended to decrease from day 2 in the RIPC group through to 28 days, in contrast to no change in the control group. There were significant differences in the change of cTnT level at day 28 from baseline [Control, median; -0.002 ng/ml (interquartile range -0.008 to 0.018) versus RIPC, median; -0.015 ng/ml (interquartile range -0.055 to 0.004), P = 0.012]. RIPC reduced cTnT release in chronic conventional HD patients, suggesting that this simple, cheap, safe, and well-tolerated procedure has a protective effect against HD-induced ischemia.

  4. Effects of ischemic preconditioning on short-duration cycling performance.

    PubMed

    Cruz, Rogério Santos de Oliveira; de Aguiar, Rafael Alves; Turnes, Tiago; Salvador, Amadeo Félix; Caputo, Fabrizio

    2016-08-01

    It has been demonstrated that ischemic preconditioning (IPC) improves endurance performance. However, the potential benefits during anaerobic events and the mechanism(s) underlying these benefits remain unclear. Fifteen recreational cyclists were assessed to evaluate the effects of IPC of the upper thighs on anaerobic performance, skeletal muscle activation, and metabolic responses during a 60-s sprint performance. After an incremental test and a familiarization visit, subjects were randomly submitted in visits 3 and 4 to a performance protocol preceded by intermittent bilateral cuff inflation (4 × (5 min of blood flow restriction + 5 min reperfusion)) at either 220 mm Hg (IPC) or 20 mm Hg (control). To increase data reliability, each intervention was replicated, which was also in a random manner. In addition to the mean power output, the pulmonary oxygen uptake, blood lactate kinetics, and quadriceps electromyograms (EMGs) were analyzed during performance and throughout 45 min of passive recovery. After IPC, performance was improved by 2.1% compared with control (95% confidence intervals of 0.8% to 3.3%, P = 0.001), followed by increases in (i) the accumulated oxygen deficit, (ii) the amplitude of blood lactate kinetics, (iii) the total amount of oxygen consumed during recovery, and (iv) the overall EMG amplitude (P < 0.05). In addition, the ratio between EMG and power output was higher during the final third of performance after IPC (P < 0.05). These results suggest an increased skeletal muscle activation and a higher anaerobic contribution as the ultimate responses of IPC on short-term exercise performance. PMID:27404398

  5. The P2X4 receptor is required for neuroprotection via ischemic preconditioning

    PubMed Central

    Ozaki, Tomohiko; Muramatsu, Rieko; Sasai, Miwa; Yamamoto, Masahiro; Kubota, Yoshiaki; Fujinaka, Toshiyuki; Yoshimine, Toshiki; Yamashita, Toshihide

    2016-01-01

    Ischemic preconditioning (IPC), a procedure consisting of transient ischemia and subsequent reperfusion, provides ischemic tolerance against prolonged ischemia in the brain. Although the blood flow changes mediated by IPC are primarily perceived by vascular endothelial cells, the role of these cells in ischemic tolerance has not been fully clarified. In this study, we found that the P2X4 receptor, which is abundantly expressed in vascular endothelial cells, is required for ischemic tolerance following middle artery occlusion (MCAO) in mice. Mechanistically, the P2X4 receptor was stimulated by fluid shear stress, which mimics reperfusion, thus promoting the increased expression of osteopontin, a neuroprotective molecule. Furthermore, we found that the intracerebroventricular administration of osteopontin was sufficient to exert a neuroprotective effect mediated by preconditioning-stimulated P2X4 receptor activation. These results demonstrate a novel mechanism whereby vascular endothelial cells are involved in ischemic tolerance. PMID:27173846

  6. Remote Ischemic Preconditioning Reduces Cerebral Oxidative Stress Following Hypothermic Circulatory Arrest in a Porcine Model.

    PubMed

    Arvola, Oiva; Haapanen, Henri; Herajärvi, Johanna; Anttila, Tuomas; Puistola, Ulla; Karihtala, Peeter; Tuominen, Hannu; Anttila, Vesa; Juvonen, Tatu

    2016-01-01

    Remote ischemic precondition has become prominent as one of the most promising methods to mitigate neurological damage following ischemic insult. The purpose of this study was to investigate whether the effects of remote ischemic preconditioning can be seen in the markers of oxidative stress or in redox-regulating enzymes in a porcine model. A total of 12 female piglets were randomly assigned to 2 groups. The study group underwent an intervention of 4 cycles of 5-minute ischemic preconditioning on the right hind leg. All piglets underwent 60-minute hypothermic circulatory arrest. Oxidative stress marker 8-hydroxydeoxyguanosine (8-OHdG) was measured from blood samples with enzyme-linked immunosorbent assay. After 7 days of follow-up, samples from the brain, heart, kidney, and ovary were harvested for histopathologic examination. The immunohistochemical stainings of hypoxia marker hypoxia-inducible factor-1-α, oxidative stress marker 8-OHdG, DNA repair enzyme 8-oxoguanine glycosylase, and antioxidant response regulators nuclear factor erythroid 2-related factor 2 and protein deglycase were analyzed. The level of 8-OHdG referred to baseline was decreased in the sagittal sinus׳ blood samples in the study group after a prolonged deep hypothermic circulatory arrest at 360 minutes after reperfusion. Total histopathologic score was 3.8 (1.8-6.0) in the study group and was 4.4 (2.5-6.5) in the control group (P = 0.72), demonstrating no statistically significant difference in cerebral injury. Our findings demonstrate that the positive effects of remote ischemic preconditioning can be seen in cellular oxidative balance regulators in an animal model after 7 days of preconditioned ischemic insult. PMID:27568144

  7. Minocycline-Preconditioned Neural Stem Cells Enhance Neuroprotection after Ischemic Stroke in Rats

    PubMed Central

    Sakata, Hiroyuki; Niizuma, Kuniyasu; Yoshioka, Hideyuki; Kim, Gab Seok; Jung, Joo Eun; Katsu, Masataka; Narasimhan, Purnima; Maier, Carolina M.; Nishiyama, Yasuhiro; Chan, Pak H.

    2012-01-01

    Transplantation of neural stem cells (NSCs) offers a novel therapeutic strategy for stroke; however, massive grafted-cell death following transplantation, possibly due to a hostile host-brain environment, lessens the effectiveness of this approach. Here, we have investigated whether reprogramming NSCs with minocycline, a broadly-used antibiotic also known to possess cytoprotective properties, enhances survival of grafted cells and promotes neuroprotection in ischemic stroke. NSCs harvested from the subventricular zone of fetal rats were preconditioned with minocycline in vitro and transplanted into rat brains 6 h after transient middle cerebral artery occlusion. Histological and behavioral tests were examined from days 0–28 after stroke. For in vitro experiments, NSCs were subjected to oxygen-glucose deprivation and reoxygenation. Cell viability and antioxidant gene expression were analyzed. Minocycline preconditioning protected the grafted NSCs from ischemic reperfusion injury via up-regulation of Nrf2 and Nrf2-regulated antioxidant genes. Additionally, preconditioning with minocycline induced the NSCs to release paracrine factors, including brain-derived neurotrophic factor, nerve growth factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor. Moreover, transplantation of the minocycline-preconditioned NSCs significantly attenuated infarct size and improved neurological performance, compared with non-preconditioned NSCs. Minocycline-induced neuroprotection was abolished by transfecting the NSCs with Nrf2-small interfering RNA before transplantation. Thus, preconditioning with minocycline, which reprograms NSCs to tolerate oxidative stress after ischemic reperfusion injury and to express higher levels of paracrine factors through Nrf2 up-regulation, is a simple and safe approach to enhance the effectiveness of transplantation therapy in ischemic stroke. PMID:22399769

  8. Remote preconditioning-endocrine factors in organ protection against ischemic injury.

    PubMed

    Bolte, Craig S; Liao, Siyun; Gross, Garrett J; Schultz, Jo El J

    2007-09-01

    Cardiovascular disease is the leading cause of death in the United States and developing world. Experimental and clinical studies have demonstrated that a number of interventions including brief periods of ischemia or hypoxia and certain endogenous factors such as opioids, bradykinin, growth factors or pharmacological agents are capable of protecting the heart against post-ischemic contractile dysfunction, arrhythmias and myocardial infarction. This conventional cardioprotection occurs via an autocrine or paracrine action in which these protective factors are released from the heart to act upon itself. Over the last ten years, a growing body of evidence indicates that a brief ischemic insult on one organ releases endogenous factors that protect other organs against a prolonged ischemic insult. This phenomenon, termed remote preconditioning or preconditioning at a distance, implicates an endocrine action, and may involve humoral or neural-endocrine signaling. This review will summarize the endocrine factors identified and implicated in this inter-organ cytoprotection. PMID:17897043

  9. Preconditioning: can nature's shield be raised against surgical ischemic-reperfusion injury?

    PubMed

    Perrault, L P; Menasché, P

    1999-11-01

    Endogenous myocardial protection refers to the natural defense mechanisms available to the heart to withstand an ischemic injury. So far, these mechanisms have been shown to encompass two phenomena most likely interrelated: ischemic preconditioning and stress protein synthesis. Ischemic preconditioning can be defined as the adaptive mechanism induced by a brief period of reversible ischemia increasing the heart's resistance to a subsequent longer period of ischemia. The therapeutic exploitation of these natural adaptive mechanisms in cardiac surgery is an appealing prospect, as preconditioning could be used before aortic cross-clamping to enhance the current methods of myocardial protection. Two major conclusions emerge from the bulk of experimental data on preconditioning: First, the adaptive phenomenon reduces infarct size after regional ischemia in animal preparations across a wide variety of species but its effects on arrhythmias and on preservation of function after global ischemia are less consistent. This is relevant to cardiac surgery where postbypass pump failure is more often due to stunning than to discrete necrosis. Second, regardless of the various components of the intracellular signaling pathway elicited by the preconditioning stimulus, it seems that the major mechanisms by which this pathway leads to a cardioprotective effect are a slowing of adenosine triphosphate depletion and a limitation of acidosis during the protracted period of ischemia. If the latter is true, then it can reasonably be predicted that these energy-sparing and acidosis-limiting effects may become redundant to those of cardioplegia. From these observations, it can be inferred that preconditioning may find an elective indication in situations where the potential for suboptimal protection increases the risk of necrosis (extensive coronary artery disease, severe left ventricular hypertrophy, long ischemic time, and beating heart operations where occlusion of the target vessels

  10. Remote ischemic preconditioning for kidney protection: GSK3β-centric insights into the mechanism of action.

    PubMed

    Liu, Zhangsuo; Gong, Rujun

    2015-11-01

    Preventing acute kidney injury (AKI) in high-risk patients following medical interventions is a paramount challenge for clinical practice. Recent data from animal experiments and clinical trials indicate that remote ischemic preconditioning, represented by limb ischemic preconditioning, confers a protective action on the kidney. Ischemic preconditioning is effective in reducing the risk for AKI following cardiovascular interventions and the use of iodinated radiocontrast media. Nevertheless, the underlying mechanisms for this protective effect are elusive. A protective signal is conveyed from the remote site undergoing ischemic preconditioning, such as the limb, to target organs, such as the kidney, by multiple potential communication pathways, which may involve humoral, neuronal, and systemic mechanisms. Diverse transmitting pathways trigger a variety of signaling cascades, including the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, all of which converge on glycogen synthase kinase 3β (GSK3β). Inhibition of GSK3β subsequent to ischemic preconditioning reinforces the Nrf2-mediated antioxidant defense, diminishes the nuclear factor-κB-dependent proinflammatory response, and exerts prosurvival effects ensuing from the desensitized mitochondria permeability transition. Thus, therapeutic targeting of GSK3β by ischemic preconditioning or by pharmacologic preconditioning with existing US Food and Drug Administration-approved drugs having GSK3β-inhibitory activities might represent a pragmatic and cost-effective adjuvant strategy for kidney protection and prophylaxis against AKI.

  11. Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

    PubMed

    Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep

    2015-06-01

    Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion. PMID:25743572

  12. Advance in spinal cord ischemia reperfusion injury: Blood-spinal cord barrier and remote ischemic preconditioning.

    PubMed

    Yu, Qijing; Huang, Jinxiu; Hu, Ji; Zhu, Hongfei

    2016-06-01

    The blood-spinal cord barrier (BSCB) is the physiological and metabolic substance diffusion barrier between blood circulation and spinal cord tissues. This barrier plays a vital role in maintaining the microenvironment stability of the spinal cord. When the spinal cord is subjected to ischemia/reperfusion (I/R) injury, the structure and function of the BSCB is disrupted, further destroying the spinal cord homeostasis and ultimately leading to neurological deficit. Remote ischemic preconditioning (RIPC) is an approach in which interspersed cycles of preconditioning ischemia is followed by reperfusion to tissues/organs to protect the distant target tissues/organs against subsequent lethal ischemic injuries. RIPC is an innovation of the treatment strategies that protect the organ from I/R injury. In this study, we review the morphological structure and function of the BSCB, the injury mechanism of BSCB resulting from spinal cord I/R, and the effect of RIPC on it.

  13. Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats.

    PubMed

    Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi

    2013-01-01

    This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (p<0.05) compared with the IR and ILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes.

  14. Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats.

    PubMed

    Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi

    2013-01-01

    This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (p<0.05) compared with the IR and ILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes. PMID:23936589

  15. Remote ischemic preconditioning for prevention of high-altitude diseases: fact or fiction?

    PubMed

    Berger, Marc Moritz; Macholz, Franziska; Mairbäurl, Heimo; Bärtsch, Peter

    2015-11-15

    Preconditioning refers to exposure to brief episodes of potentially adverse stimuli and protects against injury during subsequent exposures. This was first described in the heart, where episodes of ischemia/reperfusion render the myocardium resistant to subsequent ischemic injury, which is likely caused by reactive oxygen species (ROS) and proinflammatory processes. Protection of the heart was also found when preconditioning was performed in an organ different from the target, which is called remote ischemic preconditioning (RIPC). The mechanisms causing protection seem to include stimulation of nitric oxide (NO) synthase, increase in antioxidant enzymes, and downregulation of proinflammatory cytokines. These pathways are also thought to play a role in high-altitude diseases: high-altitude pulmonary edema (HAPE) is associated with decreased bioavailability of NO and increased generation of ROS, whereas mechanisms causing acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) seem to involve cytotoxic effects by ROS and inflammation. Based on these apparent similarities between ischemic damage and AMS, HACE, and HAPE, it is reasonable to assume that RIPC might be protective and improve altitude tolerance. In studies addressing high-altitude/hypoxia tolerance, RIPC has been shown to decrease pulmonary arterial systolic pressure in normobaric hypoxia (13% O2) and at high altitude (4,342 m). Our own results indicate that RIPC transiently decreases the severity of AMS at 12% O2. Thus preliminary studies show some benefit, but clearly, further experiments to establish the efficacy and potential mechanism of RIPC are needed.

  16. Myocardial protection by ischemic preconditioning: the influence of the composition of myocardial phospholipids.

    PubMed

    al Makdessi, S; Brändle, M; Ehrt, M; Sweidan, H; Jacob, R

    1995-04-12

    It was the aim of this study to investigate (1) whether preconditioning modifies the fatty acid (FA) composition of myocardial phospholipids (PL), (2) whether a previous modification of membrane PL composition by the administration of coconut oil or fish oil influences the preconditioning, and (3) to compare the protective effects of preconditioning to those of dietary fish oil. To this end, three groups of rats were given during 10 weeks either a standard diet, or a standard diet + 10% coconut oil, or a standard diet + 10% fish oil. The preconditioning was performed in situ in the anesthetized open-chest rats by 2 cycles of 3 min left anterior descending coronary artery occlusion and 10 min reperfusion. It was followed by a 40 min ischemia and a 60 min reperfusion. ECG was recorded and used for the continuous count of the salves of extrasystoles, ventricular flutter and fibrillation. These rhythm disturbances were subsequently added and evaluated as total arrhythmias. The FA of tissue PL were analyzed in a sample of the ischemic zone the size of which was determined by means of malachite green. Coconut oil diet (rich in saturated FA) modified slightly the myocardial PL by increasing oleic acid and decreasing linoleic acid and resulted in the highest incidence of arrhythmias. Fish oil diet had the opposite effect in modifying drastically the PLFA (replacement of the n-6 FA by the n-3 FA) and minimizing significantly the arrhythmias in comparison with the standard diet group.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. 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-α (TNF-α) 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-α 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-α expression. PMID:23685868

  18. DNA Content in Extracellular Vesicles Isolated from Porcine Coronary Venous Blood Directly after Myocardial Ischemic Preconditioning

    PubMed Central

    Rodsand, Pouria; Hellman, Urban; Waldenström, Anders; Lundholm, Marie; Ahrén, Dag; Biber, Björn; Ronquist, Gunnar; Haney, Michael

    2016-01-01

    Background Extracellular vesicles (EV) are nano-sized membranous structures released from most cells. They have the capacity to carry bioactive molecules and gene expression signals between cells, thus mediating intercellular communication. It is believed that EV confer protection after ischemic preconditioning (IPC). We hypothesize that myocardial ischemic preconditioning will lead to rapid alteration of EV DNA content in EV collected from coronary venous effluent. Materials and Methods In a porcine myocardial ischemic preconditioning model, EV were isolated from coronary venous blood before and after IPC by differential centrifugation steps culminating in preparative ultracentrifugation combined with density gradient ultracentrifugation. The EV preparation was validated, the DNA was extracted and further characterized by DNA sequencing followed by bioinformatics analysis. Results Porcine genomic DNA fragments representing each chromosome, including mitochondrial DNA sequences, were detected in EV isolated before and after IPC. There was no difference detected in the number of sequenced gene fragments (reads) or in the genomic coverage of the sequenced DNA fragments in EV isolated before and after IPC. Gene ontology analysis showed an enrichment of genes coding for ion channels, enzymes and proteins for basal metabolism and vesicle biogenesis and specific cardiac proteins. Conclusions This study demonstrates that porcine EV isolated from coronary venous blood plasma contain fragments of DNA from the entire genome, including the mitochondria. In this model we did not find specific qualitative or quantitative changes of the DNA content in EV collected immediately after an in vivo myocardial IPC provocation. This does not rule out the possibility that EV DNA content changes in response to myocardial IPC which could occur in a later time frame. PMID:27434143

  19. Ischemic Preconditioning Mediates Neuroprotection against Ischemia in Mouse Hippocampal CA1 Neurons by Inducing Autophagy

    PubMed Central

    Zhang, Xuebin; Huang, Huiling; Wang, Jin; Wang, Yajing; Tong, Xiaoguang; Wang, Jinhuan; Wu, Jialing

    2015-01-01

    The hippocampal CA1 region is sensitive to hypoxic and ischemic injury but can be protected by ischemic preconditioning (IPC). However, the mechanism through which IPC protects hippocampal CA1 neurons is still under investigation. Additionally, the role of autophagy in determining the fate of hippocampal neurons is unclear. Here, we examined whether IPC induced autophagy to alleviate hippocampal CA1 neuronal death in vitro and in vivo with oxygen glucose deprivation (OGD) and bilateral carotid artery occlusion (BCCAO) models. Survival of hippocampal neurons increased from 51.5% ± 6.3% in the non-IPC group (55 min of OGD) to 77.3% ± 7.9% in the IPC group (15 min of OGD, followed by 55 min of OGD 24 h later). The number of hippocampal CA1 layer neurons increased from 182 ± 26 cells/mm2 in the non-IPC group (20 min of BCCAO) to 278 ± 55 cells/mm2 in the IPC group (1 min × 3 BCCAO, followed by 20 min of BCCAO 24 h later). Akt phosphorylation and microtubule-associated protein light chain 3 (LC3)-II/LC3-I expression were increased in the preconditioning group. Moreover, the protective effects of IPC were abolished only by inhibiting the activity of autophagy, but not by blocking the activation of Akt in vitro. Using in vivo experiments, we found that LC3 expression was upregulated, accompanied by an increase in neuronal survival in hippocampal CA1 neurons in the preconditioning group. The neuroprotective effects of IPC on hippocampal CA1 neurons were completely inhibited by treatment with 3-MA. In contrast, hippocampal CA3 neurons did not show changes in autophagic activity or beneficial effects of IPC. These data suggested that IPC may attenuate ischemic injury in hippocampal CA1 neurons through induction of Akt-independent autophagy. PMID:26325184

  20. Indomethacin preconditioning induces ischemic tolerance by modifying zinc availability in the brain.

    PubMed

    Lee, Joo-Yong; Oh, Shin Bi; Hwang, Jung-Jin; Suh, Nayoung; Jo, Dong-Gyu; Kim, Jong S; Koh, Jae-Young

    2015-09-01

    Intracellular zinc overload causes neuronal injury during the course of neurological disorders, whereas mild levels of zinc are beneficial to neurons. Previous reports indicated that non-steroidal anti-inflammatory drugs, including indomethacin and aspirin, can reduce the risk of ischemic stroke. This study found that chronic pretreatment of rats with indomethacin, a non-selective cyclooxygenase inhibitor, provided tolerance to ischemic injuries in an animal model of stroke by eliciting moderate zinc elevation in neurons. Consecutive intraperitoneal injection of indomethacin (3mg/kg/day for 28 days) led to modest increases in intraneuronal zinc as well as synaptic zinc content, with no significant stimulation of neuronal death. Furthermore, indomethacin induced the expressions of intracellular zinc homeostatic and neuroprotective proteins, rendering the brain resistant against ischemic damages and improving neurological outcomes. However, administration of a zinc-chelator, N,N,N',N'-tetra(2-picolyl)ethylenediamine (TPEN; 15 mg/kg/day), immediately after indomethacin administration eliminated the beneficial actions of the drug. Therefore, indomethacin preconditioning can modulate intracellular zinc availability, contributing to ischemic tolerance in the brain after stroke.

  1. TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis.

    PubMed

    Zhou, Jun-Hao; Zhang, Tong-Tong; Song, Dan-Dan; Xia, Yun-Fei; Qin, Zheng-Hong; Sheng, Rui

    2016-01-01

    Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia-reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH), and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis. PMID:27256465

  2. TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis

    PubMed Central

    Zhou, Jun-Hao; Zhang, Tong-Tong; Song, Dan-Dan; Xia, Yun-Fei; Qin, Zheng-Hong; Sheng, Rui

    2016-01-01

    Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia-reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH), and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis. PMID:27256465

  3. Myths and Facts About the Effects of Ischemic Preconditioning on Performance.

    PubMed

    Marocolo, M; da Mota, G R; Simim, M A M; Appell Coriolano, H-J

    2016-02-01

    Although numerous studies have demonstrated the effect of ischemic preconditioning (IPC) in clinical application, the effectiveness of this procedure on performance and physiological variables is still debatable. Therefore a systematic review was performed, including a meta-analysis and evaluation of the quality of the papers that addressed this scope. The electronic databases of the National Library of Medicine (PubMed), Google Scholar (using [advanced search], [all fields]) and other online journals were searched, for the following descriptors: a) "ischemic preconditioning"; b) "blood flow" and "hyperemia"; c) "blood flow occlusion," combined with "exercise performance", "athletes", "exercise" and "performance". Relevant studies were included, if they conformed to strict pre-formulated criteria, excluding systematic review articles, meta-analyses and studies with only animals or non-healthy subjects. The 20 studies included had high quality scores (87%). The majority of the studies lacked statistical significance (P<0.05) for both performance and physiological variables when comparing IPC, placebo and control groups. Most studies showed that IPC has no significant influence on performance. The few studies with significant differences mainly described an improvement only in performance without altered physiological parameters. Therefore, the influence of IPC on performance is still unclear and physiologically highly debatable.

  4. A Clinical Experimental Model to Evaluate Analgesic Effect of Remote Ischemic Preconditioning in Acute Postoperative Pain

    PubMed Central

    Pereira, Francisco Elano Carvalho; Mello, Irene Lopes; Pimenta, Fernando Heladio de Oliveira Medeiros; Costa, Debora Maia; Wong, Deysi Viviana Tenazoa; Fernandes, Claudia Regina; Lima Junior, Roberto César; Gomes, Josenília M. Alves

    2016-01-01

    This study aims to evaluate the viability of a clinical model of remote ischemic preconditioning (RIPC) and its analgesic effects. It is a prospective study with twenty (20) patients randomly divided into two groups: control group and RIPC group. The opioid analgesics consumption in the postoperative period, the presence of secondary mechanical hyperalgesia, the scores of postoperative pain by visual analog scale, and the plasma levels interleukins (IL-6) were evaluated. The tourniquet applying after spinal anesthetic block was safe, producing no pain for all patients in the tourniquet group. The total dose of morphine consumption in 24 hours was significantly lower in RIPC group than in the control group (p = 0.0156). The intensity analysis of rest pain, pain during coughing and pain in deep breathing, showed that visual analogue scale (VAS) scores were significantly lower in RIPC group compared to the control group: p = 0.0087, 0.0119, and 0.0015, respectively. There were no differences between groups in the analysis of presence or absence of mechanical hyperalgesia (p = 0.0704) and in the serum levels of IL-6 dosage over time (p < 0.0001). This clinical model of remote ischemic preconditioning promoted satisfactory analgesia in patients undergoing conventional cholecystectomy, without changing serum levels of IL-6. PMID:27446611

  5. A Clinical Experimental Model to Evaluate Analgesic Effect of Remote Ischemic Preconditioning in Acute Postoperative Pain.

    PubMed

    Pereira, Francisco Elano Carvalho; Mello, Irene Lopes; Pimenta, Fernando Heladio de Oliveira Medeiros; Costa, Debora Maia; Wong, Deysi Viviana Tenazoa; Fernandes, Claudia Regina; Lima Junior, Roberto César; Gomes, Josenília M Alves

    2016-01-01

    This study aims to evaluate the viability of a clinical model of remote ischemic preconditioning (RIPC) and its analgesic effects. It is a prospective study with twenty (20) patients randomly divided into two groups: control group and RIPC group. The opioid analgesics consumption in the postoperative period, the presence of secondary mechanical hyperalgesia, the scores of postoperative pain by visual analog scale, and the plasma levels interleukins (IL-6) were evaluated. The tourniquet applying after spinal anesthetic block was safe, producing no pain for all patients in the tourniquet group. The total dose of morphine consumption in 24 hours was significantly lower in RIPC group than in the control group (p = 0.0156). The intensity analysis of rest pain, pain during coughing and pain in deep breathing, showed that visual analogue scale (VAS) scores were significantly lower in RIPC group compared to the control group: p = 0.0087, 0.0119, and 0.0015, respectively. There were no differences between groups in the analysis of presence or absence of mechanical hyperalgesia (p = 0.0704) and in the serum levels of IL-6 dosage over time (p < 0.0001). This clinical model of remote ischemic preconditioning promoted satisfactory analgesia in patients undergoing conventional cholecystectomy, without changing serum levels of IL-6. PMID:27446611

  6. 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...

  7. Effects of ischemic preconditioning on myocardium Caspase-3, SOCS-1, SOCS-3, TNF-α and IL-6 mRNA expression levels in myocardium IR rats.

    PubMed

    Ma, Jiangwei; Qiao, Zengyong; Xu, Biao

    2013-10-01

    The aim of this study was to characterise the effects of ischemic preconditioning (IP) on heart function parameters (ΔST and ΔT), activities of serum creatine kinase (CK), lactate dehydrogenase (LDH), and levels of serum nitric oxide (NO), malondialdehyde (MDA), and myocardium Caspase-3 mRNA, SOCS-1, SOCS-3, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression levels and Apoptosis index in myocardium IR rats. Results showed that ΔST and ΔST values in IP group were markedly lower than those in IR group. Compared with IR group, IP significantly (p < 0.01) decreased serum CK (0.83 ± 0.09 vs 1.36 ± 0.15), LDH (5613 ± 462 vs 7106 ± 492) activities and MDA (11.32 ± 1.05 vs 15.49 ± 1.26) level, increased the serum NO (86.39 ± 7.03 vs 53.77 ± 4.27) level in IR group. The IP induced a significant decreased in myocardium Caspase-3 mRNA (0.303 ± 0.021 vs 0.515 ± 0.022) gene expression (p < 0.01) compared to IR model group. The IP induced a significant decreased in myocardium SOCS-1 (0.241 ± 0.031 vs 0.596 ± 0.036), SOCS-3 (0.258 ± 0.031 vs 0.713 ± 0.057), TNF-α (0.137 ± 0.011 vs 0.427 ± 0.035) and IL-6 (0.314 ± 0.021 vs 0.719 ± 0.064) mRNA gene expression (p < 0.01) compared to IR model group. We conclude that IP is effective in the therapy of heart disease. These findings may have implications for the clinical development of preconditioning-based therapies for ischemic heart disease.

  8. A MultiCenter Pilot Randomized Controlled Trial of Remote Ischemic Preconditioning in Major Vascular Surgery.

    PubMed

    Healy, D A; Boyle, E; McCartan, D; Bourke, M; Medani, M; Ferguson, J; Yagoub, H; Bashar, K; O'Donnell, M; Newell, J; Canning, C; McMonagle, M; Dowdall, J; Cross, S; O'Daly, S; Manning, B; Fulton, G; Kavanagh, E G; Burke, P; Grace, P A; Moloney, M Clarke; Walsh, S R

    2015-11-01

    A pilot randomized controlled trial that evaluated the effect of remote ischemic preconditioning (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed.

  9. Ischemia-induced mitochondrial apoptosis is significantly attenuated by ischemic preconditioning.

    PubMed

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

    2009-09-01

    Ischemic preconditioning (IPC) represents an important adaptation of CNS to sub-lethal ischemia, which results in increased tolerance of CNS to the lethal ischemia. Ischemia-induced mitochondrial apoptosis is considered to be an important event leading to neuronal cell death after cerebral blood flow arrest. In presented study, we have determined the effect of IPC on ischemia/reperfusion-induced mitochondrial apoptosis. Global brain ischemia was induced by permanent occlusion of vertebral arteries and temporal occlusion of carotid arteries for 15 min. Rats were preconditioned by 5 min of sub-lethal ischemia and 2 days later 15 min of lethal ischemia was induced. With respect to mitochondrial apoptosis initiation, translocation of p53 to mitochondria was observed in hippocampus but not in cerebral cortex. However, level of both apoptotic bax and anti-apoptotic bcl-xl in both hippocampal and cortical mitochondria was unchanged after global brain ischemia. Detection of genomic DNA fragmentation as well as Fluoro-Jade C staining showed that ischemia induces apoptosis in vulnerable CA1 layer of rat hippocampus. IPC abolished completely ischemia-induced translocation of p53 to mitochondria and had significant protective effect on ischemia-induced DNA fragmentation. In addition, significant decrease of Fluoro-Jade C positive cells was observed as well. Our results indicate that IPC abolished almost completely both initiation and execution of mitochondrial apoptosis induced by global brain ischemia. PMID:19283470

  10. Remote ischemic preconditioning for cerebral and cardiac protection during carotid endarterectomy: results from a pilot randomized clinical trial.

    PubMed

    Walsh, Stewart R; Nouraei, S A; Tang, Tjun Y; Sadat, Umar; Carpenter, Roger H; Gaunt, Michael E

    2010-08-01

    Remote ischemic preconditioning (RIPC) is a physiological mechanism whereby brief ischemia-reperfusion episodes attenuate damage by subsequent prolonged ischemic insults. It reduces myocardial injury following cardiac and aortic aneurysm surgery. We aimed to determine whether RIPC affects neurological or cardiac injury following carotid endarterectomy (CEA). Patients were preconditioned using 10 minutes of lower limb ischemia-reperfusion. The primary neurological outcome was saccadic latency deterioration. The primary cardiac outcome measure was increased in serum troponin I >0.15 mg/dL. In all, 70 patients were randomized, of whom 55 completed the neurological surveillance protocol. Although there were fewer saccadic latency deteriorations in the RIPC arm, this did not reach statistical significance (32% versus 53%; P = .11). The primary cardiac outcome occurred in 1 patient in each arm (P = .97). There were no adverse events related to the preconditioning protocol. Remote ischemic preconditioning appears safe in patients with CEA. Large-scale trials are required to determine whether RIPC confers clinical benefits.

  11. Accumulation of natural killer cells in ischemic brain tissues and the chemotactic effect of IP-10

    PubMed Central

    2014-01-01

    Background Stroke is accompanied by a distinguished inflammatory reaction that is initiated by the infiltration of immunocytes, expression of cytokines, and other inflammatory mediators. As natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the innate immune system, we investigated the mechanism of NK cells-induced brain injuries after cerebral ischemia and the chemotactic effect of IP-10 simultaneously. Methods NK cells infiltration, interferon-gamma (IFN-γ) and IP-10 expression were detected by immunohistochemistry, immunofluorescence, PCR and flow cytometry in human and C57/BL6 wild type mouse ischemic brain tissues. The ischemia area was detected via 2,3,5-triphenyltetrazolium chloride staining. CXCR3 mean fluorescence intensity of isolated NK cells was measured by flow cytometry. The neuronal injury made by NK cells was examined via apoptosis experiment. The chemotactic of IP-10 was detected by migration and permeability assays. Results In human ischemic brain tissue, infiltrations of NK cells were observed and reached a peak at 2 to 5 days. In a permanent middle cerebral artery occlusion (pMCAO) model, infiltration of NK cells into the ischemic infarct region reached their highest levels 12 hours after ischemia. IFN-γ-positive NK cells and levels of the chemokine IP-10 were also detected within the ischemic region, from 6 hours up to 4 days after pMCAO was performed, and IFN-γ levels decreased after NK cells depletion in vivo. Co-culture experiments of neural cells with NK cells also showed that neural necrosis was induced via IFN-γ. In parallel experiments with IP-10, the presence of CXCR3 indicates that NK cells were affected by IP-10 via CXCR3, and the effect was dose-dependent. After IP-10 depletion in vivo, NK cells decreased. In migration assays and permeability experiments, disintegration of the blood–brain barrier (BBB) was observed following the addition of NK cells. Moreover, in the presence of IP-10 this injury

  12. Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning.

    PubMed

    Miyake, Shin-ichi; Wakita, Hideaki; Bernstock, Joshua D; Castri, Paola; Ruetzler, Christl; Miyake, Junko; Lee, Yang-Ja; Hallenbeck, John M

    2015-12-01

    Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, D-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented. Mammalian hibernation provides a valuable model of tolerance to ischemic stress. Herein, we demonstrate that marked reductions in the phosphorylation of ribosomal protein S6 (rpS6), extracellular signal-regulated kinase family of mitogen-activated protein (MAP) kinase p44/42 (p44/42MAPK) and ribosomal protein S6 kinase (S6K) occur within the brains of both hibernating squirrels and rats, which have undergone an ischemic

  13. Dilazep dihydrochloride prolongs the infarct size-limiting effect of ischemic preconditioning in rabbits.

    PubMed

    Yamasaki, K; Tanaka, M; Yokota, R; Fujiwara, H; Sasayama, S

    2000-01-01

    Recent studies have indicated the key role of adenosine receptor activation as a trigger for ischemic preconditioning (PC). Hence, the augmentation of endogenous adenosine may potentiate the cardioprotective effects of PC. In this study. we aimed to test the hypothesis that dilazep dihydrochloride, an adenosine transport inhibitor, potentiates the PC effect. Protocol 1: Infarcts were produced in open-chest anesthetized rabbits by 30-min occlusion of a coronary artery and 2 days' reperfusion. PC was elicited by a preceding 5-min occlusion and either 5, 40, or 120 min of reperfusion. PC with the 5-min reperfusion markedly limited the infarct size after the 30-min ischemia (infarct size to area at risk (IS): 10%+/-3% vs 41%+/-3%, P < 0.05). PC was not protective when the reperfusion periods were 40 or 120 min (IS: 47%+/-5% and 44%+/-3%. P = not significant (NS) vs control, respectively). However, concomitant treatment with dilazep (0.2mg/kg) preserved the PC effect in the 40-min reperfusion group (18%+/-5%, P < 0.05 vs control) but not in the 120-min reperfusion group (43%+/-4%, P = NS vs control). Protocol 2: Infarct was produced in a similar rabbit model by either a 45- or 50-min occlusion of a coronary artery and 2 days of reperfusion. PC was elicited by a preceding 5-min occlusion and a 5-min reperfusion. PC was protective in the 45-min occlusion group (30%+/-7% vs 67%+/-3%, P < 0.05) but not in the 50-min occlusion group (74%+/-4% vs 79%+/-5%, P = NS). Treatment with dilazep (0.2mg/kg) failed to retrieve protection in this preconditioned group (77%+/-6%, P = NS vs 50-min occlusion group without PC). Thus, dilazep prolonged the infarct size-limiting effect of PC, but failed to retrieve protection in the group with a longer sustained ischemia.

  14. Evidence for role of epoxyeicosatrienoic acids in mediating ischemic preconditioning and postconditioning in dog

    PubMed Central

    Gross, Garrett J.; Gauthier, Kathryn M.; Moore, Jeannine; Campbell, William B.; Falck, John R.; Nithipatikom, Kasem

    2009-01-01

    Cytochrome P-450 (CYP) epoxygenases and their arachidonic acid (AA) metabolites, the epoxyeicosatrienoic acids (EETs), have been shown to produce marked reductions in infarct size (IS) in canine myocardium either given before an ischemic insult or at reperfusion similar to that produced in ischemic preconditioning (IPC) and postconditioning (POC) protocols. However, no studies have addressed the possibility that EETs serve a beneficial role in IPC or POC. We tested the hypothesis that EETs may play a role in these two phenomena by preconditioning dog hearts with one 5-min period of total coronary occlusion followed by 10 min of reperfusion before 60 min of occlusion and 3 h of reperfusion or by postconditioning with three 30-s periods of reperfusion interspersed with three 30-s periods of occlusion. To test for a role of EETs in IPC and POC, the selective EET antagonists 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) or its derivative, 14,15-epoxyeicosa-5(Z)-enoic acid 2-[2-(3-hydroxy-propoxy)-ethoxy]-ethyl ester (14,15-EEZE-PEG), were administered 10 min before IPC, 5 min after IPC, or 5 min before POC. In a separate series, the selective EET synthesis inhibitor N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide (MS-PPOH) was administered 10 min before IPC. Infarct size was determined by tetrazolium staining and coronary collateral blood flow at 30 min of occlusion and reperfusion flow at 3 h by radioactive microspheres. Both IPC and POC produced nearly equivalent reductions in IS expressed as a percentage of the area at risk (AAR) [Control 21.2 ± 1.2%, IPC 8.3 ± 2.2%, POC 10.1 ± 1.8% (P < 0.001)]. 14,15-EEZE, 14,15-EEZE-PEG, and MS-PPOH markedly attenuated the cardioprotective effects of IPC and POC (14,15-EEZE and 14,15-EEZE-PEG) at doses that had no effect on IS/AAR when given alone. These results suggest a unique role for endogenous EETs in both IPC and POC. PMID:19448143

  15. Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles.

    PubMed

    Giricz, Zoltán; Varga, Zoltán V; Baranyai, Tamás; Sipos, Péter; Pálóczi, Krisztina; Kittel, Ágnes; Buzás, Edit I; Ferdinandy, Péter

    2014-03-01

    Remote ischemic preconditioning (RIPC) of the heart is exerted by brief ischemic insults affected on a remote organ or a remote area of the heart before a sustained cardiac ischemia. To date, little is known about the inter-organ transfer mechanisms of cardioprotection by RIPC. Exosomes and microvesicles/microparticles are vesicles of 30-100 nm and 100-1000 nm in diameter, respectively (collectively termed extracellular vesicles [EVs]). Their content of proteins, mRNAs and microRNAs, renders EV ideal conveyors of inter-organ communication. However, whether EVs are involved in RIPC, is unknown. Therefore, here we investigated whether (1) IPC induces release of EVs from the heart, and (2) EVs are necessary for cardioprotection by RIPC. Hearts of male Wistar rats were isolated and perfused in Langendorff mode. A group of donor hearts was exposed to 3 × 5-5 min global ischemia and reperfusion (IPC) or 30 min aerobic perfusion, while coronary perfusates were collected. Coronary perfusates of these hearts were given to another set of recipient isolated hearts. A group of recipient hearts received IPC effluent depleted of EVs by differential ultracentrifugation. Infarct size was determined after 30 min global ischemia and 120 min reperfusion. The presence or absence of EVs in perfusates was confirmed by dynamic light scattering, the EV marker HSP60 Western blot, and electron microscopy. IPC markedly increased EV release from the heart as assessed by HSP60. Administration of coronary perfusate from IPC donor hearts attenuated infarct size in non-preconditioned recipient hearts (12.9 ± 1.6% vs. 25.0 ± 2.7%), similarly to cardioprotection afforded by IPC (7.3 ± 2.7% vs. 22.1 ± 2.9%) on the donor hearts. Perfusates of IPC hearts depleted of EVs failed to exert cardioprotection in recipient hearts (22.0 ± 2.3%). This is the first demonstration that EVs released from the heart after IPC are necessary for cardioprotection by RIPC, evidencing the importance of vesicular

  16. Sympathetic nervous response to ischemia-reperfusion injury in humans is altered with remote ischemic preconditioning.

    PubMed

    Lambert, Elisabeth A; Thomas, Colleen J; Hemmes, Robyn; Eikelis, Nina; Pathak, Atul; Schlaich, Markus P; Lambert, Gavin W

    2016-08-01

    Sympathetic neural activation may be detrimentally involved in tissue injury caused by ischemia-reperfusion (IR). We examined the effects of experimental IR in the forearm on sympathetic nerve response, finger reactive hyperemia, and oxidative stress, and the protection afforded by applying remote ischemic preconditioning (RIPC). Ischemia was induced in the forearm for 20 min in healthy volunteers. RIPC was induced by applying two cycles, 5 min each, of ischemia and reperfusion to the upper leg immediately before IR. We examined muscle sympathetic nerve activity (MSNA) in the contralateral leg using microneurography, finger reactive hyperemia [ischemic reactive hyperemia index (RHI)], erythrocyte production of reduced gluthathione (GSH), and plasma nitric oxide (NO) concentration. In controls (no RIPC; n = 15), IR increased MSNA in the early and late phase of ischemia (70% at 5 min; 101% at 15 min). In subjects who underwent RIPC (n = 15), the increase in MSNA was delayed to the late phase of ischemia and increased only by 40%. GSH increased during ischemia in the control group (P = 0.05), but not in those who underwent RIPC. Nitrate and nitrite concentration, taken as an index of NO availability, decreased during the reperfusion period in control individuals (P < 0.05), while no change was observed in those who underwent RIPC. Experimental IR did not affect RHI in the control condition, but a significant vasodilatory response occurred in the RIPC group (P < 0.05). RIPC attenuated ischemia-induced sympathetic activation, prevented the production of an erythrocyte marker of oxidative stress and the reduction of NO availability, and ameliorated RHI. PMID:27288436

  17. Beneficial Effects of Ischemic Preconditioning in Resistance Exercise Fade Over Time.

    PubMed

    Marocolo, M; Marocolo, I C; da Mota, G R; Simão, R; Maior, A S; Coriolano, H-J Appell

    2016-09-01

    This study evaluated the effect of ischemic preconditioning (IPC) on resistance exercise performance in upper limbs. After 12-RM load determination, 21 men attended 4 trials separated by 3 days in a randomized crossover design: IPC (4×5-min occlusion 220 mmHg/reperfusion 0 mmHg) in arms and in thighs, and SHAM (equal to the IPC protocol but "occlusion" at 20 mmHg) in arms and in thighs. 8 min following the respective interventions, the subjects performed one set of resistance exercise in elbow flexion with the 12-RM load until concentric failure. The number of repetitions increased for both protocols in arm (IPC=14.1±2.5 and SHAM=14.4±3.0) and in thigh (IPC=14.3±2.2 and SHAM=13.4±1.7). However, the number of repetitions tended to decrease over the 4 trials and no more effect was found in the fourth trial. Therefore, IPC or SHAM may enhance performance in resistance exercise for upper limbs, but this effect apparently fades over time.

  18. Are the Beneficial Effects of Ischemic Preconditioning on Performance Partly a Placebo Effect?

    PubMed

    Marocolo, M; da Mota, G R; Pelegrini, V; Appell Coriolano, H J

    2015-10-01

    The acute effect of ischemic preconditioning (IPC) on the maximal performance in the 100-m freestyle event was studied in recreational swimmers. 15 swimmers (21.0±3.2 years) participated in a random crossover model on 3 different days (control [CON], IPC or SHAM), separated by 3-5 days. IPC consisted of 4 cycles of 5-min occlusion (220 mmHg)/5-min reperfusion in each arm, and the SHAM protocol was similar to IPC but with only 20 mmHg during the occlusion phase. The subjects were informed that both maneuvers (IPC and SHAM) would improve their performance. After IPC, CON or SHAM, the volunteers performed a maximal 100-m time trial. IPC improved performance (p=0.036) compared to CON. SHAM performance was only better than CON (p=0.059) as a tendency but did not differ from IPC performance. The individual response of the subjects to the different maneuvers was very heterogeneous. We conclude that IPC may improve performance in recreational swimmers, but this improvement could mainly be a placebo effect. PMID:26058479

  19. Consequences of Ischemic Preconditioning of Kidney: Comparing between Male and Female Rats

    PubMed Central

    Ebrahimi, Seyyed Meisam; Aboutaleb, Nahid; Nobakht, Maliheh

    2012-01-01

    Objective(s) Ischemia-reperfusion injury (IRI) is a leading cause of kidney transplantation failure, and ischemic-preconditioning (IPC) is a protective method against the IRI. In the present study, the defensive effect of IPC on rats’ kidney was investigated and more importantly the differences between two genders were appraised. Materials and Methods Thirty two Wistar rats were randomly allocated to four groups: group A (8 male IR), B (8 female IR), C (8 male IPC) and D (8 female IPC). Ischemia was induced by clamping of left renal arteries for 45 min in groups A and B. Rats in groups C and D experienced four cycles of 4 min arterial clamping followed by 11 min of de-clamping prior to the final 45 min of ischemia. 24 hr later, serum was provided to assess the blood urea nitrogen (BUN) and creatinine values. Also, renal tissues were obtained for histological measurements. Results Induction of IPC in both male and female rats led to significant decrease in creatinine levels in comparison with sham groups (P<0.01). The same results were seen in BUN levels (P<0.01). However, there were no significant difference between two genders. Besides, histological protective effects of IPC was proved especially in female rats (P<0.01). Conclusion Findings of our study confirmed that renal IPC reduces the damages in both genders especially females. Thus, the IPC procedure seems to be a useful method mainly in females. PMID:23653843

  20. Ischemic Preconditioning and Exercise Performance: A Systematic Review and Meta-Analysis.

    PubMed

    Salvador, Amadeo F; De Aguiar, Rafael A; Lisbôa, Felipe D; Pereira, Kayo L; Cruz, Rogério S; Caputo, Fabrizio

    2016-01-01

    Although the amount of evidence demonstrating the beneficial effects of ischemic preconditioning (IPC) on exercise performance is increasing, conclusions about its efficacy cannot yet be drawn. Therefore, the purposes of this review were to determine the effect of IPC on exercise performance and identify the effects of different IPC procedures, exercise types, and subject characteristics on exercise performance. The analysis comprised 19 relevant studies from 2000 to 2015, 15 of which were included in the meta-analyses. Effect sizes (ES) were calculated as the standardized mean difference. Overall, IPC had a small beneficial effect on exercise performance (ES = 0.43; 90% confidence interval [CI], 0.28 to 0.51). The largest ES were found for aerobic (ES = 0.51; 90% CI, 0.35 to 0.67) and anaerobic (ES = 0.23; 90% CI, -0.12 to 0.58) exercise. In contrast, an unclear effect was observed in power and sprint performance (ES = 0.16; 90% CI, -0.20 to 0.52). In conclusion, IPC can effectively enhance aerobic and anaerobic exercise performance.

  1. Impact of Ischemic Preconditioning on Outcome in Clinical Liver Surgery: A Systematic Review

    PubMed Central

    Chu, Michael J. J.; Vather, Ryash; Hickey, Anthony J. R.; Phillips, Anthony R. J.; Bartlett, Adam S. J. R.

    2015-01-01

    Background. Ischemia-reperfusion injury is a major cause of post-liver-surgery complications. Ischemic preconditioning (IPC) has been demonstrated to protect against ischemia-reperfusion injury. Clinical studies have examined IPC in liver surgery but with conflicting results. This systematic review aimed to evaluate the effects of IPC on outcome in clinical liver surgery. Methods. An electronic search of OVID Medline and Embase databases was performed to identify studies that reported outcomes in patients undergoing liver surgery subjected to IPC. Basic descriptive statistics were used to summarise data from individual clinical studies. Results. 1093 articles were identified, of which 24 met the inclusion criteria. Seven topics were selected and analysed by subgroup. There were 10 studies in cadaveric liver transplantation, 2 in living-related liver transplantation, and 12 in liver resection. IPC decreases hepatocellular damage in liver surgery as determined by transaminases but does not translate to any significant clinical benefit in orthotopic liver transplant or liver resection. Conclusions. Available clinical evidence does not support routine use of IPC in liver surgery as it does not offer any apparent benefit in perioperative outcome. Further clinical studies will need to be carried out to determine the subset of patients that will benefit from IPC. PMID:25756045

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

    PubMed Central

    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 (PKCɛ) 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 (PKCɛ activation) promoted BDNF-induced neuroprotection, if neuroprotection by IPC or PKCɛ 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 PKCɛ 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 PKCɛ activation in vivo, the onset of anoxic depolarization during OGD was significantly delayed in hippocampal slices. Overall, these results suggest that after IPC or PKCɛ activation, there are BDNF-dependent electrophysiologic modifications that lead to neuroprotection. PMID:25370861

  3. Astrocytic Toll-Like Receptor 3 Is Associated with Ischemic Preconditioning- Induced Protection against Brain Ischemia in Rodents

    PubMed Central

    Li, Yang; Xu, Xu-lin; Guo, Lian-jun; Lu, Qing; Wang, Jian

    2014-01-01

    Background Cerebral ischemic preconditioning (IPC) protects brain against ischemic injury. Activation of Toll-like receptor 3 (TLR3) signaling can induce neuroprotective mediators, but whether astrocytic TLR3 signaling is involved in IPC-induced ischemic tolerance is not known. Methods IPC was modeled in mice with three brief episodes of bilateral carotid occlusion. In vitro, IPC was modeled in astrocytes by 1-h oxygen-glucose deprivation (OGD). Injury and components of the TLR3 signaling pathway were measured after a subsequent protracted ischemic event. A neutralizing antibody against TLR3 was used to evaluate the role of TLR3 signaling in ischemic tolerance. Results IPC in vivo reduced brain damage from permanent middle cerebral artery occlusion in mice and increased expression of TLR3 in cortical astrocytes. IPC also reduced damage in isolated astrocytes after 12-h OGD. In astrocytes, IPC or 12-h OGD alone increased TLR3 expression, and 12-h OGD alone increased expression of phosphorylated NFκB (pNFκB). However, IPC or 12-h OGD alone did not alter the expression of Toll/interleukin receptor domain-containing adaptor-inducing IFNβ (TRIF) or phosphorylated interferon regulatory factor 3 (pIRF3). Exposure to IPC before OGD increased TRIF and pIRF3 expression but decreased pNFκB expression. Analysis of cytokines showed that 12-h OGD alone increased IFNβ and IL-6 secretion; 12-h OGD preceded by IPC further increased IFNβ secretion but decreased IL-6 secretion. Preconditioning with TLR3 ligand Poly I:C increased pIRF3 expression and protected astrocytes against ischemic injury; however, cells treated with a neutralizing antibody against TLR3 lacked the IPC- and Poly I:C-induced ischemic protection and augmentation of IFNβ. Conclusions The results suggest that IPC-induced ischemic tolerance is mediated by astrocytic TLR3 signaling. This reprogramming of TLR3 signaling by IPC in astrocytes may play an important role in suppression of the post-ischemic

  4. 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

  5. The Impact of Remote Ischemic Preconditioning on Arterial Stiffness and Heart Rate Variability in Patients with Angina Pectoris.

    PubMed

    Zagidullin, Naufal; Scherbakova, Elena; Safina, Yuliana; Zulkarneev, Rustem; Zagidullin, Shamil

    2016-01-01

    Remote ischemic preconditioning (RIPC) is the set of ischemia episodes that protects against subsequent periods of prolonged ischemia through the cascade of adaptive responses; however, the mechanisms of RIPC are not entirely clear. Here, we aimed to study the impact of RIPC in patients with stable angina pectoris and compare it with healthy individuals with respect to arterial stiffness and heart rate variability. In the randomized, sham-controlled, crossover blind design study, a group of 30 coronary heart disease (CHD) patients (63.9 ± 1.6 years) with stable angina pectoris NYHA II-III and a control group of 20 healthy individuals (58.2 ± 2.49) were both randomly allocated for remote RIPC or sham RIPC. Arterial stiffness, pulse wave velocity (Spygmacor, Australia), and heart rate variability (HRV) were recorded before and after the procedure followed by the crossover examination. In the group of healthy individuals, RIPC showed virtually no impact on the cardiovascular parameters, while, in the CHD group, the systolic and central systolic blood pressure, central pulse pressure, and augmentation decreased, and total power of HRV improved. We conclude that ischemic preconditioning reduces not only systolic blood pressure, but also reduces central systolic blood pressure and improves arterial compliance and heart rate modulation reserve, which may be associated with the antianginal effect of preconditioning. PMID:27348009

  6. The Impact of Remote Ischemic Preconditioning on Arterial Stiffness and Heart Rate Variability in Patients with Angina Pectoris

    PubMed Central

    Zagidullin, Naufal; Scherbakova, Elena; Safina, Yuliana; Zulkarneev, Rustem; Zagidullin, Shamil

    2016-01-01

    Remote ischemic preconditioning (RIPC) is the set of ischemia episodes that protects against subsequent periods of prolonged ischemia through the cascade of adaptive responses; however, the mechanisms of RIPC are not entirely clear. Here, we aimed to study the impact of RIPC in patients with stable angina pectoris and compare it with healthy individuals with respect to arterial stiffness and heart rate variability. In the randomized, sham-controlled, crossover blind design study, a group of 30 coronary heart disease (CHD) patients (63.9 ± 1.6 years) with stable angina pectoris NYHA II-III and a control group of 20 healthy individuals (58.2 ± 2.49) were both randomly allocated for remote RIPC or sham RIPC. Arterial stiffness, pulse wave velocity (Spygmacor, Australia), and heart rate variability (HRV) were recorded before and after the procedure followed by the crossover examination. In the group of healthy individuals, RIPC showed virtually no impact on the cardiovascular parameters, while, in the CHD group, the systolic and central systolic blood pressure, central pulse pressure, and augmentation decreased, and total power of HRV improved. We conclude that ischemic preconditioning reduces not only systolic blood pressure, but also reduces central systolic blood pressure and improves arterial compliance and heart rate modulation reserve, which may be associated with the antianginal effect of preconditioning. PMID:27348009

  7. The Impact of Remote Ischemic Preconditioning on Arterial Stiffness and Heart Rate Variability in Patients with Angina Pectoris.

    PubMed

    Zagidullin, Naufal; Scherbakova, Elena; Safina, Yuliana; Zulkarneev, Rustem; Zagidullin, Shamil

    2016-06-23

    Remote ischemic preconditioning (RIPC) is the set of ischemia episodes that protects against subsequent periods of prolonged ischemia through the cascade of adaptive responses; however, the mechanisms of RIPC are not entirely clear. Here, we aimed to study the impact of RIPC in patients with stable angina pectoris and compare it with healthy individuals with respect to arterial stiffness and heart rate variability. In the randomized, sham-controlled, crossover blind design study, a group of 30 coronary heart disease (CHD) patients (63.9 ± 1.6 years) with stable angina pectoris NYHA II-III and a control group of 20 healthy individuals (58.2 ± 2.49) were both randomly allocated for remote RIPC or sham RIPC. Arterial stiffness, pulse wave velocity (Spygmacor, Australia), and heart rate variability (HRV) were recorded before and after the procedure followed by the crossover examination. In the group of healthy individuals, RIPC showed virtually no impact on the cardiovascular parameters, while, in the CHD group, the systolic and central systolic blood pressure, central pulse pressure, and augmentation decreased, and total power of HRV improved. We conclude that ischemic preconditioning reduces not only systolic blood pressure, but also reduces central systolic blood pressure and improves arterial compliance and heart rate modulation reserve, which may be associated with the antianginal effect of preconditioning.

  8. Protective effect of ischemic preconditioning on the jejunal graft mucosa injury during cold preservation.

    PubMed

    Jonecova, Zuzana; Toth, Stefan; Maretta, Milan; Ciccocioppo, Rachele; Varga, Jan; Rodrigo, Luis; Kruzliak, Peter

    2015-10-01

    Protection of intestinal graft mucosa during cold preservation is still an unmet need in clinical practice, thus affecting the success of transplantation. The present study investigates the ability of two ischemic preconditioning (IPC) procedures to limit cold preservation injury. Three groups of Sprague-Dawley rats were recruited (n=11 each) as follows: the short IPC (SIPC) performed through 4 cycles of mesenteric ischemia of 4 min each followed by 10 min of reperfusion, the long IPC (LIPC) obtained by 2 ischemic cycles of 12 min each followed by 10 min of reperfusion, and the control group (C) without IPC. Grafts were then stored in cold histidine-tryptophan-ketoglutarate solution and samples were taken at 0, 3, 6 and 9 h lasting preservation. Both IPC groups showed an advanced degree of preservation with delayed development of graft mucosa damage, mainly in the crypt region. At the beginning of preservation, the graft mucosa in both IPC groups showed lower degree of mucosal injury index (MII) by 50% in comparison with C group. Specifically, a significant improvement of MII was observed after 3h of preservation in the LIPC group (p<0.05) in comparison with untreated C grafts. Significant atrophy of the intestinal mucosa in C group was found after 3h of preservation (p<0.01), in SIPC group the progress of atrophy was delayed to 6 h (p<0.001), and in LIPC group only moderate decrease in that was found. A parallel increase of laminin expression with the MII rate after 6 and 9h of preservation in comparison with the level at time 0 was observed in all grafts (p<0.001 and p<0.01, respectively). In both IPC groups the apoptotic cell (AC) rate was significantly reduced at the beginning of cold preservation (p<0.05 both). Moreover, in both the SIPC and C groups, the progressive increase in MII rate connected with AC rate decrease was due to a predominance of necrosis. By contrast in the LIPC group, after an increase of nearly 50% in the AC rate at the 3rd hour, its level

  9. Effect of one-cycle remote ischemic preconditioning to reduce myocardial injury during percutaneous coronary intervention.

    PubMed

    Zografos, Theodoros A; Katritsis, George D; Tsiafoutis, Ioannis; Bourboulis, Nikolaos; Katsivas, Apostolos; Katritsis, Demosthenes G

    2014-06-15

    Up to 1/3 of percutaneous coronary interventions (PCIs) are complicated by troponin release. Remote ischemic preconditioning (IPC) confers effective cardioprotection; however, a 30-minute remote IPC protocol may be difficult to implement during ad hoc PCI. This study was performed to assess the ability of a brief remote IPC protocol to attenuate cardiac troponin I (cTnI) release after ad hoc PCI. Ninety-four patients undergoing ad hoc PCI for stable coronary artery disease, with undetectable preprocedural cTnI, were recruited and randomized to receive remote IPC (induced by one 5-minute inflation of a blood pressure cuff to 200 mm Hg around the upper arm) or control after the decision for PCI was made. The primary outcome was the difference between cTnI levels 24 hours after PCI and cTnI levels before coronary angiography (ΔcTnI). ΔcTnI in the remote IPC group was significantly lower compared with the control group (0.04 ng/ml [interquartile range 0.01 to 0.14] vs 0.19 ng/ml [interquartile range 0.18 to 0.59], p <0.001). The incidence of PCI-related myocardial infarction (MI) was greater in the control group (42.6% vs 19.1%, p = 0.014). In multivariate analysis, remote IPC was independently associated with ΔcTnI and PCI-related MI. In conclusion, our results suggest that even 1 cycle of remote IPC immediately before ad hoc PCI attenuates periprocedural cTnI release and reduces the incidence of type 4a MI.

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

    PubMed

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

    2015-06-01

    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.

  11. Ischemic preconditioning increases muscle perfusion, oxygen uptake, and force in strength-trained athletes.

    PubMed

    Paradis-Deschênes, Pénélope; Joanisse, Denis R; Billaut, François

    2016-09-01

    Muscle ischemia and reperfusion induced by ischemic preconditioning (IPC) can improve performance in various activities. However, the underlying mechanisms are still poorly understood. The purpose of this study was to examine the effects of IPC on muscle hemodynamics and oxygen (O2) uptake during repeated maximal contractions. In a cross-over, randomized, single-blind study, 10 strength-trained men performed 5 sets of 5 maximal voluntary knee extensions of the right leg on an isokinetic dynamometer, preceded by either IPC of the right lower limb (3×5-min compression/5-min reperfusion cycles at 200 mm Hg) or sham (20 mm Hg). Changes in deoxyhemoglobin, expressed as a percentage of arterial occlusion, and total hemoglobin ([THb]) concentrations of the vastus lateralis muscle were monitored continuously by near-infrared spectroscopy. Differences between IPC and sham were analyzed using Cohen's effect size (ES) ± 90% confidence limits, and magnitude-based inferences. Compared with sham, IPC likely increased muscle blood volume at rest (↑[THb], 46.5%; ES, 0.56; 90% confidence limits for ES, -0.21, 1.32). During exercise, peak force was almost certainly higher (11.8%; ES, 0.37; 0.27, 0.47), average force was very likely higher (12.6%; ES, 0.47; 0.29, 0.66), and average muscle O2 uptake was possibly increased (15.8%; ES, 0.36; -0.07, 0.79) after IPC. In the recovery periods between contractions, IPC also increased blood volume after sets 1 (23.6%; ES, 0.30; -0.05, 0.65) and 5 (25.1%; ES, 0.32; 0.09, 0.55). Three cycles of IPC immediately increased muscle perfusion and O2 uptake, conducive to higher repeated force capacity in strength-trained athletes. This maneuver therefore appears relevant to enhancing exercise training stimulus. PMID:27574913

  12. Muscle microdialysis to confirm sublethal ischemia in the induction of remote ischemic preconditioning.

    PubMed

    Bilgin-Freiert, Arzu; Dusick, Joshua R; Stein, Nathan R; Etchepare, Maria; Vespa, Paul; Gonzalez, Nestor R

    2012-06-01

    Exposure of one tissue to ischemia-reperfusion confers a systemic protective effect, referred to as remote ischemic preconditioning (RIPC). Confirmation that the desired effect of ischemia is occurring in tissues used to induce RIPC requires an objective demonstration before this technique can be used consistently in the clinical practice. Enrolled patients underwent three to four RIPC sessions on non-consecutive days. Sessions consisted of 4 cycles of 5 min of leg cuff inflation to 30 mmHg above the systolic blood pressure followed by reperfusion. Absence of leg pulse was confirmed by Doppler evaluation. To evaluate limb transient ischemia, patients were monitored with muscle microdialysis. Glucose, lactate, lactate/pyruvate ratio, and glycerol levels were measured. Fourteen microdialysis sessions were performed in seven patients undergoing RIPC (42.8 % male; mean age, 51.8; Fisher grade 4 in all seven patients, Hunt and Hess grade 5 in five patients, four in one patient and one in one patient). An average follow-up of 29 days demonstrated no complications associated with the procedure. Muscle microdialysis during RIPC sessions showed a significant increase in lactate/pyruvate ratio (21.2 to 26.8, p = 0.001) and lactate (3.0 to 3.9 mmol/L, p = 0.002), indicating muscle ischemia. There was no significant variation in glycerol (234 to 204 μg/L, p = 0.43), indicating no permanent cell damage. The RIPC protocol used in this study is safe, well tolerated, and induces transient metabolic changes consistent with sublethal ischemia. Muscle microdialysis can be used safely as a confirmatory tool in the induction of RIPC. PMID:24323782

  13. Role of Endogenous Vitamin E in Renal Ischemic Preconditioning Process: Differences between Male and Female Rats

    PubMed Central

    Aryamanesh, Simin; Ebrahimi, Seyyed Meisam; Abotaleb, Nahid; Nobakht, Maliheh; Rahimi-Moghaddam, Parvaneh

    2012-01-01

    Background: Antioxidants such as α-tocopherol (vitamin E) and β-carotene (vitamin A) play an important role in protective effect of repeated brief periods of ischemia, namely ischemic preconditioning (IPC). Values of these antioxidants were investigated and compared after induction of ischemia reperfusion (IR) and kidney IPC in both male and female rats. Methods: Forty eight Wistar rats were divided randomly into six groups of 8: groups A and B (male and female controls, respectively), group C (male IR or IR cases), group D (female IR cases) and groups E and F (male and female IPC cases, respectively). In groups C and D, ischemia was induced by clamping of left renal arteries for 45 min. In groups E and F, rats underwent four cycles of 4 min of arterial clamping and 11 min of de-clamping before final 45 min ischemia induction. Afterward, serum was collected to assess the blood urea nitrogen, creatinine and vitamins E and A values. Renal tissues were obtained for histological assessments. Results: α-tocopherol levels in male and female rats showed a significant increase in IPC compared with IR group (P<0.01) and also in female IPC compared with male IPC group. β-carotene levels had no significant variations. Histological evaluation showed that IR-induced renal injuries were less in female rats. Also, protective effects of IPC were more in female rats (P<0.01). Conclusions: Renal IPC reduced damages in both male and female rats, but tissue injuries in females were decreased much more along with the increase of endogenous vitamin E. PMID:22562032

  14. Effects of remote ischemic preconditioning and myocardial ischemia on microRNA-1 expression in the rat heart in vivo.

    PubMed

    Brandenburger, Timo; Grievink, Hilbert; Heinen, Nicole; Barthel, Franziska; Huhn, Ragnar; Stachuletz, Friederike; Kohns, Malte; Pannen, Benedikt; Bauer, Inge

    2014-09-01

    Remote ischemic preconditioning (RIPC) is an easily applicable method for protecting the heart against a subsequent ischemia and reperfusion (I/R) injury. However, the exact molecular mechanisms underlying RIPC are unknown. We examined the involvement of microRNAs (miRNAs) and in particular the expression of miRNA-1 (miR-1) in RIPC and myocardial ischemia. Remote ischemic preconditioning was conducted by four cycles of 5-min bilateral hind-limb ischemia in male Wistar rats. Cardiac ischemia was induced by ligation of the left anterior descending coronary artery for 35 min followed by 2 or 6 h of reperfusion. MicroRNA expression was analyzed by Taqman miRNA arrays and quantitative polymerase chain reaction assays. Luciferase assays were performed to validate the miR-1 target gene brain-derived neurotrophic factor (BDNF). Brain-derived neurotrophic factor mRNA and protein levels were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Remote ischemic preconditioning led to a differential expression of miRNAs. The most abundant cardiac miRNA, miR-1, was downregulated by RIPC without following ischemia as well as after I/R and RIPC followed by I/R after 2 h of reperfusion. After 6 h of reperfusion, RIPC led to an upregulation of miR-1, whereas ischemia had no effect on miR-1 expression. Luciferase assays confirmed the interaction of miR-1 with BDNF, a protein that has been shown to exert cardioprotective effects. Brain-derived neurotrophic factor protein levels in rat hearts measured by enzyme-linked immunosorbent assay were not significantly altered after 2 or 6 h of reperfusion in all intervention groups. Remote ischemic preconditioning leads to changes in the expression levels of the most abundant cardiac miRNA, miR-1. MicroRNA 1 levels did not correlate with protein levels of BDNF, a known miR-1 target, in vivo. Further studies are needed to explore the biological significance of changes in miR-1 expression levels and the

  15. Effects of ischemic preconditioning on maximal constant-load cycling performance.

    PubMed

    Cruz, Rogério Santos de Oliveira; de Aguiar, Rafael Alves; Turnes, Tiago; Pereira, Kayo Leonardo; Caputo, Fabrizio

    2015-11-01

    This study investigated the effects of ischemic preconditioning (IPC) on the ratings of perceived exertion (RPE), surface electromyography, and pulmonary oxygen uptake (V̇o2) onset kinetics during cycling until exhaustion at the peak power output attained during an incremental test. A group of 12 recreationally trained cyclists volunteered for this study. After determination of peak power output during an incremental test, they were randomly subjected on different days to a performance protocol preceded by intermittent bilateral cuff pressure inflation to 220 mmHg (IPC) or 20 mmHg (control). To increase data reliability, the performance visits were replicated, also in a random manner. There was an 8.0% improvement in performance after IPC (control: 303 s, IPC 327 s, factor SDs of ×/÷1.13, P = 0.01). This change was followed by a 2.9% increase in peak V̇o2 (control: 3.95 l/min, IPC: 4.06 l/min, factor SDs of ×/÷1.15, P = 0.04), owing to a higher amplitude of the slow component of the V̇o2 kinetics (control: 0.45 l/min, IPC: 0.63 l/min, factor SDs of ×/÷2.21, P = 0.05). There was also an attenuation in the rate of increase in RPE (P = 0.01) and a progressive increase in the myoelectrical activity of the vastus lateralis muscle (P = 0.04). Furthermore, the changes in peak V̇o2 (r = 0.73, P = 0.007) and the amplitude of the slow component (r = 0.79, P = 0.002) largely correlated with performance improvement. These findings provide a link between improved aerobic metabolism and enhanced severe-intensity cycling performance after IPC. Furthermore, the delayed exhaustion after IPC under lower RPE and higher skeletal muscle activation suggest they have a role on the ergogenic effects of IPC on endurance performance.

  16. Effects of ischemic preconditioning on maximal constant-load cycling performance.

    PubMed

    Cruz, Rogério Santos de Oliveira; de Aguiar, Rafael Alves; Turnes, Tiago; Pereira, Kayo Leonardo; Caputo, Fabrizio

    2015-11-01

    This study investigated the effects of ischemic preconditioning (IPC) on the ratings of perceived exertion (RPE), surface electromyography, and pulmonary oxygen uptake (V̇o2) onset kinetics during cycling until exhaustion at the peak power output attained during an incremental test. A group of 12 recreationally trained cyclists volunteered for this study. After determination of peak power output during an incremental test, they were randomly subjected on different days to a performance protocol preceded by intermittent bilateral cuff pressure inflation to 220 mmHg (IPC) or 20 mmHg (control). To increase data reliability, the performance visits were replicated, also in a random manner. There was an 8.0% improvement in performance after IPC (control: 303 s, IPC 327 s, factor SDs of ×/÷1.13, P = 0.01). This change was followed by a 2.9% increase in peak V̇o2 (control: 3.95 l/min, IPC: 4.06 l/min, factor SDs of ×/÷1.15, P = 0.04), owing to a higher amplitude of the slow component of the V̇o2 kinetics (control: 0.45 l/min, IPC: 0.63 l/min, factor SDs of ×/÷2.21, P = 0.05). There was also an attenuation in the rate of increase in RPE (P = 0.01) and a progressive increase in the myoelectrical activity of the vastus lateralis muscle (P = 0.04). Furthermore, the changes in peak V̇o2 (r = 0.73, P = 0.007) and the amplitude of the slow component (r = 0.79, P = 0.002) largely correlated with performance improvement. These findings provide a link between improved aerobic metabolism and enhanced severe-intensity cycling performance after IPC. Furthermore, the delayed exhaustion after IPC under lower RPE and higher skeletal muscle activation suggest they have a role on the ergogenic effects of IPC on endurance performance. PMID:26359484

  17. 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.

  18. p-ERK involvement in the neuroprotection exerted by ischemic preconditioning in rat hippocampus subjected to four vessel occlusion.

    PubMed

    Kovalska, M; Kovalska, L; Mikuskova, K; Adamkov, M; Tatarkova, Z; Lehotsky, J

    2014-12-01

    Global brain ischemia-reperfusion causes delayed cell death in hippocampal CA1 (cornus ammonis 1) pyramidal neurons after reperfusion. Ischemic tolerance evoked by preconditioning (IPC) represents a phenomenon of CNS adaptation to any subsequent ischemia. This paper was designed to describe changes in the mitogen-activated protein kinases (MAPK) protein pathways of the hippocampal area following by IPC. Ischemia was induced by a 4-vessels occlusion (4VO) and the rats were preconditioned by a non-injurious ischemia. Apoptotic markers were used to follow the degeneration process. Western blot and immunohistochemistry identified p-ERK (phosphorylated extracellular signal-regulated protein kinase) and p38 proteins in injured hippocampal areas. P-ERK quantification increased after IPC and reached the highest level at 24 hours after ischemia. Interestingly, neuroprotection induced by IPC lead to the opposite effect on MAPK/p38, where the level was lowest at 24 hours after ischemia. Taken together, the present study clearly demonstrates that p-ERK takes part in complex cascades triggered by IPC in the selectively vulnerable hippocampal region. In addition, paper describes a crosstalk between p-ERK and p-p38 which occurs after preconditioning maneuver in 4VO model of global ischemia. PMID:25554980

  19. The Loss of Myocardial Benefit following Ischemic Preconditioning Is Associated with Dysregulation of Iron Homeostasis in Diet-Induced Diabetes

    PubMed Central

    Berenshtein, Eduard; Eliashar, Ron; Chevion, Mordechai

    2016-01-01

    Whether the diabetic heart benefits from ischemic preconditioning (IPC), similar to the non-diabetic heart, is a subject of controversy. We recently proposed new roles for iron and ferritin in IPC-protection in Type 1-like streptozotocin-induced diabetic rat heart. Here, we investigated iron homeostasis in Cohen diabetic sensitive rat (CDs) that develop hyperglycemia when fed on a high-sucrose/low-copper diet (HSD), but maintain normoglycemia on regular-diet (RD). Control Cohen-resistant rats (CDr) maintain normoglycemia on either diet. The IPC procedure improved the post-ischemic recovery of normoglycemic hearts (CDr-RD, CDr-HSD and CDs-RD). CDs-HSD hearts failed to show IPC-associated protection. The recovery of these CDs-HSD hearts following I/R (without prior IPC) was better than their RD controls. During IPC ferritin levels increased in normoglycemic hearts, and its level was maintained nearly constant during the subsequent prolonged ischemia, but decayed to its baseline level during the reperfusion phase. In CDs-HSD hearts the baseline levels of ferritin and ferritin-saturation with iron were notably higher than in the controls, and remained unchanged during the entire experiment. This unique and abnormal pattern of post-ischemic recovery of CDs-HSD hearts is associated with marked changes in myocardial iron homeostasis, and suggests that iron and iron-proteins play a causative role/s in the etiology of diabetes-associated cardiovascular disorders. PMID:27458721

  20. The Loss of Myocardial Benefit following Ischemic Preconditioning Is Associated with Dysregulation of Iron Homeostasis in Diet-Induced Diabetes.

    PubMed

    Vinokur, Vladimir; Weksler-Zangen, Sarah; Berenshtein, Eduard; Eliashar, Ron; Chevion, Mordechai

    2016-01-01

    Whether the diabetic heart benefits from ischemic preconditioning (IPC), similar to the non-diabetic heart, is a subject of controversy. We recently proposed new roles for iron and ferritin in IPC-protection in Type 1-like streptozotocin-induced diabetic rat heart. Here, we investigated iron homeostasis in Cohen diabetic sensitive rat (CDs) that develop hyperglycemia when fed on a high-sucrose/low-copper diet (HSD), but maintain normoglycemia on regular-diet (RD). Control Cohen-resistant rats (CDr) maintain normoglycemia on either diet. The IPC procedure improved the post-ischemic recovery of normoglycemic hearts (CDr-RD, CDr-HSD and CDs-RD). CDs-HSD hearts failed to show IPC-associated protection. The recovery of these CDs-HSD hearts following I/R (without prior IPC) was better than their RD controls. During IPC ferritin levels increased in normoglycemic hearts, and its level was maintained nearly constant during the subsequent prolonged ischemia, but decayed to its baseline level during the reperfusion phase. In CDs-HSD hearts the baseline levels of ferritin and ferritin-saturation with iron were notably higher than in the controls, and remained unchanged during the entire experiment. This unique and abnormal pattern of post-ischemic recovery of CDs-HSD hearts is associated with marked changes in myocardial iron homeostasis, and suggests that iron and iron-proteins play a causative role/s in the etiology of diabetes-associated cardiovascular disorders. PMID:27458721

  1. 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...

  2. Determinants of the Efficacy of Cardiac Ischemic Preconditioning: A Systematic Review and Meta-Analysis of Animal Studies

    PubMed Central

    Wever, Kimberley E.; Hooijmans, Carlijn R.; Riksen, Niels P.; Sterenborg, Thomas B.; Sena, Emily S.; Ritskes-Hoitinga, Merel; Warlé, Michiel C.

    2015-01-01

    Background Ischemic preconditioning (IPC) of the heart is a protective strategy in which a brief ischemic stimulus immediately before a lethal ischemic episode potently limits infarct size. Although very promising in animal models of myocardial infarction, IPC has not yet been successfully translated to benefit for patients. Objective To appraise all preclinical evidence on IPC for myocardial infarction and identify factors hampering translation. Methods and results Using systematic review and meta-analysis, we identified 503 animal studies reporting infarct size data from 785 comparisons between IPC-treated and control animals. Overall, IPC reduced myocardial infarction by 24.6% [95%CI 23.5, 25.6]. Subgroup analysis showed that IPC efficacy was reduced in comorbid animals and non-rodents. Efficacy was highest in studies using 2–3 IPC cycles applied <45 minutes before myocardial infarction. Local and remote IPC were equally effective. Reporting of study quality indicators was low: randomization, blinding and a sample size calculation were reported in 49%, 11% and 2% of publications, respectively. Conclusions Translation of IPC to the clinical setting may be hampered by the observed differences between the animals used in preclinical IPC studies and the patient population, regarding comorbidity, sex and age. Furthermore, the IPC protocols currently used in clinical trials could be optimized in terms of timing and the number of ischemic cycles applied. In order to inform future clinical trials successfully, future preclinical studies on IPC should aim to maximize both internal and external validity, since poor methodological quality may limit the value of the preclinical evidence. PMID:26580958

  3. Isoflurane Preconditioning Induces Neuroprotection by Up-Regulation of TREK1 in a Rat Model of Spinal Cord Ischemic Injury

    PubMed Central

    Wang, Kun; Kong, Xiangang

    2016-01-01

    This study aimed to explore the neuroprotection and mechanism of isoflurane on rats with spinal cord ischemic injury. Total 40 adult male Sprague-Dawley rats were divided into the four groups (n=10). Group A was sham-operation group; group B was ischemia group; group C was isoflurane preconditioning group; group D was isoflurane preconditioning followed by ischemia treatment group. Then the expressions of TWIK-related K+ channel 1 (TREK1) in the four groups were detected by immunofluorescent assay, real time-polymerase chain reactions (RT-PCR) and western blot. The primary neurons of rats were isolated and cultured under normal and hypoxic conditions. Besides, the neurons under two conditions were transfected with green fluorescent protein (GFP)-TREK1 and lentivirual to overexpress and silence TREK1. Additionally, the neurons were treated with isoflurane or not. Then caspase-3 activity and cell cycle of neurons under normal and hypoxic conditions were detected. Furthermore, nicotinamide adenine dinucleotide hydrate (NADH) was detected using NAD+/NADH quantification colorimetric kit. Results showed that the mRNA and protein expressions of TREK1 increased significantly in group C and D. In neurons, when TREK1 silenced, isoflurane treatment improved the caspase-3 activity. In hypoxic condition, the caspase-3 activity and sub-G1 cell percentage significantly increased, however, when TREK1 overexpressed the caspase-3 activity and sub-G1 cell percentage decreased significantly. Furthermore, both isoflurane treatment and overexpression of TREK1 significantly decreased NADH. In conclusion, isoflurane-induced neuroprotection in spinal cord ischemic injury may be associated with the up-regulation of TREK1. PMID:27469140

  4. Cardioprotective Effect of Extended Remote Ischemic Preconditioning in Patients Undergoing Coronary Artery Bypass Grafting : A Randomized Clinical Trial

    PubMed Central

    Karami, Ali; Khosravi, Mohamad Bagher; Shafa, Masih; Azemati, Simin; Khademi, Saeed; Akhlagh, Seyed Hedayatalla; Maghsodi, Behzad

    2016-01-01

    Background: The cardioprotective effect of ischemic preconditioning has been known for many years. Since the temporary ischemia in the heart may cause lethal cardiac effects, the idea of creating ischemia in organs far from the heart such as limbs was raised as remote ischemic preconditioning (RIPC). We hypothesized that the extension of RIPC has more cardioprotective effect in patients undergoing coronary artery bypass graft (CABG) surgeries. Methods: In this triple-blind randomized clinical trial study, 96 patients were randomly divided into 3 groups and two blood pressure cuffs were placed on both upper and lower extremities. In group A, only upper extremity cuff and in group B upper limb and lower limb cuff was inflated intermittently and group C was the control group. RIPC was induced with three 5-min cycles of cuff inflation about 100 mmHg over the initial systolic blood pressure before starting cardiopulmonary bypass. The primary endpoints were troponin I and creatine phosphokinase-myoglobin isoenzyme (CK-MB). Results: Six hours after the termination of CPB, there was a peak release of the troponin I level in all groups (group A=4.90 ng/ml, group B=4.40 ng/ml, and group C=4.50 ng/ml). There was a rise in plasma CK-MB in all groups postoperatively and there were not any significant differences in troponin I and CK-MB release between the three groups. Conclusion: RIPC induced by upper and lower limb ischemia does not reduce postoperative myocardial enzyme elevation in adult patients undergoing CABG. Trial Registration Number: IRCT2012071710311N1 PMID:27365547

  5. Isoflurane Preconditioning Induces Neuroprotection by Up-Regulation of TREK1 in a Rat Model of Spinal Cord Ischemic Injury.

    PubMed

    Wang, Kun; Kong, Xiangang

    2016-09-01

    This study aimed to explore the neuroprotection and mechanism of isoflurane on rats with spinal cord ischemic injury. Total 40 adult male Sprague-Dawley rats were divided into the four groups (n=10). Group A was sham-operation group; group B was ischemia group; group C was isoflurane preconditioning group; group D was isoflurane preconditioning followed by ischemia treatment group. Then the expressions of TWIK-related K⁺ channel 1 (TREK1) in the four groups were detected by immunofluorescent assay, real time-polymerase chain reactions (RT-PCR) and western blot. The primary neurons of rats were isolated and cultured under normal and hypoxic conditions. Besides, the neurons under two conditions were transfected with green fluorescent protein (GFP)-TREK1 and lentivirual to overexpress and silence TREK1. Additionally, the neurons were treated with isoflurane or not. Then caspase-3 activity and cell cycle of neurons under normal and hypoxic conditions were detected. Furthermore, nicotinamide adenine dinucleotide hydrate (NADH) was detected using NAD+/NADH quantification colorimetric kit. Results showed that the mRNA and protein expressions of TREK1 increased significantly in group C and D. In neurons, when TREK1 silenced, isoflurane treatment improved the caspase-3 activity. In hypoxic condition, the caspase-3 activity and sub-G1 cell percentage significantly increased, however, when TREK1 overexpressed the caspase-3 activity and sub-G1 cell percentage decreased significantly. Furthermore, both isoflurane treatment and overexpression of TREK1 significantly decreased NADH. In conclusion, isoflurane-induced neuroprotection in spinal cord ischemic injury may be associated with the up-regulation of TREK1. PMID:27469140

  6. AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay

    PubMed Central

    Gersch, Robert P.; Fourman, Mitchell S.; Phillips, Brett T.; Nasser, Ahmed; McClain, Steve A.; Khan, Sami U.; Dagum, Alexander B.

    2015-01-01

    Background: Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Methods: Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (109 pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. Results: AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm2, P < 0.01 and 12.4 ± 1.2 cm2, P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm2). Conclusions: AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not. PMID:26495207

  7. Remote Liver Ischemic Preconditioning Protects against Sudden Cardiac Death via an ERK/GSK-3β-Dependent Mechanism

    PubMed Central

    Hu, Zhaoyang; Hu, Sheng; Yang, Shuai; Chen, Mou; Zhang, Ping; Liu, Jin; Abbott, Geoffrey W.

    2016-01-01

    Background Preconditioning stimuli conducted in remote organs can protect the heart against subsequent ischemic injury, but effects on arrhythmogenesis and sudden cardiac death (SCD) are unclear. Here, we investigated the effect of remote liver ischemia preconditioning (RLIPC) on ischemia/reperfusion (I/R)-induced cardiac arrhythmia and sudden cardiac death (SCD) in vivo, and determined the potential role of ERK/GSK-3βsignaling. Methods/Results Male Sprague Dawley rats were randomized to sham-operated, control, or RLIPC groups. RLIPC was induced by alternating four 5-minute cycles of liver ischemia with 5-minute intermittent reperfusions. To investigate I/R-induced arrhythmogenesis, hearts in each group were subsequently subjected to 5-minute left main coronary artery ligation followed by 20-minute reperfusion. RLIPC reduced post-I/R ventricular arrhythmias, and decreased the incidence of SCD >threefold. RLIPC increased phosphorylation of cardiac ERK1/2, and GSK-3β Ser9 but not Tyr216 post-I/R injury. Inhibition of either GSK-3β (with SB216763) or ERK1/2 (with U0126) abolished RLIPC-induced antiarrhythmic activity and GSK-3β Ser9 and ERK1/2 phosphorylation, leaving GSK-3β Tyr216 phosphorylation unchanged. Conclusions RLIPC exerts a powerful antiarrhythmic effect and reduces predisposition to post-IR SCD. The underlying mechanism of RLIPC cardioprotection against I/R-induced early arrhythmogenesis may involve ERK1/2/GSK-3β Ser9-dependent pathways. PMID:27768739

  8. Improved resistance to ischemia and reperfusion, but impaired protection by ischemic preconditioning in patients with type 1 diabetes mellitus: a pilot study

    PubMed Central

    2012-01-01

    Background In patients with type 1 diabetes mellitus (T1DM), cardiovascular events are more common, and the outcome following a myocardial infarction is worse than in nondiabetic subjects. Ischemic or pharmacological preconditioning are powerful interventions to reduce ischemia reperfusion (IR)-injury. However, animal studies have shown that the presence of T1DM can limit these protective effects. Therefore, we aimed to study the protective effect of ischemic preconditioning in patients with T1DM, and to explore the role of plasma insulin and glucose on this effect. Methods 99mTechnetium-annexin A5 scintigraphy was used to detect IR-injury. IR-injury was induced by unilateral forearm ischemic exercise. At reperfusion, Tc-annexin A5 was administered, and IR-injury was expressed as the percentage difference in radioactivity in the thenar muscle between the experimental and control arm 4 hours after reperfusion. 15 patients with T1DM were compared to 21 nondiabetic controls. The patients were studied twice, with or without ischemic preconditioning (10 minutes of forearm ischemia and reperfusion). Patients were studied in either normoglycemic hyperinsulinemic conditions (n = 8) or during hyperglycemic normoinsulinemia (n = 7). The controls were studied once either with (n = 8) or without (n = 13) ischemic preconditioning. Results Patients with diabetes were less vulnerable to IR-injury than nondiabetic healthy controls (12.8 ± 2.4 and 11.0 ± 5.1% versus 27.5 ± 4.5% in controls; p < 0.05). The efficacy of ischemic preconditioning to reduce IR-injury, however, was lower in the patients and was even completely abolished during hyperglycemia. Conclusions Patients with T1DM are more tolerant to forearm IR than healthy controls in our experimental model. The efficacy of ischemic preconditioning to limit IR-injury, however, is reduced by acute hyperglycemia. Trial Registration The study is registered at www.clinicaltrials.gov (NCT00184821

  9. Maintenance of anti-inflammatory cytokines and reduction of glial activation in the ischemic hippocampal CA1 region preconditioned with lipopolysaccharide.

    PubMed

    Yu, Jia Tian; Lee, Choong Hyun; Yoo, Ki-Yeon; Choi, Jung Hoon; Li, Hua; Park, Ok Kyu; Yan, Bingchun; Hwang, In Koo; Kwon, Young-Guen; Kim, Young-Myeong; Won, Moo-Ho

    2010-09-15

    Lipopolysaccharide (LPS) induces a strong immune response, and pretreatment with low dose of LPS suppresses the production of proinflammatory mediators. In the present study, we investigated the effect of LPS preconditioning on the delayed neuronal death in the gerbil hippocampal CA1 region after 5 min of transient cerebral ischemia. LPS preconditioning showed neuroprotective effects against ischemic damage in the hippocampal CA1 region after ischemic insult: about 92% of neurons in the CA1 region survived in the LPS-treated ischemia group. LPS preconditioning maintained anti-inflammatory cytokines, such as interleukin (IL)-4 and IL-13, in pyramidal neurons in the CA1 region after ischemia/reperfusion. In addition, IL-4 and IL-13 protein levels in the CA1 region of the LPS-treated ischemia group were similar to the vehicle-treated sham group. We found that reactive gliosis was markedly attenuated in the CA1 region of the LPS-treated ischemia group compared to the vehicle-treated ischemia group using immunohistochemistry of glial fibrillary acidic protein for astrocytes, and ionized calcium-binding adapter molecule 1 and isolectin B4 for microglia. These results indicate that LPS preconditioning may provide neuroprotection in the ischemic hippocampal CA1 region via maintenance of anti-inflammatory cytokines and suppression of glial activation.

  10. Effect of ischemic preconditioning on antioxidant status in the gerbil hippocampal CA1 region after transient forebrain ischemia.

    PubMed

    Park, Seung Min; Park, Chan Woo; Lee, Tae-Kyeong; Cho, Jeong Hwi; Park, Joon Ha; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich-Na; Ahn, Ji Hyeon; Tae, Hyun-Jin; Shin, Myoung Cheol; Ohk, Taek Geun; Cho, Jun Hwi; Won, Moo-Ho; Choi, Soo Young; Kim, In Hye

    2016-07-01

    Ischemic preconditioning (IPC) is a condition of sublethal transient global ischemia and exhibits neuroprotective effects against subsequent lethal ischemic insult. We, in this study, examined the neuroprotective effects of IPC and its effects on immunoreactive changes of antioxidant enzymes including superoxide dismutase (SOD) 1 and SOD2, catalase (CAT) and glutathione peroxidase (GPX) in the gerbil hippocampal CA1 region after transient forebrain ischemia. Pyramidal neurons of the stratum pyramidale (SP) in the hippocampal CA1 region of animals died 5 days after lethal transient ischemia without IPC (8.6% (ratio of remanent neurons) of the sham-operated group); however, IPC prevented the pyramidal neurons from subsequent lethal ischemic injury (92.3% (ratio of remanent neurons) of the sham-operated group). SOD1, SOD2, CAT and GPX immunoreactivities in the sham-operated animals were easily detected in pyramidal neurons in the stratum pyramidale (SP) of the hippocampal CA1 region, while all of these immunoreactivities were rarely detected in the stratum pyramidale at 5 days after lethal transient ischemia without IPC. Meanwhile, their immunoreactivities in the sham-operated animals with IPC were similar to (SOD1, SOD2 and CAT) or higher (GPX) than those in the sham-operated animals without IPC. Furthermore, their immunoreactivities in the stratum pyramidale of the ischemia-operated animals with IPC were steadily maintained after lethal ischemia/reperfusion. Results of western blot analysis for SOD1, SOD2, CAT and GPX were similar to immunohistochemical data. In conclusion, IPC maintained or increased the expression of antioxidant enzymes in the stratum pyramidale of the hippocampal CA1 region after subsequent lethal transient forebrain ischemia and IPC exhibited neuroprotective effects in the hippocampal CA1 region against transient forebrain ischemia. PMID:27630689

  11. Effect of ischemic preconditioning on antioxidant status in the gerbil hippocampal CA1 region after transient forebrain ischemia

    PubMed Central

    Park, Seung Min; Park, Chan Woo; Lee, Tae-Kyeong; Cho, Jeong Hwi; Park, Joon Ha; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich-Na; Ahn, Ji Hyeon; Tae, Hyun-Jin; Shin, Myoung Cheol; Ohk, Taek Geun; Cho, Jun Hwi; Won, Moo-Ho; Choi, Soo Young; Kim, In Hye

    2016-01-01

    Ischemic preconditioning (IPC) is a condition of sublethal transient global ischemia and exhibits neuroprotective effects against subsequent lethal ischemic insult. We, in this study, examined the neuroprotective effects of IPC and its effects on immunoreactive changes of antioxidant enzymes including superoxide dismutase (SOD) 1 and SOD2, catalase (CAT) and glutathione peroxidase (GPX) in the gerbil hippocampal CA1 region after transient forebrain ischemia. Pyramidal neurons of the stratum pyramidale (SP) in the hippocampal CA1 region of animals died 5 days after lethal transient ischemia without IPC (8.6% (ratio of remanent neurons) of the sham-operated group); however, IPC prevented the pyramidal neurons from subsequent lethal ischemic injury (92.3% (ratio of remanent neurons) of the sham-operated group). SOD1, SOD2, CAT and GPX immunoreactivities in the sham-operated animals were easily detected in pyramidal neurons in the stratum pyramidale (SP) of the hippocampal CA1 region, while all of these immunoreactivities were rarely detected in the stratum pyramidale at 5 days after lethal transient ischemia without IPC. Meanwhile, their immunoreactivities in the sham-operated animals with IPC were similar to (SOD1, SOD2 and CAT) or higher (GPX) than those in the sham-operated animals without IPC. Furthermore, their immunoreactivities in the stratum pyramidale of the ischemia-operated animals with IPC were steadily maintained after lethal ischemia/reperfusion. Results of western blot analysis for SOD1, SOD2, CAT and GPX were similar to immunohistochemical data. In conclusion, IPC maintained or increased the expression of antioxidant enzymes in the stratum pyramidale of the hippocampal CA1 region after subsequent lethal transient forebrain ischemia and IPC exhibited neuroprotective effects in the hippocampal CA1 region against transient forebrain ischemia. PMID:27630689

  12. Effect of ischemic preconditioning on antioxidant status in the gerbil hippocampal CA1 region after transient forebrain ischemia

    PubMed Central

    Park, Seung Min; Park, Chan Woo; Lee, Tae-Kyeong; Cho, Jeong Hwi; Park, Joon Ha; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich-Na; Ahn, Ji Hyeon; Tae, Hyun-Jin; Shin, Myoung Cheol; Ohk, Taek Geun; Cho, Jun Hwi; Won, Moo-Ho; Choi, Soo Young; Kim, In Hye

    2016-01-01

    Ischemic preconditioning (IPC) is a condition of sublethal transient global ischemia and exhibits neuroprotective effects against subsequent lethal ischemic insult. We, in this study, examined the neuroprotective effects of IPC and its effects on immunoreactive changes of antioxidant enzymes including superoxide dismutase (SOD) 1 and SOD2, catalase (CAT) and glutathione peroxidase (GPX) in the gerbil hippocampal CA1 region after transient forebrain ischemia. Pyramidal neurons of the stratum pyramidale (SP) in the hippocampal CA1 region of animals died 5 days after lethal transient ischemia without IPC (8.6% (ratio of remanent neurons) of the sham-operated group); however, IPC prevented the pyramidal neurons from subsequent lethal ischemic injury (92.3% (ratio of remanent neurons) of the sham-operated group). SOD1, SOD2, CAT and GPX immunoreactivities in the sham-operated animals were easily detected in pyramidal neurons in the stratum pyramidale (SP) of the hippocampal CA1 region, while all of these immunoreactivities were rarely detected in the stratum pyramidale at 5 days after lethal transient ischemia without IPC. Meanwhile, their immunoreactivities in the sham-operated animals with IPC were similar to (SOD1, SOD2 and CAT) or higher (GPX) than those in the sham-operated animals without IPC. Furthermore, their immunoreactivities in the stratum pyramidale of the ischemia-operated animals with IPC were steadily maintained after lethal ischemia/reperfusion. Results of western blot analysis for SOD1, SOD2, CAT and GPX were similar to immunohistochemical data. In conclusion, IPC maintained or increased the expression of antioxidant enzymes in the stratum pyramidale of the hippocampal CA1 region after subsequent lethal transient forebrain ischemia and IPC exhibited neuroprotective effects in the hippocampal CA1 region against transient forebrain ischemia.

  13. Role of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase during Early Anesthetic and Ischemic Preconditioning

    PubMed Central

    Amour, Julien; Brzezinska, Anna K.; Weihrauch, Dorothee; Billstrom, Amie R.; Zielonka, Jacek; Krolikowski, John G.; Bienengraeber, Martin W.; Warltier, David C.; Pratt, Philip F.; Kersten, Judy R.

    2009-01-01

    Background Nitric oxide is known to be essential for early anesthetic (APC) and ischemic (IPC) preconditioning of myocardium. Heat shock protein 90 (Hsp90) regulates endothelial nitric oxide synthase (eNOS) activity. In this study, we tested the hypothesis that Hsp90-eNOS interactions modulate APC and IPC. Methods Myocardial infarct size was measured in rabbits after coronary occlusion and reperfusion in the absence or presence of preconditioning with 30 min of isoflurane (APC) or 5 min of coronary artery occlusion (IPC), and with or without pre-treatment with geldanamycin or radicicol, two chemically distinct Hsp90 inhibitors, or NG-nitro-L-arginine methylester, a non-specific NOS inhibitor. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells or mouse cardiomyocytes, in the absence or presence of Hsp90 inhibitors or NG-nitro-L-arginine methylester. Interactions between Hsp90 and eNOS, and eNOS activation were assessed with immunoprecipitation, immunoblotting, and confocal microscopy. Results APC and IPC decreased infarct size (50% and 59%, respectively) and this action was abolished by Hsp90 inhibitors. NG-nitro-L-arginine methylester blocked APC but not IPC. Isoflurane increased nitric oxide production in human coronary artery endothelial cells, concomitantly with an increase in Hsp90-eNOS interaction (immunoprecipitation, immunoblotting, and immunohistochemistry). Pretreatment with Hsp90 inhibitors abolished isoflurane-dependent nitric oxide production and decreased Hsp90-eNOS interactions. Isoflurane did not increase nitric oxide production in mouse cardiomyocytes and eNOS was below the level of detection. Conclusion The results indicate that Hsp90 plays a critical role in mediating APC and IPC through protein-protein interactions, and suggest that endothelial cells are important contributors to nitric oxide-mediated signalling during APC. PMID:19194158

  14. p63 Expression in the Gerbil Hippocampus Following Transient Ischemia and Effect of Ischemic Preconditioning on p63 Expression in the Ischemic Hippocampus.

    PubMed

    Lee, Jae-Chul; Cho, Geum-Sil; Kim, In Hye; Park, Joon Ha; Cho, Jeong-Hwi; Ahn, Ji Hyeon; Bae, Eun Joo; Ahn, Ji Yun; Park, Chan Woo; Cho, Jun Hwi; Kim, Young-Myeong; Won, Moo-Ho; Lee, Hui Young

    2015-05-01

    p63 is a transcription factor of p53 gene family, which are involved in development, differentiation and cell response to stress; however, its roles in ischemic preconditioning (IPC) in the brain are not clear. In the present study, we investigated the effect of IPC on p63 immunoreactivity caused by 5 min of transient cerebral ischemia in gerbils. IPC was induced by subjecting the gerbils to 2 min of transie ischemia 1 day prior to 5 min of transient ischemia. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+)-sham-operated-group and IPC + ischemia-operated-group). The number of viable neurons in the stratum pyramidale of the hippocampal CA1 region (CA1) was significantly increased by IPC + ischemia-operated-group compared with that in the ischemia-operated-group 5 days after ischemic insult. We found that strong p63 immunoreactivity was detected in the CA1 pyramidal neurons in the sham-operated-group, and the immunoreactivity was decreased with time after ischemia-reperfusion. In addition, strong p63 immunoreactivity was newly expressed in microglial cells of the CA1 region from 2 days after ischemia-reperfusion. In all the IPC + sham-operated-groups, p63 immunoreactivity in the CA1 pyramidal neurons was similar to that in the sham-operated-group, and the immunoreactivity was well maintained in the IPC + ischemia-operated-groups after cerebral ischemia. In brief, our present findings show that IPC dramatically protected the reduction of p63 immunoreactivity in the pyramidal neurons of the CA1 region after ischemia-reperfusion, and this result suggests that the expression of p63 may be necessary for neurons to survive after transient cerebral ischemia.

  15. p63 Expression in the Gerbil Hippocampus Following Transient Ischemia and Effect of Ischemic Preconditioning on p63 Expression in the Ischemic Hippocampus.

    PubMed

    Lee, Jae-Chul; Cho, Geum-Sil; Kim, In Hye; Park, Joon Ha; Cho, Jeong-Hwi; Ahn, Ji Hyeon; Bae, Eun Joo; Ahn, Ji Yun; Park, Chan Woo; Cho, Jun Hwi; Kim, Young-Myeong; Won, Moo-Ho; Lee, Hui Young

    2015-05-01

    p63 is a transcription factor of p53 gene family, which are involved in development, differentiation and cell response to stress; however, its roles in ischemic preconditioning (IPC) in the brain are not clear. In the present study, we investigated the effect of IPC on p63 immunoreactivity caused by 5 min of transient cerebral ischemia in gerbils. IPC was induced by subjecting the gerbils to 2 min of transie ischemia 1 day prior to 5 min of transient ischemia. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+)-sham-operated-group and IPC + ischemia-operated-group). The number of viable neurons in the stratum pyramidale of the hippocampal CA1 region (CA1) was significantly increased by IPC + ischemia-operated-group compared with that in the ischemia-operated-group 5 days after ischemic insult. We found that strong p63 immunoreactivity was detected in the CA1 pyramidal neurons in the sham-operated-group, and the immunoreactivity was decreased with time after ischemia-reperfusion. In addition, strong p63 immunoreactivity was newly expressed in microglial cells of the CA1 region from 2 days after ischemia-reperfusion. In all the IPC + sham-operated-groups, p63 immunoreactivity in the CA1 pyramidal neurons was similar to that in the sham-operated-group, and the immunoreactivity was well maintained in the IPC + ischemia-operated-groups after cerebral ischemia. In brief, our present findings show that IPC dramatically protected the reduction of p63 immunoreactivity in the pyramidal neurons of the CA1 region after ischemia-reperfusion, and this result suggests that the expression of p63 may be necessary for neurons to survive after transient cerebral ischemia. PMID:25777256

  16. Remote Ischemic Preconditioning for the Prevention of Contrast-Induced Acute Kidney Injury in Diabetics Receiving Elective Percutaneous Coronary Intervention

    PubMed Central

    Balbir Singh, Gillian; Ann, Soe Hee; Park, Jongha; Chung, Hyun Chul; Lee, Jong Soo; Kim, Eun-Sook; Choi, Jung Il; Lee, Jiho; Kim, Shin-Jae; Shin, Eun-Seok

    2016-01-01

    Objective Remote ischemic preconditioning (RIPC) induces transient episodes of ischemia by the occlusion of blood flow in non-target tissue, before a subsequent ischemia-reperfusion injury. When RIPC is applied before percutaneous coronary intervention (PCI), the kidneys may be protected against ischemia-reperfusion injury and subsequently contrast-induced acute kidney injury (CI-AKI). The aim of this study was to evaluate the efficacy of RIPC for the prevention of CI-AKI in patients with diabetes with pre-existing chronic kidney disease (CKD) undergoing elective PCI. Methods This randomized, double-blind, sham-controlled study enrolled patients with diabetes scheduled for elective PCI with eGFR ≤60 ml/min/1.73 m2 or urinary albumin creatinine ratio of >300 mg/g to receive either RIPC or the sham ischemic preconditioning. Results One hundred and two patients (68.9 ± 8.2 years old, 47.1% men) were included. Baseline eGFR, creatinine and serum NGAL was similar between RIPC and control groups (48.5 ± 12 ml/min vs. 46.6 ± 10 ml/min, p = 0.391; 1.42 ± 0.58 mg/dl vs. 1.41 ± 0.34 mg/dl, p = 0.924; and 136.0 ± 45.0 ng/ml vs. 137.6 ± 43.3 ng/ml, p = 0.961, respectively). CI-AKI occurred in 13.7% (14/102) of the total subjects, with both RIPC and control groups having an equal incidence of 13.7% (7/51). No significant differences were seen in creatinine, NGAL, cardiac enzymes (troponin T, CKMB) and hs-CRP between the groups post-procedure. Conclusions In this study, RIPC applied prior to elective PCI was not effective in preventing CI-AKI in patients with diabetes with pre-existing CKD. Trial Registration ClinicalTrials.gov NCT02329444 PMID:27723839

  17. Metabolomic profiling of the heart during acute ischemic preconditioning reveals a role for SIRT1 in rapid cardioprotective metabolic adaptation.

    PubMed

    Nadtochiy, Sergiy M; Urciuoli, William; Zhang, Jimmy; Schafer, Xenia; Munger, Joshua; Brookes, Paul S

    2015-11-01

    Ischemic preconditioning (IPC) protects tissues such as the heart from prolonged ischemia-reperfusion (IR) injury. We previously showed that the lysine deacetylase SIRT1 is required for acute IPC, and has numerous metabolic targets. While it is known that metabolism is altered during IPC, the underlying metabolic regulatory mechanisms are unknown, including the relative importance of SIRT1. Thus, we sought to test the hypothesis that some of the metabolic adaptations that occur in IPC may require SIRT1 as a regulatory mediator. Using both ex-vivo-perfused and in-vivo mouse hearts, LC-MS/MS based metabolomics and (13)C-labeled substrate tracing, we found that acute IPC altered several metabolic pathways including: (i) stimulation of glycolysis, (ii) increased synthesis of glycogen and several amino acids, (iii) increased reduced glutathione levels, (iv) elevation in the oncometabolite 2-hydroxyglutarate, and (v) inhibition of fatty-acid dependent respiration. The majority (83%) of metabolic alterations induced by IPC were ablated when SIRT1 was acutely inhibited with splitomicin, and a principal component analysis revealed that metabolic changes in response to IPC were fundamentally different in nature when SIRT1 was inhibited. Furthermore, the protective benefit of IPC was abrogated by eliminating glucose from perfusion media while sustaining normal cardiac function by burning fat, thus indicating that glucose dependency is required for acute IPC. Together, these data suggest that SIRT1 signaling is required for rapid cardioprotective metabolic adaptation in acute IPC.

  18. Hippocampal hypertrophy and sleep apnea: a role for the ischemic preconditioning?

    PubMed

    Rosenzweig, Ivana; Kempton, Matthew J; Crum, William R; Glasser, Martin; Milosevic, Milan; Beniczky, Sandor; Corfield, Douglas R; Williams, Steven C; Morrell, Mary J

    2013-01-01

    The full impact of multisystem disease such as obstructive sleep apnoea (OSA) on regions of the central nervous system is debated, as the subsequent neurocognitive sequelae are unclear. Several preclinical studies suggest that its purported major culprits, intermittent hypoxia and sleep fragmentation, can differentially affect adult hippocampal neurogenesis. Although the prospective biphasic nature of chronic intermittent hypoxia in animal models of OSA has been acknowledged, so far the evidence for increased 'compensatory' neurogenesis in humans is uncertain. In a cross-sectional study of 32 patients with mixed severity OSA and 32 non-apnoeic matched controls inferential analysis showed bilateral enlargement of hippocampi in the OSA group. Conversely, a trend for smaller thalami in the OSA group was noted. Furthermore, aberrant connectivity between the hippocampus and the cerebellum in the OSA group was also suggested by the correlation analysis. The role for the ischemia/hypoxia preconditioning in the neuropathology of OSA is herein indicated, with possible further reaching clinical implications. PMID:24349453

  19. Effects of ischemic preconditioning on VEGF and pFlk-1 immunoreactivities in the gerbil ischemic hippocampus after transient cerebral ischemia.

    PubMed

    Park, Yoo Seok; Cho, Jun Hwi; Kim, In Hye; Cho, Geum-Sil; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Shin, Myoung Cheol; Tae, Hyun-Jin; Cho, Young Shin; Lee, Yun Lyul; Kim, Young-Myeong; Won, Moo-Ho; Lee, Jae-Chul

    2014-12-15

    Ischemia preconditioning (IPC) displays an important adaptation of the CNS to sub-lethal ischemia. In the present study, we examined the effect of IPC on immunoreactivities of VEGF-, and phospho-Flk-1 (pFlk-1) following transient cerebral ischemia in gerbils. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) sham-operated-group, and IPC+ischemia-operated-group). IPC was induced by subjecting gerbils to 2 min of ischemia followed by 1 day of recovery. In the ischemia-operated-group, a significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) alone 5 days after ischemia-reperfusion, however, in all the IPC+ischemia-operated-groups, pyramidal neurons in the SP were well protected. In immunohistochemical study, VEGF immunoreactivity in the ischemia-operated-group was increased in the SP at 1 day post-ischemia and decreased with time. Five days after ischemia-reperfusion, strong VEGF immunoreactivity was found in non-pyramidal cells, which were identified as pericytes, in the stratum oriens (SO) and radiatum (SR). In the IPC+sham-operated- and IPC+ischemia-operated-groups, VEGF immunoreactivity was significantly increased in the SP. pFlk-1 immunoreactivity in the sham-operated- and ischemia-operated-groups was hardly found in the SP, and, from 2 days post-ischemia, pFlk-1 immunoreactivity was strongly increased in non-pyramidal cells, which were identified as pericytes. In the IPC+sham-operated-group, pFlk-1 immunoreactivity was significantly increased in both pyramidal and non-pyramidal cells; in the IPC+ischemia-operated-groups, the similar pattern of VEGF immunoreactivity was found in the ischemic CA1, although the VEGF immunoreactivity was strong in non-pyramidal cells at 5 days post-ischemia. In brief, our findings show that IPC dramatically augmented the induction of VEGF and pFlk-1 immunoreactivity in the pyramidal cells of the CA1 after ischemia

  20. Effects of ischemic preconditioning on VEGF and pFlk-1 immunoreactivities in the gerbil ischemic hippocampus after transient cerebral ischemia.

    PubMed

    Park, Yoo Seok; Cho, Jun Hwi; Kim, In Hye; Cho, Geum-Sil; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Shin, Myoung Cheol; Tae, Hyun-Jin; Cho, Young Shin; Lee, Yun Lyul; Kim, Young-Myeong; Won, Moo-Ho; Lee, Jae-Chul

    2014-12-15

    Ischemia preconditioning (IPC) displays an important adaptation of the CNS to sub-lethal ischemia. In the present study, we examined the effect of IPC on immunoreactivities of VEGF-, and phospho-Flk-1 (pFlk-1) following transient cerebral ischemia in gerbils. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) sham-operated-group, and IPC+ischemia-operated-group). IPC was induced by subjecting gerbils to 2 min of ischemia followed by 1 day of recovery. In the ischemia-operated-group, a significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) alone 5 days after ischemia-reperfusion, however, in all the IPC+ischemia-operated-groups, pyramidal neurons in the SP were well protected. In immunohistochemical study, VEGF immunoreactivity in the ischemia-operated-group was increased in the SP at 1 day post-ischemia and decreased with time. Five days after ischemia-reperfusion, strong VEGF immunoreactivity was found in non-pyramidal cells, which were identified as pericytes, in the stratum oriens (SO) and radiatum (SR). In the IPC+sham-operated- and IPC+ischemia-operated-groups, VEGF immunoreactivity was significantly increased in the SP. pFlk-1 immunoreactivity in the sham-operated- and ischemia-operated-groups was hardly found in the SP, and, from 2 days post-ischemia, pFlk-1 immunoreactivity was strongly increased in non-pyramidal cells, which were identified as pericytes. In the IPC+sham-operated-group, pFlk-1 immunoreactivity was significantly increased in both pyramidal and non-pyramidal cells; in the IPC+ischemia-operated-groups, the similar pattern of VEGF immunoreactivity was found in the ischemic CA1, although the VEGF immunoreactivity was strong in non-pyramidal cells at 5 days post-ischemia. In brief, our findings show that IPC dramatically augmented the induction of VEGF and pFlk-1 immunoreactivity in the pyramidal cells of the CA1 after ischemia

  1. Dietary (n-3) long-chain polyunsaturated fatty acids inhibit ischemia and reperfusion arrhythmias and infarction in rat heart not enhanced by ischemic preconditioning.

    PubMed

    Abdukeyum, Grace G; Owen, Alice J; McLennan, Peter L

    2008-10-01

    Ischemic preconditioning (IPC) and (n-3) PUFA are both cardioprotective. This study compared effects of dietary fish oil, IPC, and their interactions on heart function and injury during myocardial ischemia and reperfusion. Male Wistar rats were fed diets containing 10% wt:wt fat comprising either 7% high-docosahexaenoic acid (DHA) [22:6(n-3)] tuna fish oil + 3% olive oil [(n-3) PUFA]; 5% sunflower seed oil + 5% olive oil [(n-6) PUFA]; or 7% beef tallow + 3% olive oil [saturated fat (SF)] for 6 wk. In control experiments, isolated perfused hearts were subjected to 30-min regional ischemia and reperfused for 120 min. The IPC hearts were subjected to 3 cycles of 5-min global ischemia before the ischemia and reperfusion. Control (n-3) PUFA hearts had significantly lower heart rate, coronary flow, end diastolic pressure, maximum relaxation rate, and ischemic and reperfusion arrhythmias. In reperfusion, they had greater developed pressure and maximum relaxation rate and smaller infarct (10.9 +/- 0.6% ischemic zone, n = 6) than (n-6) PUFA (47.4 +/- 0.3%, n = 6) or SF (50.3 +/- 0.3%, n = 6). Compared with control, IPC significantly improved heart function and reduced infarct in (n-6) PUFA (11.8 +/- 0.4%, n = 6) and SF hearts (13.1 +/- 0.1%, n = 6). Heart function and infarct [(n-3) PUFA 9.6 +/- 0.1%, n = 6] did not differ among dietary IPC groups. Arrhythmias, significantly reduced by IPC in (n-6) PUFA and SF hearts, were significantly lower in (n-3) PUFA IPC hearts. Dietary fish oil induces a form of preconditioning, nutritional preconditioning, limiting ischemic cardiac injury, and myocardial infarction and endows cardioprotection as powerful as IPC, which provides no additional protection in (n-3) PUFA hearts.

  2. Postoperative Neurocognitive Dysfunction in Patients Undergoing Cardiac Surgery after Remote Ischemic Preconditioning: A Double-Blind Randomized Controlled Pilot Study

    PubMed Central

    Meybohm, Patrick; Renner, Jochen; Broch, Ole; Caliebe, Dorothee; Albrecht, Martin; Cremer, Jochen; Haake, Nils; Scholz, Jens; Zacharowski, Kai; Bein, Berthold

    2013-01-01

    Background Remote ischemic preconditioning (RIPC) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery. Methods We conducted a prospective, randomized, double-blind, controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomized either to RIPC or to control group. Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery. Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD (1 SD criterion) or if the combined Z score was 1.96 or greater (Z score criterion). Results According to 1 SD criterion, 52% of control and 46% of RIPC patients had cognitive deterioration 5–7 days after surgery (p = 0.753). The summarized Z score showed a trend to more cognitive decline in the control group (2.16±5.30) compared to the RIPC group (1.14±4.02; p = 0.228). Three months after surgery, incidence and severity of neurocognitive dysfunction did not differ between control and RIPC. RIPC tended to decrease postoperative troponin T release at both 12 hours [0.60 (0.19–1.94) µg/L vs. 0.48 (0.07–1.84) µg/L] and 24 hours after surgery [0.36 (0.14–1.89) µg/L vs. 0.26 (0.07–0.90) µg/L]. Conclusions We failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery. Therefore, definitive large-scale multicenter trials are needed. Trial Registration ClinicalTrials.gov NCT00877305 PMID:23741380

  3. Effects of wortmannin on cardioprotection exerted by ischemic preconditioning in rat hearts subjected to ischemia-reperfusion.

    PubMed

    Vélez, Débora Elisabet; Hermann, Romina; Barreda Frank, Mariángeles; Mestre Cordero, Victoria Evangelina; Savino, Enrique Alberto; Varela, Alicia; Marina Prendes, Maria Gabriela

    2016-03-01

    Ischemic preconditioning (IPC) is one of the most powerful interventions to reduce ischemia-reperfusion injury. The aim of the present study was to investigate the involvement of the phosphatidylinositol-3-kinases (PI3Ks) family in cardioprotection exerted by IPC and the relationship between preservation of mitochondrial morphology and ATP synthesis capacity. In this regard, macroautophagy (autophagy) is considered a dynamic process involved in the replacement of aged or defective organelles under physiological conditions. IPC consisted of four 5-min cycles of ischemia-reperfusion followed by sustained ischemia. Wortmannin (W), a PI3K family inhibitor, was added to the perfusion medium to study the involvement of autophagy in the beneficial effects of IPC. In the present study, LC3-II/I expression was significantly increased in the IPC group when compared with the control group. The hearts subjected to IPC showed greater degradation of p62 than control groups, establishing the existence of an autophagic flow. Electron microscopy showed that IPC preserves the structural integrity of mitochondria after ischemia and at the end of reperfusion. Moreover, hearts subjected to IPC exhibited increased mitochondrial ATP synthesis. The beneficial effects of IPC were abolished by W in all trials of this study, abolishing the differences between the IPC and control groups. These results suggest that IPC could partly reduce injury by ischemia-reperfusion (I/R) by decreasing mitochondrial damage and promoting autophagy. Since W is a nonspecific inhibitor of the PI3Ks family, further research is required to confirm participation of PI3K in the response to IPC.

  4. Corticosteroid responses following hypoxic preconditioning provide neuroprotection against subsequent hypoxic-ischemic brain injury in the newborn rats.

    PubMed

    Feng, Yangzheng; Bhatt, Abhay J

    2015-08-01

    Limited research has evaluated the corticosteroids (CS) response in hypoxic preconditioning (PC) induced neuroprotection against subsequent hypoxic-ischemic (HI) brain injury in newborns. To measure, CS response to hypoxic PC, at postnatal day 6 (P6), rat pups were randomly divided into sham, NoPC (exposure to 21% O2) and PC (exposure to 8% O2 for 3h) groups. In a separate experiment, at P6, rat pups were randomly divided into three groups (sham, NoPC+HI, PC+HI). Rat pups in NoPC+HI and PC+HI groups, respectively had normoxic or hypoxic exposure for 3h at P6 and then had the right carotid artery permanently ligated followed by 140 min of hypoxia at P7 (HI). Plasma CS levels were measured at 0.5, 1, 3, 6 and 12h after hypoxic PC and hypoxic PC followed by HI. To investigate whether CS response to hypoxic PC provides neuroprotection against HI, at P6, rat pups were randomly divided into five groups. Fifteen minutes prior to PC or normoxic exposure, rat pups in DMSO+PC+HI and DMSO+NoPC+HI groups received DMSO while in RU486+PC+HI and RU486+NoPC+HI groups received RU486 (glucocorticoid receptor blocker, 60 mg/kg) s.c., respectively. Afterwards, rat pups were exposed to normoxia (DMSO+NoPC+HI, RU486+NoPC+HI) or hypoxia (DMSO+PC+HI, RU486+PC+HI) for 3h and then HI 24h later (P7). Rat pups at the corresponding age without any exposure to PC or HI or RU486/DMSO were used as sham. We found that hypoxic PC caused CS surge as well as augmented CS surge and preserved the glucocorticoid feedback regulation after HI. Hypoxic PC reduced HI induced early and delayed brain damage. RU486 partially but significantly inhibited hypoxic PC induced neuroprotection.

  5. Ischemic preconditioning elevates cardiac stress protein but does not limit infarct size 24 or 48 h later in rabbits.

    PubMed

    Tanaka, M; Fujiwara, H; Yamasaki, K; Miyamae, M; Yokota, R; Hasegawa, K; Fujiwara, T; Sasayama, S

    1994-10-01

    We investigated whether ischemic preconditioning (PC) produced a second window of protection by delayed synthesis of cardioprotective proteins. Anesthetized open-chest rabbits were subjected to 30 min of coronary occlusion and 3 h of reperfusion. PC was elicited by 5 min of ischemia and was separated from sustained ischemia by 5 min, 2 h, or 24 h of reperfusion. Infarct size (% area at risk) was markedly limited by PC with 5 min of reperfusion when compared with controls (13.3 +/- 2.5 vs. 46.8 +/- 7.0%; P < 0.05). This protective effect was lost when the interval between PC and sustained ischemia was extended to 2 h (47.8 +/- 4.8%; P = NS vs. control) and did not reoccur even when it was extended to 24 h (44.2 +/- 6.5%; P = NS vs. sham-operated control). To potentiate induction of heat shock proteins (HSPs), a PC protocol involving four 5-min episodes of ischemia and reperfusion was also used and was separated from sustained ischemia by 24 or 48 h of reperfusion. However, neither of these protocols was protective, and limitation of infarct size was not observed (55.5 +/- 5.9 and 53.4 +/- 6.5% in 24 and 48 h of reperfusion, respectively; P = NS vs. corresponding sham-operated control). Myocardial expression of HSPs was examined using a monoclonal antibody against 72- to 73-kDa HSP in additional rabbits. Immunoreactivity was observed in the myocardium at 24 and 48 h after PC, but not immediately after PC.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Plasma from human volunteers subjected to remote ischemic preconditioning protects human endothelial cells from hypoxia-induced cell damage.

    PubMed

    Weber, Nina C; Riedemann, Isabelle; Smit, Kirsten F; Zitta, Karina; van de Vondervoort, Djai; Zuurbier, Coert J; Hollmann, Markus W; Preckel, Benedikt; Albrecht, Martin

    2015-03-01

    Short repeated cycles of peripheral ischemia/reperfusion (I/R) can protect distant organs from subsequent prolonged I/R injury; a phenomenon known as remote ischemic preconditioning (RIPC). A RIPC-mediated release of humoral factors might play a key role in this protection and vascular endothelial cells are potential targets for these secreted factors. In the present study, RIPC-plasma obtained from healthy male volunteers was tested for its ability to protect human umbilical endothelial cells (HUVEC) from hypoxia-induced cell damage. 10 healthy male volunteers were subjected to a RIPC-protocol consisting of 4 × 5 min inflation/deflation of a blood pressure cuff located at the upper arm. Plasma was collected before (T0; control), directly after (T1) and 1 h after (T2) the RIPC procedure. HUVEC were subjected to 24 h hypoxia damage and simultaneously incubated with 5% of the respective RIPC-plasma. Cell damage was evaluated by lactate dehydrogenase (LDH)-measurements. Western blot experiments of hypoxia inducible factor 1 alpha (HIF1alpha), phosphorylated signal transducer and activator of transcription 5 (STAT5), protein kinase B (AKT) and extracellular signal-related kinase 1/2 (ERK-1/2) were performed. Furthermore, the concentrations of hVEGF were evaluated in the RIPC-plasma by sandwich ELISA. Hypoxia-induced cell damage was significantly reduced by plasma T1 (p = 0.02 vs T0). The protective effect of plasma T1 was accompanied by an augmentation of the intracellular HIF1alpha (p = 0.01 vs T0) and increased phosphorylation of ERK-1/2 (p = 0.03 vs T0). Phosphorylation of AKT and STAT5 remained unchanged. Analysis of the protective RIPC-plasma T1 showed significantly reduced levels of hVEGF (p = 0.01 vs T0). RIPC plasma protects endothelial cells from hypoxia-induced cell damage and humoral mediators as well as intracellular HIF1alpha may be involved.

  7. Hexokinase cellular trafficking in ischemia-reperfusion and ischemic preconditioning is altered in type I diabetic heart.

    PubMed

    Gurel, Ebru; Ustunova, Savas; Kapucu, Aysegul; Yilmazer, Nadim; Eerbeek, Otto; Nederlof, Rianne; Hollmann, Markus W; Demirci-Tansel, Cihan; Zuurbier, Coert J

    2013-07-01

    Diabetes mellitus (DM) has been reported to alter the cardiac response to ischemia-reperfusion (IR). In addition, cardioprotection induced by ischemic preconditioning (IPC) is often impaired in diabetes. We have previously shown that the subcellular localisation of the glycolytic enzyme hexokinase (HK) is causally related to IR injury and IPC protective potential. Especially the binding of HK to mitochondria and prevention of HK solubilisation (HK detachment from mitochondria) during ischemia confers cardioprotection. It is unknown whether diabetes affects HK localisation during IR and IPC as compared to non-diabetes. In this study we hypothesize that DM alters cellular trafficking of hexokinase in response to IR and IPC, possibly explaining the altered response to IR and IPC in diabetic heart. Control (CON) and type I diabetic (DM) rat hearts (65 mg/kg streptozotocin, 4 weeks) were isolated and perfused in Langendorff-mode and subjected to 35 min I and 30 min R with or without IPC (3 times 5 min I). Cytosolic and mitochondrial fractions were obtained at (1) baseline, i.e. after IPC but before I, (2) 35 min I, (3) 5 min R and (4) 30 min R. DM improved rate-pressure product recovery (RPP; 71 ± 10 % baseline (DM) versus 9 ± 1 % baseline (CON) and decreased contracture (end-diastolic pressure: 24 ± 8 mmHg (DM) vs 77 ± 4 mmHg (CON)) after IR as compared to control, and was associated with prevention of HK solubilisation at 35 min I. IPC improved cardiac function in CON but not in DM hearts. IPC in CON prevented HK solubilisation at 35 min I and at 5 min R, with a trend for increased mitochondrial HK. In contrast, the non-effective IPC in DM was associated with solubilisation of HK and decreased mitochondrial HK at early reperfusion and a reciprocal behaviour at late reperfusion. We conclude that type I DM significantly altered cellular HK translocation patterns in the heart in response to IR and IPC, possibly explaining altered response to IR and IPC in diabetes.

  8. In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain.

    PubMed

    Theus, Michelle Hedrick; Wei, Ling; Cui, Lin; Francis, Kevin; Hu, Xinyang; Keogh, Christine; Yu, Shan Ping

    2008-04-01

    Hypoxic preconditioning (HP) and stem cell transplantation have been extensively studied as individual therapies for ischemic stroke. The present investigation is an initial effort to combine these methods to achieve increased therapeutic effects after brain ischemia. Sublethal in vitro hypoxia pretreatment significantly enhanced the tolerance of neurally-differentiating embryonic stem (ES) cells and primary bone marrow mesenchymal stem cells (BMSC) to apoptotic cell death (40-50% reduction in cell death and caspase-3 activation). The HP protective effects on cultured cells lasted for at least 6 days. HP increased secretion of erythropoietin (EPO) and upregulated expression of bcl-2, hypoxia-inducible factor (HIF-1alpha), erythropoietin receptor (EPOR), neurofilament (NF), and synaptophysin in ES cell-derived neural progenitor cells (ES-NPCs). The HP cytoprotective effect was diminished by blocking EPOR, while pretreatment of ES-NPCs with recombinant human EPO mimicked the HP effect. HP-primed ES-NPCs survived better 3 days after transplantation into the ischemic brain (30-40% reduction in cell death and caspase-3 activation). Finally, transplanted HP-primed ES-NPCs exhibited extensive neuronal differentiation in the ischemic brain, accelerated and enhanced recovery of sensorimotor function when compared to transplantation of non-HP-treated ES-NPCs. The cell-priming strategy aimed to promote transplanted cell survival and their tissue repair capability provides a simple yet effective way of optimizing cell transplantation therapy.

  9. Remote ischemic preconditioning mitigates myocardial and neurological dysfunction via K(ATP) channel activation in a rat model of hemorrhagic shock.

    PubMed

    Hu, Xianwen; Yang, Zhengfei; Yang, Min; Qian, Jie; Cahoon, Jena; Xu, Jiefeng; Sun, Shijie; Tang, Wanchun

    2014-09-01

    Severe hemorrhagic shock and resuscitation is a state of global body ischemia and reperfusion that causes myocardial and cerebral dysfunction. We investigated whether remote ischemic preconditioning (RIPC) would reduce myocardial and cerebral ischemia and reperfusion injuries after hemorrhagic shock as the result of the K(ATP) channel activation. Twenty-one male rats were randomized into three groups: RIPC, RIPC with K(ATP) channel blocker, and control. Remote ischemic preconditioning was induced by four cycles of 5 min of limb ischemia followed by reperfusion for 5 min. Hemorrhagic shock was induced by removing 50% of the estimated total blood volume during an interval of 1 h. Thirty minutes after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The animals were monitored for 2 h and observed for an additional 72 h. Myocardial function was measured by echocardiography, and sublingual microcirculation was measured by a sidestream dark-field imaging device at baseline, 1 h after bleeding, 30 min after the completion of bleeding, 30 min after reinfusion, and hourly intervals thereafter. The survival and neurological function were evaluated at 12, 24, 48, and 72 h after reinfusion. At 2 h after reinfusion, ejection fraction and myocardial performance index were significantly better in the RIPC group than in the control group (P < 0.01). The sublingual microvascular flow index and perfused vessel density were significantly greater after reinfusion in the RIPC group than that in the control group (P < 0.01). The duration of survival was significantly longer, and neurological deficit score was significantly better in the RIPC group than the control animals (P < 0.01). Pretreatment with the K(ATP) channel blocker (glibenclamide) completely abolished the myocardial and cerebral protective effects of RIPC. We demonstrate, for the first time, that after severe hemorrhagic shock and resuscitation, RIPC mitigated myocardial and

  10. Remote ischemic preconditioning mitigates myocardial and neurological dysfunction via K(ATP) channel activation in a rat model of hemorrhagic shock.

    PubMed

    Hu, Xianwen; Yang, Zhengfei; Yang, Min; Qian, Jie; Cahoon, Jena; Xu, Jiefeng; Sun, Shijie; Tang, Wanchun

    2014-09-01

    Severe hemorrhagic shock and resuscitation is a state of global body ischemia and reperfusion that causes myocardial and cerebral dysfunction. We investigated whether remote ischemic preconditioning (RIPC) would reduce myocardial and cerebral ischemia and reperfusion injuries after hemorrhagic shock as the result of the K(ATP) channel activation. Twenty-one male rats were randomized into three groups: RIPC, RIPC with K(ATP) channel blocker, and control. Remote ischemic preconditioning was induced by four cycles of 5 min of limb ischemia followed by reperfusion for 5 min. Hemorrhagic shock was induced by removing 50% of the estimated total blood volume during an interval of 1 h. Thirty minutes after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The animals were monitored for 2 h and observed for an additional 72 h. Myocardial function was measured by echocardiography, and sublingual microcirculation was measured by a sidestream dark-field imaging device at baseline, 1 h after bleeding, 30 min after the completion of bleeding, 30 min after reinfusion, and hourly intervals thereafter. The survival and neurological function were evaluated at 12, 24, 48, and 72 h after reinfusion. At 2 h after reinfusion, ejection fraction and myocardial performance index were significantly better in the RIPC group than in the control group (P < 0.01). The sublingual microvascular flow index and perfused vessel density were significantly greater after reinfusion in the RIPC group than that in the control group (P < 0.01). The duration of survival was significantly longer, and neurological deficit score was significantly better in the RIPC group than the control animals (P < 0.01). Pretreatment with the K(ATP) channel blocker (glibenclamide) completely abolished the myocardial and cerebral protective effects of RIPC. We demonstrate, for the first time, that after severe hemorrhagic shock and resuscitation, RIPC mitigated myocardial and

  11. 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-κB 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 IκB-α 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-1β, TNF-α and Bax, and up-regulated IκB-α 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

  12. Molecular mechanism of preconditioning.

    PubMed

    Das, Manika; Das, Dipak K

    2008-04-01

    During the last 20 years, since the appearance of the first publication on ischemic preconditioning (PC), our knowledge of this phenomenon has increased exponentially. PC is defined as an increased tolerance to ischemia and reperfusion induced by previous sublethal period ischemia. This is the most powerful mechanism known to date for limiting the infract size. This adaptation occurs in a biphasic pattern (i) early preconditioning (lasts for 2-3 h) and (ii) late preconditioning (starting at 24 h lasting until 72-96 h after initial ischemia). Early preconditioning is more potent than delayed preconditioning in reducing infract size. Late preconditioning attenuates myocardial stunning and requires genomic activation with de novo protein synthesis. Early preconditioning depends on adenosine, opioids and to a lesser degree, on bradykinin and prostaglandins, released during ischemia. These molecules activate G-protein-coupled receptor, initiate activation of K(ATP) channel and generate oxygen-free radicals, and stimulate a series of protein kinases, which include protein kinase C, tyrosine kinase, and members of MAP kinase family. Late preconditioning is triggered by a similar sequence of events, but in addition essentially depends on newly synthesized proteins, which comprise iNOS, COX-2, manganese superoxide dismutase, and possibly heat shock proteins. The final mechanism of PC is still not very clear. The present review focuses on the possible role signaling molecules that regulate cardiomyocyte life and death during ischemia and reperfusion. PMID:18344203

  13. Effect of ischemic preconditioning on the expression of c-myb in the CA1 region of the gerbil hippocampus after ischemia/reperfusion injury

    PubMed Central

    Lee, Hui Young; Tae, Hyun-Jin; Cho, Geum-Sil; Kim, In Hye; Cho, Jeong Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Won, Moo-Ho; Park, Chan Woo; Cho, Jun Hwi; Seo, Jeong Yeol; Lee, Jae-Chul

    2016-01-01

    Objective(s): In the present study, we investigated the effect of ischemic preconditioning (IPC) on c-myb immunoreactivity as well as neuronal damage/death after a subsequent lethal transient ischemia in gerbils. Materials and Methods: IPC was subjected to a 2 min sublethal ischemia and a lethal transient ischemia was given 5 min transient ischemia. The animals in all of the groups were given recovery times of 1 day, 2 days and 5 days and we examined change in c-myb immunoreactivity as well as neuronal damage/death in the hippocampus induced by a lethal transient ischemia. Results: A lethal transient ischemia induced a significant loss of cells in the stratum pyramidale (SP) of the hippocampal CA1 region at 5 days post-ischemia, and this insult showed that c-myb immunoreactivity in cells of the SP of the CA1 region was significantly decreased at 2 days post-ischemia and disappeared at 5 days post-ischemia. However, IPC effectively prevented the neuronal loss in the SP and showed that c-myb immunoreactivity was constitutively maintained in the SP after a lethal transient ischemia. Conclusion: Our results show that a lethal transient ischemia significantly decreased c-myb immunoreactivity in the SP of the CA1 region and that IPC well preserved c-myb immunoreactivity in the SP of the CA1 region. We suggest that the maintenance of c-myb might be related with IPC-mediated neuroprotection after a lethal ischemic insult. PMID:27482343

  14. Proteomic analysis of hepatic ischemia/reperfusion injury and ischemic preconditioning in mice revealed the protective role of ATP5beta.

    PubMed

    Xu, Chengfu; Zhang, Xuequn; Yu, Chaohui; Lu, Guohua; Chen, Shaohua; Xu, Liming; Ding, Wei; Shi, Qiaojuan; Li, Youming

    2009-01-01

    Hepatic ischemia/reperfusion (I/R) injury is an inevitable consequence during liver surgery. Ischemic preconditioning (IPC) has been shown to protect the livers from I/R injury, partially mediated by preservation of hepatic ATP contents. However, the precise molecular mechanisms of these events remain poorly elucidated. In this study, liver proteomes of the mice subjected to I/R injury pretreated with or without IPC were analyzed using 2-DE combined with MALDI-TOF/TOF mass analysis. Twenty proteins showing more than 1.5-fold difference were identified in the livers upon I/R injury. Among these proteins, four proteins were further regulated by IPC when compared with nonpretreated controls. One of these proteins, ATP synthase beta subunit (ATP5beta) catalyzes the rate-limiting step of ATP formation. The expression level of ATP5beta, which was further validated by Western blot analysis, was significantly decreased upon I/R injury while turned over by IPC pretreatment. Change pattern of hepatic ATP corresponded with that of ATP5beta expression, indicating that increasing hepatic ATP5beta expression might be a reason for ATP-preserving effect of IPC. In summary, this study provided new clues for understanding the mechanisms of IPC against I/R injury. The protective role of ATP5beta might give evidences for developing new therapeutic approaches against hepatic I/R injury.

  15. Ischemic preconditioning inhibits expression of Na(+)/H(+) exchanger 1 (NHE1) in the gerbil hippocampal CA1 region after transient forebrain ischemia.

    PubMed

    Lee, Jae-Chul; Cho, Jeong-Hwi; Kim, In Hye; Ahn, Ji Hyeon; Park, Joon Ha; Cho, Geum-Sil; Chen, Bai Hui; Shin, Bich Na; Tae, Hyun-Jin; Park, Seung Min; Ahn, Ji Yun; Kim, Dong Won; Cho, Jun Hwi; Bae, Eun Joo; Yong, Jun-Hwan; Kim, Young-Myeong; Won, Moo-Ho; Lee, Yun Lyul

    2015-04-15

    The participation of Na(+)/H(+) exchanger (NHE) in neuronal damage/death in the hippocampal CA1 region (CA1) induced by transient forebrain ischemia has not been well established, although acidosis may be involved in neuronal damage/death. In the present study, we examined the effect of ischemic preconditioning (IPC) on NHE1 immunoreactivity following a 5min of transient forebrain ischemia in gerbils. The animals used in the study were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) sham-operated-group and IPC+ischemia-operated-group). IPC was induced by subjecting animals to 2min of ischemia followed by 1day of recovery. A significant neuronal loss was found in the stratum pyramidale (SP) of the CA1, not the CA2/3, of the ischemia-operated-group at 5days post-ischemia. However, in the IPC+ischemia-operated-group, neurons in the SP of the CA1 were well protected. NHE1 immunoreactivity was not detected in any regions of the CA1-3 of the sham- and IPC+sham-operated-groups. However, the immunoreactivity was apparently expressed in the SP of the CA1-3 after ischemia, and the NHE1immunoreactivity was very weak 5days after ischemia; however, at this point in time, strong NHE1immunoreactivity was found in astrocytes in the CA1. In the CA2/3, NHE1immunoreactivity was slightly changed, although NHE1immunoreactivity was expressed in the SP. In the IPC+ischemia-operated-groups, NHE1 immunoreactivity was also expressed in the SP of the CA1-3; however, the immunoreactivity was more slightly changed than that in the ischemia-operated-groups. In brief, our findings show that IPC dramatically protected CA1 pyramidal neurons and strongly inhibited NHE1 expression in the SP of the CA1 after ischemia-reperfusion. These findings suggest that the inhibition of NHE1 expression may be necessary for neuronal survival from transient ischemic damage.

  16. Remote Ischemic Preconditioning Reduces Perioperative Cardiac and Renal Events in Patients Undergoing Elective Coronary Intervention: A Meta-Analysis of 11 Randomized Trials

    PubMed Central

    Pei, Hanjun; Wu, Yongjian; Wei, Yingjie; Yang, Yuejin; Teng, Siyong; Zhang, Haitao

    2014-01-01

    Background Results from randomized controlled trials (RCT) concerning cardiac and renal effect of remote ischemic preconditioning(RIPC) in patients with stable coronary artery disease(CAD) are inconsistent. The aim of this study was to explore whether RIPC reduce cardiac and renal events after elective percutaneous coronary intervention (PCI). Methods and Results RCTs with data on cardiac or renal effect of RIPC in PCI were searched from Pubmed, EMBase, and Cochrane library (up to July 2014). Meta-regression and subgroup analysis were performed to identify the potential sources of significant heterogeneity(I2≥40%). Eleven RCTs enrolling a total of 1713 study subjects with stable CAD were selected. Compared with controls, RIPC significantly reduced perioperative incidence of myocardial infarction (MI) [odds ratio(OR)  = 0.68; 95% CI, 0.51 to 0.91; P = 0.01; I2 = 41.0%] and contrast-induced acute kidney injury(AKI) (OR = 0.61; 95% CI, 0.38 to 0.98; P = 0.04; I2 = 39.0%). Meta-regression and subgroup analyses confirmed that the major source of heterogeneity for the incidence of MI was male proportion (coefficient  = −0.049; P = 0.047; adjusted R2 = 0.988; P = 0.02 for subgroup difference). Conclusions The present meta-analysis of RCTs suggests that RIPC may offer cardiorenal protection by reducing the incidence of MI and AKI in patients undergoing elective PCI. Moreover, this effect on MI is more pronounced in male subjects. Future high-quality, large-scale clinical trials should focus on the long-term clinical effect of RIPC. PMID:25551671

  17. Remote ischemic preconditioning regulates HIF-1α levels, apoptosis and inflammation in heart tissue of cardiosurgical patients: a pilot experimental study.

    PubMed

    Albrecht, Martin; Zitta, Karina; Bein, Berthold; Wennemuth, Gunther; Broch, Ole; Renner, Jochen; Schuett, Torben; Lauer, Fabian; Maahs, Daniela; Hummitzsch, Lars; Cremer, Jochen; Zacharowski, Kai; Meybohm, Patrick

    2013-01-01

    Transient episodes of ischemia in a remote organ (remote ischemic preconditioning, RIPC) bears the potential to attenuate myocardial injury, but the underlying mechanisms are only poorly understood. In the pilot experimental study presented we investigated cellular and molecular effects of RIPC in heart tissue of cardiosurgical patients with cardiopulmonary bypass (CPB) and focussed on apoptotic events, local and systemic inflammation as well as the regulation of the hypoxia induced factor-1α (HIF-1α). RIPC was induced by four 5-min cycles of transient upper limb ischemia/reperfusion using a blood-pressure cuff. Right atrial tissue and serum were obtained from patients receiving RIPC (N = 32) and control patients (N = 29) before and after CPB. RIPC patients showed reduced troponin T serum concentrations in the first 48 h after surgery (P < 0.05 vs. control) indicating cardioprotective effects of RIPC. Samples from RIPC patients that were collected before CPB contained significantly increased amounts of HIF-1α and procaspase-3 (HIF-1α: P < 0.05 vs. control, procaspase-3: P < 0.05 vs. control), whereas activities of caspases 3 and 7 were by trend reduced. Samples from RIPC patients that were taken after CPB showed an increased activity of myeloperoxidase (P < 0.05 vs. control; P < 0.05 vs. RIPC before CPB) as well as elevated tissue concentrations of the interleukin (IL)-1β (P < 0.05 vs. RIPC before CPB). Serum levels of IL-8, IL-1β and TNFα were significantly increased in RIPC patients before CPB (P < 0.05 vs. control before CPB). In summary, RIPC regulates HIF-1α levels, apoptosis and inflammation in the myocardium of cardiosurgical patients and leads to increased concentrations of circulating cytokines.

  18. Serum from Patients Undergoing Remote Ischemic Preconditioning Protects Cultured Human Intestinal Cells from Hypoxia-Induced Damage: Involvement of Matrixmetalloproteinase-2 and -9

    PubMed Central

    Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Heinrich, Christin; Renner, Jochen; Cremer, Jochen; Steinfath, Markus; Scholz, Jens; Albrecht, Martin

    2012-01-01

    Remote ischemic preconditioning (RIPC) can be induced by transient occlusion of blood flow to a limb with a blood pressure cuff and exerts multiorgan protection from ischemia/reperfusion injury. Ischemia/reperfusion injury in the intestinal tract leads to intestinal barrier dysfunction and can result in multiple organ failure. Here we used an intestinal cell line (CaCo-2) to evaluate the effects of RIPC-conditioned patient sera on hypoxia-induced cell damage in vitro and to identify serum factors that mediate RIPC effects. Patient sera (n = 10) derived before RIPC (T0), directly after RIPC (T1) and 1 h after RIPC (T2) were added to the culture medium at the onset of hypoxia until 48 h after hypoxia. Reverse transcription–polymerase chain reaction, lactate dehydrogenase (LDH) assays, caspase-3/7 assays, silver staining, gelatin zymography and Western blotting were performed. Hypoxia led to morphological signs of cell damage and increased the release of LDH in cultures containing sera T0 (P < 0.01) and T1 (P < 0.05), but not sera T2, which reduced the hypoxia-mediated LDH release compared with sera T0 (P < 0.05). Gelatin zymography revealed a significant reduction of activities of the matrixmetalloproteinase (MMP)-2 and MMP-9 in the protective sera T2 compared with the nonprotective sera T0 (MMP-2: P < 0.01; MMP-9: P < 0.05). Addition of human recombinant MMP-2 and MMP-9 to MMP-deficient culture media increased the sensitivity of CaCo-2 cells to hypoxia-induced cell damage (P < 0.05), but did not result in a reduced phosphorylation of prosurvival kinases p42/44 and protein kinase B (Akt) or increased activity of caspase-3/7. Our results suggest MMP-2 and MMP-9 as currently unknown humoral factors that may be involved in RIPC-mediated cytoprotection in the intestine. PMID:22009279

  19. Remote Ischemic Preconditioning for Prevention of Acute Kidney Injury in Patients Undergoing On-Pump Cardiac Surgery: A Systematic Review and Meta-Analysis.

    PubMed

    Zhang, Yabing; Zhang, Xiyang; Chi, Dongmei; Wang, Siyang; Wei, Hua; Yu, Hong; Li, Qian; Liu, Bin

    2016-09-01

    Remote ischemic preconditioning (RIPC) may attenuate acute kidney injury (AKI). However, results of studies evaluating the effect of RIPC on AKI after cardiac surgery have been controversial and contradictory.The aim of this meta-analysis is to examine the association between RIPC and AKI after on-pump cardiac surgery.The authors searched relevant studies in PubMed, EMBASE, and the Cochrane Library through December 2015.We considered for inclusion all randomized controlled trials that the role of RIPC in reducing AKI and renal replacement therapy (RRT) among patients underwent on-pump cardiac surgical procedures.We collected the data on AKI, initiation of RRT, serum creatinine (sCr) levels, and in-hospital mortality. Random- and fixed-effect models were used for pooling data.Nineteen trials including 5100 patients were included. The results of this meta-analysis showed a significant benefit of RIPC for reducing the incidence of AKI after cardiac interventions (odds ratio [OR] = 0.84; 95% confidence interval [CI], 0.73-0.98; P = 0.02). No significant difference was found in the incidence of RRT between RIPC and control (OR, 0.76, 95% CI, 0.46-1.24; P = 0.36). In addition, compared with standard medical care, RIPC showed no significant difference in postoperative sCr (IV 0.07; 95% CI, -0.03 to 0.16; P = 0.20; postoperative day 1; IV 0.00; 95% CI, -0.08 to 0.09; P = 0.92; postoperative day 2; IV 0.04; 95% CI, -0.05 to 0.12; P = 0.39; postoperative day 3), and in-hospital mortality (OR, 1.21, 95% CI, 0.64-2.30; P = 0.56).According to the results from present meta-analysis, RIPC was associated with a significant reduction AKI after on-pump cardiac surgery but incidence of RRT, postoperative sCr, and in-hospital mortality. Further high-quality randomized controlled trials and experimental researches comparing RIPC are desirable. PMID:27631199

  20. A pilot study investigating the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomised controlled double-blind protocol.

    PubMed

    Young, Paul Jeffrey; Dalley, Paul; Garden, Alexander; Horrocks, Christopher; La Flamme, Anne; Mahon, Barry; Miller, John; Pilcher, Janine; Weatherall, Mark; Williams, Jenni; Young, William; Beasley, Richard

    2012-05-01

    The efficacy of remote ischemic preconditioning (RIPC) in high-risk cardiac surgery is uncertain. In this study, 96 adults undergoing high-risk cardiac surgery were randomised to RIPC (3 cycles of 5 min of upper-limb ischemia induced by inflating a blood pressure cuff to 200 mmHg with 5 min of reperfusion) or control. Main endpoints were plasma high-sensitivity troponin T (hsTNT) levels at 6 and 12 h, worst post-operative acute kidney injury (AKI) based on RIFLE criteria, and noradrenaline duration. hsTNT levels were log-normally distributed and higher with RIPC than control at 6-h post cross-clamp removal [810 ng/ml (IQR 527-1,724) vs. 634 ng/ml (429-1,012); ratio of means 1.41 (99.17% CI 0.92-2.17); P=0.04] and 12 h [742 ng/ml (IQR 427-1,700) vs. 514 ng/ml (IQR 356-833); ratio of means 1.56 (99.17% CI 0.97-2.53); P=0.01]. After adjustment for baseline confounders, the ratio of means of hsTNT at 6 h was 1.23 (99.17% CI 0.88-1.72; P=0.10) and at 12 h was 1.30 (99.17% CI 0.92-1.84; P=0.05). In the RIPC group, 35/48 (72.9%) had no AKI, 5/48 (10.4%) had AKI risk, and 8/48 (16.7%) had either renal injury or failure compared to the control group where 34/48 (70.8%) had no AKI, 7/48 (14.6%) had AKI risk, and 7/48 (14.6%) had renal injury or failure (Chi-squared 0.41; two degrees of freedom; P = 0.82). RIPC increased post-operative duration of noradrenaline support [21 h (IQR 7-45) vs. 9 h (IQR 3-19); ratio of means 1.70 (99.17% CI 0.86-3.34); P=0.04]. RIPC does not reduce hsTNT, AKI, or ICU-support requirements in high-risk cardiac surgery.

  1. The Impact of Remote Ischemic Pre-Conditioning on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography and Angioplasty: A Double-Blind Randomized Clinical Trial

    PubMed Central

    Gholoobi, Arash; Sajjadi, Seyyed Masoud; Shabestari, Mahmoud Mohammadzadeh; Eshraghi, Ali; Shamloo, Alireza Sepehri

    2015-01-01

    Background and objective Contrast-induced nephropathy (CIN) is an acute major complication following intravascular administration of iodinated contrast agents; however, the best approach for preventing CIN is not clear. Remote ischemic pre-conditioning (RIPC) is a new, non-pharmacological method that has been considered for the prevention of CIN following coronary angiography. This study assessed the effects of RIPC with four brief episodes of upper limb ischemia and reperfusion in the prevention of contrast-induced nephropathy (CIN) after coronary angiography and/or angioplasty. Methods In this double-blind randomized clinical trial, we enrolled 51 patients with chronic stable angina and non-ST elevation acute coronary syndrome (NSTE.ACS), and they underwent coronary angiography and/or angioplasty. Standard fluid therapy with normal saline was prescribed for all patients before and after the procedure. The patients were divided into two groups, i.e., a study group of patients who had undergone RIPC intervention and a control group of patients who had not undergone RIPC. One hour before the procedure, a sphygmomanometer cuff was placed around one arm and inflated up to 50 mmHg above the systolic pressure for five minutes; then, the cuff was deflated for another five minutes, and this cycle was repeated four times. The patients’ serum creatinine levels were measured at baseline and 48 hours after the procedure, and the incidence of CIN was calculated. Results Twenty-one males and 30 females were studied in two groups, i.e., an RIPC intervention group (n = 25) and a control group (n = 26) that were homogenous considering baseline characteristics. No significant difference was observed in the mean level of serum creatinine between the two groups at a post-intervention time of 48 hours (RICP: 1.74 ± 0.70 mg/dL vs. Control: 1.75 ± 0.87 mg/dL; P = 0.64). However, a lower incidence rate of CIN was observed 48 hours after the administration of the contrast medium in

  2. Pharmacological Preconditioning by Adenosine A2a Receptor Stimulation: Features of the Protected Liver Cell Phenotype

    PubMed Central

    Alchera, Elisa; Imarisio, Chiara; Mandili, Giorgia; Merlin, Simone; Chandrashekar, Bangalore R.; Novelli, Francesco; Follenzi, Antonia; Carini, Rita

    2015-01-01

    Ischemic preconditioning (IP) of the liver by a brief interruption of the blood flow protects the damage induced by a subsequent ischemia/reperfusion (I/R) preventing parenchymal and nonparenchymal liver cell damage. The discovery of IP has shown the existence of intrinsic systems of cytoprotection whose activation can stave off the progression of irreversible tissue damage. Deciphering the molecular mediators that underlie the cytoprotective effects of preconditioning can pave the way to important therapeutic possibilities. Pharmacological activation of critical mediators of IP would be expected to emulate or even to intensify its salubrious effects. In vitro and in vivo studies have demonstrated the role of the adenosine A2a receptor (A2aR) as a trigger of liver IP. This review will provide insight into the phenotypic changes that underline the resistance to death of liver cells preconditioned by pharmacological activation of A2aR and their implications to develop innovative strategies against liver IR damage. PMID:26539478

  3. Dynamic Changes in DNA Methylation in Ischemic Tolerance

    PubMed Central

    Meller, Robert; Pearson, Andrea; Simon, Roger P.

    2015-01-01

    Epigenetic mediators of gene expression are hypothesized to regulate transcriptomic responses to preconditioning ischemia and ischemic tolerance. Here, we utilized a methyl-DNA enrichment protocol and sequencing (ChIP-seq) to identify patterns of DNA methylation in an established model of ischemic tolerance in neuronal cultures (oxygen and glucose deprivation: OGD). We observed an overall decrease in global DNA methylation at 4 h following preconditioning ischemia (30 min OGD), harmful ischemia (120 min OGD), and in ischemic tolerant neuronal cultures (30 min OGD, 24 h recovery, 120 min OGD). We detected a smaller cohort of hypermethylated regions following ischemic conditions, which were further analyzed revealing differential chromosomal localization of methylation, and a differential concentration of methylation on genomic regions. Together, these data show that the temporal profiles of DNA methylation with respect to chromatin hyper- and hypo-methylation following various ischemic conditions are highly dynamic, and may reveal novel targets for neuroprotection. PMID:26029158

  4. Sp3/REST/HDAC1/HDAC2 Complex Represses and Sp1/HIF-1/p300 Complex Activates ncx1 Gene Transcription, in Brain Ischemia and in Ischemic Brain Preconditioning, by Epigenetic Mechanism.

    PubMed

    Formisano, Luigi; Guida, Natascia; Valsecchi, Valeria; Cantile, Maria; Cuomo, Ornella; Vinciguerra, Antonio; Laudati, Giusy; Pignataro, Giuseppe; Sirabella, Rossana; Di Renzo, Gianfranco; Annunziato, Lucio

    2015-05-13

    The Na(+)-Ca(2+) exchanger 1 (NCX1) is reduced in stroke by the RE1-silencing transcription factor (REST), whereas it is increased in ischemic brain preconditioning (PC) by hypoxia-inducible factor 1 (HIF-1). Because ncx1 brain promoter (ncx1-Br) has five putative consensus sequences, named Sp1A-E, for the specificity protein (Sp) family of transcription factors (Sp1-4), we investigated the role of this family in regulating ncx1 transcription in rat cortical neurons. Here we found that Sp1 is a transcriptional activator, whereas Sp3 is a transcriptional repressor of ncx1, and that both bind ncx1-Br in a sequence-specific manner, modulating ncx1 transcription through the Sp1 sites C-E. Furthermore, by transient middle cerebral artery occlusion (tMCAO) in rats, the transcriptional repressors Sp3 and REST colocalized with the two histone-deacetylases (HDACs) HDAC1 and HDAC2 on the ncx1-Br, with a consequent hypoacetylation. Contrarily, in PC+tMCAO the transcriptional activators Sp1 and HIF-1 colocalized with histone acetyltransferase p300 on ncx1-Br with a consequent hyperacetylation. In addition, in neurons silenced with siRNA of NCX1 and subjected to oxygen and glucose deprivation (OGD) (3 h) plus reoxygenation (RX) (24 h), the neuroprotection of Class I HDAC inhibitor MS-275 was counteracted, whereas in neurons overexpressing NCX1 and subjected to ischemic preconditioning (PC+OGD/RX), the neurotoxic effect of p300 inhibitor C646 was prevented. Collectively, these results demonstrate that NCX1 expression is regulated by the Sp3/REST/HDAC1/HDAC2 complex in tMCAO and by the Sp1/HIF-1/p300 complex in PC+tMCAO and that epigenetic intervention, by modulating the acetylation of ncx1-Br, may be a strategy for the development of innovative therapeutic intervention in stroke. PMID:25972164

  5. Preconditioning, postconditioning and their application to clinical cardiology.

    PubMed

    Kloner, Robert A; Rezkalla, Shereif H

    2006-05-01

    Ischemic preconditioning is a well-established phenomenon first described in experimental preparations in which brief episodes of ischemia/reperfusion applied prior to a longer coronary artery occlusion reduce myocardial infarct size. There are ample correlates of ischemic preconditioning in the clinical realm. Preconditioning mimetic agents that stimulate the biochemical pathways of ischemic preconditioning and protect the heart without inducing ischemia have been examined in numerous experimental studies. However, despite the effectiveness of ischemic preconditioning and preconditioning mimetics for protecting ischemic myocardium, there are no preconditioning-based therapies that are routinely used in clinical medicine at the current time. Part of the problem is the need to administer therapy prior to the known ischemic event. Other issues are that percutaneous coronary intervention technology has advanced so far (with the development of stents and drug-eluting stents) that ischemic preconditioning or preconditioning mimetics have not been needed in most interventional cases. Recent clinical trials such as AMISTAD I and II (Acute Myocardial Infarction STudy of ADenosine) suggest that some preconditioning mimetics may reduce myocardial infarct size when given along with reperfusion or, as in the IONA trial, have benefit on clinical events when administered chronically in patients with known coronary artery disease. It is possible that some of the benefit described for adenosine in the AMISTAD 1 and 2 trials represents a manifestation of the recently described postconditioning phenomenon. It is probable that postconditioning--in which reperfusion is interrupted with brief coronary occlusions and reperfusion sequences--is more likely than preconditioning to be feasible as a clinical application to patients undergoing percutaneous coronary intervention for acute myocardial infarction. PMID:16516180

  6. Remifentanil-induced preconditioning has cross-talk with A1 and A2B adenosine receptors in ischemic-reperfused rat heart.

    PubMed

    Lee, Yong-Cheol; Jung, Jiyoon; Park, Sang-Jin

    2016-01-01

    The purpose of this study was to determine whether there is a cross-talk between opioid receptors (OPRs) and adenosine receptors (ADRs) in remifentanil preconditioning (R-Pre) and, if so, to investigate the types of ADRs involved in the cross-talk. Isolated rat hearts received 30 min of regional ischemia followed by 2 hr of reperfusion. OPR and ADR antagonists were perfused from 10 min before R-Pre until the end of R-Pre. The heart rate, left ventricular developed pressure (LVDP),velocity of contraction (+dP/dtmax), and coronary flow (CF) were recorded. The area at risk and area of necrosis were measured. After reperfusion, the LVDP, +dP/dtmax,and CF showed a significant increase in the R-Pre group compared with the control group (no intervention before or after regional ischemia). These increases in the R-Pre group were blocked by naloxone, a nonspecific ADR antagonist, an A1 ADR antagonist, and an A2B ADR antagonist. The infarct size was reduced significantly in the R-Pre group compared with the control group. The infarct-reducing effect in the R-Pre group was blocked by naloxone, the nonspecific ADR antagonist, the A1 ADR antagonist, and the A2B ADR antagonist. The results of this study demonstrate that there is cross-talk between ADRs and OPRs in R-Pre and that A1 ADR and A2B ADR appear to be involved in the cross-talk. PMID:26773185

  7. Preconditioning for traumatic brain injury

    PubMed Central

    Yokobori, Shoji; Mazzeo, Anna T; Hosein, Khadil; Gajavelli, Shyam; Dietrich, W. Dalton; Bullock, M. Ross

    2016-01-01

    Traumatic brain injury (TBI) treatment is now focused on the prevention of primary injury and reduction of secondary injury. However, no single effective treatment is available as yet for the mitigation of traumatic brain damage in humans. Both chemical and environmental stresses applied before injury, have been shown to induce consequent protection against post-TBI neuronal death. This concept termed “preconditioning” is achieved by exposure to different pre-injury stressors, to achieve the induction of “tolerance” to the effect of the TBI. However, the precise mechanisms underlying this “tolerance” phenomenon are not fully understood in TBI, and therefore even less information is available about possible indications in clinical TBI patients. In this review we will summarize TBI pathophysiology, and discuss existing animal studies demonstrating the efficacy of preconditioning in diffuse and focal type of TBI. We will also review other non-TBI preconditionng studies, including ischemic, environmental, and chemical preconditioning, which maybe relevant to TBI. To date, no clinical studies exist in this field, and we speculate on possible futureclinical situation, in which pre-TBI preconditioning could be considered. PMID:24323189

  8. Cardiac sodium/calcium exchanger preconditioning promotes anti-arrhythmic and cardioprotective effects through mitochondrial calcium-activated potassium channel

    PubMed Central

    Zhang, Jian-Ying; Cheng, Kang; Lai, Dong; Kong, Ling-Heng; Shen, Min; Yi, Fu; Liu, Bing; Wu, Feng; Zhou, Jing-Jun

    2015-01-01

    Background: Reverse-mode of the Na+/Ca2+ exchanger (NCX) stimulation provides cardioprotective effects for the ischemic/reperfused heart during ischemic preconditioning (IP). This study was designed to test the hypothesis that pretreatment with an inhibitor of cardiac delayed-rectifying K+ channel (IKr), E4031, increases reverse-mode of NCX activity, and triggers preconditioning against infarct size (IS) and arrhythmias caused by ischemia/reperfusion injury through mitoKCa channels. Materials and methods: In the isolated perfused rat heart, myocardial ischemia/reperfusion injury was created by occlusion of the left anterior descending coronary artery for 30 min followed by 120 min reperfusion. Two cycles of coronary occlusion for 5 min and reperfusion were performed, or pretreatment with E4031 or sevoflurane (Sevo) before the 30 min occlusion with the reversed-mode of NCX inhibitor (KB-R7943) or not. Results: E4031 or Sevo preconditioning not only markedly decreased IS but also reduced arrhythmias, which was significantly blunted by KB-R7943. Furthermore, these effects of E4031 preconditioning on IS and arrhythmias were abolished by inhibition of the mitoKCa channels. Similarly, pretreatment with NS1619, an opener of the mitoKCa channels, for 10 min before occlusion reduced both the infarct size and arrhythmias caused by ischemia/reperfusion. However, these effects weren’t affected by blockade of the NCX with KB-R7943. Conclusion: Taken together, these preliminary results conclude that pretreatment with E4031 reduces infarct size and produces anti-arrhythmic effect via stimulating the reverse-mode NCX, and that the mitoKCa channels mediate the protective effects. PMID:26617732

  9. Physiology and pharmacology of myocardial preconditioning.

    PubMed

    Raphael, Jacob

    2010-03-01

    Perioperative myocardial ischemia and infarction are not only major sources of morbidity and mortality in patients undergoing surgery but also important causes of prolonged hospital stay and resource utilization. Ischemic and pharmacological preconditioning and postconditioning have been known for more than two decades to provide protection against myocardial ischemia and reperfusion and limit myocardial infarct size in many experimental animal models, as well as in clinical studies (1-3). This paper will review the physiology and pharmacology of ischemic and drug-induced preconditioning and postconditioning of the myocardium with special emphasis on the mechanisms by which volatile anesthetics provide myocardial protection. Insights gained from animal and clinical studies will be presented and reviewed and recommendations for the use of perioperative anesthetics and medications will be given.

  10. Astrocyte-mediated ischemic tolerance.

    PubMed

    Hirayama, Yuri; Ikeda-Matsuo, Yuri; Notomi, Shoji; Enaida, Hiroshi; Kinouchi, Hiroyuki; Koizumi, Schuichi

    2015-03-01

    Preconditioning (PC) using a preceding sublethal ischemic insult is an attractive strategy for protecting neurons by inducing ischemic tolerance in the brain. Although the underlying molecular mechanisms have been extensively studied, almost all studies have focused on neurons. Here, using a middle cerebral artery occlusion model in mice, we show that astrocytes play an essential role in the induction of brain ischemic tolerance. PC caused activation of glial cells without producing any noticeable brain damage. The spatiotemporal pattern of astrocytic, but not microglial, activation correlated well with that of ischemic tolerance. Interestingly, such activation in astrocytes lasted at least 8 weeks. Importantly, inhibiting astrocytes with fluorocitrate abolished the induction of ischemic tolerance. To investigate the underlying mechanisms, we focused on the P2X7 receptor as a key molecule in astrocyte-mediated ischemic tolerance. P2X7 receptors were dramatically upregulated in activated astrocytes. PC-induced ischemic tolerance was abolished in P2X7 receptor knock-out mice. Moreover, our results suggest that hypoxia-inducible factor-1α, a well known mediator of ischemic tolerance, is involved in P2X7 receptor-mediated ischemic tolerance. Unlike previous reports focusing on neuron-based mechanisms, our results show that astrocytes play indispensable roles in inducing ischemic tolerance, and that upregulation of P2X7 receptors in astrocytes is essential. PMID:25740510

  11. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation.

  12. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  13. Beneficial effect of zinc chloride and zinc ionophore pyrithione on attenuated cardioprotective potential of preconditioning phenomenon in STZ-induced diabetic rat heart.

    PubMed

    Jamwal, Sumit; Kumar, Kushal; Reddy, B V Krishna

    2016-05-01

    Ischemic preconditioning (IPC) is well demonstrated to produce cardioprotection by phosphorylation and subsequent inactivation of glycogen synthase kinase-3β (GSk-3β) in the normal rat heart, but its effect is attenuated in the diabetic rat heart. This study was designed to investigate the effect of zinc chloride and zinc ionophore pyrithione (ZIP) on the attenuated cardioprotective potential of IPC in the diabetic rat heart. Diabetes mellitus (DM) was induced by a single intraperitoneal administration of streptozotocin (STZ) (50 mg/kg; i.p). The isolated perfused rat heart was subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and cardiac injury was measured by estimating lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the coronary effluent. Also, GSK-3β was measured and neutrophil accumulation was measured by estimating myeloperoxidase (MPO) levels. IPC significantly decreased the myocardial infarct size, the release of LDH and CK-MB, the GSK-3β levels and the MPO levels in the normal rat heart. Pre- and post-ischemic treatment with zinc chloride and zinc ionophore pyrithione (ZIP) in the normal and diabetic rat hearts significantly decreased the myocardial infarct size, the level of CK-MB and LDH in the coronary effluent and GSK-3β and MPO levels. Our results suggest that pharmacological preconditioning with zinc chloride and ZIP significantly restored the attenuated cardioprotective potential of IPC in the diabetic rat heart. PMID:26423303

  14. [Preconditioning impact on coronary perfusion during ischemia and reperfusion of heart].

    PubMed

    Maslov, L N; Lishmanov, Iu B; Oeltgen, P; Peĭ, J-M; Krylatov, A V; Barzakh, E I; Portnichenko, A G; Meshoulam, R

    2012-04-01

    Recent studies have confirmed that ischemic preconditioning prevents appearance of reperfusion endothelial dysfunction. However, the issue of preconditioning impact on no-reflow phenomenon remains unresolved. The receptor mechanisms involved in the cardioprotective and vasoprotective effects of preconditioning are different. The ability of preconditioning in preventing reperfusion endothelial dysfunction is dependent upon bradykinin B2-receptor activation and not dependent upon adenosine receptor stimulation. The vasoprotective effect of preconditioning is mediated via mechanisms relying in part on activation of protein kinase C, NO-synthase, cyclooxygenase, mitochondrial K(ATP)-channel opening and an enhancement of antioxidative protection of the heart. The delayed preconditioning also exerts endothelium-protective effect. Peroxynitrite, NO* and O2* are the triggers of this effect but a possible end-effector involves endothelial NO-synthase. PMID:22834333

  15. Protein kinase C-mediated sodium glucose transporter 1 activation in precondition-induced cardioprotection

    PubMed Central

    Kanwal, Abhinav; Kasetti, Sujatha; Putcha, Uday Kumar; Asthana, Shailendra; Banerjee, Sanjay K

    2016-01-01

    The concept of cardioprotection through preconditioning against ischemia–reperfusion (I/R) injury is well known and established. However, among different proposed mechanisms regarding the concept of ischemic preconditioning, protein kinase C (PKC)-mediated cardioprotection through ischemic preconditioning plays a key role in myocardial I/R injury. Thus, this study was designed to find the relationship between PKC and sodium glucose transporter 1 (SGLT1) in preconditioning-induced cardioprotection, which is ill reported till now. By applying a multifaceted approach, we demonstrated that PKC activates SGLT1, which curbed oxidative stress and apoptosis against I/R injury. PKC activation enhances cardiac glucose uptake through SGLT1 and seems essential in preventing I/R-induced cardiac injury, indicating a possible cross-talk between PKC and SGLT1.

  16. Protein kinase C-mediated sodium glucose transporter 1 activation in precondition-induced cardioprotection

    PubMed Central

    Kanwal, Abhinav; Kasetti, Sujatha; Putcha, Uday Kumar; Asthana, Shailendra; Banerjee, Sanjay K

    2016-01-01

    The concept of cardioprotection through preconditioning against ischemia–reperfusion (I/R) injury is well known and established. However, among different proposed mechanisms regarding the concept of ischemic preconditioning, protein kinase C (PKC)-mediated cardioprotection through ischemic preconditioning plays a key role in myocardial I/R injury. Thus, this study was designed to find the relationship between PKC and sodium glucose transporter 1 (SGLT1) in preconditioning-induced cardioprotection, which is ill reported till now. By applying a multifaceted approach, we demonstrated that PKC activates SGLT1, which curbed oxidative stress and apoptosis against I/R injury. PKC activation enhances cardiac glucose uptake through SGLT1 and seems essential in preventing I/R-induced cardiac injury, indicating a possible cross-talk between PKC and SGLT1. PMID:27695290

  17. Ischemic perinatal stroke: challenge and opportunities.

    PubMed

    Raju, Tonse N K

    2008-08-01

    The second highest risk group for developing a cerebral stroke is the perinatal period, generally defined as 20 weeks of gestation through 28th postnatal day of age. In this commentary, a brief overview of ischemic perinatal strokes is presented. Ischemic perinatal stroke (IPS) occurs at a rate of 1 : 2300 to 1 : 5000 births, accounting for 30% of children with hemiplegic cerebral palsy (CP). Thus, IPS is the most common known cause for CP [1-3]. Although they occur frequently, much remains to be studied about perinatal strokes in general and the ischemic variety in particular. PMID:18705894

  18. Ischemic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  19. [PRECONDITIONING AT THE STAGES OF INVASIVE AND REHABILITATIVE TREATMENT OF PATIENTS WITH CORONARY HEART DISEASE].

    PubMed

    Lyamina, N P; Karpova, E S; Kotel'nikova, E V; Bizyaeva, E A

    2015-01-01

    The comprehensive analysis of efficiency of different variants of preconditioning is currently of special importance since the realization of the potential of endogenous protective effects extends possibilities for anti-ischemic protection of myocardium at different stages of CHD. Today, the main principles of preconditioning are purposefully applied to the development of therapeutic strategies for the treatment of CHD. The most widely used in the clinical practice are local and distant preconditioning modalities as well as preconditioning by physical exercises whose well-known protective effects are used in cardiosurgery and routine clinical practice. Elaboration of rehabilitative and preventive programs taking account of vaso- and cardioprotective effects of preconditioning may significantly increase the effectiveness of the rehabilitative treatment of CHD patients with poor organic coronary and myocardial reserve.

  20. Roles of thioredoxin in nitric oxide-dependent preconditioning-induced tolerance against MPTP neurotoxin

    SciTech Connect

    Chiueh, C.C. . E-mail: chiueh@tmu.edu.tw; Andoh, Tsugunobu; Chock, P. Boon

    2005-09-01

    Hormesis, a stress tolerance, can be induced by ischemic preconditioning stress. In addition to preconditioning, it may be induced by other means, such as gas anesthetics. Preconditioning mechanisms, which may be mediated by reprogramming survival genes and proteins, are obscure. A known neurotoxicant, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causes less neurotoxicity in the mice that are preconditioned. Pharmacological evidences suggest that the signaling pathway of {center_dot}NO-cGMP-PKG (protein kinase G) may mediate preconditioning phenomenon. We developed a human SH-SY5Y cell model for investigating {sup {center_dot}}NO-mediated signaling pathway, gene regulation, and protein expression following a sublethal preconditioning stress caused by a brief 2-h serum deprivation. Preconditioned human SH-SY5Y cells are more resistant against severe oxidative stress and apoptosis caused by lethal serum deprivation and 1-mehtyl-4-phenylpyridinium (MPP{sup +}). Both sublethal and lethal oxidative stress caused by serum withdrawal increased neuronal nitric oxide synthase (nNOS/NOS1) expression and {sup {center_dot}}NO levels to a similar extent. In addition to free radical scavengers, inhibition of nNOS, guanylyl cyclase, and PKG blocks hormesis induced by preconditioning. S-nitrosothiols and 6-Br-cGMP produce a cytoprotection mimicking the action of preconditioning tolerance. There are two distinct cGMP-mediated survival pathways: (i) the up-regulation of a redox protein thioredoxin (Trx) for elevating mitochondrial levels of antioxidant protein Mn superoxide dismutase (MnSOD) and antiapoptotic protein Bcl-2, and (ii) the activation of mitochondrial ATP-sensitive potassium channels [K(ATP)]. Preconditioning induction of Trx increased tolerance against MPP{sup +}, which was blocked by Trx mRNA antisense oligonucleotide and Trx reductase inhibitor. It is concluded that Trx plays a pivotal role in {sup {center_dot}}NO-dependent preconditioning hormesis against

  1. Enhanced hypoxic preconditioning by isoflurane: signaling gene expression and requirement of intracellular Ca2+ and inositol triphosphate receptors

    PubMed Central

    Bickler, Philip E.; Fahlman, Christian S.

    2012-01-01

    Neurons preconditioned with non-injurious hypoxia or the anesthetic isoflurane express different genes but are equally protected against severe hypoxia/ischemia. We hypothesized that neuroprotection would be augmented when preconditioning with isoflurane and hypoxic preconditioning are combined. We also tested if preconditioning requires intracellular Ca2+ and the inositol triphosphate receptor, and if gene expression is similar in single agent and combined preconditioning. Hippocampal slice cultures prepared from 9 day-old rats were preconditioned with hypoxia (95% N2, 5% CO2 for 15 min, HPC), 1% isoflurane for 15 min (APC) or their combination (CPC) for 15 min. A day later cultures were deprived of O2 and glucose (OGD) to produce neuronal injury. Cell death was assessed 48 hr after OGD. mRNA encoding 119 signal transduction genes was quantified with cDNA micro arrays. Intracellular Ca2+ in CA1 region was measured with fura-2 during preconditioning. The cell-permeable Ca2+ buffer BAPTA-AM, the IP3 receptor antagonist Xestospongin C and RNA silencing were used to investigate preconditioning mechanisms. CPC decreased CA1, CA3 and dentate region death by 64–86% following OGD, more than HPC or APC alone (P<0.01). Gene expression following CPC was an amalgam of gene expression in HPC and APC, with simultaneous increases in growth/development and survival/apoptosis regulation genes. Intracellular Ca2+ chelation and RNA silencing of IP3 receptors prevented preconditioning neuroprotection and gene responses. We conclude that combined isoflurane-hypoxia preconditioning augments neuroprotection compared to single agents in immature rat hippocampal slice cultures. The mechanism involves genes for growth, development, apoptosis regulation and cell survival as well as IP3 receptors and intracellular Ca2+. PMID:20434434

  2. Enhanced hypoxic preconditioning by isoflurane: signaling gene expression and requirement of intracellular Ca2+ and inositol triphosphate receptors.

    PubMed

    Bickler, Philip E; Fahlman, Christian S

    2010-06-22

    Neurons preconditioned with non-injurious hypoxia or the anesthetic isoflurane express different genes but are equally protected against severe hypoxia/ischemia. We hypothesized that neuroprotection would be augmented when preconditioning with isoflurane and hypoxic preconditioning are combined. We also tested if preconditioning requires intracellular Ca(2+) and the inositol triphosphate receptor, and if gene expression is similar in single agent and combined preconditioning. Hippocampal slice cultures prepared from 9 day old rats were preconditioned with hypoxia (95% N(2), 5% CO(2) for 15 min, HPC), 1% isoflurane for 15 min (APC) or their combination (CPC) for 15 min. A day later cultures were deprived of O(2) and glucose (OGD) to produce neuronal injury. Cell death was assessed 48 h after OGD. mRNA encoding 119 signal transduction genes was quantified with cDNA micro arrays. Intracellular Ca(2+) in CA1 region was measured with fura-2 during preconditioning. The cell-permeable Ca(2+) buffer BAPTA-AM, the IP(3) receptor antagonist Xestospongin C and RNA silencing were used to investigate preconditioning mechanisms. CPC decreased CA1, CA3 and dentate region death by 64-86% following OGD, more than HPC or APC alone (P<0.01). Gene expression following CPC was an amalgam of gene expression in HPC and APC, with simultaneous increases in growth/development and survival/apoptosis regulation genes. Intracellular Ca(2+) chelation and RNA silencing of IP(3) receptors prevented preconditioning neuroprotection and gene responses. We conclude that combined isoflurane-hypoxia preconditioning augments neuroprotection compared to single agents in immature rat hippocampal slice cultures. The mechanism involves genes for growth, development, apoptosis regulation and cell survival as well as IP(3) receptors and intracellular Ca(2+).

  3. PVM and IP multicast

    SciTech Connect

    Dunigan, T.H.; Hall, K.A.

    1996-12-01

    This report describes a 1994 demonstration implementation of PVM that uses IP multicast. PVM`s one-to-many unicast implementation of its pvm{_}mcast() function is replaced with reliable IP multicast. Performance of PVM using IP multicast over local and wide-area networks is measured and compared with the original unicast implementation. Current limitations of IP multicast are noted.

  4. Cardioprotection by remote ischemic conditioning: Mechanisms and clinical evidences

    PubMed Central

    Aimo, Alberto; Borrelli, Chiara; Giannoni, Alberto; Pastormerlo, Luigi Emilio; Barison, Andrea; Mirizzi, Gianluca; Emdin, Michele; Passino, Claudio

    2015-01-01

    In remote ischemic conditioning (RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site (remote ischemic preconditioning), during the ischemic insult (remote ischemic perconditioning) or at the onset of reperfusion (remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy. PMID:26516416

  5. Preconditioning Provides Neuroprotection in Models of CNS Disease: Paradigms and Clinical Significance

    PubMed Central

    Stetler, R. Anne; Leak, Rehana K.; Gan, Yu; Li, Peiying; Hu, Xiaoming; Jing, Zheng; Chen, Jun; Zigmond, Michael J.; Gao, Yanqin

    2014-01-01

    Preconditioning is a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. Preconditioning has been observed in multiple organisms and can occur in the brain as well as other tissues. Extensive animal studies suggest that the brain can be preconditioned to resist acute injuries, such as ischemic stroke, neonatal hypoxia/ischemia, trauma, and agents that are used in models of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Effective preconditioning stimuli are numerous and diverse, ranging from transient ischemia, hypoxia, hyperbaric oxygen, hypothermia and hyperthermia, to exposure to neurotoxins and pharmacological agents. The phenomenon of “cross-tolerance,” in which a sublethal stress protects against a different type of injury, suggests that different preconditioning stimuli may confer protection against a wide range of injuries. Research conducted over the past few decades indicates that brain preconditioning is complex, involving multiple effectors such as metabolic inhibition, activation of extra- and intracellular defense mechanisms, a shift in the neuronal excitatory/inhibitory balance, and reduction in inflammatory sequelae. An improved understanding of brain preconditioning should help us identify innovative therapeutic strategies that prevent or at least reduce neuronal damage in susceptible patients. In this review, we focus on the experimental evidence of preconditioning in the brain and systematically survey the models used to develop paradigms for neuroprotection, and then discuss the clinical potential of brain preconditioning. In a subsequent components of this two-part series, we will discuss the cellular and molecular events that are likely to underlie these phenomena. PMID:24389580

  6. Is Local Nitric Oxide Availability Responsible for Myocardial Salvage after Remote Preconditioning?

    PubMed Central

    Arroyo-Martínez, Esbeidira Aranet; Meaney, Alejandra; Gutiérrez-Salmeán, Gabriela; Rivera-Capello, Juan Miguel; González-Coronado, Vidal; Alcocer-Chauvet, Alejandro; Castillo, Genaro; Nájera, Nayelli; Ceballos, Guillermo; Meaney, Eduardo

    2016-01-01

    Background: Remote ischemic preconditioning (RIPC) represents an attractive therapy for myocardial protection, particularly when ischemic events can be anticipated. Although several hypothetic mechanisms have been proposed, no definite molecular pathways have been elucidated. Objective: We evaluated the effect of brachial circulation cuff occlusion on myocardial ischemic tolerance, necrosis, and nitric oxide (NO) in patients with ischemic heart disease undergoing elective percutaneous coronary interventions (PCI). Methods: 46 patients were randomly allocated into two groups: control and RIPC before PCI procedures. Electrocardiographic analysis, serum concentrations of troponin I (cTn-I) were measured at baseline and 24 hours after PCI. A blood sample from the atherosclerotic plaque was drawn to determine nitrate and nitrites. Results: RIPC increased the availability of NO in the stented coronary artery. Control patients presented a small but significant increase in cTn-I, whilst it remained unchanged in preconditioned group. The preconditioning maneuver not only preserved but also enhanced the sum of R waves. Conclusions: RIPC induced an intracoronary increase of NO levels associated with a decrease in myocardial damage (measured as no increase in cTn-I) with electrocardiographic increases in the sum of R waves, suggesting an improved myocardium after elective PCI. PMID:27411096

  7. Orderings for conjugate gradient preconditionings

    NASA Technical Reports Server (NTRS)

    Ortega, James M.

    1991-01-01

    The effect of orderings on the rate of convergence of the conjugate gradient method with SSOR or incomplete Cholesky preconditioning is examined. Some results also are presented that help to explain why red/black ordering gives an inferior rate of convergence.

  8. 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.

  9. Ischemic Colitis

    PubMed Central

    FitzGerald, James F.; Hernandez III, Luis O.

    2015-01-01

    Most clinicians associate ischemic colitis with elderly patients who have underlying cardiovascular comorbidities. While the majority of cases probably occur in this population, the disease can present in younger patients as a result of different risk factors, making the diagnosis challenging. While a majority of patients respond to medical management, surgery is required in approximately 20% of the cases and is associated with high morbidity and mortality. PMID:26034405

  10. Systemic chemokine levels, coronary heart disease, and ischemic stroke events

    PubMed Central

    Canouï-Poitrine, F.; Luc, G.; Mallat, Z.; Machez, E.; Bingham, A.; Ferrieres, J.; Ruidavets, J.-B.; Montaye, M.; Yarnell, J.; Haas, B.; Arveiler, D.; Morange, P.; Kee, F.; Evans, A.; Amouyel, P.; Ducimetiere, P.

    2011-01-01

    Objectives: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. Methods: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. Results: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05–2.74), IP-10 (HR = 1.53; 95% CI 1.06–2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02–2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68–1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). Conclusions: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors. PMID:21849651

  11. Hypoxic Preconditioning Increases Survival and Pro-Angiogenic Capacity of Human Cord Blood Mesenchymal Stromal Cells In Vitro

    PubMed Central

    Bader, Andreas Matthäus; Klose, Kristin; Bieback, Karen; Korinth, Dirk; Schneider, Maria; Seifert, Martina; Choi, Yeong-Hoon; Kurtz, Andreas; Falk, Volkmar; Stamm, Christof

    2015-01-01

    Hypoxic preconditioning was shown to improve the therapeutic efficacy of bone marrow-derived multipotent mesenchymal stromal cells (MSCs) upon transplantation in ischemic tissue. Given the interest in clinical applications of umbilical cord blood-derived MSCs, we developed a specific hypoxic preconditioning protocol and investigated its anti-apoptotic and pro-angiogenic effects on cord blood MSCs undergoing simulated ischemia in vitro by subjecting them to hypoxia and nutrient deprivation with or without preceding hypoxic preconditioning. Cell number, metabolic activity, surface marker expression, chromosomal stability, apoptosis (caspases-3/7 activity) and necrosis were determined, and phosphorylation, mRNA expression and protein secretion of selected apoptosis and angiogenesis-regulating factors were quantified. Then, human umbilical vein endothelial cells (HUVEC) were subjected to simulated ischemia in co-culture with hypoxically preconditioned or naïve cord blood MSCs, and HUVEC proliferation was measured. Migration, proliferation and nitric oxide production of HUVECs were determined in presence of cord blood MSC-conditioned medium. Cord blood MSCs proved least sensitive to simulated ischemia when they were preconditioned for 24 h, while their basic behavior, immunophenotype and karyotype in culture remained unchanged. Here, “post-ischemic” cell number and metabolic activity were enhanced and caspase-3/7 activity and lactate dehydrogenase release were reduced as compared to non-preconditioned cells. Phosphorylation of AKT and BAD, mRNA expression of BCL-XL, BAG1 and VEGF, and VEGF protein secretion were higher in preconditioned cells. Hypoxically preconditioned cord blood MSCs enhanced HUVEC proliferation and migration, while nitric oxide production remained unchanged. We conclude that hypoxic preconditioning protects cord blood MSCs by activation of anti-apoptotic signaling mechanisms and enhances their angiogenic potential. Hence, hypoxic preconditioning

  12. Pharmacological preconditioning with L-carnitine: relevance to myocardial hemodynamic function and glycogen and lactate content.

    PubMed

    Najafi, Moslem; Javidnia, Ali; Ghorbani-Haghjo, Amir; Mohammadi, Sadollah; Garjani, Alireza

    2010-07-01

    Carnitine is a vital biologic substance facilitating fatty acids transport into mitochondria for ATP production. This study was to investigate the effects of pre-ischemic pharmacological preconditioning (PC) with L-carnitine (L-Car) on myocardial infarct size and cardiac functions in ischemic and reperfused isolated rat heart and meanwhile on left ventricular glycogen and lactate content. Isolated rat hearts were subjected to 30 min coronary artery occlusion followed by 120 min reperfusion. The hearts (n= 8-12) were perfused with L-Car (0.5-5 mM) only for 15 min before to 10 min after induction of ischemia. Preconditioning of the hearts with L-Car provided concentration-dependent cardioprotection as evidenced by improved postischemic ventricular functional recovery (developed pressure, left ventricular end diastolic pressure and coronary flow rate) and reduced myocardial infarct size (p<0.001). L-Car (2.5 mM) decreased both glycogen (p<0.001) and lactate (p>0.05) content in left ventricle during ischemia compared with the control. The results of this study demonstrate that L-Car pharmacologically precondition the hearts against ischemic and reperfusion injury in part by recovery of postischemic ventricular hemodynamic functions, depletion of glycogen and therefore reduction of lactate accumulation.

  13. [Hypoxic preconditioning is a phenomenon increasing tolerance of cardiomyocytes to hypoxia-reoxygenation].

    PubMed

    Maslov, L N; Lishmanov, Iu B; Kolar, F; Portnichenko, A G; Podoksenov, Iu K; Khaliulin, I G; Wang, H; Pei, J M

    2010-12-01

    The work covers the problem of hypoxic preconditioning (HP) carried out in isolated cardiomyocytes. Papers on delayed HP in vivo are comparatively few, and only some single works are devoted to early preconditioning in vivo. It has been established that the HP limits necrosis and apoptosis of cardiomyocytes and improves contractility of the isolated heart after ischemia (hypoxia) and reperfusion (reoxygenation). It was found that adenosine was a trigger of iP in vitro. It was proved that NO* was a trigger of HP both in vitro and in vivo. It was shown that reactive oxygen species also were triggers of hypoxic preconditioning. It was shown that ERK1/2 and p38 kinase played important role in delayed HP in vitro. PMID:21473105

  14. Lipopolysaccharide preconditioning prevents acceleration of kindling epileptogenesis induced by traumatic brain injury.

    PubMed

    Eslami, Mansoureh; Sayyah, Mohammad; Soleimani, Mansoureh; Alizadeh, Leila; Hadjighassem, Mahmoudreza

    2015-12-15

    10-20% of symptomatic epilepsies are post-traumatic. We examined effect of LPS preconditioning on epileptogenesis after controlled cortical impact (CCI). LPS (0.01, 0.1 and 0.5 mg/kg) was injected i.p. to rats 5 days before induction of CCI to parieto-temporal cortex. Kindling started 24h after CCI by i.p. injection of 30 mg/kg of pentylenetetrazole every other day until manifestation of 3 consecutive generalized seizures. CCI injury accelerated the rate of kindled seizures acquisition. LPS (0.1 and 0.5 mg/kg) prevented the acceleration of kindling. LPS preconditioning significantly decreased IL-1β and TNF-α over-expression and the number of damaged neurons in the hippocampus of traumatic rats.

  15. Long-term window of ischemic tolerance: An evolutionarily conserved form of metabolic plasticity regulated by epigenetic modifications?

    PubMed Central

    Khoury, Nathalie; Koronowski, Kevin B.; Perez-Pinzon, Miguel A.

    2016-01-01

    In the absence of effective neuroprotective agents in the clinic, ischemic and pharmacological preconditioning are gaining increased interest in the field of cerebral ischemia. Our lab recently reported that resveratrol preconditioning affords tolerance against a focal cerebral ischemic insult in mice that can last for at least 14 days in vivo making it the longest window of ischemic tolerance discovered to date by a single administration of a pharmacological agent. The mechanism behind this novel extended window of ischemic tolerance remains elusive. In the below commentary we discuss potential mechanisms that could explain this novel extended window of ischemic tolerance in the context of previously identified windows and the known mechanisms behind them. We also draw parallels from the fields of hibernation and hypoxia-tolerance, which are chronic adaptations to severe conditions of hypoxia and ischemia known to be mediated by a form of metabolic depression. We also briefly discuss the importance of epigenetic modifications in maintaining this depressed state of metabolism.

  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. Preconditioned iterations to calculate extreme eigenvalues

    SciTech Connect

    Brand, C.W.; Petrova, S.

    1994-12-31

    Common iterative algorithms to calculate a few extreme eigenvalues of a large, sparse matrix are Lanczos methods or power iterations. They converge at a rate proportional to the separation of the extreme eigenvalues from the rest of the spectrum. Appropriate preconditioning improves the separation of the eigenvalues. Davidson`s method and its generalizations exploit this fact. The authors examine a preconditioned iteration that resembles a truncated version of Davidson`s method with a different preconditioning strategy.

  18. Sevoflurane Preconditioning Confers Neuroprotection via Anti-apoptosis Effects.

    PubMed

    Wang, Hailian; Shi, Hong; Yu, Qiong; Chen, Jun; Zhang, Feng; Gao, Yanqin

    2016-01-01

    Neuroprotection against cerebral ischemia afforded by volatile anesthetic preconditioning (APC) has been demonstrated both in vivo and in vitro, yet the underlying mechanism is poorly understood. We previously reported that repeated sevoflurane APC reduced infarct size in rats after focal ischemia. In this study, we investigated whether inhibition of apoptotic signaling cascades contributes to sevoflurane APC-induced neuroprotection. Male Sprague-Dawley rats were exposed to ambient air or 2.4 % sevoflurane for 30 min per day for 4 consecutive days and then subjected to occlusion of the middle cerebral artery (MCAO) for 60 min at 24 h after the last sevoflurane intervention. APC with sevoflurane markedly decreased apoptotic cell death in rat brains, which was accompanied by decreased caspase-3 cleavage and cytochrome c release. The apoptotic suppression was associated with increased ratios of anti-apoptotic Bcl-2 family proteins over pro-apoptotic proteins and with decreased activation of JNK and p53 pathways. Thus, our data suggest that suppression of apoptotic cell death contributes to the neuroprotection against ischemic brain injury conferred by sevoflurane preconditioning. PMID:26463923

  19. 40 CFR 80.52 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... accordance with the “General vehicle handling requirements” per 40 CFR 86.132-96, up to and including the completion of the hot start exhaust test. (b) The preconditioning procedure prescribed at 40 CFR 86.132-96... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Vehicle preconditioning. 80.52...

  20. 40 CFR 80.52 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... accordance with the “General vehicle handling requirements” per 40 CFR 86.132-96, up to and including the completion of the hot start exhaust test. (b) The preconditioning procedure prescribed at 40 CFR 86.132-96... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Vehicle preconditioning. 80.52...

  1. 40 CFR 1065.518 - Engine preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., such as with a diesel engine that relies on urea-based selective catalytic reduction. Note that § 1065... catalyst. Perform preconditioning as follows, noting that the specific cycles for preconditioning are the... cycle specified in 40 CFR 1039.505(b)(1), the second half of the cycle consists of modes three...

  2. Neurophysiological preconditions of syntax acquisition.

    PubMed

    Friederici, Angela D; Oberecker, Regine; Brauer, Jens

    2012-03-01

    Although the neural network for language processing in the adult brain is well specified, the neural underpinning of language acquisition is still underdetermined. Here, we define the milestones of syntax acquisition and discuss the possible neurophysiological preconditions thereof. Early language learning seems to be based on the bilateral temporal cortices. Subsequent syntax acquisition apparently primarily recruits a neural network involving the left frontal cortex and the temporal cortex connected by a ventrally located fiber system. The late developing ability to comprehend syntactically complex sentences appears to require a neural network that connects Broca's area to the left posterior temporal cortex via a dorsally located fiber pathway. Thus, acquisition of syntax requires the maturation of fiber bundles connecting the classical language-relevant brain regions. PMID:21706312

  3. Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model

    PubMed Central

    Tanaka, Yuya; Shirasawa, Bungo; Takeuchi, Yuriko; Kawamura, Daichi; Nakamura, Tamami; Samura, Makoto; Nishimoto, Arata; Ueno, Koji; Morikage, Noriyasu; Hosoyama, Tohru; Hamano, Kimikazu

    2016-01-01

    Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts. PMID:27347329

  4. Preconditioning strategies to enhance physical performance on the day of competition.

    PubMed

    Kilduff, Liam P; Finn, Charlotte V; Baker, Julien S; Cook, Christian J; West, Daniel J

    2013-11-01

    Sports scientists and strength and conditioning professionals spend the majority of the competition season trying to ensure that their athletes' training and recovery strategies are appropriate to ensure optimal performance on competition day. However, there is an additional window on the day of competition where performance can be acutely enhanced with a number of preconditioning strategies. These strategies include appropriately designed warm-up, passive heat maintenance, postactivation potentiation, remote ischemic preconditioning, and, more recently, prior exercise and hormonal priming. The aim of this review was to explore the potential practical use of these strategies and propose a theoretical timeline outlining how they may be incorporated into athlete's precompetition routine to enhance performance. For the purpose of this review the discussion is confined to strategies that may enhance performance of short-duration, high-intensity sports (eg, sprinting, jumping, throwing). PMID:23689163

  5. Myocardial ischemic conditioning: Physiological aspects and clinical applications in cardiac surgery.

    PubMed

    Bousselmi, Radhouane; Lebbi, Mohamed Anis; Ferjani, Mustapha

    2014-04-01

    Ischemia-reperfusion is a major determinant of myocardial impairment in patients undergoing cardiac surgery. The main goal of research in cardioprotection is to develop effective techniques to avoid ischemia-reperfusion lesions. Myocardial ischemic conditioning is a powerful endogenous cardioprotective phenomenon. First described in animals in 1986, myocardial ischemic conditioning consists of applying increased tolerance of the myocardium to sustained ischemia by exposing it to brief episodes of ischemia-reperfusion. Several studies have sought to demonstrate its effective cardioprotective action in humans and to understand its underlying mechanisms. Myocardial ischemic conditioning has two forms: ischemic preconditioning (IPC) when the conditioning stimulus is applied before the index ischemia and ischemic postconditioning when the conditioning stimulus is applied after it. The cardioprotective action of ischemic conditioning was reproduced by applying the ischemia-reperfusion stimulus to organs remote from the heart. This non-invasive manner of applying ischemic conditioning has led to its application in clinical settings. Clinical trials for the different forms of ischemic conditioning were mainly developed in cardiac surgery. Many studies suggest that this phenomenon can represent an interesting adjuvant to classical cardioprotection during on-pump cardiac surgery. Ischemic conditioning was also tested in interventional cardiology with interesting results. Finally, advances made in the understanding of mechanisms that underlie the cardioprotective action of ischemic conditioning have paved the way to a new form of myocardial conditioning which is pharmacological conditioning.

  6. Persimmon leaf flavonoid induces brain ischemic tolerance in mice.

    PubMed

    Miao, Mingsan; Zhang, Xuexia; Wang, Linan

    2013-05-25

    The persimmon leaf has been shown to improve cerebral ischemic outcomes; however, its mechanism of action remains unclear. In this study, mice were subjected to 10 minutes of ischemic preconditioning, and persimmon leaf flavonoid was orally administered for 5 days. Results showed that the persimmon leaf flavonoid significantly improved the content of tissue type plasminogen activator and 6-keto prostaglandin-F1 α in the cerebral cortex, decreased the content of thromboxane B2, and reduced the content of plasminogen activator inhibitor-1 in mice. Following optical microscopy, persimmon leaf flavonoid was also shown to reduce cell swelling and nuclear hyperchromatism in the cerebral cortex and hippocampus of mice. These results suggested that persimmon leaf flavonoid can effectively inhibit brain thrombosis, improve blood supply to the brain, and relieve ischemia-induced pathological damage, resulting in brain ischemic tolerance.

  7. Methamphetamine Preconditioning Alters Midbrain Transcriptional Responses to Methamphetamine-Induced Injury in the Rat Striatum

    PubMed Central

    Cadet, Jean Lud; McCoy, Michael T.; Cai, Ning Sheng; Krasnova, Irina N.; Ladenheim, Bruce; Beauvais, Genevieve; Wilson, Natascha; Wood, William; Becker, Kevin G.; Hodges, Amber B.

    2009-01-01

    Methamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge. Quantitative PCR confirmed METH-induced changes in genes of interest and identified additional genes that were differentially impacted by the toxic METH challenge in the presence of METH preconditioning. These genes include small heat shock 27 kD 27 protein 2 (HspB2), thyrotropin-releasing hormone (TRH), brain derived neurotrophic factor (BDNF), c-fos, and some encoding antioxidant proteins including CuZn superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx)-1, and heme oxygenase-1 (Hmox-1). These observations are consistent, in part, with the transcriptional alterations reported in models of lethal ischemic injuries which are preceded by ischemic or pharmacological preconditioning. Our findings suggest that multiple molecular pathways might work in tandem to protect the nigrostriatal dopaminergic pathway against the deleterious effects of the toxic psychostimulant. Further analysis of the molecular and cellular pathways regulated by these genes should help to provide some

  8. Preconditioned Krylov subspace methods for eigenvalue problems

    SciTech Connect

    Wu, Kesheng; Saad, Y.; Stathopoulos, A.

    1996-12-31

    Lanczos algorithm is a commonly used method for finding a few extreme eigenvalues of symmetric matrices. It is effective if the wanted eigenvalues have large relative separations. If separations are small, several alternatives are often used, including the shift-invert Lanczos method, the preconditioned Lanczos method, and Davidson method. The shift-invert Lanczos method requires direct factorization of the matrix, which is often impractical if the matrix is large. In these cases preconditioned schemes are preferred. Many applications require solution of hundreds or thousands of eigenvalues of large sparse matrices, which pose serious challenges for both iterative eigenvalue solver and preconditioner. In this paper we will explore several preconditioned eigenvalue solvers and identify the ones suited for finding large number of eigenvalues. Methods discussed in this paper make up the core of a preconditioned eigenvalue toolkit under construction.

  9. Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury

    PubMed Central

    Yildirim, Ferah; Ji, Shengbo; Kronenberg, Golo; Barco, Angel; Olivares, Roman; Benito, Eva; Dirnagl, Ulrich; Gertz, Karen; Endres, Matthias

    2014-01-01

    Epigenetic transcriptional regulation by histone acetylation depends on the balance between histone acetyltransferase (HAT) and deacetylase activities (HDAC). Inhibition of HDAC activity provides neuroprotection, indicating that the outcome of cerebral ischemia depends crucially on the acetylation status of histones. In the present study, we characterized the changes in histone acetylation levels in ischemia models of focal cerebral ischemia and identified cAMP-response element binding protein (CREB)–binding protein (CBP) as a crucial factor in the susceptibility of neurons to ischemic stress. Both neuron-specific RNA interference and neurons derived from CBP heterozygous knockout mice showed increased damage after oxygen-glucose deprivation (OGD) in vitro. Furthermore, we demonstrated that ischemic preconditioning by a short (5 min) subthreshold occlusion of the middle cerebral artery (MCA), followed 24 h afterwards by a 30 min occlusion of the MCA, increased histone acetylation levels in vivo. Ischemic preconditioning enhanced CBP recruitment and histone acetylation at the promoter of the neuroprotective gene gelsolin leading to increased gelsolin expression in neurons. Inhibition of CBP's HAT activity attenuated neuronal ischemic preconditioning. Taken together, our findings suggest that the levels of CBP and histone acetylation determine stroke outcome and are crucially associated with the induction of an ischemia-resistant state in neurons. PMID:24748101

  10. Ischemic optic neuropathy.

    PubMed

    Athappilly, Geetha; Pelak, Victoria S; Mandava, Naresh; Bennett, Jeffrey L

    2008-10-01

    Ischemic optic neuropathy is the most frequent cause of vision loss in middle age. Clinical and laboratory research studies have begun to clarify the natural history, clinical presentation, diagnostic criteria and pathogenesis of various ischemic nerve injuries. As a result, physicians are acquiring new tools to aid in the diagnosis and potential treatment of ischemic nerve injury. The aim of this review is to examine recent data on anterior and posterior ischemic optic neuropathy and to provide a framework for physicians to manage and counsel affected individuals. PMID:18826805

  11. Acute adenosinergic cardioprotection in ischemic-reperfused hearts.

    PubMed

    Headrick, John P; Hack, Ben; Ashton, Kevin J

    2003-11-01

    Cells of the cardiovascular system generate and release purine nucleoside adenosine in increasing quantities when constituent cells are "stressed" or subjected to injurious stimuli. This increased adenosine can interact with surface receptors in myocardial, vascular, fibroblast, and inflammatory cells to modulate cellular function and phenotype. Additionally, adenosine is rapidly reincorporated back into 5'-AMP to maintain the adenine nucleotide pool. Via these receptor-dependent and independent (metabolic) paths, adenosine can substantially modify the acute response to ischemic insult, in addition to generating a more sustained ischemia-tolerant phenotype (preconditioning). However, the molecular basis for acute adenosinergic cardioprotection remains incompletely understood and may well differ from more widely studied preconditioning. Here we review current knowledge and some controversies regarding acute cardioprotection via adenosine and adenosine receptor activation.

  12. Tumorigenic development of induced pluripotent stem cells in ischemic mouse brain.

    PubMed

    Yamashita, Toru; Kawai, Hiromi; Tian, Fengfeng; Ohta, Yasuyuki; Abe, Koji

    2011-01-01

    Induced pluripotent stem (iPS) cells may provide cures for various neurological diseases. However, undifferentiated iPS cells have high tumorigenicity, and evaluation of the cells fates, especially in pathologic condition model, is needed. In this study, we demonstrated the effect of ischemic condition to undifferentiated iPS cells fates in a mouse model of transient middle cerebral artery occlusion (MCAO). Undifferentiated iPS cells were characterized with immunofluorescent staining. The iPS cells (5 × 10⁵) were injected into ipsilateral striatum and cortex after 24 h of MCAO. Histological analysis was performed from 3 to 28 days after cell transplantation. iPS cells in ischemic brain formed teratoma with higher probability (p < 0.05) and larger volume (p < 0.01) compared with those in intact brain. Among the four transcriptional factors to produce iPS cells, c-Myc, Oct3/4, and Sox2 strongly expressed in iPS-derived tumors in ischemic brain (p < 0.01). Additionally, expression of matrix metalloproteinase-9 (MMP-9) and phosphorylated vascular endothelial growth factor receptor2 (phospho-VEGFR2) were significantly increased in iPS-derived tumors in the ischemic brain (p < 0.05). These results suggest that the transcriptional factors might increase expression of MMP-9 and activate VEGFR2, promoting teratoma formation in the ischemic brain. We strongly propose that the safety of iPS cells should be evaluated not only in normal condition, but also in a pathologic, disease model.

  13. Projection preconditioning for Lanczos-type methods

    SciTech Connect

    Bielawski, S.S.; Mulyarchik, S.G.; Popov, A.V.

    1996-12-31

    We show how auxiliary subspaces and related projectors may be used for preconditioning nonsymmetric system of linear equations. It is shown that preconditioned in such a way (or projected) system is better conditioned than original system (at least if the coefficient matrix of the system to be solved is symmetrizable). Two approaches for solving projected system are outlined. The first one implies straightforward computation of the projected matrix and consequent using some direct or iterative method. The second approach is the projection preconditioning of conjugate gradient-type solver. The latter approach is developed here in context with biconjugate gradient iteration and some related Lanczos-type algorithms. Some possible particular choices of auxiliary subspaces are discussed. It is shown that one of them is equivalent to using colorings. Some results of numerical experiments are reported.

  14. Preconditioning for first-order spectral discretization

    NASA Technical Reports Server (NTRS)

    Streett, C. L.; Macaraeg, M. G.

    1986-01-01

    Efficient solution of the equations from spectral discretizations is essential if the high-order accuracy of these methods is to be realized. Direct solution of these equations is rarely feasible, thus iterative techniques are required. A preconditioning scheme for first-order Chebyshev collocation operators is proposed herein, in which the central finite difference mesh is finer than the collocation mesh. Details of the proper techniques for transferring information between the meshes are given here, and the scheme is analyzed by examination of the eigenvalue spectra of the preconditioned operators. The effect of artificial viscosity required in the inversion of the finite difference operator is examined. A second preconditioning scheme, involving a high-order upwind finite difference operator of the van Leer type is also analyzed to provide a comparison with the present scheme. Finally, the performance of the present scheme is verified by application to several test problems.

  15. Minimal residual method stronger than polynomial preconditioning

    SciTech Connect

    Faber, V.; Joubert, W.; Knill, E.

    1994-12-31

    Two popular methods for solving symmetric and nonsymmetric systems of equations are the minimal residual method, implemented by algorithms such as GMRES, and polynomial preconditioning methods. In this study results are given on the convergence rates of these methods for various classes of matrices. It is shown that for some matrices, such as normal matrices, the convergence rates for GMRES and for the optimal polynomial preconditioning are the same, and for other matrices such as the upper triangular Toeplitz matrices, it is at least assured that if one method converges then the other must converge. On the other hand, it is shown that matrices exist for which restarted GMRES always converges but any polynomial preconditioning of corresponding degree makes no progress toward the solution for some initial error. The implications of these results for these and other iterative methods are discussed.

  16. Preconditioned techniques for large eigenvalue problems

    NASA Astrophysics Data System (ADS)

    Wu, Kesheng

    1997-11-01

    This research focuses on finding a large number of eigenvalues and eigen-vectors of a sparse symmetric or Hermitian matrix, for example, finding 1000 eigenpairs of a 100,000 × 100,000 matrix. These eigenvalue problems are challenging because the matrix size is too large for traditional QR based algorithms and the number of desired eigenpairs is too large for most common sparse eigenvalue algorithms. In this thesis, we approach this problem in two steps. First, we identify a sound preconditioned eigenvalue procedure for computing multiple eigenpairs. Second, we improve the basic algorithm through new preconditioning schemes and spectrum transformations. Through careful analysis, we see that both the Arnoldi and Davidson methods have an appropriate structure for computing a large number of eigenpairs with preconditioning. We also study three variations of these two basic algorithms. Without preconditioning, these methods are mathematically equivalent but they differ in numerical stability and complexity. However, the Davidson method is much more successful when preconditioned. Despite its success, the preconditioning scheme in the Davidson method is seen as flawed because the preconditioner becomes ill-conditioned near convergence. After comparison with other methods, we find that the effectiveness of the Davidson method is due to its preconditioning step being an inexact Newton method. We proceed to explore other Newton methods for eigenvalue problems to develop preconditioning schemes without the same flaws. We found that the simplest and most effective preconditioner is to use the Conjugate Gradient method to approximately solve equations generated by the Newton methods. Also, a different strategy of enhancing the performance of the Davidson method is to alternate between the regular Davidson iteration and a polynomial method for eigenvalue problems. To use these polynomials, the user must decide which intervals of the spectrum the polynomial should suppress. We

  17. Transient Ischemic Attack

    MedlinePlus

    Transient Ischemic Attack TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood clot blocks an artery for a short time. The only ... TIA is that with TIA the blockage is transient (temporary). TIA symptoms occur rapidly and last a ...

  18. [STRESS AND INFARCT LIMITING EFFECTS OF EARLY HYPOXIC PRECONDITIONING].

    PubMed

    Lishmanov, Yu B; Maslov, L N; Sementsov, A S; Naryzhnaya, N V; Tsibulnikov, S Yu

    2015-09-01

    It was established that early hypoxic preconditioning is an adaptive state different from eustress and distress. Hypoxic preconditioning has the cross effects, increasing the tolerance of the heart to ischemia-reperfusion and providing antiulcerogenic effect during immobilization stress.

  19. Identification of a major IP5 kinase in Cryptococcus neoformans confirms that PP-IP5/IP7, not IP6, is essential for virulence.

    PubMed

    Li, Cecilia; Lev, Sophie; Saiardi, Adolfo; Desmarini, Desmarini; Sorrell, Tania C; Djordjevic, Julianne T

    2016-01-01

    Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP3 to inositol pyrophosphate, PP-IP5/IP7, which is essential for virulence of Cryptococcus neoformans. Cryptococcal Kcs1 converts IP6 to PP-IP5/IP7, but the kinase converting IP5 to IP6 is unknown. Deletion of a putative IP5 kinase-encoding gene (IPK1) alone (ipk1Δ), and in combination with KCS1 (ipk1Δkcs1Δ), profoundly reduced virulence in mice. However, deletion of KCS1 and IPK1 had a greater impact on virulence attenuation than that of IPK1 alone. ipk1Δkcs1Δ and kcs1Δ lung burdens were also lower than those of ipk1Δ. Unlike ipk1Δ, ipk1Δkcs1Δ and kcs1Δ failed to disseminate to the brain. IP profiling confirmed Ipk1 as the major IP5 kinase in C. neoformans: ipk1Δ produced no IP6 or PP-IP5/IP7 and, in contrast to ipk1Δkcs1Δ, accumulated IP5 and its pyrophosphorylated PP-IP4 derivative. Kcs1 is therefore a dual specificity (IP5 and IP6) kinase producing PP-IP4 and PP-IP5/IP7. All mutants were similarly attenuated in virulence phenotypes including laccase, urease and growth under oxidative/nitrosative stress. Alternative carbon source utilisation was also reduced significantly in all mutants except ipk1Δ, suggesting that PP-IP4 partially compensates for absent PP-IP5/IP7 in ipk1Δ grown under this condition. In conclusion, PP-IP5/IP7, not IP6, is essential for fungal virulence. PMID:27033523

  20. Functional Genomics of Cardioprotection by Ischemic Conditioning and the Influence of Comorbid Conditions: Implications in Target Identification.

    PubMed

    Varga, Zoltan V; Giricz, Zoltan; Bencsik, Peter; Madonna, Rosalinda; Gyongyosi, Mariann; Schulz, Rainer; Mayr, Manuel; Thum, Thomas; Puskas, Laszlo G; Ferdinandy, Peter

    2015-01-01

    Ischemic heart disease including myocardial infarction develops on the basis of several risk-factors and comorbidities such as obesity, diabetes, hypertension, and hypercholesterolemia. Ischemic heart disease is the leading cause of mortality worldwide, therefore, identification of novel drug targets for cardioprotection is of great importance. Ischemic preconditioning, postconditioning, and remote conditioning trigger endogenous cardioprotective mechanisms that render the heart more resistant to lethal ischemic-reperfusion injury. However, major cardiovascular co-morbidities such as hyperlipidemia, diabetes, and their co-medications interfere with these cardioprotective mechanisms thereby limiting the efficacy of cardioprotective ischemic conditioning maneuvers. Ischemia reperfusion injury and cardioprotection by conditioning have been shown to affect global myocardial gene expression profile at the transcript level. Further understanding and the comprehensive analysis of the cardioprotective gene expression fingerprint in normal, protected, and in comorbid conditions may lead to identification of novel molecular targets for cardioprotection.

  1. 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-1β, TNF-α 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

  2. DAB2IP in cancer

    PubMed Central

    Hsieh, Jer-Tsong; Gong, Jianping; Xie, Daxing

    2016-01-01

    DOC-2/DAB2 is a member of the disable gene family that features tumor-inhibiting activity. The DOC-2/DAB2 interactive protein, DAB2IP, is a new member of the Ras GTPase-activating protein family. It interacts directly with DAB2 and has distinct cellular functions such as modulating different signal cascades associated with cell proliferation, survival, apoptosis and metastasis. Recently, DAB2IP has been found significantly down regulated in multiple types of cancer. The aberrant alteration of DAB2IP in cancer is caused by a variety of mechanisms, including the aberrant promoter methylation, histone deacetylation, and others. Reduced expression of DAB2IP in neoplasm may indicate a poor prognosis of many malignant cancers. Moreover, DAB2IP stands for a promising direction for developing targeted therapies due to its capacity to inhibit tumor cell growth in vitro and in vivo. Here, we summarize the present understanding of the tumor suppressive role of DAB2IP in cancer progression; the mechanisms underlying the dysregulation of DAB2IP; the gene functional mechanism and the prospects of DAB2IP in the future cancer research. PMID:26658103

  3. Health and Nutrition: Preconditions for Educational Achievement.

    ERIC Educational Resources Information Center

    Negussie, Birgit

    This paper discusses the importance of maternal and infant health for children's educational achievement. Education, health, and nutrition are so closely related that changes in one causes changes in the others. Improvement of maternal and preschooler health and nutrition is a precondition for improved educational achievement. Although parental…

  4. 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,…

  5. Remote preconditioning as a novel "conditioning" approach to repair the broken heart: potential mechanisms and clinical applications.

    PubMed

    Ravingerova, T; Farkasova, V; Griecsova, L; Carnicka, S; Murarikova, M; Barlaka, E; Kolar, F; Bartekova, M; Lonek, L; Slezak, J; Lazou, A

    2016-09-19

    Remote ischemic preconditioning (RIPC) is a novel strategy of protection against ischemia-reperfusion (IR) injury in the heart (and/or other organs) by brief episodes of non-lethal IR in a distant organ/tissue. Importantly, RIPC can be induced noninvasively by limitation of blood flow in the extremity implying the applicability of this method in clinical situations. RIPC (and its delayed phase) is a form of relatively short-term adaptation to ischemia, similar to ischemic PC, and likely they both share triggering mechanisms, whereas mediators and end-effectors may differ. It is hypothesized that communication between the signals triggered in the remote organs and protection in the target organ may be mediated through substances released from the preconditioned organ and transported via the circulation (humoral pathways), by neural pathways and/or via systemic anti-inflammatory and antiapoptotic response to short ischemic bouts. Identification of molecules involved in RIPC cascades may have therapeutic and diagnostic implications in the management of myocardial ischemia. Elucidation of the mechanisms of endogenous cardioprotection triggered in the remote organ could lead to the development of diverse pharmacological RIPC mimetics. In the present article, the authors provide a short overview of RIPC-induced protection, proposed underlying mechanisms and factors modulating RIPC as a promising cardioprotective strategy. PMID:27643940

  6. Condition number estimation of preconditioned matrices.

    PubMed

    Kushida, Noriyuki

    2015-01-01

    The present paper introduces a condition number estimation method for preconditioned matrices. The newly developed method provides reasonable results, while the conventional method which is based on the Lanczos connection gives meaningless results. The Lanczos connection based method provides the condition numbers of coefficient matrices of systems of linear equations with information obtained through the preconditioned conjugate gradient method. Estimating the condition number of preconditioned matrices is sometimes important when describing the effectiveness of new preconditionerers or selecting adequate preconditioners. Operating a preconditioner on a coefficient matrix is the simplest method of estimation. However, this is not possible for large-scale computing, especially if computation is performed on distributed memory parallel computers. This is because, the preconditioned matrices become dense, even if the original matrices are sparse. Although the Lanczos connection method can be used to calculate the condition number of preconditioned matrices, it is not considered to be applicable to large-scale problems because of its weakness with respect to numerical errors. Therefore, we have developed a robust and parallelizable method based on Hager's method. The feasibility studies are curried out for the diagonal scaling preconditioner and the SSOR preconditioner with a diagonal matrix, a tri-daigonal matrix and Pei's matrix. As a result, the Lanczos connection method contains around 10% error in the results even with a simple problem. On the other hand, the new method contains negligible errors. In addition, the newly developed method returns reasonable solutions when the Lanczos connection method fails with Pei's matrix, and matrices generated with the finite element method.

  7. Combined iron sucrose and protoporphyrin treatment protects against ischemic and toxin-mediated acute renal failure.

    PubMed

    Zager, Richard A; Johnson, Ali C M; Frostad, Kirsten B

    2016-07-01

    Tissue preconditioning, whereby various short-term stressors initiate organ resistance to subsequent injury, is well recognized. However, clinical preconditioning of the kidney for protection against acute kidney injury (AKI) has not been established. Here we tested whether a pro-oxidant agent, iron sucrose, combined with a protoporphyrin (Sn protoporphyrin), can induce preconditioning and protect against acute renal failure. Mice were pretreated with iron sucrose, protoporphyrin, cyanocobalamin, iron sucrose and protoporphyrin, or iron sucrose and cyanocobalamin. Eighteen hours later, ischemic, maleate, or glycerol models of AKI were induced, and its severity was assessed the following day (blood urea nitrogen, plasma creatinine concentrations; post-ischemic histology). Agent impact on cytoprotective gene expression (heme oxygenase 1, hepcidin, haptoglobin, hemopexin, α1-antitrypsin, α1-microglobulin, IL-10) was assessed as renal mRNA and protein levels. AKI-associated myocardial injury was gauged by plasma troponin I levels. Combination agent administration upregulated multiple cytoprotective genes and, unlike single agent administration, conferred marked protection against each tested model of acute renal failure. Heme oxygenase was shown to be a marked contributor to this cytoprotective effect. Preconditioning also blunted AKI-induced cardiac troponin release. Thus, iron sucrose and protoporphyrin administration can upregulate diverse cytoprotective genes and protect against acute renal failure. Associated cardiac protection implies potential relevance to both AKI and its associated adverse downstream effects. PMID:27165818

  8. Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia-Reperfusion Injury

    PubMed Central

    Theodoraki, Kassiani; Karmaniolou, Iosifina; Tympa, Aliki; Tasoulis, Marios-Konstantinos; Nastos, Constantinos; Vassiliou, Ioannis; Arkadopoulos, Nikolaos; Smyrniotis, Vassilios

    2016-01-01

    Liver ischemia/reperfusion injury may significantly compromise hepatic postoperative function. Various hepatoprotective methods have been improvised, aiming at attenuating IR injury. With ischemic preconditioning (IPC), the liver is conditioned with a brief ischemic period followed by reperfusion, prior to sustained ischemia. Ischemic postconditioning (IPostC), consisting of intermittent sequential interruptions of blood flow in the early phase of reperfusion, seems to be a more feasible alternative than IPC, since the onset of reperfusion is more predictable. Regarding the potential mechanisms involved, it has been postulated that the slow intermittent oxygenation through controlled reperfusion decreases the burst production of oxygen free radicals, increases antioxidant activity, suppresses neutrophil accumulation, and modulates the apoptotic cascade. Additionally, favorable effects on mitochondrial ultrastructure and function, and upregulation of the cytoprotective properties of nitric oxide, leading to preservation of sinusoidal structure and maintenance of blood flow through the hepatic circulation could also underlie the protection afforded by postconditioning. Clinical studies are required to show whether biochemical and histological improvements afforded by the reperfusion/reocclusion cycles of postconditioning during early reperfusion can be translated to a substantial clinical benefit in liver resection and transplantation settings or to highlight more aspects of its molecular mechanisms. PMID:27340509

  9. Combination of hyperhomocysteinemia and ischemic tolerance in experimental model of global ischemia in rats.

    PubMed

    Kovalska, M; Kovalska, L; Tothova, B; Mahmood, S; Adamkov, M; Lehotsky, J

    2015-12-01

    Epidemiological studies show positive relationship between mild-to-moderate hyperhomocysteinemia (hHcy) and the risk of cerebrovascular diseases. The study determines whether hyperhomocysteinemia (risk factor of brain ischemia) alone or in combination with the ischemic preconditioning (IPC) affects the ischemia-induced neurodegenerative changes and imbalance in MAPK/p-ERK1/2 and MAPK/p-p38 expression in the rat brains. hHcy was induced by subcutaneous administration of homocysteine (0.45 μmol/g body weight) twice a day at 8 h intervals for 14 days. Rats were preconditioned by 5 min ischemia and 2 days later, 15 min of global forebrain ischemia was induced by four vessel occlusion. We observed that hHcy alone significantly increased neurodegeneration by Fluoro-Jade C and TUNEL possitive cells in hippocampus as well as in cortex. We found elevated level of MAPK/p-ERK and decreased level of MAPK/p-p38 after pre-ischemic challenge by Western blot and fluorescent immunohistochemistry. In conclusion, preconditioning even if combined with hHcy could preserve the neuronal tissue from lethal ischemic effect. This study provides evidence for the interplay and tight integration between ERK and p38 MAPKs signalling mechanisms in response to the hHcy and also if in association with brain ischemia/IPC challenge in the rat brain. PMID:26769838

  10. Glaucoma-induced degeneration of retinal ganglion cells prevented by hypoxic preconditioning: a model of glaucoma tolerance.

    PubMed

    Zhu, Yanli; Zhang, Lihong; Schmidt, Jimena F; Gidday, Jeffrey M

    2012-01-01

    Like all cells, neurons adapt to stress by transient alterations in phenotype, an epigenetic response that forms the basis for preconditioning against acute ischemic injury in the central nervous system. We recently showed that a modified repetitive hypoxic preconditioning (RHP) regimen significantly extends the window of ischemic tolerance to acute retinal ischemic injury from days to months. The present study was undertaken to determine if this uniquely protracted neuroprotective phenotype would also confer resistance to glaucomatous neurodegeneration. Retinal ganglion cell death at somatic and axonal levels was assessed after both 3 and 10 wks of sustained intraocular hypertension in an adult mouse model of inducible, open-angle glaucoma, with or without RHP before intraocular pressure elevation. Loss of brn3-positive ganglion cell soma after 3 wks of experimental glaucoma, along with increases in several apoptotic endpoints, were all significantly and robustly attenuated in mice subjected to RHP. Soma protection by RHP was also confirmed after 10 wks of intraocular hypertension by brn3 and SMI32 immunostaining. In addition, quantification of axon density in the postlaminar optic nerve documented robust preservation in RHP-treated mice, and neurofilament immunostaining also revealed preconditioning-induced improvements in axon integrity/survival in both retina and optic nerve after 10 wks of experimental glaucoma. This uniquely protracted period of phenotypic change, established in retinal ganglion cells by the activation of latent antiapoptotic, prosurvival mechanisms at both somatic and axonal levels, reflects a novel form of inducible neuronal plasticity that may provide innovative therapeutic targets for preventing and treating glaucoma and other neurodegenerative diseases. PMID:22396016

  11. Time to Give Up on Cardioprotection? A Critical Appraisal of Clinical Studies on Ischemic Pre-, Post-, and Remote Conditioning.

    PubMed

    Heusch, Gerd; Rassaf, Tienush

    2016-08-19

    The mortality from acute myocardial infarction (AMI) remains significant, and the prevalence of post-myocardial infarction heart failure is increasing. Therefore, cardioprotection beyond timely reperfusion is needed. Conditioning procedures are the most powerful cardioprotective interventions in animal experiments. However, ischemic preconditioning cannot be used to reduce infarct size in patients with AMI because its occurrence is not predictable; several studies in patients undergoing surgical coronary revascularization report reduced release of creatine kinase and troponin. Ischemic postconditioning reduces infarct size in most, but not all, studies in patients undergoing interventional reperfusion of AMI, but may require direct stenting and exclusion of patients with >6 hours of symptom onset to protect. Remote ischemic conditioning reduces infarct size in patients undergoing interventional reperfusion of AMI, elective percutaneous or surgical coronary revascularization, and other cardiovascular surgery in many, but not in all, studies. Adequate dose-finding phase II studies do not exist. There are only 2 phase III trials, both on remote ischemic conditioning in patients undergoing cardiovascular surgery, both with neutral results in terms of infarct size and clinical outcome, but also both with major problems in trial design. We discuss the difficulties in translation of cardioprotection from animal experiments and proof-of-concept trials to clinical practice. Given that most studies on ischemic postconditioning and all studies on remote ischemic preconditioning in patients with AMI reported reduced infarct size, it would be premature to give up on cardioprotection. PMID:27539973

  12. 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.

  13. 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.

  14. Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing.

    PubMed

    Schaafsma, W; Zhang, X; van Zomeren, K C; Jacobs, S; Georgieva, P B; Wolf, S A; Kettenmann, H; Janova, H; Saiepour, N; Hanisch, U-K; Meerlo, P; van den Elsen, P J; Brouwer, N; Boddeke, H W G M; Eggen, B J L

    2015-08-01

    Microglia, the innate immune cells of the central nervous system (CNS), react to endotoxins like bacterial lipopolysaccharides (LPS) with a pronounced inflammatory response. To avoid excess damage to the CNS, the microglia inflammatory response needs to be tightly regulated. Here we report that a single LPS challenge results in a prolonged blunted pro-inflammatory response to a subsequent LPS stimulation, both in primary microglia cultures (100 ng/ml) and in vivo after intraperitoneal (0.25 and 1mg/kg) or intracerebroventricular (5 μg) LPS administration. Chromatin immunoprecipitation (ChIP) experiments with primary microglia and microglia acutely isolated from mice showed that LPS preconditioning was accompanied by a reduction in active histone modifications AcH3 and H3K4me3 in the promoters of the IL-1β and TNF-α genes. Furthermore, LPS preconditioning resulted in an increase in the amount of repressive histone modification H3K9me2 in the IL-1β promoter. ChIP and knock-down experiments showed that NF-κB subunit RelB was bound to the IL-1β promoter in preconditioned microglia and that RelB is required for the attenuated LPS response. In addition to a suppressed pro-inflammatory response, preconditioned primary microglia displayed enhanced phagocytic activity, increased outward potassium currents and nitric oxide production in response to a second LPS challenge. In vivo, a single i.p. LPS injection resulted in reduced performance in a spatial learning task 4 weeks later, indicating that a single inflammatory episode affected memory formation in these mice. Summarizing, we show that LPS-preconditioned microglia acquire an epigenetically regulated, immune-suppressed phenotype, possibly to prevent excessive damage to the central nervous system in case of recurrent (peripheral) inflammation.

  15. The macrophage mediates the renoprotective effects of endotoxin preconditioning.

    PubMed

    Hato, Takashi; Winfree, Seth; Kalakeche, Rabih; Dube, Shataakshi; Kumar, Rakesh; Yoshimoto, Momoko; Plotkin, Zoya; Dagher, Pierre C

    2015-06-01

    Preconditioning is a preventative approach, whereby minimized insults generate protection against subsequent larger exposures to the same or even different insults. In immune cells, endotoxin preconditioning downregulates the inflammatory response and yet, preserves the ability to contain infections. However, the protective mechanisms of preconditioning at the tissue level in organs such as the kidney remain poorly understood. Here, we show that endotoxin preconditioning confers renal epithelial protection in various models of sepsis in vivo. We also tested the hypothesis that this protection results from direct interactions between the preconditioning dose of endotoxin and the renal tubules. This hypothesis is on the basis of our previous findings that endotoxin toxicity to nonpreconditioned renal tubules was direct and independent of immune cells. Notably, we found that tubular protection after preconditioning has an absolute requirement for CD14-expressing myeloid cells and particularly, macrophages. Additionally, an intact macrophage CD14-TRIF signaling pathway was essential for tubular protection. The preconditioned state was characterized by increased macrophage number and trafficking within the kidney as well as clustering of macrophages around S1 proximal tubules. These macrophages exhibited increased M2 polarization and upregulation of redox and iron-handling molecules. In renal tubules, preconditioning prevented peroxisomal damage and abolished oxidative stress and injury to S2 and S3 tubules. In summary, these data suggest that macrophages are essential mediators of endotoxin preconditioning and required for renal tissue protection. Preconditioning is, therefore, an attractive model to investigate novel protective pathways for the prevention and treatment of sepsis.

  16. 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.

  17. Caloric restriction restores the cardioprotective effect of preconditioning in the rat heart.

    PubMed

    Long, Paige; Nguyen, Quang; Thurow, Chantelle; Broderick, Tom L

    2002-07-01

    Preconditioning (PC) describes the observation that brief periods of ischemia paradoxically protect the heart and limit necrosis caused by a subsequent more prolonged period of ischemia. However, the PC response is attenuated in hearts from 9- to 12-month-old Sprague-Dawley rats, as compared to young adults. This study determined whether long-term caloric restriction (CR) could preserve the PC response, since CR increases ischemic tolerance in these hearts. Following 6 months of CR, isolated hearts underwent PC followed by ischemia and reperfusion. In contrast to control hearts in which PC response was attenuated, PC in CR hearts was clearly of benefit. In these hearts, aortic flow was increased resulting in a dramatic improvement of cardiac output. Our study suggests that CR is effective in preserving the PC response.

  18. Running TCP/IP over ATM Networks.

    ERIC Educational Resources Information Center

    Witt, Michael

    1995-01-01

    Discusses Internet protocol (IP) and subnets and describes how IP may operate over asynchronous transfer mode (ATM). Topics include TCP (transmission control protocol), ATM cells and adaptation layers, a basic architectural model for IP over ATM, address resolution, mapping IP to a subnet technology, and connection management strategy. (LRW)

  19. Hyperbaric oxygen preconditioning attenuates early apoptosis after spinal cord ischemia in rats.

    PubMed

    Wang, Liping; Li, Wenxian; Kang, Zhimin; Liu, Yun; Deng, Xiaoming; Tao, Hengyi; Xu, Weigang; Li, Runping; Sun, Xuejun; Zhang, John H

    2009-01-01

    This study tested the hypothesis that spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning (HBO-PC) is mediated by inhibition of early apoptosis. Male Sprague-Dawley rats were preconditioned with consecutive 4 cycles of 1-h HBO exposures (2.5 atmospheres absolute [ATA], 100% O(2)) at a 12-h interval. At 24 h after the last HBO pretreatment, rats underwent 9 min of spinal cord ischemia induced by occlusion of the descending thoracic aorta in combination with systemic hypotension (40 mmHg). Spinal cord ischemia produced marked neuronal death and neurological dysfunction in animals. HBO-PC enhanced activities of Mn-superoxide dismutase (Mn-SOD) and catalase, as well as the expression of Bcl-2 in the mitochondria in the normal spinal cord at 24 h after the last pretreatment (before spinal cord ischemia), and retained higher levels throughout the early reperfusion in the ischemic spinal cord. In parallel, superoxide and hydrogen peroxide levels in mitochondria were decreased, cytochrome c release into the cytosol was reduced at 1 h after reperfusion, and activation of caspase-3 and -9 was subsequently attenuated. HBO-PC improved neurobehavioral scores and reduced neuronal apoptosis in the anterior, intermediate, and dorsal gray matter of lumbar segment at 24 h after spinal cord ischemia. HBO-PC increased nitric oxide (NO) production. L-nitroarginine-methyl-ester (L-NAME; 10 mg/kg), a nonselective NO synthase (NOS) inhibitor, applied before each HBO-PC protocol abolished these beneficial effects of HBO-PC. We conclude that HBO-PC reduced spinal cord ischemia-reperfusion injury by increasing Mn-SOD, catalase, and Bcl-2, and by suppressing mitochondrial apoptosis pathway. NO may be involved in this neuroprotection. PMID:19196076

  20. The Protective Effect of Remote Renal Preconditioning Against Hippocampal Ischemia Reperfusion Injury: Role of KATP Channels.

    PubMed

    Mehrjerdi, Fatemeh Zare; Aboutaleb, Nahid; Pazoki-Toroudi, Hamidreza; Soleimani, Mansoureh; Ajami, Marjan; Khaksari, Mehdi; Safari, Fatemeh; Habibey, Rouhollah

    2015-12-01

    Remote ischemic preconditioning (RIPC), which consists of several brief ischemia/reperfusion applied at the remote site of lethal ischemia reperfusion, can, through activating different mechanisms, increase the ability of the body's endogenous protection against prolonged ischemia/reperfusion. Recent studies have shown that RIPC has neuroprotective effects, but its mechanisms are not well elucidated. The present study aimed to determine whether activation of KATP channels in remote renal preconditioning decreases hippocampus damage induced by global cerebral ischemia. RIPC was induced by ischemia of the left renal artery (IPC); 24 h later, global cerebral ischemia reperfusion (IR) was induced by common carotid arteries occlusion. 5hydroxydecanoate (5HD) and glibenclamide (Gli) were injected before of IPC. The levels of malondialdehyde (MDA) and catalase (CAT) activity were assessed in hippocampus. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was assessed to detect apoptotic cells in hippocampus. RIPC inhibited apoptosis by decreasing positive TUNEL cells (P < 0.05). KATP channels blocking with 5HD and Gli markedly increased apoptosis in hippocampal cells in RIPC group (P < 0.001). RIPC decreased MDA level and increased CAT activity in ischemic hippocampus (P < 0.01). Also, 5HD and Gli inhibited the effect of RIPC on MDA level and CAT activity (P < 0.05). The present study shows that RIPC can effectively attenuate programmed cell death, increase activity of CAT, and reduce MDA levels. Blocking of KATP channels inhibited the protective effects of RIPC. PMID:26254913

  1. Matrix preconditioning: a robust operation for optical linear algebra processors.

    PubMed

    Ghosh, A; Paparao, P

    1987-07-15

    Analog electrooptical processors are best suited for applications demanding high computational throughput with tolerance for inaccuracies. Matrix preconditioning is one such application. Matrix preconditioning is a preprocessing step for reducing the condition number of a matrix and is used extensively with gradient algorithms for increasing the rate of convergence and improving the accuracy of the solution. In this paper, we describe a simple parallel algorithm for matrix preconditioning, which can be implemented efficiently on a pipelined optical linear algebra processor. From the results of our numerical experiments we show that the efficacy of the preconditioning algorithm is affected very little by the errors of the optical system.

  2. 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

  3. Approximate polynomial preconditioning applied to biharmonic equations on vector supercomputers

    NASA Technical Reports Server (NTRS)

    Wong, Yau Shu; Jiang, Hong

    1987-01-01

    Applying a finite difference approximation to a biharmonic equation results in a very ill-conditioned system of equations. This paper examines the conjugate gradient method used in conjunction with the generalized and approximate polynomial preconditionings for solving such linear systems. An approximate polynomial preconditioning is introduced, and is shown to be more efficient than the generalized polynomial preconditionings. This new technique provides a simple but effective preconditioning polynomial, which is based on another coefficient matrix rather than the original matrix operator as commonly used.

  4. Ouabain triggers preconditioning through activation of the Na+,K+-ATPase signaling cascade in rat hearts

    PubMed Central

    Pierre, Sandrine V.; Yang, Changjun; Yuan, Zhaokan; Seminerio, Jennifer; Mouas, Christian; Garlid, Keith D.; Dos-Santos, Pierre; Xie, Zijian

    2007-01-01

    Objective Because ouabain activates several pathways that are critical to cardioprotective mechanisms such as ischemic preconditioning, we tested if this digitalis compound could protect the heart against ischemia-reperfusion injury through activation of the Na+,K+-ATPase/c-Src receptor complex. Methods and Results In Langendorff-perfused rat hearts, a short (4 min) administration of ouabain 10 μM followed by an 8-minute washout before 30 minutes of global ischemia and reperfusion improved cardiac function, decreased lactate dehydrogenase release and reduced infarct size by 40%. Western blot analysis revealed that ouabain activated the cardioprotective phospholipase Cγ1/protein kinase Cε (PLC-γ1/PKCε) pathway. Pre-treatment of the hearts with the Src kinase family inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2) blocked not only ouabain-induced activation of PLC-γ1/PKCε pathway, but also cardiac protection. This protection was also blocked by a PKCε translocation inhibitor peptide (PKCε TIP). Conclusion Short exposure to a low concentration of ouabain protects the heart against ischemia/reperfusion injury. This effect of ouabain on the heart is most likely due to the activation of the Na+,K+-ATPase/c-Src receptor complex and subsequent stimulation of key mediators of preconditioning, namely PLC-γ1 and PKCε. PMID:17157283

  5. Simple Machine Perfusion Significantly Enhances Hepatocyte Yields of Ischemic and Fresh Rat Livers

    PubMed Central

    Izamis, Maria-Louisa; Calhoun, Candice; Uygun, Basak E.; Guzzardi, Maria Angela; Price, Gavrielle; Luitje, Martha; Saeidi, Nima; Yarmush, Martin L.; Uygun, Korkut

    2013-01-01

    The scarcity of viable hepatocytes is a significant bottleneck in cell transplantation, drug discovery, toxicology, tissue engineering, and bioartificial assist devices, where trillions of high-functioning hepatocytes are needed annually. We took the novel approach of using machine perfusion to maximize cell recovery, specifically from uncontrolled cardiac death donors, the largest source of disqualified donor organs. In a rat model, we developed a simple 3-h room temperature (20 ± 2°C) machine perfusion protocol to treat nonpremedicated livers exposed to 1 h of warm (34°C) ischemia. Treated ischemic livers were compared to fresh, fresh-treated, and untreated ischemic livers using viable hepatocyte yields and in vitro performance as quantitative endpoints. Perfusion treatment resulted in both a 25-fold increase in viable hepatocytes from ischemic livers and a 40% increase from fresh livers. While cell morphology and function in suspension and plate cultures of untreated warm ischemic cells was significantly impaired, treated warm ischemic cells were indistinguishable from fresh hepatocytes. Furthermore, a strong linear correlation between tissue ATP and cell yield enabled accurate evaluation of the extent of perfusion recovery. Maximal recovery of warm ischemic liver ATP content appears to be correlated with optimal flow through the microvasculature. These data demonstrate that the inclusion of a simple perfusion-preconditioning step can significantly increase the efficiency of functional hepatocyte yields and the number of donor livers that can be gainfully utilized. PMID:25431743

  6. 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.

  7. 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.

  8. Extremely Intense Magnetospheric Substorms : External Triggering? Preconditioning?

    NASA Astrophysics Data System (ADS)

    Tsurutani, Bruce; Echer, Ezequiel; Hajra, Rajkumar

    2016-07-01

    We study particularly intense substorms using a variety of near-Earth spacecraft data and ground observations. We will relate the solar cycle dependences of events, determine whether the supersubstorms are externally or internally triggered, and their relationship to other factors such as magnetospheric preconditioning. If time permits, we will explore the details of the events and whether they are similar to regular (Akasofu, 1964) substorms or not. These intense substorms are an important feature of space weather since they may be responsible for power outages.

  9. Towards bulk based preconditioning for quantum dotcomputations

    SciTech Connect

    Dongarra, Jack; Langou, Julien; Tomov, Stanimire; Channing,Andrew; Marques, Osni; Vomel, Christof; Wang, Lin-Wang

    2006-05-25

    This article describes how to accelerate the convergence of Preconditioned Conjugate Gradient (PCG) type eigensolvers for the computation of several states around the band gap of colloidal quantum dots. Our new approach uses the Hamiltonian from the bulk materials constituent for the quantum dot to design an efficient preconditioner for the folded spectrum PCG method. The technique described shows promising results when applied to CdSe quantum dot model problems. We show a decrease in the number of iteration steps by at least a factor of 4 compared to the previously used diagonal preconditioner.

  10. Parallel preconditioning techniques for sparse CG solvers

    SciTech Connect

    Basermann, A.; Reichel, B.; Schelthoff, C.

    1996-12-31

    Conjugate gradient (CG) methods to solve sparse systems of linear equations play an important role in numerical methods for solving discretized partial differential equations. The large size and the condition of many technical or physical applications in this area result in the need for efficient parallelization and preconditioning techniques of the CG method. In particular for very ill-conditioned matrices, sophisticated preconditioner are necessary to obtain both acceptable convergence and accuracy of CG. Here, we investigate variants of polynomial and incomplete Cholesky preconditioners that markedly reduce the iterations of the simply diagonally scaled CG and are shown to be well suited for massively parallel machines.

  11. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  12. Thiazolidinedione Drugs Promote Onset, Alter Characteristics, and Increase Mortality of Ischemic Ventricular Fibrillation in Pigs

    PubMed Central

    Sarraf, Mohammad; Lu, Li; Ye, Shuyu; Reiter, Michael J.; Greyson, Clifford R.

    2016-01-01

    Purpose Despite favorable metabolic and vascular effects, thiazolidinedione (TZD) drugs have not convincingly reduced cardiovascular mortality in clinical trials, raising the possibility of countervailing, off-target effects. We previously showed that TZDs block cardiac ATP-sensitive potassium (KATP) channels in pigs. In this study, we investigated whether TZDs affect onset, spectral characteristics, and mortality of ischemic ventricular fibrillation (VF) and whether such effects are recapitulated by a non-selective KATP blocker (glyburide) or a mitochondrial KATP blocker (5-hydroxydecanoate). Methods A total of 121 anesthetized pigs were pre-treated with TZD (pioglitazone or rosiglitazone, 1 mg/kg IV, resulting in clinically relevant plasma concentrations), glyburide (1 mg/kg IV), 5-hydroxydecanoate (5 mg/kg IV) or inert vehicle. Ischemia was produced by occlusion of the left anterior descending coronary artery. In a subset of pigs treated with rosiglitazone or vehicle, ischemic preconditioning was performed. Results VF developed in all but 6 pigs. In non-preconditioned pigs, onset of VF occurred sooner with pioglitazone (11± 3 min, p<0.05) or rosiglitazone (14±3 min, p=0.06) than with vehicle (20±2 min). Defibrillation of VF was successful in 44% of pigs treated with vehicle, compared with 0% with pioglitazone (p=0.057) and 33% with rosiglitazone (NS). After ischemic preconditioning, defibrillation was successful in 62% of pigs treated with vehicle, compared with 26% treated with rosiglitazone (p=0.03). TZDs attenuated slowing of conduction due to ischemia and shifted ECG power spectra during VF toward higher frequencies. All effects of TZDs were recapitulated by glyburide, but not by 5-hydroxydecanoate, supporting an interaction of TZDs with the sarcolemmal KATP channel. Conclusion In a porcine model, TZDs promote onset and increase mortality of ischemic VF, associated with alterations of conduction and VF spectral characteristics. Similar effects in a

  13. Continuously Connected With Mobile IP

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Cisco Systems developed Cisco Mobile Networks, making IP devices mobile. With this innovation, a Cisco router and its connected IP devices can roam across network boundaries and connection types. Because a mobile user is able to keep the same IP address while roaming, a live IP connection can be maintained without interruption. Glenn Research Center jointly tested the technology with Cisco, and is working to use it on low-earth-orbiting research craft. With Cisco's Mobile Networks functionality now available in Cisco IOS Software release 12.2(4)T, the commercial advantages and benefits are numerous. The technology can be applied to public safety, military/homeland security, emergency management services, railroad and shipping systems, and the automotive industry. It will allow ambulances, police, firemen, and the U.S. Coast Guard to stay connected to their networks while on the move. In the wireless battlefield, the technology will provide rapid infrastructure deployment for U.S. national defense. Airline, train, and cruise passengers utilizing Cisco Mobile Networks can fly all around the world with a continuous Internet connection. Cisco IOS(R) Software is a registered trademark of Cisco Systems.

  14. [STRESS AND INFARCT LIMITING EFFECTS OF EARLY HYPOXIC PRECONDITIONING].

    PubMed

    Lishmanov, Yu B; Maslov, L N; Sementsov, A S; Naryzhnaya, N V; Tsibulnikov, S Yu

    2015-09-01

    It was established that early hypoxic preconditioning is an adaptive state different from eustress and distress. Hypoxic preconditioning has the cross effects, increasing the tolerance of the heart to ischemia-reperfusion and providing antiulcerogenic effect during immobilization stress. PMID:26672158

  15. 40 CFR 86.1232-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 19 2011-07-01 2011-07-01 false Vehicle preconditioning. 86.1232-96... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Evaporative... Methanol-Fueled Heavy-Duty Vehicles § 86.1232-96 Vehicle preconditioning. (a) Fuel tank cap(s) of...

  16. 40 CFR 86.532-78 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Vehicle preconditioning. 86.532-78... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1978 and Later New Motorcycles; Test Procedures § 86.532-78 Vehicle preconditioning. (a) The...

  17. 40 CFR 86.532-78 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Vehicle preconditioning. 86.532-78... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1978 and Later New Motorcycles; Test Procedures § 86.532-78 Vehicle preconditioning. (a) The...

  18. 40 CFR 1066.407 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) Prepare the vehicle for testing as described in 40 CFR 86.131. (b) If testing will include measurement of refueling emissions, perform the vehicle preconditioning steps as described in 40 CFR 86.153. Otherwise, perform the vehicle preconditioning steps as described in 40 CFR 86.132....

  19. 40 CFR 1066.407 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Prepare the vehicle for testing as described in 40 CFR 86.131. (b) If testing will include measurement of refueling emissions, perform the vehicle preconditioning steps as described in 40 CFR 86.153. Otherwise, perform the vehicle preconditioning steps as described in 40 CFR 86.132....

  20. Preconditioning cortical lesions reduce the incidence of peri-infarct depolarizations during focal ischemia in the Spontaneously Hypertensive Rat: interaction with prior anesthesia and the impact of hyperglycemia

    PubMed Central

    Zhao, Liang; Nowak Jr, Thaddeus S

    2015-01-01

    The relationship between peri-infarct depolarizations (PIDs) and infarction was investigated in a model of preconditioning by cortical freeze lesions (cryogenic lesions, CL) in the Spontaneously Hypertensive Rat. Small (< 5 mm3) lesions produced 24 hours before permanent focal ischemia were protective, without impacting baseline cerebral blood flow (CBF) and metabolism. Prior CL reduced infarct volume, associated with improved penumbral CBF as previously showed for ischemic preconditioning. The brief initial procedure avoided sham effects on infarct volume after subsequent occlusion under brief anesthesia. However, under prolonged isoflurane anesthesia for perfusion monitoring both sham and CL rats showed reduced PID incidence relative to naive animals. This anesthesia effect could be eliminated by using α-chloralose during perfusion imaging. As an additional methodological concern, blood glucose was frequently elevated at the time of the second surgery, reflecting buprenorphine-induced pica and other undefined mechanisms. Even modest hyperglycemia (>10 mmol/L) reduced PID incidence. In normoglycemic animals CL preconditioning reduced PID number by 50%, demonstrating associated effects on PID incidence, penumbral perfusion, and infarct progression. Hyperglycemia suppressed PIDs without affecting the relationship between CBF and infarction. This suggests that the primary effect of preconditioning is to improve penumbral perfusion, which in turn impacts PID incidence and infarct size. PMID:25757750

  1. Preconditioning cortical lesions reduce the incidence of peri-infarct depolarizations during focal ischemia in the Spontaneously Hypertensive Rat: interaction with prior anesthesia and the impact of hyperglycemia.

    PubMed

    Zhao, Liang; Nowak, Thaddeus S

    2015-07-01

    The relationship between peri-infarct depolarizations (PIDs) and infarction was investigated in a model of preconditioning by cortical freeze lesions (cryogenic lesions, CL) in the Spontaneously Hypertensive Rat. Small (< 5 mm(3)) lesions produced 24 hours before permanent focal ischemia were protective, without impacting baseline cerebral blood flow (CBF) and metabolism. Prior CL reduced infarct volume, associated with improved penumbral CBF as previously showed for ischemic preconditioning. The brief initial procedure avoided sham effects on infarct volume after subsequent occlusion under brief anesthesia. However, under prolonged isoflurane anesthesia for perfusion monitoring both sham and CL rats showed reduced PID incidence relative to naive animals. This anesthesia effect could be eliminated by using α-chloralose during perfusion imaging. As an additional methodological concern, blood glucose was frequently elevated at the time of the second surgery, reflecting buprenorphine-induced pica and other undefined mechanisms. Even modest hyperglycemia (>10 mmol/L) reduced PID incidence. In normoglycemic animals CL preconditioning reduced PID number by 50%, demonstrating associated effects on PID incidence, penumbral perfusion, and infarct progression. Hyperglycemia suppressed PIDs without affecting the relationship between CBF and infarction. This suggests that the primary effect of preconditioning is to improve penumbral perfusion, which in turn impacts PID incidence and infarct size. PMID:25757750

  2. The Spacelab IPS Star Simulator

    NASA Technical Reports Server (NTRS)

    Wessling, Francis C., III

    1993-01-01

    The cost of doing business in space is very high. If errors occur while in orbit the costs grow and desired scientific data may be corrupted or even lost. The Spacelab Instrument Pointing System (IPS) Star Simulator is a unique test bed that allows star trackers to interface with simulated stars in a laboratory before going into orbit. This hardware-in-the-loop testing of equipment on earth increases the probability of success while in space. The IPS Star Simulator provides three fields of view 2.55 x 2.55 deg each for input into star trackers. The fields of view are produced on three separate monitors. Each monitor has 4096 x 4096 addressable points and can display 50 stars (pixels) maximum at a given time. The pixel refresh rate is 1000 Hz. The spectral output is approximately 550 nm. The available relative visual magnitude range is two to eight visual magnitudes. The star size is less than 100 arcsec. The minimum star movement is less than 5 arcsec and the relative position accuracy is approximately 40 arcsec. The purpose of this paper is to describe the IPS Star Simulator design and to provide an operational scenario so others may gain from the approach and possible use of the system.

  3. A fast, preconditioned conjugate gradient Toeplitz solver

    NASA Technical Reports Server (NTRS)

    Pan, Victor; Schrieber, Robert

    1989-01-01

    A simple factorization is given of an arbitrary hermitian, positive definite matrix in which the factors are well-conditioned, hermitian, and positive definite. In fact, given knowledge of the extreme eigenvalues of the original matrix A, an optimal improvement can be achieved, making the condition numbers of each of the two factors equal to the square root of the condition number of A. This technique is to applied to the solution of hermitian, positive definite Toeplitz systems. Large linear systems with hermitian, positive definite Toeplitz matrices arise in some signal processing applications. A stable fast algorithm is given for solving these systems that is based on the preconditioned conjugate gradient method. The algorithm exploits Toeplitz structure to reduce the cost of an iteration to O(n log n) by applying the fast Fourier Transform to compute matrix-vector products. Matrix factorization is used as a preconditioner.

  4. Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

    PubMed

    Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

    2016-08-17

    Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase. PMID:27362436

  5. VoIP in a Campus Environment

    ERIC Educational Resources Information Center

    Young, Dan

    2005-01-01

    Internet Protocol (IP) Telephony, or voice-over IP (VoIP), has proved to be a wise decision for many organizations. This technology crosses the boundaries of public and private networks, enterprise and residential markets, voice and data technologies, as well as local and long-distance services. The convergence of voice and data into a single,…

  6. Photodynamic impact induces ischemic tolerance in models in vivo and in vitro

    NASA Astrophysics Data System (ADS)

    Demyanenko, Svetlana; Sharifulina, Svetlana; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Maria; Zhukovskaya, Ludmila

    2016-04-01

    Ischemic tolerance determines resistance to lethal ischemia gained by a prior sublethal stimulus (i.e., preconditioning). We reproduced this effect in two variants. In vitro the preliminary short (5 s) photodynamic treatment (PDT) (photosensitizer Photosens, 10 nM, 30 min preincubation; laser: 670 nm, 100 mW/cm2) significantly reduced the necrosis of neurons and glial cells in the isolated crayfish stretch receptor, which was caused by following 30-min PDT by 66% and 46%, respectively. In vivo PDT of the rat cerebral cortex with hydrophilic photosensitizer Rose Bengal (i.v. administration, laser irradiation: 532 nm, 60 mW/cm2, 3 mm beam diameter, 30 min) caused occlusion of small brain vessels and local photothrombotic infarct (PTI). It is a model of ischemic stroke. Cerebral tissue edema and global necrosis of neurons and glial cells occurred in the infarction core, which was surrounded by a 1.5 mm transition zone, penumbra. The maximal pericellular edema, hypo- and hyperchromia of neurons were observed in penumbra 24 h after PTI. The repeated laser irradiation of the contralateral cerebral cortex also caused PTI but lesser as compared with single PDT. Preliminary unilateral PTI provided ischemic tolerance: at 14 day after second exposure the PTI volume significantly decreased by 24% than in the case of a single exposure. Sensorimotor deficits in PDT-treated rats was registered using the behavioral tests. The preliminary PTI caused the preconditioning effect.

  7. Acute ischemic stroke update.

    PubMed

    Baldwin, Kathleen; Orr, Sean; Briand, Mary; Piazza, Carolyn; Veydt, Annita; McCoy, Stacey

    2010-05-01

    Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for

  8. Hyperbaric oxygen preconditioning protects rats against CNS oxygen toxicity.

    PubMed

    Arieli, Yehuda; Kotler, Doron; Eynan, Mirit; Hochman, Ayala

    2014-06-15

    We examined the hypothesis that repeated exposure to non-convulsive hyperbaric oxygen (HBO) as preconditioning provides protection against central nervous system oxygen toxicity (CNS-OT). Four groups of rats were used in the study. Rats in the control and the negative control (Ctl-) groups were kept in normobaric air. Two groups of rats were preconditioned to non-convulsive HBO at 202 kPa for 1h once every other day for a total of three sessions. Twenty-four hours after preconditioning, one of the preconditioned groups and the control rats were exposed to convulsive HBO at 608 kPa, and latency to CNS-OT was measured. Ctl- rats and the second preconditioned group (PrC-) were not subjected to convulsive HBO exposure. Tissues harvested from the hippocampus and frontal cortex were evaluated for enzymatic activity and nitrotyrosine levels. In the group exposed to convulsive oxygen at 608 kPa, latency to CNS-OT increased from 12.8 to 22.4 min following preconditioning. A significant decrease in the activity of glutathione reductase and glucose-6-phosphate dehydrogenase, and a significant increase in glutathione peroxidase activity, was observed in the hippocampus of preconditioned rats. Nitrotyrosine levels were significantly lower in the preconditioned animals, the highest level being observed in the control rats. In the cortex of the preconditioned rats, a significant increase was observed in glutathione S-transferase and glutathione peroxidase activity. Repeated exposure to non-convulsive HBO provides protection against CNS-OT. The protective mechanism involves alterations in the enzymatic activity of the antioxidant system and lower levels of peroxynitrite, mainly in the hippocampus.

  9. Non-Coding RNAs as Potential Neuroprotectants against Ischemic Brain Injury.

    PubMed

    Kaur, Prameet; Liu, Fujia; Tan, Jun Rong; Lim, Kai Ying; Sepramaniam, Sugunavathi; Karolina, Dwi Setyowati; Armugam, Arunmozhiarasi; Jeyaseelan, Kandiah

    2013-03-20

    Over the past decade, scientific discoveries have highlighted new roles for a unique class of non-coding RNAs. Transcribed from the genome, these non-coding RNAs have been implicated in determining the biological complexity seen in mammals by acting as transcriptional and translational regulators. Non-coding RNAs, which can be sub-classified into long non-coding RNAs, microRNAs, PIWI-interacting RNAs and several others, are widely expressed in the nervous system with roles in neurogenesis, development and maintenance of the neuronal phenotype. Perturbations of these non-coding transcripts have been observed in ischemic preconditioning as well as ischemic brain injury with characterization of the mechanisms by which they confer toxicity. Their dysregulation may also confer pathogenic conditions in neurovascular diseases. A better understanding of their expression patterns and functions has uncovered the potential use of these riboregulators as neuroprotectants to antagonize the detrimental molecular events taking place upon ischemic-reperfusion injury. In this review, we discuss the various roles of non-coding RNAs in brain development and their mechanisms of gene regulation in relation to ischemic brain injury. We will also address the future directions and open questions for identifying promising non-coding RNAs that could eventually serve as potential neuroprotectants against ischemic brain injury.

  10. Preconditioning principles for preventing sports injuries in adolescents and children.

    PubMed

    Dollard, Mark D; Pontell, David; Hallivis, Robert

    2006-01-01

    Preseason preconditioning can be accomplished well over a 4-week period with a mandatory period of rest as we have discussed. Athletic participation must be guided by a gradual increase of skills performance in the child assessed after a responsible preconditioning program applying physiologic parameters as outlined. Clearly, designing a preconditioning program is a dynamic process when accounting for all the variables in training discussed so far. Despite the physiologic demands of sport and training, we still need to acknowledge the psychologic maturity and welfare of the child so as to ensure that the sport environment is a wholesome and emotionally rewarding experience.

  11. Combinatorial Treatment with Apelin-13 Enhances the Therapeutic Efficacy of a Preconditioned Cell-Based Therapy for Peripheral Ischemia

    PubMed Central

    Samura, Makoto; Morikage, Noriyasu; Suehiro, Kotaro; Tanaka, Yuya; Nakamura, Tamami; Nishimoto, Arata; Ueno, Koji; Hosoyama, Tohru; Hamano, Kimikazu

    2016-01-01

    Hypoxic pretreatment of peripheral blood mononuclear cells (PBMNCs) enhances therapeutic angiogenesis in ischemic tissues after cell transplantation. However, newly formed vessels generated using this approach are immature and insufficient for promoting functional recovery from severe ischemia. In this study, we examined whether apelin-13, a regulator of vessel maturation, could be an effective promoter of therapeutic angiogenesis, following severe limb ischemia. Combinatorial treatment of hypoxic preconditioned PBMNCs with apelin-13 resulted in increased blood perfusion and vascular reactivity in ischemic mouse hindlimbs compared with a monotherapy comprising each factor. Apelin-13 upregulated expression of PDGF-BB and TGF-β1 in hypoxic PBMNCs, as well as that of PDGFR-β in vascular smooth muscle cells (VSMCs). Proliferation and migration of VSMCs treated with apelin-13 was accelerated in the presence of PDGF-BB. Interestingly, expression of an apelin receptor, APJ, in PBMNC was increased under hypoxia but not under normoxia. In addition, an in vitro angiogenesis assay using a co-culture model comprising mouse thoracic aorta, hypoxic PBMNCs, and apelin-13 demonstrated that combinatorial treatment recruited mural cells to sprouted vessel outgrowths from the aortic ring, thereby promoting neovessel maturation. Thus, combinatorial injection of hypoxic PBMNCs and apelin-13 could be an effective therapeutic strategy for patients with severe ischemic diseases. PMID:26763337

  12. Mobile-ip Aeronautical Network Simulation Study

    NASA Technical Reports Server (NTRS)

    Ivancic, William D.; Tran, Diepchi T.

    2001-01-01

    NASA is interested in applying mobile Internet protocol (mobile-ip) technologies to its space and aeronautics programs. In particular, mobile-ip will play a major role in the Advanced Aeronautic Transportation Technology (AATT), the Weather Information Communication (WINCOMM), and the Small Aircraft Transportation System (SATS) aeronautics programs. This report presents the results of a simulation study of mobile-ip for an aeronautical network. The study was performed to determine the performance of the transmission control protocol (TCP) in a mobile-ip environment and to gain an understanding of how long delays, handoffs, and noisy channels affect mobile-ip performance.

  13. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    SciTech Connect

    Hong, Kyung-Soo; Park, Jun-Ik; Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won; Dao, Trong Tuan; Oh, Won Keun; Kang, Chi-Dug; Kim, Sun-Hee

    2012-03-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  14. IP Profiling via Service Cluster Membership Vectors

    SciTech Connect

    Bartoletti, A

    2009-02-23

    This study investigates the feasibility of establishing and maintaining a system of compact IP behavioral profiles as a robust means of computer anomaly definition and detection. These profiles are based upon the degree to which a system's (IP's) network traffic is distributed among stable characteristic clusters derived of the aggregate session traffic generated by each of the major network services. In short, an IP's profile represents its degree of membership in these derived service clusters. The goal is to quantify and rank behaviors that are outside of the statistical norm for the services in question, or present significant deviation from profile for individual client IPs. Herein, we establish stable clusters for accessible features of common session traffic, migrate these clusters over time, define IP behavior profiles with respect to these clusters, migrate individual IP profiles over time, and demonstrate the detection of IP behavioral changes in terms of deviation from profile.

  15. 40 CFR 1065.516 - Sample system decontamination and preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Cycles § 1065.516 Sample system decontamination and preconditioning. This section describes how to manage... purified air or nitrogen. (3) When calculating zero emission levels, apply all applicable...

  16. Preconditioning methods for improved convergence rates in iterative reconstructions

    SciTech Connect

    Clinthorne, N.H.; Chiao, Pingchun; Rogers, W.L. . Div. of Nuclear Medicine); Pan, T.S. . Dept. of Nuclear Medicine); Stamos, J.A. . Dept. of Nuclear Engineering)

    1993-03-01

    Because of the characteristics of the tomographic inversion problem, iterative reconstruction techniques often suffer from poor convergence rates--especially at high spatial frequencies. By using preconditioning methods, the convergence properties of most iterative methods can be greatly enhanced without changing their ultimate solution. To increase reconstruction speed, the authors have applied spatially-invariant preconditioning filters that can be designed using the tomographic system response and implemented using 2-D frequency-domain filtering techniques. In a sample application, the authors performed reconstructions from noiseless, simulated projection data, using preconditioned and conventional steepest-descent algorithms. The preconditioned methods demonstrated residuals that were up to a factor of 30 lower than the unassisted algorithms at the same iteration. Applications of these methods to regularized reconstructions from projection data containing Poisson noise showed similar, although not as dramatic, behavior.

  17. 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.

  18. Effect of atropine and gammahydroxybutyrate on ischemically induced changes in the level of radioactivity in (/sup 3/H)inositol phosphates in gerbil brain in vivo

    SciTech Connect

    Wikiel, H.; Halat, G.; Strosznajder, J.

    1988-05-01

    Brain ischemia in gerbils was induced by ligation of both common carotid arteries for 1 min or 10 min. Sham-operated animals served as controls. Intracerebral injection of (3H)inositol into gerbil brain 16 hr before ischemic insult resulted in equilibration of the label between inositol lipids and water-soluble inositol phosphate. A short ischemic period (1 min) resulted in a statistically significant increase in the radioactivity of inositol triphosphate (IP3) and inositol monophosphate (IP), by about 48% and 79%, respectively, with little change in that of the intermediate inositol biphosphate (IP2), which increased by about 16%. When the ischemic period was prolonged (10 min), an increase in the radioactivity of inositol monophosphate exclusively, by about 84%, was observed. The level of radioactivity in inositol phosphates IP2 and IP3 decreased by about 50%, probably as a consequence of phosphatase activation by the ischemic insult. The agonist of the cholinergic receptor, carbachol, injected intracerebrally (40 micrograms per animal) increased accumulation of radioactivity in all inositol phosphates. The level of radioactivity in IP3, IP2, and IP was elevated by about 40, 23, and 147%, respectively. The muscarinic cholinergic antagonist, atropine, injected intraperitoneally in doses of 100 mg/kg body wt. depressed phosphoinositide metabolism in control animals. The level of radioactivity in water-soluble inositol metabolites in the brain of animals pretreated with atropine was evidently about 32% lower than in untreated animals. Pretreatment with atropine decreased the radioactivity of all inositol phosphates in the brain of animals subjected to 1-min ischemia and the radioactivity of IP in the case of 10-min brain ischemia.

  19. The Spacelab IPS Star Simulator

    NASA Technical Reports Server (NTRS)

    Wessling, Francis C., III

    1993-01-01

    The cost of doing business in space is very high. If errors occur while in orbit the costs grow and desired scientific data may be corrupted or even lost. The Spacelab Instrument Pointing System (IPS) Star Simulator is a unique test bed that allows star trackers to interface with simulated stars in a laboratory before going into orbit. This hardware-in-the loop testing of equipment on earth increases the probability of success while in space. The IPS Star Simulator provides three fields of view 2.55 x 2.55 degrees each for input into star trackers. The fields of view are produced on three separate monitors. Each monitor has 4096 x 4096 addressable points and can display 50 stars (pixels) maximum at a given time. The pixel refresh rate is 1000 Hz. The spectral output is approximately 550 nm. The available relative visual magnitude range is 2 to 8 visual magnitudes. The star size is less than 100 arc seconds. The minimum star movement is less than 5 arc seconds and the relative position accuracy is approximately 40 arc seconds. The purpose of this paper is to describe the LPS Star Simulator design and to provide an operational scenario so others may gain from the approach and possible use of the system.

  20. Vaccines and IP Rights: A Multifaceted Relationship.

    PubMed

    Durell, Karen

    2016-01-01

    Just as there are many forms of vaccines and components to vaccines-particular compositions, delivery systems, components, and distribution networks-there are a variety of intellectual property (IP) protections applicable for vaccines. IP rights such as patent, copyright, trademarks, plant breeders' rights, and trade secrets may all be applicable to vaccines. Thus, discussion of IP rights and vaccines should not begin and end with the application of one IP right to a vaccine. The discussion should engage considerations of multiple IP rights applicable to a vaccine and how these can be utilized in an integrated manner in a strategy aimed at supporting the development and distribution of the vaccine. Such an approach to IP rights to vaccines allows for the integrated rights to be considered in light of the justifications for protecting vaccines with IP rights, as well as the issues relating to specific IP rights for vaccines, such as compulsory license regimes, available humanitarian purpose IP credits, etc. To view vaccines as the subject of multiple IP protections involves a refocusing, but the outcome can provide significant benefits for vaccine development and distribution.

  1. Vaccines and IP Rights: A Multifaceted Relationship.

    PubMed

    Durell, Karen

    2016-01-01

    Just as there are many forms of vaccines and components to vaccines-particular compositions, delivery systems, components, and distribution networks-there are a variety of intellectual property (IP) protections applicable for vaccines. IP rights such as patent, copyright, trademarks, plant breeders' rights, and trade secrets may all be applicable to vaccines. Thus, discussion of IP rights and vaccines should not begin and end with the application of one IP right to a vaccine. The discussion should engage considerations of multiple IP rights applicable to a vaccine and how these can be utilized in an integrated manner in a strategy aimed at supporting the development and distribution of the vaccine. Such an approach to IP rights to vaccines allows for the integrated rights to be considered in light of the justifications for protecting vaccines with IP rights, as well as the issues relating to specific IP rights for vaccines, such as compulsory license regimes, available humanitarian purpose IP credits, etc. To view vaccines as the subject of multiple IP protections involves a refocusing, but the outcome can provide significant benefits for vaccine development and distribution. PMID:27076338

  2. Speciesism as a precondition to justice.

    PubMed

    Barilan, Y Michael

    2004-03-01

    Over and above fairness, the concept of justice presupposes that in any community no one member's wellbeing or life plan is inexorably dependent on the consumption or exploitation of other members. Renunciation of such use of others constitutes moral sociability, without which moral considerability is useless and possibly meaningless. To know if a creature is morally sociable, we must know it in its community; we must know its ecological profile, its species. Justice can be blind to species no more than to circumstance. Speciesism, the recognition of rights on the basis of group membership rather than solely on the basis of moral considerations at the level of the individual creature, embodies this assertion but is often described as a variant of Nazi racism. I consider this description and find it unwarranted, most obviously because Nazi racism extolled the stronger and the abuser and condemned the weaker and the abused, be they species or individuals, humans or animals. To the contrary, I present an argument for speciesism as a precondition to justice.

  3. Preconditioning stimuli that augment chromaffin cell secretion.

    PubMed

    Tapia, Laura; García-Eguiagaray, Josefina; García, Antonio G; Gandía, Luis

    2009-04-01

    We have investigated here whether a preconditioned stimulation of nicotinic and muscarinic receptors augmented the catecholamine release responses elicited by supramaximal 3-s pulses of 100 muM acetylcholine (100ACh) or 100 mM K(+) (100K(+)) applied to fast-perifused bovine adrenal chromaffin cells. Threshold concentrations of nicotine (1-3 muM) that caused only a tiny secretion did, however, augment the responses elicited by 100ACh or 100K(+) by 2- to 3.5-fold. This effect was suppressed by mecamylamine and by Ca(2+) deprivation, was developed with a half-time (t(1/2)) of 1 min, and was reversible. The nicotine effect was mimicked by threshold concentrations of ACh, choline, epibatidine, and oxotremorine-M but not by methacholine. Threshold concentrations of K(+) caused lesser potentiation of secretion compared with that of threshold nicotine. The data are compatible with an hypothesis implying 1) that continuous low-frequency sympathetic discharge places chromaffin cells at the adrenal gland in a permanent "hypersensitive" state; and 2) this allows an explosive secretion of catecholamines by high-frequency sympathetic discharge during stress.

  4. Responsive corneosurfametry following in vivo skin preconditioning.

    PubMed

    Uhoda, E; Goffin, V; Pierard, G E

    2003-12-01

    Skin is subjected to many environmental threats, some of which altering the structure and function of the stratum corneum. Among them, surfactants are recognized factors that may influence irritant contact dermatitis. The present study was conducted to compare the variations in skin capacitance and corneosurfametry (CSM) reactivity before and after skin exposure to repeated subclinical injuries by 2 hand dishwashing liquids. A forearm immersion test was performed on 30 healthy volunteers. 2 daily soak sessions were performed for 5 days. At inclusion and the day following the last soak session, skin capacitance was measured and cyanoacrylate skin-surface strippings were harvested. The latter specimens were used for the ex vivo microwave CSM. Both types of assessments clearly differentiated the 2 hand dishwashing liquids. The forearm immersion test allowed the discriminant sensitivity of CSM to increase. Intact skin capacitance did not predict CSM data. By contrast, a significant correlation was found between the post-test conductance and the corresponding CSM data. In conclusion, a forearm immersion test under realistic conditions can discriminate the irritation potential between surfactant-based products by measuring skin conductance and performing CSM. In vivo skin preconditioning by surfactants increases CSM sensitivity to the same surfactants. PMID:15025702

  5. A Weakest Precondition Approach to Robustness

    NASA Astrophysics Data System (ADS)

    Balliu, Musard; Mastroeni, Isabella

    With the increasing complexity of information management computer systems, security becomes a real concern. E-government, web-based financial transactions or military and health care information systems are only a few examples where large amount of information can reside on different hosts distributed worldwide. It is clear that any disclosure or corruption of confidential information in these contexts can result fatal. Information flow controls constitute an appealing and promising technology to protect both data confidentiality and data integrity. The certification of the security degree of a program that runs in untrusted environments still remains an open problem in the area of language-based security. Robustness asserts that an active attacker, who can modify program code in some fixed points (holes), is unable to disclose more private information than a passive attacker, who merely observes unclassified data. In this paper, we extend a method recently proposed for checking declassified non-interference in presence of passive attackers only, in order to check robustness by means of weakest precondition semantics. In particular, this semantics simulates the kind of analysis that can be performed by an attacker, i.e., from public output towards private input. The choice of semantics allows us to distinguish between different attacks models and to characterize the security of applications in different scenarios.

  6. Responsive corneosurfametry following in vivo skin preconditioning.

    PubMed

    Uhoda, E; Goffin, V; Pierard, G E

    2003-12-01

    Skin is subjected to many environmental threats, some of which altering the structure and function of the stratum corneum. Among them, surfactants are recognized factors that may influence irritant contact dermatitis. The present study was conducted to compare the variations in skin capacitance and corneosurfametry (CSM) reactivity before and after skin exposure to repeated subclinical injuries by 2 hand dishwashing liquids. A forearm immersion test was performed on 30 healthy volunteers. 2 daily soak sessions were performed for 5 days. At inclusion and the day following the last soak session, skin capacitance was measured and cyanoacrylate skin-surface strippings were harvested. The latter specimens were used for the ex vivo microwave CSM. Both types of assessments clearly differentiated the 2 hand dishwashing liquids. The forearm immersion test allowed the discriminant sensitivity of CSM to increase. Intact skin capacitance did not predict CSM data. By contrast, a significant correlation was found between the post-test conductance and the corresponding CSM data. In conclusion, a forearm immersion test under realistic conditions can discriminate the irritation potential between surfactant-based products by measuring skin conductance and performing CSM. In vivo skin preconditioning by surfactants increases CSM sensitivity to the same surfactants.

  7. Imaging acute ischemic stroke.

    PubMed

    González, R Gilberto; Schwamm, Lee H

    2016-01-01

    Acute ischemic stroke is common and often treatable, but treatment requires reliable information on the state of the brain that may be provided by modern neuroimaging. Critical information includes: the presence of hemorrhage; the site of arterial occlusion; the size of the early infarct "core"; and the size of underperfused, potentially threatened brain parenchyma, commonly referred to as the "penumbra." In this chapter we review the major determinants of outcomes in ischemic stroke patients, and the clinical value of various advanced computed tomography and magnetic resonance imaging methods that may provide key physiologic information in these patients. The focus is on major strokes due to occlusions of large arteries of the anterior circulation, the most common cause of a severe stroke syndrome. The current evidence-based approach to imaging the acute stroke patient at the Massachusetts General Hospital is presented, which is applicable for all stroke types. We conclude with new information on time and stroke evolution that imaging has revealed, and how it may open the possibilities of treating many more patients. PMID:27432672

  8. Analysis of Handoff Mechanisms in Mobile IP

    NASA Astrophysics Data System (ADS)

    Jayaraj, Maria Nadine Simonel; Issac, Biju; Haldar, Manas Kumar

    2011-06-01

    One of the most important challenges in mobile Internet Protocol (IP) is to provide service for a mobile node to maintain its connectivity to network when it moves from one domain to another. IP is responsible for routing packets across network. The first major version of IP is the Internet Protocol version 4 (IPv4). It is one of the dominant protocols relevant to wireless network. Later a newer version of IP called the IPv6 was proposed. Mobile IPv6 is mainly introduced for the purpose of mobility. Mobility management enables network to locate roaming nodes in order to deliver packets and maintain connections with them when moving into new domains. Handoff occurs when a mobile node moves from one network to another. It is a key factor of mobility because a mobile node can trigger several handoffs during a session. This paper briefly explains on mobile IP and its handoff issues, along with the drawbacks of mobile IP.

  9. Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats

    PubMed Central

    de Resende, Marco A. C.; Pantoja, Alberto V.; Barcellos, Bruno M.; Reis, Eduardo P.; Consolo, Thays D.; Módolo, Renata P.; Domingues, Maria A. C.; Assad, Alexandra R.; Cavalcanti, Ismar L.; Castiglia, Yara M. M.; Módolo, Norma S. P.

    2015-01-01

    Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model. PMID:26413552

  10. Structure of mouse IP-10, a chemokine

    SciTech Connect

    Jabeen, Talat; Leonard, Philip; Jamaluddin, Haryati; Acharya, K. Ravi

    2008-06-01

    The structure of mouse IP-10 shows a novel tetrameric association. Interferon-γ-inducible protein (IP-10) belongs to the CXC class of chemokines and plays a significant role in the pathophysiology of various immune and inflammatory responses. It is also a potent angiostatic factor with antifibrotic properties. The biological activities of IP-10 are exerted by interactions with the G-protein-coupled receptor CXCR3 expressed on Th1 lymphocytes. IP-10 thus forms an attractive target for structure-based rational drug design of anti-inflammatory molecules. The crystal structure of mouse IP-10 has been determined and reveals a novel tetrameric association. In the tetramer, two conventional CXC chemokine dimers are associated through their N-terminal regions to form a 12-stranded elongated β-sheet of ∼90 Å in length. This association differs significantly from the previously studied tetramers of human IP-10, platelet factor 4 and neutrophil-activating peptide-2. In addition, heparin- and receptor-binding residues were mapped on the surface of IP-10 tetramer. Two heparin-binding sites were observed on the surface and were present at the interface of each of the two β-sheet dimers. The structure supports the formation of higher order oligomers of IP-10, as observed in recent in vivo studies with mouse IP-10, which will have functional relevance.

  11. Internet topology: connectivity of IP graphs

    NASA Astrophysics Data System (ADS)

    Broido, Andre; claffy, kc

    2001-07-01

    In this paper we introduce a framework for analyzing local properties of Internet connectivity. We compare BGP and probed topology data, finding that currently probed topology data yields much denser coverage of AS-level connectivity. We describe data acquisition and construction of several IP- level graphs derived from a collection of 220 M skitter traceroutes. We find that a graph consisting of IP nodes and links contains 90.5% of its 629 K nodes in the acyclic subgraph. In particular, 55% of the IP nodes are in trees. Full bidirectional connectivity is observed for a giant component containing 8.3% of IP nodes.

  12. Reduction in postsystolic wall thickening during late preconditioning.

    PubMed

    Monnet, Xavier; Lucats, Laurence; Colin, Patrice; Derumeaux, Geneviève; Dubois-Rande, Jean-Luc; Hittinger, Luc; Ghaleh, Bijan; Berdeaux, Alain

    2007-01-01

    Brief coronary artery occlusion (CAO) and reperfusion induce myocardial stunning and late preconditioning. Postsystolic wall thickening (PSWT) also develops with CAO and reperfusion. However, the time course of PSWT during stunning and the regional function pattern of the preconditioned myocardium remain unknown. The goal of this study was to investigate the evolution of PSWT during myocardial stunning and its modifications during late preconditioning. Dogs were chronically instrumented to measure (sonomicrometry) systolic wall thickening (SWT), PSWT, total wall thickening (TWT = SWT + PSWT), and maximal rate of thickening (dWT/dt(max)). Two 10-min CAO (circumflex artery) were performed 24 h apart (day 0 and day 1, n = 7). At day 0, CAO decreased SWT and increased PSWT. During the first hours of the subsequent stunning, evolution of PSWT was symmetrical to that of SWT. At day 1, baseline SWT was similar to day 0, but PSWT was reduced (-66%), while dWT/dt(max) and SWT/TWT ratio increased (+48 and +14%, respectively). After CAO at day 1, stunning was reduced, indicating late preconditioning. Simultaneously vs. day 0, PSWT was significantly reduced, and dWT/dt(max) as well as SWT/TWT ratio were increased, i.e., a greater part of TWT was devoted to ejection. Similar decrease in PSWT was observed with a nonischemic preconditioning stimulus (rapid ventricular pacing, n = 4). In conclusion, a major contractile adaptation occurs during late preconditioning, i.e., the rate of wall thickening is enhanced and PWST is almost abolished. These phenotype adaptations represent potential approaches for characterizing stunning and late preconditioning with repetitive ischemia in humans.

  13. [Cerebrolysin for acute ischemic stroke].

    PubMed

    iganshina, L E; Abakumova, T R

    2013-01-01

    The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke.

  14. Remote Ischemic Conditioning

    PubMed Central

    Heusch, Gerd; Bøtker, Hans Erik; Przyklenk, Karin; Redington, Andrew; Yellon, Derek

    2014-01-01

    In remote ischemic conditioning (RIC) brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microRNA-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible and inexpensive. PMID:25593060

  15. Ischemic bowel disease

    PubMed Central

    Castelli, M. F.; Qizilbash, A. H.; Salem, S.; Fyshe, T. G.

    1974-01-01

    The clinical, radiologic and pathologic features of 25 cases of ischemic bowel disease are presented. The majority of patients presented with the triad of abdominal pain, diarrhea and vomiting. In 13 patients the diarrhea was associated with the passage of bright red blood per rectum. There were 10 cases of infarction, 11 of enterocolitis and 4 had resulted in stricture formation. In five cases of enterocolitis the lesion was transient; symptoms improved with conservative medical management and the radiologic findings returned to normal. Barium enema examination yielded abnormal findings in the majority of the cases in which it was performed. Plain films of the abdomen, however, were not helpful. The actual mortality in this group of patients was 44%, 80% in those with infarction of the bowel and 20% in the other two groups. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7 PMID:4419659

  16. Berberine Preconditioning Protects Neurons Against Ischemia via Sphingosine-1-Phosphate and Hypoxia-Inducible Factor-1[Formula: see text].

    PubMed

    Zhang, Qichun; Bian, Huimin; Guo, Liwei; Zhu, Huaxu

    2016-01-01

    Berberine exerts neuroprotective and modulates hypoxia inducible factor-1-alpha (HIF-1[Formula: see text]. Based on the role of HIF-1[Formula: see text] in hypoxia preconditioning and association between HIF-1[Formula: see text] and sphingosine-1-phosphate (S1P), we hypothesized that berberine preconditioning (BP) would ameliorate the cerebral injury induced by ischemia through activating the system of HIF-1[Formula: see text] and S1P. Adult male rats with middle cerebral artery occlusion (MCAO) and rat primary cortical neurons treated with oxygen and glucose deprivation (OGD) with BP at 24[Formula: see text]h (40[Formula: see text]mg/kg) and 2[Formula: see text]h (10[Formula: see text][Formula: see text]mol/L), respectively, were used to determine the neuroprotective effects. The HIF-1[Formula: see text] accumulation, and S1P metabolism were assayed in the berberine-preconditioned neurons, and the HIF-1[Formula: see text]-mediated transcriptional modulation of sphingosine kinases (Sphk) 1 and 2 was analyzed using chromatin immunoprecipitation and real-time polymerase chain reaction. BP significantly prevented cerebral ischemic injury in the MCAO rats at 24[Formula: see text]h and 72[Formula: see text]h following ischemia/reperfusion. In OGD-treated neurons, BP enhanced HIF-1[Formula: see text] accumulation with activation of PI3K/Akt, and induced S1P production by activating Sphk2 via the promotion of HIF-1[Formula: see text]-mediated Sphk2 transcription. In conclusion, BP activated endogenous neuroprotective mechanisms associated with the S1P/HIF-1 pathway and helped protect neuronal cells against hypoxia/ischemia.

  17. Berberine Preconditioning Protects Neurons Against Ischemia via Sphingosine-1-Phosphate and Hypoxia-Inducible Factor-1[Formula: see text].

    PubMed

    Zhang, Qichun; Bian, Huimin; Guo, Liwei; Zhu, Huaxu

    2016-01-01

    Berberine exerts neuroprotective and modulates hypoxia inducible factor-1-alpha (HIF-1[Formula: see text]. Based on the role of HIF-1[Formula: see text] in hypoxia preconditioning and association between HIF-1[Formula: see text] and sphingosine-1-phosphate (S1P), we hypothesized that berberine preconditioning (BP) would ameliorate the cerebral injury induced by ischemia through activating the system of HIF-1[Formula: see text] and S1P. Adult male rats with middle cerebral artery occlusion (MCAO) and rat primary cortical neurons treated with oxygen and glucose deprivation (OGD) with BP at 24[Formula: see text]h (40[Formula: see text]mg/kg) and 2[Formula: see text]h (10[Formula: see text][Formula: see text]mol/L), respectively, were used to determine the neuroprotective effects. The HIF-1[Formula: see text] accumulation, and S1P metabolism were assayed in the berberine-preconditioned neurons, and the HIF-1[Formula: see text]-mediated transcriptional modulation of sphingosine kinases (Sphk) 1 and 2 was analyzed using chromatin immunoprecipitation and real-time polymerase chain reaction. BP significantly prevented cerebral ischemic injury in the MCAO rats at 24[Formula: see text]h and 72[Formula: see text]h following ischemia/reperfusion. In OGD-treated neurons, BP enhanced HIF-1[Formula: see text] accumulation with activation of PI3K/Akt, and induced S1P production by activating Sphk2 via the promotion of HIF-1[Formula: see text]-mediated Sphk2 transcription. In conclusion, BP activated endogenous neuroprotective mechanisms associated with the S1P/HIF-1 pathway and helped protect neuronal cells against hypoxia/ischemia. PMID:27430910

  18. Conventional protein kinase Cβ-mediated phosphorylation inhibits collapsin response-mediated protein 2 proteolysis and alleviates ischemic injury in cultured cortical neurons and ischemic stroke-induced mice.

    PubMed

    Yang, Xuan; Zhang, Xinxin; Li, Yun; Han, Song; Howells, David W; Li, Shujuan; Li, Junfa

    2016-05-01

    We previously reported that conventional protein kinase C (cPKC)β participated in hypoxic preconditioning-induced neuroprotection against cerebral ischemic injury, and collapsin response-mediated protein 2 (CRMP2) was identified as a cPKCβ interacting protein. In this study, we explored the regulation of CRMP2 phosphorylation and proteolysis by cPKCβ, and their role in ischemic injury of oxygen-glucose deprivation (OGD)-treated cortical neurons and brains of mice with middle cerebral artery occlusion-induced ischemic stroke. The results demonstrated that cPKCβ-mediated CRMP2 phosphorylation via the cPKCβ-selective activator 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPA) and inhibition of calpain-mediated CRMP2 proteolysis by calpeptin and a fusing peptide containing TAT peptide and the calpain cleavage site of CRMP2 (TAT-CRMP2) protected neurons against OGD-induced cell death through inhibiting CRMP2 proteolysis in cultured cortical neurons. The OGD-induced nuclear translocation of the CRMP2 breakdown product was inhibited by DOPPA, calpeptin, and TAT-CRMP2 in cortical neurons. In addition, both cPKCβ activation and CRMP2 proteolysis inhibition by hypoxic preconditioning and intracerebroventricular injections of DOPPA, calpeptin, and TAT-CRMP2 improved the neurological deficit in addition to reducing the infarct volume and proportions of cells with pyknotic nuclei in the peri-infact region of mice with ischemic stroke. These results suggested that cPKCβ modulates CRMP2 phosphorylation and proteolysis, and cPKCβ activation alleviates ischemic injury in the cultured cortical neurons and brains of mice with ischemic stroke through inhibiting CRMP2 proteolysis by phosphorylation. Focal cerebral ischemia induces a large flux of Ca(2+) to activate calpain which cleaves collapsin response mediator (CRMP) 2 into breakdown product (BDP). Inhibition of CRMP2 cleavage by calpeptin and TAT-CRMP2 alleviates ischemic injury. Conventional protein kinase C (c

  19. Inositol 1,4,5-triphosphate receptors and NAD(P)H mediate Ca2+ signaling required for hypoxic preconditioning of hippocampal neurons.

    PubMed

    Bickler, P E; Fahlman, C S; Gray, J; McKleroy, W

    2009-04-21

    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 with xestospongin, and RNA interference against subtype 1 of the IP3 receptor all blunted the moderate increases in [Ca2+](i) (50-100 nM) required for tolerance induction. Increases in [Ca2+](i) during HPC and neuroprotection following HPC were not prevented with NMDA receptor block or by removing Ca2+ from the bathing medium. Increased NAD(P)H fluorescence in CA1 neurons during hypoxia and demonstration that NADH manipulation increases [Ca2+](i) in an IP3R-dependent manner revealed a primary role of cellular redox state in liberation of Ca2+ from the ER. Blockade of IP3Rs and intracellular Ca2+ chelation prevented phosphorylation of known HPC signaling targets, including MAPK p42/44 (ERK), protein kinase B (Akt) and CREB. We conclude that the endoplasmic reticulum, acting via redox/NADH-dependent intracellular Ca2+ store release, is an important mediator of the neuroprotective response to hypoxic stress.

  20. Implementation of Preconditioned Dual-Time Procedures in OVERFLOW

    NASA Technical Reports Server (NTRS)

    Pandya, Shishir A.; Venkateswaran, Sankaran; Pulliam, Thomas H.; Kwak, Dochan (Technical Monitor)

    2003-01-01

    Preconditioning methods have become the method of choice for the solution of flowfields involving the simultaneous presence of low Mach and transonic regions. It is well known that these methods are important for insuring accurate numerical discretization as well as convergence efficiency over various operating conditions such as low Mach number, low Reynolds number and high Strouhal numbers. For unsteady problems, the preconditioning is introduced within a dual-time framework wherein the physical time-derivatives are used to march the unsteady equations and the preconditioned time-derivatives are used for purposes of numerical discretization and iterative solution. In this paper, we describe the implementation of the preconditioned dual-time methodology in the OVERFLOW code. To demonstrate the performance of the method, we employ both simple and practical unsteady flowfields, including vortex propagation in a low Mach number flow, flowfield of an impulsively started plate (Stokes' first problem) arid a cylindrical jet in a low Mach number crossflow with ground effect. All the results demonstrate that the preconditioning algorithm is responsible for improvements to both numerical accuracy and convergence efficiency and, thereby, enables low Mach number unsteady computations to be performed at a fraction of the cost of traditional time-marching methods.

  1. Preterm Hypoxic–Ischemic Encephalopathy

    PubMed Central

    Gopagondanahalli, Krishna Revanna; Li, Jingang; Fahey, Michael C.; Hunt, Rod W.; Jenkin, Graham; Miller, Suzanne L.; Malhotra, Atul

    2016-01-01

    Hypoxic–ischemic encephalopathy (HIE) is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic–ischemic episode before or during birth. However, in the preterm infant, defining hypoxic–ischemic injury (HII), its clinical course, monitoring, and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic–ischemic insult in preterm infants is probably higher than recognized and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia–ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools, and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies. PMID:27812521

  2. Rational modulation of the innate immune system for neuroprotection in ischemic stroke

    PubMed Central

    Amantea, Diana; Micieli, Giuseppe; Tassorelli, Cristina; Cuartero, María I.; Ballesteros, Iván; Certo, Michelangelo; Moro, María A.; Lizasoain, Ignacio; Bagetta, Giacinto

    2015-01-01

    The innate immune system plays a dualistic role in the evolution of ischemic brain damage and has also been implicated in ischemic tolerance produced by different conditioning stimuli. Early after ischemia, perivascular astrocytes release cytokines and activate metalloproteases (MMPs) that contribute to blood–brain barrier (BBB) disruption and vasogenic oedema; whereas at later stages, they provide extracellular glutamate uptake, BBB regeneration and neurotrophic factors release. Similarly, early activation of microglia contributes to ischemic brain injury via the production of inflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-1, reactive oxygen and nitrogen species and proteases. Nevertheless, microglia also contributes to the resolution of inflammation, by releasing IL-10 and tumor growth factor (TGF)-β, and to the late reparative processes by phagocytic activity and growth factors production. Indeed, after ischemia, microglia/macrophages differentiate toward several phenotypes: the M1 pro-inflammatory phenotype is classically activated via toll-like receptors or interferon-γ, whereas M2 phenotypes are alternatively activated by regulatory mediators, such as ILs 4, 10, 13, or TGF-β. Thus, immune cells exert a dualistic role on the evolution of ischemic brain damage, since the classic phenotypes promote injury, whereas alternatively activated M2 macrophages or N2 neutrophils prompt tissue remodeling and repair. Moreover, a subdued activation of the immune system has been involved in ischemic tolerance, since different preconditioning stimuli act via modulation of inflammatory mediators, including toll-like receptors and cytokine signaling pathways. This further underscores that the immuno-modulatory approach for the treatment of ischemic stroke should be aimed at blocking the detrimental effects, while promoting the beneficial responses of the immune reaction. PMID:25972779

  3. VoIP to the Rescue

    ERIC Educational Resources Information Center

    Milner, Jacob

    2005-01-01

    Voice over Internet Protocol (VoIP) is everywhere. The technology lets users make and receive phone calls over the Internet, transporting voice traffic alongside data traffic such as instant messages (IMs) and e-mail. While the number of consumer customers using VoIP increases every week, the technology is finding its way into K-12 education as…

  4. Selective inhibition of inositol hexakisphosphate kinases (IP6Ks) enhances mesenchymal stem cell engraftment and improves therapeutic efficacy for myocardial infarction.

    PubMed

    Zhang, Zheng; Liang, Dong; Gao, Xue; Zhao, Chuanxu; Qin, Xing; Xu, Yong; Su, Tao; Sun, Dongdong; Li, Weijie; Wang, Haichang; Liu, Bing; Cao, Feng

    2014-07-01

    5-Diphosphoinositol pentakisphosphate (IP7), formed by a family of inositol hexakisphosphate kinases (IP6Ks), has been demonstrated to be a physiologic inhibitor of Akt. IP6K inhibition may increase Akt activation in mesenchymal stem cells (MSCs), resulting in enhanced cardiac protective effect after transplantation. The aim of this study was to investigate the role of IP6Ks for improving MSCs' functional survival and cardiac protective effect after transplantation into infarcted mice hearts. Bone marrow-derived mesenchymal stem cells, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc(+)-eGFP(+)) transgenic mice, were preconditioned with IP6Ks inhibitor TNP (0.5, 1, 5, and 10 μmol/L) for 2 h followed by 6 h of hypoxia and serum deprivation (H/SD) injury. TNP concentration dependently significantly decreased IP7 production with increased Akt phosphorylation. Moreover, TNP at 10 μmol/L significantly improved the viability and enhanced the paracrine effect of MSCs after H/SD. Furthermore, MSCs were transplanted into infarcted hearts with or without selective IP6Ks inhibition. Longitudinal in vivo bioluminescence imaging and immunofluorescent staining revealed that TNP pretreatment enhanced the survival of engrafted MSCs, which promoted the anti-apoptotic and pro-angiogenic efficacy of MSCs in vivo. Furthermore, MSC therapy with IP6Ks inhibition significantly decreased fibrosis and preserved heart function. This study demonstrates that inhibition of IP6Ks promotes MSCs engraftment and paracrine effect in infarcted hearts at least in part by down-regulating IP7 production and enhancing Akt activation, which might contribute to the preservation of myocardial function after MI.

  5. On adaptive weighted polynomial preconditioning for Hermitian positive definite matrices

    NASA Technical Reports Server (NTRS)

    Fischer, Bernd; Freund, Roland W.

    1992-01-01

    The conjugate gradient algorithm for solving Hermitian positive definite linear systems is usually combined with preconditioning in order to speed up convergence. In recent years, there has been a revival of polynomial preconditioning, motivated by the attractive features of the method on modern architectures. Standard techniques for choosing the preconditioning polynomial are based only on bounds for the extreme eigenvalues. Here a different approach is proposed, which aims at adapting the preconditioner to the eigenvalue distribution of the coefficient matrix. The technique is based on the observation that good estimates for the eigenvalue distribution can be derived after only a few steps of the Lanczos process. This information is then used to construct a weight function for a suitable Chebyshev approximation problem. The solution of this problem yields the polynomial preconditioner. In particular, we investigate the use of Bernstein-Szego weights.

  6. Gpu Implementation of Preconditioning Method for Low-Speed Flows

    NASA Astrophysics Data System (ADS)

    Zhang, Jiale; Chen, Hongquan

    2016-06-01

    An improved preconditioning method for low-Mach-number flows is implemented on a GPU platform. The improved preconditioning method employs the fluctuation of the fluid variables to weaken the influence of accuracy caused by the truncation error. The GPU parallel computing platform is implemented to accelerate the calculations. Both details concerning the improved preconditioning method and the GPU implementation technology are described in this paper. Then a set of typical low-speed flow cases are simulated for both validation and performance analysis of the resulting GPU solver. Numerical results show that dozens of times speedup relative to a serial CPU implementation can be achieved using a single GPU desktop platform, which demonstrates that the GPU desktop can serve as a cost-effective parallel computing platform to accelerate CFD simulations for low-Speed flows substantially.

  7. Operator-Based Preconditioning of Stiff Hyperbolic Systems

    SciTech Connect

    Reynolds, Daniel R.; Samtaney, Ravi; Woodward, Carol S.

    2009-02-09

    We introduce an operator-based scheme for preconditioning stiff components encoun- tered in implicit methods for hyperbolic systems of partial differential equations posed on regular grids. The method is based on a directional splitting of the implicit operator, followed by a char- acteristic decomposition of the resulting directional parts. This approach allows for solution to any number of characteristic components, from the entire system to only the fastest, stiffness-inducing waves. We apply the preconditioning method to stiff hyperbolic systems arising in magnetohydro- dynamics and gas dynamics. We then present numerical results showing that this preconditioning scheme works well on problems where the underlying stiffness results from the interaction of fast transient waves with slowly-evolving dynamics, scales well to large problem sizes and numbers of processors, and allows for additional customization based on the specific problems under study.

  8. Space Network IP Services (SNIS): An Architecture for Supporting Low Earth Orbiting IP Satellite Missions

    NASA Technical Reports Server (NTRS)

    Israel, David J.

    2005-01-01

    The NASA Space Network (SN) supports a variety of missions using the Tracking and Data Relay Satellite System (TDRSS), which includes ground stations in White Sands, New Mexico and Guam. A Space Network IP Services (SNIS) architecture is being developed to support future users with requirements for end-to-end Internet Protocol (IP) communications. This architecture will support all IP protocols, including Mobile IP, over TDRSS Single Access, Multiple Access, and Demand Access Radio Frequency (RF) links. This paper will describe this architecture and how it can enable Low Earth Orbiting IP satellite missions.

  9. 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

  10. Preconditioning boosts regenerative programmes in the adult zebrafish heart

    PubMed Central

    de Preux Charles, Anne-Sophie; Bise, Thomas; Baier, Felix; Sallin, Pauline; Jaźwińska, Anna

    2016-01-01

    During preconditioning, exposure to a non-lethal harmful stimulus triggers a body-wide increase of survival and pro-regenerative programmes that enable the organism to better withstand the deleterious effects of subsequent injuries. This phenomenon has first been described in the mammalian heart, where it leads to a reduction of infarct size and limits the dysfunction of the injured organ. Despite its important clinical outcome, the actual mechanisms underlying preconditioning-induced cardioprotection remain unclear. Here, we describe two independent models of cardiac preconditioning in the adult zebrafish. As noxious stimuli, we used either a thoracotomy procedure or an induction of sterile inflammation by intraperitoneal injection of immunogenic particles. Similar to mammalian preconditioning, the zebrafish heart displayed increased expression of cardioprotective genes in response to these stimuli. As zebrafish cardiomyocytes have an endogenous proliferative capacity, preconditioning further elevated the re-entry into the cell cycle in the intact heart. This enhanced cycling activity led to a long-term modification of the myocardium architecture. Importantly, the protected phenotype brought beneficial effects for heart regeneration within one week after cryoinjury, such as a more effective cell-cycle reentry, enhanced reactivation of embryonic gene expression at the injury border, and improved cell survival shortly after injury. This study reveals that exposure to antecedent stimuli induces adaptive responses that render the fish more efficient in the activation of the regenerative programmes following heart damage. Our results open a new field of research by providing the adult zebrafish as a model system to study remote cardiac preconditioning. PMID:27440423

  11. Optimal bounds for solving tridiagonal systems with preconditioning

    SciTech Connect

    Zellini, P. )

    1988-10-01

    Let (1) Tx=f be a linear tridiagonal system system of n equations in the unknown x/sub 1/, ..., x/sub n/. It is proved that 3n-2 (nonscalar) multiplications/divisions are necessary to solve (1) in a straight-line program excluding divisions by elements of f. This bound is optimal if the cost of preconditioning of T is not counted. Analogous results are obtained in case (i) T is bidiagonal and (ii) T and f are both centrosymmetric. The existence of parallel algorithms to solve (1) with preconditioning and with minimal multiplicative redundancy is also discussed.

  12. Incomplete block SSOR preconditionings for high order discretizations

    SciTech Connect

    Kolotilina, L.

    1994-12-31

    This paper considers the solution of linear algebraic systems Ax = b resulting from the p-version of the Finite Element Method (FEM) using PCG iterations. Contrary to the h-version, the p-version ensures the desired accuracy of a discretization not by refining an original finite element mesh but by introducing higher degree polynomials as additional basis functions which permits to reduce the size of the resulting linear system as compared with the h-version. The suggested preconditionings are the so-called Incomplete Block SSOR (IBSSOR) preconditionings.

  13. Fourier analysis of finite element preconditioned collocation schemes

    NASA Technical Reports Server (NTRS)

    Deville, Michel O.; Mund, Ernest H.

    1990-01-01

    The spectrum of the iteration operator of some finite element preconditioned Fourier collocation schemes is investigated. The first part of the paper analyses one-dimensional elliptic and hyperbolic model problems and the advection-diffusion equation. Analytical expressions of the eigenvalues are obtained with use of symbolic computation. The second part of the paper considers the set of one-dimensional differential equations resulting from Fourier analysis (in the tranverse direction) of the 2-D Stokes problem. All results agree with previous conclusions on the numerical efficiency of finite element preconditioning schemes.

  14. A subspace preconditioning algorithm for eigenvector/eigenvalue computation

    SciTech Connect

    Bramble, J.H.; Knyazev, A.V.; Pasciak, J.E.

    1996-12-31

    We consider the problem of computing a modest number of the smallest eigenvalues along with orthogonal bases for the corresponding eigen-spaces of a symmetric positive definite matrix. In our applications, the dimension of a matrix is large and the cost of its inverting is prohibitive. In this paper, we shall develop an effective parallelizable technique for computing these eigenvalues and eigenvectors utilizing subspace iteration and preconditioning. Estimates will be provided which show that the preconditioned method converges linearly and uniformly in the matrix dimension when used with a uniform preconditioner under the assumption that the approximating subspace is close enough to the span of desired eigenvectors.

  15. 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.

  16. 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.

  17. Ischemic penumbra in acute stroke: Demonstration by PET with fluorine-18 fluoromisonidazole

    SciTech Connect

    Yeh, S.H.; Liu, R.S.; Hu, H.H.

    1994-05-01

    Ischemic penumbra (IP) in acute stroke has gained clinical interest since tissue functions may be recovered if perfusion can be reestablished. However, such therapeutic intervention is {open_quotes}blind{close_quotes} since clinical examination can not distinguish IP from developing infarction. In vivo demonstration of IP may have significance for stroke patient management. This study was a preliminary evaluation of detecting IP in vivo by F-18 fluoromisonidazole ([F-18]-FMISO), a hypoxic imaging agent. Static PET imaging was performed after IV injection of 370 MBq of [F-18]-FMISO at 20 and 120 min. Tomograms were reconstructed and evaluated visually in correlation with CT or MR scans. In acute stroke, patients (pts) were called back for the second PET study one month after the initial study. CT was used for confirming infarction. In 6 pts with acute cerebral infarction, three of them had intense [F-18]-FMISO retention in the penumbra surrounding the central, eclipse-like zone of absent radio-activity (infarction) at 2 hr in the acute state, and the penumbra disappeared in association with increased area of infarction on CT in one case in the chronic state. In five pts with chronic infarction, all had no penumbra of [F-18]-FMISO retention. In summary, our preliminary results demonstrate the feasibility of using [F-18]-FMISO PET to detect ischemic penumbra in vivo.

  18. 77 FR 33227 - Assessment Questionnaire-IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-05

    ... SECURITY Assessment Questionnaire--IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT) AGENCY... Protection and Programs Directorate (NPPD), Office of Infrastructure Protection (IP), Sector Outreach and...--Assessment Questionnaire--IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT). DHS...

  19. IPS guidestar selection for stellar mode (ASTRO)

    NASA Technical Reports Server (NTRS)

    Mullins, Larry; Wooten, Lewis

    1988-01-01

    This report describes how guide stars are selected for the Optical Sensor Package (OSP) for the Instrument Pointing System (IPS) when it is operating in the stellar mode on the ASTRO missions. It also describes how the objective loads are written and how the various roll angles are related; i.e., the celestial roll or position angle, the objective load roll angles, and the IPS gimbal angles. There is a brief description of how the IPS operates and its various modes of operation; i.e., IDOP, IDIN, and OSPCAL.

  20. Uniform communications software using TCP/IP

    SciTech Connect

    Bernett, M.; Oleynik, G. )

    1989-10-01

    Data acquisition applications at Fermilab require a reliable, distributed communication system for downloading, diagnostics, control, and data distribution. TCP/IP over Ethernet was chosen because of its uniform user interface and commercial availability for a number of processors and operating systems. This paper describes the authors software and hardware support for TCP/IP on VAX/VMS, VME/rhoSOS, FASTBUS/rhoSOS, and Unix systems. It includes plans to provide a portable, hardware independent implementation of TCP/IP based on Berkeley BSD software.

  1. Uniform communications software using TCP/IP

    SciTech Connect

    Bernett, M.; Oleynik, G.

    1989-05-01

    Data acquisition applications at Fermilab require a reliable, distributed communication system for downloading, diagnostics, control, and data distribution. TCP/IP over Ethernet was chosen because of its uniform user interface and commercial availability for a number of processors and operating systems. This paper describes our software and hardware support for TCP/IP on VAX/VMS, VME/pSOS, FASTBUS/pSOS, and Unix systems. It includes plans to provide a portable, hardware independent implementation of TCP/IP based on Berkeley BSD software. 8 refs., 3 figs.

  2. Ischemic Stroke after Heart Transplantation

    PubMed Central

    Acampa, Maurizio; Lazzerini, Pietro Enea; Guideri, Francesca; Tassi, Rossana; Martini, Giuseppe

    2016-01-01

    Cerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome. PMID:26915504

  3. 40 CFR 86.1232-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Methanol-Fueled Heavy-Duty Vehicles § 86.1232-96 Vehicle preconditioning. (a) Fuel tank cap(s) of gasoline... prevent entry of water or other contaminants into the fuel tank. During storage in the test area while awaiting testing, the fuel tank cap(s) may be in place. The vehicle shall be moved into the test area...

  4. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Flotation Requirements for Outboard Boats Rated for Engines of More Than 2 Horsepower General § 183.220 Preconditioning for tests. A boat must meet the... boat. (b) The boat must be loaded with a quantity of weight that, when submerged, is equal to the...

  5. 40 CFR 86.1774-99 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 19 2010-07-01 2010-07-01 false Vehicle preconditioning. 86.1774-99... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Provisions for the Voluntary National Low Emission Vehicle Program for Light-Duty Vehicles and...

  6. 40 CFR 86.1774-99 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 19 2011-07-01 2011-07-01 false Vehicle preconditioning. 86.1774-99... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Provisions for the Voluntary National Low Emission Vehicle Program for Light-Duty Vehicles and...

  7. 40 CFR 86.1232-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... system is stabilized. The additional preconditioning shall consist of an initial one hour minimum soak... step to avoid damage to the components and the integrity of the fuel system. A replacement canister may... system. A replacement canister may be temporarily installed during the soak period while the...

  8. Nanoparticle Pre-Conditioning for Enhanced Thermal Therapies in Cancer

    PubMed Central

    Shenoi, Mithun M.; Shah, Neha B.; Griffin, Robert J.; Vercellotti, Gregory M.; Bischof, John C.

    2011-01-01

    Nanoparticles show tremendous promise in the safe and effective delivery of molecular adjuvants to enhance local cancer therapy. One important form of local cancer treatment that suffers from local recurrence and distant metastases is thermal therapy. Here we review a new concept involving the use of nanoparticle delivered adjuvants to “pre-condition” or alter the vascular and immunological biology of the tumor to enhance its susceptibility to thermal therapy. To this end, a number of opportunities to combine nanoparticles with vascular and immunologically active agents are reviewed. One specific example of pre-conditioning involves a gold nanoparticle tagged with a vascular targeting agent (i.e. TNF-α). This nanoparticle embodiment demonstrates pre-conditioning through a dramatic reduction in tumor blood flow and induction of vascular damage which recruits a strong and sustained inflammatory infiltrate in the tumor. The ability of this nanoparticle pre-conditioning to enhance subsequent heat or cold thermal therapy in a variety of tumor models is reviewed. Finally, the potential for future clinical imaging to judge the extent of pre-conditioning and thus the optimal timing and extent of combinatorial thermal therapy is discussed. PMID:21542691

  9. 40 CFR 1066.405 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Vehicle preparation and preconditioning. 1066.405 Section 1066.405 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS VEHICLE-TESTING PROCEDURES Preparing Vehicles and Running an Exhaust...

  10. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... conditioning (SC03) can be run immediately or up to 72 hours after the official FTP and/or evaporative test... than two hours, preconditioning consists of one full Urban Dynamometer Driving Cycle. Manufacturers, at... this section, the test vehicle is turned off, the vehicle cooling fan(s) is turned off, and the...

  11. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... conditioning (SC03) can be run immediately or up to 72 hours after the official FTP and/or evaporative test... than two hours, preconditioning consists of one full Urban Dynamometer Driving Cycle. Manufacturers, at... this section, the test vehicle is turned off, the vehicle cooling fan(s) is turned off, and the...

  12. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... conditioning (SC03) can be run immediately or up to 72 hours after the official FTP and/or evaporative test... than two hours, preconditioning consists of one full Urban Dynamometer Driving Cycle. Manufacturers, at... this section, the test vehicle is turned off, the vehicle cooling fan(s) is turned off, and the...

  13. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., on a dynamometer and operated through one Urban Dynamometer Driving Schedule (UDDS), specified in... additional preconditioning allows the vehicle to adapt to the new fuel before the next test run. (A) Purge.... (G) Following the dynamometer drive, the vehicle shall be turned off for 5 minutes, then...

  14. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... conditioning (SC03) can be run immediately or up to 72 hours after the official FTP and/or evaporative test... than two hours, preconditioning consists of one full Urban Dynamometer Driving Cycle. Manufacturers, at... this section, the test vehicle is turned off, the vehicle cooling fan(s) is turned off, and the...

  15. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... conditioning (SC03) can be run immediately or up to 72 hours after the official FTP and/or evaporative test... than two hours, preconditioning consists of one full Urban Dynamometer Driving Cycle. Manufacturers, at... this section, the test vehicle is turned off, the vehicle cooling fan(s) is turned off, and the...

  16. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., on a dynamometer and operated through one Urban Dynamometer Driving Schedule (UDDS), specified in... additional preconditioning allows the vehicle to adapt to the new fuel before the next test run. (A) Purge.... (G) Following the dynamometer drive, the vehicle shall be turned off for 5 minutes, then...

  17. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., on a dynamometer and operated through one Urban Dynamometer Driving Schedule (UDDS), specified in... additional preconditioning allows the vehicle to adapt to the new fuel before the next test run. (A) Purge.... (G) Following the dynamometer drive, the vehicle shall be turned off for 5 minutes, then...

  18. IP-1 Certification of Cargo Containers

    SciTech Connect

    Hagler, Lisle

    2010-10-05

    The purpose and scope of this engineering note is to demonstrate that the structural design of the cargo container complies with the IP-1 container requirements of 49 CFR 173.410 as required by CFR 173.411.

  19. Comparative calibration of IP scanning equipment

    NASA Astrophysics Data System (ADS)

    Ingenito, F.; Andreoli, P.; Batani, D.; Boutoux, G.; Cipriani, M.; Consoli, F.; Cristofari, G.; Curcio, A.; De Angelis, R.; Di Giorgio, G.; Ducret, J.; Forestier-Colleoni, P.; Hulin, S.; Jakubowska, K.; Rabhi, N.

    2016-05-01

    Imaging Plates (IP) are diagnostic devices which contain a photostimulable phosphor layer that stores the incident radiation dose as a latent image. The image is read with a scanner which stimulates the decay of electrons, previously excited by the incident radiation, by exposition to a laser beam. This results in emitted light, which is detected by photomultiplier tubes; so the latent image is reconstructed. IPs have the interesting feature that can be reused many times, after erasing stored information. Algorithms to convert signals stored in the detector to Photostimulated luminescence (PSL) counts depend on the scanner and are not available on every model. A comparative cross-calibration of the IP scanner Dürr CR35 BIO, used in ABC laboratory, was performed, using the Fujifilm FLA 7000 scanner as a reference, to find the equivalence between grey-scale values given by the Dürr scanner to PSL counts. Using an IP and a 55Fe β-source, we produced pairs of samples with the same exposition times, which were analysed by both scanners, placing particular attention to fading times of the image stored on IPs. Data analysis led us to the determine a conversion formula which can be used to compare data of experiments obtained in different laboratories and to use IP calibrations available, till now, only for Fujifilm scanners.

  20. MicroRNA-378 Alleviates Cerebral Ischemic Injury by Negatively Regulating Apoptosis Executioner Caspase-3

    PubMed Central

    Zhang, Nan; Zhong, Jie; Han, Song; Li, Yun; Yin, Yanling; Li, Junfa

    2016-01-01

    miRNAs have been linked to many human diseases, including ischemic stroke, and are being pursued as clinical diagnostics and therapeutic targets. Among the aberrantly expressed miRNAs in our previous report using large-scale microarray screening, the downregulation of miR-378 in the peri-infarct region of middle cerebral artery occluded (MCAO) mice can be reversed by hypoxic preconditioning (HPC). In this study, the role of miR-378 in the ischemic injury was further explored. We found that miR-378 levels significantly decreased in N2A cells following oxygen-glucose deprivation (OGD) treatment. Overexpression of miR-378 significantly enhanced cell viability, decreased TUNEL-positive cells and the immunoreactivity of cleaved-caspase-3. Conversely, downregulation of miR-378 aggravated OGD-induced apoptosis and ischemic injury. By using bioinformatic algorithms, we discovered that miR-378 may directly bind to the predicted 3′-untranslated region (UTR) of Caspase-3 gene. The protein level of caspase-3 increased significantly upon OGD treatment, and can be downregulated by pri-miR-378 transfection. The luciferase reporter assay confirmed the binding of miR-378 to the 3′-UTR of Caspase-3 mRNA and repressed its translation. In addition, miR-378 agomir decreased cleaved-caspase-3 ratio, reduced infarct volume and neural cell death induced by MCAO. Furthermore, caspase-3 knockdown could reverse anti-miR-378 mediated neuronal injury. Taken together, our data demonstrated that miR-378 attenuated ischemic injury by negatively regulating the apoptosis executioner, caspase-3, providing a potential therapeutic target for ischemic stroke. PMID:27598143

  1. MicroRNA-378 Alleviates Cerebral Ischemic Injury by Negatively Regulating Apoptosis Executioner Caspase-3.

    PubMed

    Zhang, Nan; Zhong, Jie; Han, Song; Li, Yun; Yin, Yanling; Li, Junfa

    2016-01-01

    miRNAs have been linked to many human diseases, including ischemic stroke, and are being pursued as clinical diagnostics and therapeutic targets. Among the aberrantly expressed miRNAs in our previous report using large-scale microarray screening, the downregulation of miR-378 in the peri-infarct region of middle cerebral artery occluded (MCAO) mice can be reversed by hypoxic preconditioning (HPC). In this study, the role of miR-378 in the ischemic injury was further explored. We found that miR-378 levels significantly decreased in N2A cells following oxygen-glucose deprivation (OGD) treatment. Overexpression of miR-378 significantly enhanced cell viability, decreased TUNEL-positive cells and the immunoreactivity of cleaved-caspase-3. Conversely, downregulation of miR-378 aggravated OGD-induced apoptosis and ischemic injury. By using bioinformatic algorithms, we discovered that miR-378 may directly bind to the predicted 3'-untranslated region (UTR) of Caspase-3 gene. The protein level of caspase-3 increased significantly upon OGD treatment, and can be downregulated by pri-miR-378 transfection. The luciferase reporter assay confirmed the binding of miR-378 to the 3'-UTR of Caspase-3 mRNA and repressed its translation. In addition, miR-378 agomir decreased cleaved-caspase-3 ratio, reduced infarct volume and neural cell death induced by MCAO. Furthermore, caspase-3 knockdown could reverse anti-miR-378 mediated neuronal injury. Taken together, our data demonstrated that miR-378 attenuated ischemic injury by negatively regulating the apoptosis executioner, caspase-3, providing a potential therapeutic target for ischemic stroke. PMID:27598143

  2. [Pregnancy and acute ischemic stroke].

    PubMed

    Bereczki, Dániel

    2016-05-15

    Pregnancy-related ischemic strokes play an important role in both maternal and fetal morbidity and mortality. Changes in hemostaseology and hemodynamics as well as risk factors related to or independent from pregnancy contribute to the increased stroke-risk during gestation and the puerperium. Potential teratogenic effects make diagnostics, acute therapy and prevention challenging. Because randomized, controlled trials are not available, a multicenter registry of patients with gestational stroke would be desirable. Until definite guidelines emerge, management of acute ischemic stroke during pregnancy remains individual, involving experts and weighing the risks and benefits.

  3. Genetic susceptibility to ischemic stroke

    PubMed Central

    Meschia, James F.; Worrall, Bradford B.; Rich, Stephen S.

    2014-01-01

    Clinicians who treat patients with stroke need to be aware of several single-gene disorders that have ischemic stroke as a major feature, including sickle cell disease, Fabry disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and retinal vasculopathy with cerebral leukodystrophy. The reported genome-wide association studies of ischemic stroke and several related phenotypes (for example, ischemic white matter disease) have shown that no single common genetic variant imparts major risk. Larger studies with samples numbering in the thousands are ongoing to identify common variants with smaller effects on risk. Pharmacogenomic studies have uncovered genetic determinants of response to warfarin, statins and clopidogrel. Despite increasing knowledge of stroke genetics, incorporating this new knowledge into clinical practice remains a challenge. The goals of this article are to review common single-gene disorders relevant to ischemic stroke, summarize the status of candidate gene and genome-wide studies aimed at discovering genetic stroke risk factors, and to briefly discuss pharmacogenomics related to stroke treatment. PMID:21629240

  4. [Phenomenon of heart ischemic postconditioning].

    PubMed

    Maslov, L N; Mrochek, A G; Hanus, L; Pei, J -M; Zhang, Y; Wang, H; Naryzhnaia, N V

    2012-08-01

    Authors of review analyzed papers on problem of heart ischemic postconditioning. In the review, it was demonstrated that postconditioning decreased an infarct size, prevented cardiomyocytes apoptosis, improved cardiac contractility in reperfusion period, augmented cardiac tolerance to arrhythmogenic impact ofreperfusion, prevented neutrophil invasion into the reperfused heart, abolished reperfusion endothelial dysfunction and suppressed reperfusion oxidative stress in myocardium. PMID:23155619

  5. Transient ischemic attack induced by melted solid lipid microparticles protects rat brains from permanent focal ischemia.

    PubMed

    Tsai, M-J; Kuo, Y-M; Tsai, Y-H

    2014-09-01

    This study aims to develop a transient ischemic attack (TIA) model in conscious animals and uses this model to investigate the effect of TIA on subsequent permanent ischemia. TIA was induced by injecting designed temperature-sensitive melted solid lipid microparticles with a melting point around body temperature into male Wistar rats via arterial cannulation. Neurologic deficit was monitored immediately after the injection without anesthesia. According to the clinical definition of TIA, rats were divided into neurologic symptom durations <24-h, 24-48-h and ≥48-h groups. The lipid microparticle-induced infarct volumes were small in the <24-h and 24-48-h groups, while the volumes were five times larger in the ≥48-h group. Permanent ischemic stroke was induced 3d after the induction of TIA by injecting a different kind of embolic particle manufactured by blending chitin and PLGA. The <24-h group had less severe neurologic deficits and smaller infarct volumes than that of 24-48-h and control (without prior lipid microparticle treatment) rats. Taken together, we successfully develop a TIA animal model which allows us to monitor the neurologic deficit in real-time. By adopting this model, we validate that TIA (<24h) preconditioning protects the brain from subsequent permanent ischemic stroke.

  6. Ischemic postconditioning provides protection against ischemia-reperfusion injury in intestines of rats.

    PubMed

    Chu, Weiwei; Li, Sheng; Wang, Shanwei; Yan, Aili; Nie, Lei

    2015-01-01

    In the present study, we investigated the protective role of ischemic postconditioning (IPOST) against intestine ischemia-reperfusion (I/R) injury in rats. Male Sprague-Dawley rats were divided into sham-operation group (S), I/R group (I/R), ischemic preconditioning group (IPC), ischemic postconditioning group (IPOST). After reperfusion, small intestines were resected for histopathologic evaluations. To evaluate DNA fragmentation, resolving agarose gel electrophoresis was performed. To measure cellular apoptotic rates in intestine tissues, we performed TUNEL staining. To examine lipid peroxidation, production of superoxide radicals and tissue neutrophil infiltration, we tested the content of malondialdehyde and activities of superoxidase dismutase and myeloperoxidase in intestine tissues, respectively. Under light microscope, intestinal mucosal impairment in IPOST and IPC groups was found milder than that in I/R group (P < 0.05). The number of apoptosis cells in I/R group was significantly higher than that in IPOST and IPC groups (P < 0.05). The content of malondialdehyde and activity of myeloperoxidase were significantly reduced in IPOST group and IPC group compared with I/R group, but the activity of superoxidase dismutase in IPOST group and IPC group was enhanced compared with I/R group (P < 0.05). These results suggest that IPOST results in protection against intestine I/R injury, which may be related to reduced production of reactive oxygen species, enhanced activities of antioxidant systems and inhibited apoptosis of intestinal mucosal cells.

  7. Regulation of IP 3 Receptors by IP 3 and Ca 2+

    NASA Astrophysics Data System (ADS)

    Taylor, Colin W.; Swatton, Jane E.

    Inositol 1,4,5-trisphosphate ( IP 3) receptors are intracellular Ca 2+ channels that mediate release of Ca 2+ from intracellular stores. The channels are oligomeric assemblies of four subunits, each of which has an N-terminal IP 3-binding domain and each of which contributes to formation of the Ca 2+ channel. In mammals, three different genes encode IP 3 receptors subunits and the type 1 receptor (and perhaps the type 2 receptor) is also expressed as splice variants. Further diversity arises from assembly of the receptor in hetero- and homo-tetrameric channels. The subtypes differ in their expression and regulation, but they share the key property of being regulated by both IP3 and cytosolic Ca 2+. All three mammalian IP 3 subtypes, and probably also the IP 3 receptors expressed in invertebrates, are biphasically regulated by cytosolic Ca2+, although the underlying mechanisms appear to differ between subtypes. The interactions between IP 3 and Ca 2+ in controlling IP 3 receptor gating, and the physiological significance of such regulation will be reviewed.

  8. Finding Chemical Reaction Paths with a Multilevel Preconditioning Protocol

    PubMed Central

    2015-01-01

    Finding transition paths for chemical reactions can be computationally costly owing to the level of quantum-chemical theory needed for accuracy. Here, we show that a multilevel preconditioning scheme that was recently introduced (Tempkin et al. J. Chem. Phys.2014, 140, 184114) can be used to accelerate quantum-chemical string calculations. We demonstrate the method by finding minimum-energy paths for two well-characterized reactions: tautomerization of malonaldehyde and Claissen rearrangement of chorismate to prephanate. For these reactions, we show that preconditioning density functional theory (DFT) with a semiempirical method reduces the computational cost for reaching a converged path that is an optimum under DFT by several fold. The approach also shows promise for free energy calculations when thermal noise can be controlled. PMID:25516726

  9. Shape reanalysis and sensitivities utilizing preconditioned iterative boundary solvers

    NASA Technical Reports Server (NTRS)

    Guru Prasad, K.; Kane, J. H.

    1992-01-01

    The computational advantages associated with the utilization of preconditined iterative equation solvers are quantified for the reanalysis of perturbed shapes using continuum structural boundary element analysis (BEA). Both single- and multi-zone three-dimensional problems are examined. Significant reductions in computer time are obtained by making use of previously computed solution vectors and preconditioners in subsequent analyses. The effectiveness of this technique is demonstrated for the computation of shape response sensitivities required in shape optimization. Computer times and accuracies achieved using the preconditioned iterative solvers are compared with those obtained via direct solvers and implicit differentiation of the boundary integral equations. It is concluded that this approach employing preconditioned iterative equation solvers in reanalysis and sensitivity analysis can be competitive with if not superior to those involving direct solvers.

  10. Reconstructing Clusters for Preconditioned Short-term Load Forecasting

    NASA Astrophysics Data System (ADS)

    Itagaki, Tadahiro; Mori, Hiroyuki

    This paper presents a new preconditioned method for short-term load forecasting that focuses on more accurate predicted value. In recent years, the deregulated and competitive power market increases the degree of uncertainty. As a result, more sophisticated short-term load forecasting techniques are required to deal with more complicated load behavior. To alleviate the complexity of load behavior, this paper presents a new preconditioned model. In this paper, clustering results are reconstructed to equalize the number of learning data after clustering with the Kohonen-based neural network. That enhances a short-term load forecasting model at each reconstructed cluster. The proposed method is successfully applied to real data of one-step ahead daily maximum load forecasting.

  11. Finding Chemical Reaction Paths with a Multilevel Preconditioning Protocol

    DOE PAGES

    Kale, Seyit; Sode, Olaseni; Weare, Jonathan; Dinner, Aaron R.

    2014-11-07

    Finding transition paths for chemical reactions can be computationally costly owing to the level of quantum-chemical theory needed for accuracy. Here, we show that a multilevel preconditioning scheme that was recently introduced (Tempkin et al. J. Chem. Phys. 2014, 140, 184114) can be used to accelerate quantum-chemical string calculations. We demonstrate the method by finding minimum-energy paths for two well-characterized reactions: tautomerization of malonaldehyde and Claissen rearrangement of chorismate to prephanate. For these reactions, we show that preconditioning density functional theory (DFT) with a semiempirical method reduces the computational cost for reaching a converged path that is an optimum undermore » DFT by several fold. In conclusion, the approach also shows promise for free energy calculations when thermal noise can be controlled.« less

  12. Finding Chemical Reaction Paths with a Multilevel Preconditioning Protocol

    SciTech Connect

    Kale, Seyit; Sode, Olaseni; Weare, Jonathan; Dinner, Aaron R.

    2014-11-07

    Finding transition paths for chemical reactions can be computationally costly owing to the level of quantum-chemical theory needed for accuracy. Here, we show that a multilevel preconditioning scheme that was recently introduced (Tempkin et al. J. Chem. Phys. 2014, 140, 184114) can be used to accelerate quantum-chemical string calculations. We demonstrate the method by finding minimum-energy paths for two well-characterized reactions: tautomerization of malonaldehyde and Claissen rearrangement of chorismate to prephanate. For these reactions, we show that preconditioning density functional theory (DFT) with a semiempirical method reduces the computational cost for reaching a converged path that is an optimum under DFT by several fold. In conclusion, the approach also shows promise for free energy calculations when thermal noise can be controlled.

  13. Combined incomplete LU and strongly implicit procedure preconditioning

    SciTech Connect

    Meese, E.A.

    1996-12-31

    For the solution of large sparse linear systems of equations, the Krylov-subspace methods have gained great merit. Their efficiency are, however, largely dependent upon preconditioning of the equation-system. A family of matrix factorisations often used for preconditioning, is obtained from a truncated Gaussian elimination, ILU(p). Less common, supposedly due to it`s restriction to certain sparsity patterns, is factorisations generated by the strongly implicit procedure (SIP). The ideas from ILU(p) and SIP are used in this paper to construct a generalized strongly implicit procedure, applicable to matrices with any sparsity pattern. The new algorithm has been run on some test equations, and efficiency improvements over ILU(p) was found.

  14. A survey of IP over ATM architectures

    SciTech Connect

    Chen, H.; Tsang, R.; Brandt, J.; Hutchins, J.

    1997-07-01

    Over the past decade, the Internet has burgeoned into a worldwide information highway consisting of approximately 5 million hosts on over 45,000 interconnected networks. This unprecedented growth, together with the introduction of multimedia workstations, has spurred the development of innovative applications that require high speed, low latency, and real-time transport. Today`s Internet can neither scale in its bandwidth nor guarantee the Quality of Services (QoS) necessary to meet these performance requirements. Many network researchers propose to use the Asynchronous Transfer Mode (ATM) technology as the underlying infrastructure for the next generation of workgroup, campus, and enterprise IP networks. Since ATM is significantly different from today`s legacy network technologies, efficient implementation of IP over ATM is especially challenging. This tutorial paper covers several existing proposals that integrate IP over ATM.

  15. Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning.

    PubMed

    Robinson, Siobhan; Todd, Travis P; Pasternak, Anna R; Luikart, Bryan W; Skelton, Patrick D; Urban, Daniel J; Bucci, David J

    2014-08-13

    An essential aspect of episodic memory is the formation of associations between neutral sensory cues in the environment. In light of recent evidence that this critical aspect of learning does not require the hippocampus, we tested the involvement of the retrosplenial cortex (RSC) in this process using a chemogenetic approach that allowed us to temporarily silence neurons along the entire rostrocaudal extent of the RSC. A viral vector containing the gene for a synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC. When the receptor was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transiently silenced (confirmed using a patch-clamp procedure). Rats expressing hM4Di and control rats were trained in a sensory preconditioning procedure in which a tone and light were paired on some trials and a white noise stimulus was presented alone on the other trials during the Preconditioning phase. Thus, rats were given the opportunity to form an association between a tone and a light in the absence of reinforcement. Later, the light was paired with food. During the test phase when the auditory cues were presented alone, controls exhibited more conditioned responding during presentation of the tone compared with the white noise reflecting the prior formation of a tone-light association. Silencing RSC neurons during the Preconditioning phase prevented the formation of an association between the tone and light and eliminated the sensory preconditioning effect. These findings indicate that RSC may contribute to episodic memory formation by linking essential sensory stimuli during learning.

  16. Parallel Domain Decomposition Preconditioning for Computational Fluid Dynamics

    NASA Technical Reports Server (NTRS)

    Barth, Timothy J.; Chan, Tony F.; Tang, Wei-Pai; Kutler, Paul (Technical Monitor)

    1998-01-01

    This viewgraph presentation gives an overview of the parallel domain decomposition preconditioning for computational fluid dynamics. Details are given on some difficult fluid flow problems, stabilized spatial discretizations, and Newton's method for solving the discretized flow equations. Schur complement domain decomposition is described through basic formulation, simplifying strategies (including iterative subdomain and Schur complement solves, matrix element dropping, localized Schur complement computation, and supersparse computations), and performance evaluation.

  17. Object-oriented design of preconditioned iterative methods

    SciTech Connect

    Bruaset, A.M.

    1994-12-31

    In this talk the author discusses how object-oriented programming techniques can be used to develop a flexible software package for preconditioned iterative methods. The ideas described have been used to implement the linear algebra part of Diffpack, which is a collection of C++ class libraries that provides high-level tools for the solution of partial differential equations. In particular, this software package is aimed at rapid development of PDE-based numerical simulators, primarily using finite element methods.

  18. Preconditioned Alternating Projection Algorithms for Maximum a Posteriori ECT Reconstruction

    PubMed Central

    Krol, Andrzej; Li, Si; Shen, Lixin; Xu, Yuesheng

    2012-01-01

    We propose a preconditioned alternating projection algorithm (PAPA) for solving the maximum a posteriori (MAP) emission computed tomography (ECT) reconstruction problem. Specifically, we formulate the reconstruction problem as a constrained convex optimization problem with the total variation (TV) regularization. We then characterize the solution of the constrained convex optimization problem and show that it satisfies a system of fixed-point equations defined in terms of two proximity operators raised from the convex functions that define the TV-norm and the constrain involved in the problem. The characterization (of the solution) via the proximity operators that define two projection operators naturally leads to an alternating projection algorithm for finding the solution. For efficient numerical computation, we introduce to the alternating projection algorithm a preconditioning matrix (the EM-preconditioner) for the dense system matrix involved in the optimization problem. We prove theoretically convergence of the preconditioned alternating projection algorithm. In numerical experiments, performance of our algorithms, with an appropriately selected preconditioning matrix, is compared with performance of the conventional MAP expectation-maximization (MAP-EM) algorithm with TV regularizer (EM-TV) and that of the recently developed nested EM-TV algorithm for ECT reconstruction. Based on the numerical experiments performed in this work, we observe that the alternating projection algorithm with the EM-preconditioner outperforms significantly the EM-TV in all aspects including the convergence speed, the noise in the reconstructed images and the image quality. It also outperforms the nested EM-TV in the convergence speed while providing comparable image quality. PMID:23271835

  19. 76 FR 81955 - Assessment Questionnaire-IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... SECURITY Assessment Questionnaire--IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT) AGENCY... Protection and Programs Directorate (NPPD), Office of Infrastructure Protection (IP), Sector Specific Agency.../IP/SSA EMO, 245 Murray Lane SW., Mail Stop 0640, Arlington, VA 20598-0630. Emailed requests should...

  20. 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 α( n) (for some constant α) which is optimal complexity for such problems.

  1. Financial preconditions for successful community initiatives for the uninsured.

    PubMed

    Song, Paula H; Smith, Dean G

    2007-01-01

    Community-based initiatives are increasingly being implemented as a strategy to address the health needs of the community, with a growing body of evidence on successes of various initiatives. This study addresses financial status indicators (preconditions) that might predict where community-based initiatives might have a better chance for success. We evaluated five community-based initiatives funded by the Communities in Charge (CIC) program sponsored by the Robert Wood Johnson Foundation. These initiatives focus on increasing access by easing financial barriers to care for the uninsured. At each site, we collected information on financial status indicators and interviewed key personnel from health services delivery and financing organizations. With full acknowledgment of the caveats associated with generalizations based on a small number of observations, we suggest four financial preconditions associated with successful initiation of CIC programs: (1) uncompensated care levels that negatively affect profitability, (2) reasonable financial stability of providers, (3) stable health insurance market, and (4) the potential to create new sources of funding. In general, sites that demonstrate successful program initiation are financially stressed enough by uncompensated care to gain the attention of local healthcare providers. However, they are not so strained and so concerned about revenue sources that they cannot afford to participate in the initiative. In addition to political and managerial indicators, we suggest that planning for community-based initiatives should include financial indicators of current health services delivery and financing organizations and consideration of whether they meet preconditions for success.

  2. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

    PubMed

    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

  3. White Matter Ischemic Changes in Hyperacute Ischemic Stroke

    PubMed Central

    Trouard, Theodore P; Lafleur, Scott R.; Krupinski, Elizabeth A.; Salamon, Noriko; Kidwell, Chelsea S.

    2015-01-01

    Background and Purpose— The purpose of this study was to evaluate changes in fractional anisotropy (FA), as measured by diffusion tensor imaging, of white matter (WM) infarction and hypoperfusion in patients with acute ischemic stroke using a quantitative voxel-based analysis. Methods— In this prospective study, diffusion tensor imaging and dynamic susceptibility contrast perfusion sequences were acquired in 21 patients with acute ischemic stroke who presented within 6 hours of symptom onset. The coregistered FA, apparent diffusion coefficient, and dynamic susceptibility contrast time to maximum (Tmax) maps were used for voxel-based quantification using a region of interest approach in the ipsilateral affected side and in the homologous contralateral WM. The regions of WM infarction versus hypoperfusion were segmented using a threshold method. Data were analyzed by regression and ANOVA. Results— There was an overall significant mean difference (P<0.001) for the apparent diffusion coefficient, Tmax, and FA values between the normal, hypoperfused, and infarcted WM. The mean±SD of FA was significantly higher (P<0.001) in hypoperfused WM (0.397±0.019) and lower (P<0.001) in infarcted WM (0.313±0.037) when compared with normal WM (0.360±0.020). Regression tree analysis of hypoperfused WM showed the largest mean FA difference at Tmax above versus below 5.4 s with a mean difference of 0.033 (P=0.0096). Conclusions— Diffusion tensor imaging-FA was decreased in regions of WM infarction and increased in hypoperfused WM in patients with hyperacute acute ischemic stroke. The significantly increased FA values in the hypoperfused WM with Tmax≥5.4 s are suggestive of early ischemic microstructural changes. PMID:25523053

  4. Oxygen radicals mediate ultrastructural and metabolic protection of preconditioning in vivo in pig hearts.

    PubMed

    Miyamae, Masami; Fujiwara, Hisayoshi; Tanaka, Masaru; Yokota, Ryoji; Takemura, Genzou; Itoh, Shuji; Domae, Naochika; Figueredo, Vincent M

    2002-01-01

    Ischemic preconditioning (PC) preserves myocardial high-energy phosphate metabolites and intracellular pH during subsequent sustained ischemia. Generation of reactive oxygen species may be required to mediate PC, as seen in vitro. In the present study, the effects of inhibiting reactive oxygen species generation during a PC protocol in vivo using an open-chest porcine model were examined. Myocyte ultrastructural changes assessed by electron microscopy were correlated with phosphorus nuclear magnetic resonance spectroscopy data. Open-chest pigs underwent 60 min of left anterior descending coronary artery occlusion. PC was elicited by a single episode of 5 min occlusion and 5 min reperfusion. The cell-diffusible hydroxyl radical and superoxide radical scavenger, N-2-mercapto-propionyl glycine (MPG, 20 mg/kg), or placebo saline were infused for 40 min, starting 30 min before PC (PC plus MPG group, n=10; and PC group, n=9). After PC, ATP and intracellular pH were significantly preserved through 25 min of ischemia (control versus PC, 46+/-3% versus 55+/-5% of baseline [P<0.05]; and control versus PC, 6.18+/-0.08 versus 6.42+/-0.03 [P<0.05], respectively). Phosphocreatine was significantly preserved through 20 min of ischemia (control versus PC, 0+/-0% versus 7+/-2% of baseline [P<0.05]). The preservation of high-energy phosphate metabolites and intracellular pH was abolished by inhibiting the generation of reactive oxygen species with MPG. Preservation of high-energy phosphate metabolites with PC was associated with reduced ultrastructural damage, as seen by electron microscopy, including less myocyte swelling, myofibrillar disruption and nuclear chromatin margination. The present study demonstrates the importance of reactive oxygen species generation in mediating PC preservation of myocyte ultrastructure and high-energy phosphate metabolites during prolonged ischemia in vivo.

  5. Arterial ischemic stroke in HIV

    PubMed Central

    Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom

    2016-01-01

    HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505

  6. Dexamethasone prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats.

    PubMed

    Ikeda, Tomoaki; Mishima, Kenichi; Yoshikawa, Tetsuya; Iwasaki, Katsunori; Fujiwara, Michihiro; Xia, Yi X; Ikenoue, Tsuyomu

    2002-10-17

    We examined for 18 weeks the effect of dexamethasone treatment on learning and memory impairment produced by hypoxic-ischemic stress at postnatal day 7 in rat in addition to brain histological study. Dexamethasone of 0.5 mg/kg was injected i.p. 4 h before hypoxic-ischemic stress, in which the left carotid artery was ligated followed by 2 h hypoxia (8% oxygen). Dexamethasone treatment improved behavior in each learning task: in choice reaction time tasks relating to the attention process, in 8-arm radial maze task examining working and reference memory, and in water maze task relating to reference memory. Improvement to the extent of the sham-control level was observed. Dexamethasone treatment also completely prevented histological brain damage. No adverse effect in learning and memory tests was observed in the animals treated with dexamethasone without hypoxic-ischemic stress. It is concluded that dexamethasone treatment is significantly effective in prevention not only of histological brain damage but also of learning and memory impairment occasioned by subsequent hypoxic-ischemic insult, warranting further clinical investigation.

  7. IP validation in remote microelectronics testing

    NASA Astrophysics Data System (ADS)

    Osseiran, Adam; Eshraghian, Kamran; Lachowicz, Stefan; Zhao, Xiaoli; Jeffery, Roger; Robins, Michael

    2004-03-01

    This paper presents the test and validation of FPGA based IP using the concept of remote testing. It demonstrates how a virtual tester environment based on a powerful, networked Integrated Circuit testing facility, aimed to complement the emerging Australian microelectronics based research and development, can be employed to perform the tasks beyond the standard IC test. IC testing in production consists in verifying the tested products and eliminating defective parts. Defects could have a number of different causes, including process defects, process migration and IP design and implementation errors. One of the challenges in semiconductor testing is that while current fault models are used to represent likely faults (stuck-at, delay, etc.) in a global context, they do not account for all possible defects. Research in this field keeps growing but the high cost of ATE is preventing a large community from accessing test and verification equipment to validate innovative IP designs. For these reasons a world class networked IC teletest facility has been established in Australia under the support of the Commonwealth government. The facility is based on a state-of-the-art semiconductor tester operating as a virtual centre spanning Australia and accessible internationally. Through a novel approach the teletest network provides virtual access to the tester on which the DUT has previously been placed. The tester software is then accessible as if the designer is sitting next to the tester. This paper presents the approach used to test and validate FPGA based IPs using this remote test approach.

  8. Operational Space Weather Products at IPS

    NASA Astrophysics Data System (ADS)

    Neudegg, D.; Steward, G.; Marshall, R.; Terkildsen, M.; Kennewell, J.; Patterson, G.; Panwar, R.

    2008-12-01

    IPS Radio and Space Services operates an extensive network (IPSNET) of monitoring stations and observatories within the Australasian and Antarctic regions to gather information on the space environment. This includes ionosondes, magnetometers, GPS-ISM, oblique HF sounding, riometers, and solar radio and optical telescopes. IPS exchanges this information with similar organisations world-wide. The Regional Warning Centre (RWC) is the Australian Space Forecast Centre (ASFC) and it utilizes this data to provide products and services to support customer operations. A wide range of customers use IPS services including; defence force and emergency services using HF radio communications and surveillance systems, organisations involved in geophysical exploration and pipeline cathodic protection, GPS users in aviation. Subscriptions to the alerts, warnings, forecasts and reports regarding the solar, geophysical and ionospheric conditions are distributed by email and Special Message Service (SMS). IPS also develops and markets widely used PC software prediction tools for HF radio skywave and surface wave (ASAPS/GWPS) and provides consultancy services for system planning.

  9. 75 FR 13235 - IP-Enabled Services

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-19

    ... 47 CFR 63.60(a) and (f), published on August 7, 2009 (74 FR 39551), were approved by the Office of... published a document in the Federal Register, 74 FR 39551, August 7, 2009, that sets forth an effective date... COMMISSION 47 CFR Part 63 IP-Enabled Services AGENCY: Federal Communications Commission ACTION: Final...

  10. EQuIP-ped for Success

    ERIC Educational Resources Information Center

    Ewing, Molly

    2015-01-01

    The Educators Evaluating the Quality of Instructional Products (EQuIP) Rubric for science is a new tool for science educators that provides criteria by which to examine the alignment and overall quality of lessons and units with respect to the "Next Generation Science Standards" ("NGSS"). The rubric criteria are divided into…

  11. How To: Be VoIP-Savvy

    ERIC Educational Resources Information Center

    Branzburg, Jeffrey

    2005-01-01

    Cablevision, Comcast, Verizon, and many other high-speed broadband Internet providers are now also offering telephone services through "Voice over Internet Protocol" (VoIP). This technology sends ordinary telephone calls over the Internet rather than over telephone lines. While impractical without the use of a broadband Internet connection, with…

  12. Call progress time measurement in IP telephony

    NASA Astrophysics Data System (ADS)

    Khasnabish, Bhumip

    1999-11-01

    Usually a voice call is established through multiple stages in IP telephony. In the first stage, a phone number is dialed to reach a near-end or call-originating IP-telephony gateway. The next stages involve user identification through delivering an m-digit user-id to the authentication and/or billing server, and then user authentication by using an n- digit PIN. After that, the caller is allowed (last stage dial tone is provided) to dial a destination phone number provided that authentication is successful. In this paper, we present a very flexible method for measuring call progress time in IP telephony. The proposed technique can be used to measure the system response time at every stage. It is flexible, so that it can be easily modified to include new `tone' or a set of tones, or `voice begin' can be used in every stage to detect the system's response. The proposed method has been implemented using scripts written in Hammer visual basic language for testing with a few commercially available IP telephony gateways.

  13. Hyperacute management of ischemic stroke.

    PubMed

    Song, Sarah

    2013-11-01

    Stroke is a devastating disease and currently the fourth leading cause of death in this country. Acute ischemic stroke is an emergency and requires effective triage, diagnosis, and critical management. The hyperacute management of ischemic stroke begins in the field, with recognition of stroke symptoms by emergency medical systems (EMS) personnel. The EMS is an important component to an effective stroke system of care, which also includes primary stroke centers, routing protocols for acute ischemic stroke, and telemedicine. Following the arrival of a potential stroke patient to the emergency room setting, patients should be stabilized and undergo assessment for potential intravenous alteplase (IV tPA) treatment. Assessments include diagnostic tests, neuroimaging, and standardized stroke evaluations. After these assessments have been performed, IV tPA, the only medication for acute stroke approved by the U.S. Food and Drug Administration, can be considered using a variety of inclusion and exclusion criteria. Previously time restrictions limited the usage of IV tPA to 3 hours, but this time window has now been extended for eligible candidates to 4.5 hours. The administration of IV tPA has specific requirements for monitoring and should be standardized via protocol across hospitals.

  14. [Ischemic cerebrovascular accidents in childhood].

    PubMed

    Pascual Pascual, S I; Pascual Castroviejo, I; Vélez, A

    1988-04-01

    Authors review 53 children, aged 0 to 14 years, affected with cerebrovascular ischemic strokes. Largest aetiological groups were: a) congenital heart disease, 16 patients; b) arteritis of unknown cause, 11; c) idiopathic arterial occlusion without arteritis images on angiography, 7; d) moyamoya disease, 6; and d) local or systemic infections, 5. The mode of onset was as completed stroke in 72% and stroke in evolution in 24%. After acute stage 17.6% of patients presented other definitive strokes, 11.7% suffered only transient ischemic strokes (TIA), and 4% reversible ischemic neurologic deficits (RIND). Mean follow-up was 4.36 years, 9.8% of patients died, 11.8% recovered completely and 52.9% improved after initial stroke. Poor global evolution was associated with heart disease (p less than 0.05) and with onset of strokes before age 2 (p less than 0.05). Most important sequelae, besides motor impairment, were epilepsy (49%) and mental retardation (50% got less than IQ 80). Late epilepsy was associated with seizures at onset (p less than 0.05). Clinical factors of adverse mental development were: a) seizures at onset, b) late epilepsy and c) stroke before age 2. 66% of cases had two or more arterial lesions in the same or in different arterial trees. Therefore, embolic and arteritic factors probably play an important role in infancy and childhood stroke. PMID:3400936

  15. Using VoIP to compete.

    PubMed

    Werbach, Kevin

    2005-09-01

    Internet telephony, or VoIP, is rapidly replacing the conventional kind. This year, for the first time, U.S. companies bought more new Internet-phone connections than standard lines. The major driver behind this change is cost. But VoIP isn't just a new technology for making old-fashioned calls cheaper, says consultant Kevin Werbach. It is fundamentally changing how companies use voice communications. What makes VoIP so powerful is that it turns voice into digital data packets that can be stored, copied, combined with other data, and distributed to virtually any device that connects to the Internet. And it makes it simple to provide all the functionality of a corporate phone-call features, directories, security-to anyone anywhere there's broadband access. That fosters new kinds of businesses such as virtual call centers, where widely dispersed agents work at all hours from their homes. The most successful early adopters, says Werbach, will focus more on achieving business objectives than on saving money. They will also consider how to push VoIP capabilities out to the extended organization, making use of everyone as a resource. Deployment may be incremental, but companies should be thinking about where VoIP could take them. Executives should ask what they could do if, on demand, they could bring all their employees, customers, suppliers, and partners together in a virtual room, with shared access to every modern communications and computing channel. They should take a fresh look at their business processes to find points at which richer and more customizable communications could eliminate bottlenecks and enhance quality. The important dividing line won't be between those who deploy Vol P and those who don't, or even between early adopters and laggards. It will be between those who see Vol P as just a new way to do the same old things and those who use itto rethink their entire businesses.

  16. Prevention of experimental stroke by hypercapnic-hypoxic preconditioning.

    PubMed

    Yakushev, N N; Bespalov, A G; Kulikov, V P

    2008-09-01

    The effectiveness of hypercapnic hypoxic training in the prevention of acute disturbances in cerebral circulation was studied under experimental conditions. Hypercapnic hypoxic training was followed by a significant decrease in the severity of neurological deficit and locomotor and coordination disorders after cerebral ischemic injury. PMID:19240841

  17. Development of New IP Cores for Spacecraft Avionics

    NASA Astrophysics Data System (ADS)

    Isomaki, Marko; Ekergarn, Jonas; Hjorth, Magnus; Wessman, Nils-Johan; Habinc, Sandi

    2010-08-01

    The GRLIB IP library is an integrated set of reusable IP cores, designed for system-on-chip (SOC) development. The IP cores are centered around a common on-chip bus, and use a coherent method for simulation and synthesis. The library is vendor independent, with support for different CAD tools and target technologies. The success of any IP core library is highly dependent on the constantly increasing number of IP cores and the improvement of existing IP cores. This paper will cover both these aspects, presenting some new developments as well as some improvements of existing items.

  18. Preconditioned iterative methods for space-time fractional advection-diffusion equations

    NASA Astrophysics Data System (ADS)

    Zhao, Zhi; Jin, Xiao-Qing; Lin, Matthew M.

    2016-08-01

    In this paper, we propose practical numerical methods for solving a class of initial-boundary value problems of space-time fractional advection-diffusion equations. First, we propose an implicit method based on two-sided Grünwald formulae and discuss its stability and consistency. Then, we develop the preconditioned generalized minimal residual (preconditioned GMRES) method and preconditioned conjugate gradient normal residual (preconditioned CGNR) method with easily constructed preconditioners. Importantly, because resulting systems are Toeplitz-like, fast Fourier transform can be applied to significantly reduce the computational cost. We perform numerical experiments to demonstrate the efficiency of our preconditioners, even in cases with variable coefficients.

  19. Stimulation of Inositol 1,4,5-Trisphosphate (IP3) Receptor Subtypes by Analogues of IP3

    PubMed Central

    Saleem, Huma; Tovey, Stephen C.; Rahman, Taufiq; Riley, Andrew M.; Potter, Barry V. L.; Taylor, Colin W.

    2013-01-01

    Most animal cells express mixtures of the three subtypes of inositol 1,4,5-trisphosphate receptor (IP3R) encoded by vertebrate genomes. Activation of each subtype by different agonists has not hitherto been examined in cells expressing defined homogenous populations of IP3R. Here we measure Ca2+ release evoked by synthetic analogues of IP3 using a Ca2+ indicator within the lumen of the endoplasmic reticulum of permeabilized DT40 cells stably expressing single subtypes of mammalian IP3R. Phosphorylation of (1,4,5)IP3 to (1,3,4,5)IP4 reduced potency by ∼100-fold. Relative to (1,4,5)IP3, the potencies of IP3 analogues modified at the 1-position (malachite green (1,4,5)IP3), 2-position (2-deoxy(1,4,5)IP3) or 3-position (3-deoxy(1,4,5)IP3, (1,3,4,5)IP4) were similar for each IP3R subtype. The potency of an analogue, (1,4,6)IP3, in which the orientations of the 2- and 3-hydroxyl groups were inverted, was also reduced similarly for all three IP3R subtypes. Most analogues of IP3 interact similarly with the three IP3R subtypes, but the decrease in potency accompanying removal of the 1-phosphate from (1,4,5)IP3 was least for IP3R3. Addition of a large chromophore (malachite green) to the 1-phosphate of (1,4,5)IP3 only modestly reduced potency suggesting that similar analogues could be used to measure (1,4,5)IP3 binding optically. These data provide the first structure-activity analyses of key IP3 analogues using homogenous populations of each mammalian IP3R subtype. They demonstrate broadly similar structure-activity relationships for all mammalian IP3R subtypes and establish the potential utility of (1,4,5)IP3 analogues with chromophores attached to the 1-position. PMID:23372785

  20. Echocardiographic assessment of ischemic mitral regurgitation.

    PubMed

    Dudzinski, David M; Hung, Judy

    2014-01-01

    Ischemic mitral regurgitation is an important consequence of LV remodeling after myocardial infarction. Echocardiographic diagnosis and assessment of ischemic mitral regurgitation are critical to gauge its adverse effects on prognosis and to attempt to tailor rational treatment strategy. There is no single approach to the echocardiographic assessment of ischemic mitral regurgitation: standard echocardiographic measures of mitral regurgitation severity and of LV dysfunction are complemented by assessments of displacement of the papillary muscles and quantitative indices of mitral valve deformation. Development of novel approaches to understand mitral valve geometry by echocardiography may improve understanding of the mechanism, clinical trajectory, and reparability of ischemic mitral regurgitation.

  1. Customer choice test is running well for IP

    SciTech Connect

    1996-06-01

    As of May 4, eight of the 21 eligible Illinois Power Company (IP) electricity customers had chosen to buy some of their power from an entity other than IP. They are free to do this because IP is conducting an experiment in customer choice, the first of its kind in the country, according to the utility. Although it is still very early, the experiment seems to be working well. {open_quotes}Our experience so far has been very good,{close_quotes} said John Dewey, a spokesman for IP. {open_quotes}Some of our customers say they expect to see substantial savings.{close_quotes} IP expects to gain knowledge of what it takes to retain customers and, when the entire industry becomes competitive, to gain new customers. IP`s own marketing affiliate, Illinova Power Marketing, based in Salt Lake City, Utah, is participating: It arranged for 4 MWe of power from another supplier to be shipped across IP`s transmission system to one of IP`s customers. IP`s tariff for such use of its transmission lines, as approved by the Federal Energy Regulatory Commission, is between 0.3 and 0.5 cents/kWh.

  2. Optimization of OSPF Routing in IP Networks

    NASA Astrophysics Data System (ADS)

    Bley, Andreas; Fortz, Bernard; Gourdin, Eric; Holmberg, Kaj; Klopfenstein, Olivier; Pióro, Michał; Tomaszewski, Artur; Ümit, Hakan

    The Internet is a huge world-wide packet switching network comprised of more than 13,000 distinct subnetworks, referred to as Autonomous Systems (ASs) autonomous system AS . They all rely on the Internet Protocol (IP) internet protocol IP for transport of packets across the network. And most of them use shortest path routing protocols shortest path routing!protocols , such as OSPF or IS-IS, to control the routing of IP packets routing!of IP packets within an AS. The idea of the routing is extremely simple — every packet is forwarded on IP links along the shortest route between its source and destination nodes of the AS. The AS network administrator can manage the routing of packets in the AS by supplying the so-called administrative weights of IP links, which specify the link lengths that are used by the routing protocols for their shortest path computations. The main advantage of the shortest path routing policy is its simplicity, allowing for little administrative overhead. From the network engineering perspective, however, shortest path routing can pose problems in achieving satisfactory traffic handling efficiency. As all routing paths depend on the same routing metric routing!metric , it is not possible to configure the routing paths for the communication demands between different pairs of nodes explicitly or individually; the routing can be controlled only indirectly and only as a whole by modifying the routing metric. Thus, one of the main tasks when planning such networks is to find administrative link weights that induce a globally efficient traffic routing

  3. Pyruvate-dependent preconditioning and cardioprotection in murine myocardium.

    PubMed

    Flood, Amanda; Hack, Benjamin D; Headrick, John P

    2003-03-01

    1. Whether pyruvate inhibits or can actually initiate myocardial preconditioning is unclear and whether pyruvate provides protection via its action as a 'cosubstrate' with glucose or via alternative mechanisms also remains controversial. We examined effects of a high concentration of pyruvate (10 mmol/L) alone or with 15 mmol/L glucose in mouse hearts subjected to 20 min ischaemia and 30 min reperfusion. 2. Provision of 10 mmol/L pyruvate alone or as a cosubstrate markedly reduced ischaemic contracture and enhanced postischaemic recovery. Time to contracture was increased from approximately 3 min to over 8 min, peak contracture was reduced from 90 mmHg to less than 60 mmHg and postischaemic pressure development was also improved. Effects on contracture were independent of the presence of pyruvate during ischaemia and improved postischaemic recovery was evident with pre-ischaemic pyruvate perfusion. 3. Cardioprotection did not require the presence of pyruvate during ischaemia or reperfusion and effects of pyruvate pretreatment could be mimicked by pretreatment with 1 mmol/L dichloroacetate (DCA), an activator of pyruvate dehydrogenase. 4. Myocardial adenosine efflux and Ca2+ content were elevated (by 215 and 65%, respectively) following pretreatment with pyruvate, potentially triggering a preconditioned state. A role for adenosine A1 receptors is supported by lack of added protection with pyruvate in hearts transgenically overexpressing adenosine A1 receptors. 5. Collectively, these observations demonstrate that pre-ischaemic treatment with pyruvate or DCA provides a beneficial preconditioning-like effect in ischaemic and postischaemic myocardium. The response appears unrelated to glycolytic inhibition, but may be mediated via transient changes in adenosine levels and/or cellular Ca2+.

  4. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

    PubMed Central

    Kernan, W.N.; Viscoli, C.M.; Furie, K.L.; Young, L.H.; Inzucchi, S.E.; Gorman, M.; Guarino, P.D.; Lovejoy, A.M.; Peduzzi, P.N.; Conwit, R.; Brass, L.M.; Schwartz, G.G.; Adams, H.P.; Berger, L.; Carolei, A.; Clark, W.; Coull, B.; Ford, G.A.; Kleindorfer, D.; O’Leary, J.R.; Parsons, M.W.; Ringleb, P.; Sen, S.; Spence, J.D.; Tanne, D.; Wang, D.; Winder, T.R.

    2016-01-01

    BACKGROUND Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P = 0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P = 0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P = 0.003). CONCLUSIONS In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of

  5. 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.

  6. Incomplete block factorization preconditioning for indefinite elliptic problems

    SciTech Connect

    Guo, Chun-Hua

    1996-12-31

    The application of the finite difference method to approximate the solution of an indefinite elliptic problem produces a linear system whose coefficient matrix is block tridiagonal and symmetric indefinite. Such a linear system can be solved efficiently by a conjugate residual method, particularly when combined with a good preconditioner. We show that specific incomplete block factorization exists for the indefinite matrix if the mesh size is reasonably small. And this factorization can serve as an efficient preconditioner. Some efforts are made to estimate the eigenvalues of the preconditioned matrix. Numerical results are also given.

  7. IPS - Instrument pointing system for Spacelab payloads

    NASA Astrophysics Data System (ADS)

    Hammesfahr, A.

    An instrument pointing system (IPS) will be flown for the first time with Spacelab 2 in Oct. 1984. The IPS is a three-axis gimbal system with payload clamp units for mounting on the Spacelab pallets. Power to drive the units comes from an integrated electronic power and digital control system and Spacelab subsystems. Control originates in either Spacelab, the Shuttle, or from the ground. An intermediate gimbal system is provided with explosive bolts in order to jettison the payload in critical situations. The system covers a conical field-of-view of 120 deg aperture with 180 deg possible in both directions of the roll axis. A block diagram is furnished for the electrical circuitry. Loads are interchangeable so long as they interface with clamps which hold the package to the Orbiter. A maximum weight of up to three tons is allowable.

  8. China IP expanding with self-sufficiency.

    PubMed

    2000-07-01

    This article reports the proceedings of the two National Workshops on the Integrated Project (IP), held in two cities in China. These workshops were organized by the National Steering Committee (NSC) of the Integrated Family Planning Project in China. About 70 representatives, project personnel from the first to the fourth cycle project areas, attended the Taicang workshop, while about 60 representatives from the fifth and sixth cycle project areas attended the Pingyao workshop. Workshop agendas included reports from the NSC, lectures by experts on new developments of reproductive health, summary report of the evaluation for the fifth cycle project, and presentation and discussion on selected project areas. The participants from each workshop took part in field trips to Taicang and Pingyao followed by discussions summarizing the trips. Overall, it is noted that pilot IP projects must not be conducted only within the pilot county, but also outside, as a model projects with appropriate directions and strategies.

  9. Research study on IPS digital controller design

    NASA Technical Reports Server (NTRS)

    Kuo, B. C.; Folkerts, C.

    1976-01-01

    The performance is investigated of the simplified continuous-data model of the Instrument Pointing System (IPS). Although the ultimate objective is to study the digital model of the system, knowledge on the performance of the continuous-data model is important in the sense that the characteristics of the digital system should approach those of the continuous-data system as the sampling period approaches zero.

  10. IP- -: A Reduced Internet Protocol for Optical Packet Networking

    NASA Astrophysics Data System (ADS)

    Ohta, Masataka; Fujikawa, Kenji

    IP- - is proposed as an Internet Protocol suitable for optical packet networking. As optical routers require much faster control than electric ones and lack of optical buffers other than those by fiber delay lines requires fixed time control, Internet Protocols must be at least as simple as IPv4 and much simpler than IPv6. IP- - also addresses issues of IP address space exhaustion and IP routing table explosion.

  11. Generation of iPS Cells from Granulosa Cells.

    PubMed

    Mao, Jian; Liu, Lin

    2016-01-01

    Various types of somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells. Somatic stem cells may generate iPS cells more efficiently than do differentiated cells. We show that granulosa cells exhibit characteristic of somatic stem cells and can be reprogrammed to iPS cells more efficiently or with few factors. Here, we describe generation of mouse and pig iPS cells from granulosa cells with high efficiency.

  12. IP-based storage of image information

    NASA Astrophysics Data System (ADS)

    Fu, Xianglin; Xie, Changsheng; Liu, Zhaobin

    2001-09-01

    With the fast growth of data in multispectral image processing, the traditional storage architecture was challenged. It is currently being replaced by Storage Area Networks (SAN), which makes storage devices externalized from servers. A SAN is a separate network for storage, isolated from the messaging network and optimized for the movement of data between servers and storage devices. Nowadays, most of current SAN use Fibre Channel to move data between servers and storage devices (FC-SAN), but because of the drawbacks of the FC-SAN: for interoperability, lack of skilled professional and management tools, high implementation cost and so on, the development and application of FC-SAN was obstructed. In this paper, we introduce an IP-based Storage Area Networks architecture, which has the good qualities of FC- SAN but overcomes the shortcoming of it. The principle is: use IP technology to move data between servers and storage devices, build a SAN with the IP-based network devices (not the FC-based network device), and through the switch, SAN is attached to the LAN(Local Area Network) through multiple access. Especially, these storage devices are acted as commercial NAS devices and PC.

  13. A Survey of Voice over IP Security Research

    NASA Astrophysics Data System (ADS)

    Keromytis, Angelos D.

    We present a survey of Voice over IP security research. Our goal is to provide a roadmap for researchers seeking to understand existing capabilities and, and to identify gaps in addressing the numerous threats and vulnerabilities present in VoIP systems. We also briefly discuss the implications of our findings with respect to actual vulnerabilities reported in a variety VoIP products.

  14. A Conjoint Analysis of Voice Over IP Attributes.

    ERIC Educational Resources Information Center

    Zubey, Michael L.; Wagner, William; Otto, James R.

    2002-01-01

    Managers need to understand the tradeoffs associated with voice over Internet protocol (VoIP) networks as compared to the Public Switched Telephone Network (PSTN). This article measures the preference structures between IP telephony and PSTN services using conjoint analysis. The purpose is to suggest VoIP technology attributes that best meet…

  15. Covert Channels in SIP for VoIP Signalling

    NASA Astrophysics Data System (ADS)

    Mazurczyk, Wojciech; Szczypiorski, Krzysztof

    In this paper, we evaluate available steganographic techniques for SIP (Session Initiation Protocol) that can be used for creating covert channels during signaling phase of VoIP (Voice over IP) call. Apart from characterizing existing steganographic methods we provide new insights by introducing new techniques. We also estimate amount of data that can be transferred in signalling messages for typical IP telephony call.

  16. Remote Ischemic Conditioning: Its Benefits and Limitations.

    PubMed

    Kloner, Robert A

    2016-03-01

    This editorial describes benefits and limitations of remote ischemic conditioning. Remote ischemic conditioning was shown to reduce myocardial intact size in at least 4 sizeable clinical trials of acute myocardial infarction. It was not effective in recent studies of cardiac surgery. Reasons for these differences are discussed.

  17. Cerebral ischemic stroke: is gender important?

    PubMed Central

    Gibson, Claire L

    2013-01-01

    Cerebral stroke continues to be a major cause of death and the leading cause of long-term disability in developed countries. Evidence reviewed here suggests that gender influences various aspects of the clinical spectrum of ischemic stroke, in terms of influencing how a patients present with ischemic stroke through to how they respond to treatment. In addition, this review focuses on discussing the various pathologic mechanisms of ischemic stroke that may differ according to gender and compares how intrinsic and hormonal mechanisms may account for such gender differences. All clinical trials to date investigating putative neuroprotective treatments for ischemic stroke have failed, and it may be that our understanding of the injury cascade initiated after ischemic injury is incomplete. Revealing aspects of the pathophysiological consequences of ischemic stroke that are gender specific may enable gender relevant and effective neuroprotective strategies to be identified. Thus, it is possible to conclude that gender does, in fact, have an important role in ischemic stroke and must be factored into experimental and clinical investigations of ischemic stroke. PMID:23756694

  18. Preconditioning 2D Integer Data for Fast Convex Hull Computations.

    PubMed

    Cadenas, José Oswaldo; Megson, Graham M; Luengo Hendriks, Cris L

    2016-01-01

    In order to accelerate computing the convex hull on a set of n points, a heuristic procedure is often applied to reduce the number of points to a set of s points, s ≤ n, which also contains the same hull. We present an algorithm to precondition 2D data with integer coordinates bounded by a box of size p × q before building a 2D convex hull, with three distinct advantages. First, we prove that under the condition min(p, q) ≤ n the algorithm executes in time within O(n); second, no explicit sorting of data is required; and third, the reduced set of s points forms a simple polygonal chain and thus can be directly pipelined into an O(n) time convex hull algorithm. This paper empirically evaluates and quantifies the speed up gained by preconditioning a set of points by a method based on the proposed algorithm before using common convex hull algorithms to build the final hull. A speedup factor of at least four is consistently found from experiments on various datasets when the condition min(p, q) ≤ n holds; the smaller the ratio min(p, q)/n is in the dataset, the greater the speedup factor achieved. PMID:26938221

  19. Parallelizable approximate solvers for recursions arising in preconditioning

    SciTech Connect

    Shapira, Y.

    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.

  20. Preconditioning 2D Integer Data for Fast Convex Hull Computations

    PubMed Central

    2016-01-01

    In order to accelerate computing the convex hull on a set of n points, a heuristic procedure is often applied to reduce the number of points to a set of s points, s ≤ n, which also contains the same hull. We present an algorithm to precondition 2D data with integer coordinates bounded by a box of size p × q before building a 2D convex hull, with three distinct advantages. First, we prove that under the condition min(p, q) ≤ n the algorithm executes in time within O(n); second, no explicit sorting of data is required; and third, the reduced set of s points forms a simple polygonal chain and thus can be directly pipelined into an O(n) time convex hull algorithm. This paper empirically evaluates and quantifies the speed up gained by preconditioning a set of points by a method based on the proposed algorithm before using common convex hull algorithms to build the final hull. A speedup factor of at least four is consistently found from experiments on various datasets when the condition min(p, q) ≤ n holds; the smaller the ratio min(p, q)/n is in the dataset, the greater the speedup factor achieved. PMID:26938221

  1. Stress Preconditioning of Spreading Depression in the Locust CNS

    PubMed Central

    Rodgers, Corinne I.; Armstrong, Gary A. B.; Shoemaker, Kelly L.; LaBrie, John D.; Moyes, Christopher D.; Robertson, R. Meldrum

    2007-01-01

    Cortical spreading depression (CSD) is closely associated with important pathologies including stroke, seizures and migraine. The mechanisms underlying SD in its various forms are still incompletely understood. Here we describe SD-like events in an invertebrate model, the ventilatory central pattern generator (CPG) of locusts. Using K+ -sensitive microelectrodes, we measured extracellular K+ concentration ([K+]o) in the metathoracic neuropile of the CPG while monitoring CPG output electromyographically from muscle 161 in the second abdominal segment to investigate the role K+ in failure of neural circuit operation induced by various stressors. Failure of ventilation in response to different stressors (hyperthermia, anoxia, ATP depletion, Na+/K+ ATPase impairment, K+ injection) was associated with a disturbance of CNS ion homeostasis that shares the characteristics of CSD and SD-like events in vertebrates. Hyperthermic failure was preconditioned by prior heat shock (3 h, 45°C) and induced-thermotolerance was associated with an increase in the rate of clearance of extracellular K+ that was not linked to changes in ATP levels or total Na+/K+ ATPase activity. Our findings suggest that SD-like events in locusts are adaptive to terminate neural network operation and conserve energy during stress and that they can be preconditioned by experience. We propose that they share mechanisms with CSD in mammals suggesting a common evolutionary origin. PMID:18159249

  2. 40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Preconditioned two speed idle test-EPA... Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements—(1...-speed mode followed immediately by a first-chance idle mode. (ii) The second-chance test as...

  3. 40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 19 2013-07-01 2013-07-01 false Preconditioned two speed idle test-EPA... Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements—(1...-speed mode followed immediately by a first-chance idle mode. (ii) The second-chance test as...

  4. 40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Preconditioned two speed idle test-EPA... Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements—(1...-speed mode followed immediately by a first-chance idle mode. (ii) The second-chance test as...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Preconditioned two speed idle test-EPA... Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements—(1...-speed mode followed immediately by a first-chance idle mode. (ii) The second-chance test as...

  6. Sensory Preconditioning in Newborn Rabbits: From Common to Distinct Odor Memories

    ERIC Educational Resources Information Center

    Coureaud, Gerard; Tourat, Audrey; Ferreira, Guillaume

    2013-01-01

    This study evaluated whether olfactory preconditioning is functional in newborn rabbits and based on joined or independent memory of odorants. First, after exposure to odorants A+B, the conditioning of A led to high responsiveness to odorant B. Second, responsiveness to B persisted after amnesia of A. Third, preconditioning was also functional…

  7. The preconditioned Gauss-Seidel iterative methods for solving Fredholm integral equations of the second kind

    NASA Astrophysics Data System (ADS)

    Muthuvalu, Mohana Sundaram

    2016-06-01

    In this paper, performance analysis of the preconditioned Gauss-Seidel iterative methods for solving dense linear system arise from Fredholm integral equations of the second kind is investigated. The formulation and implementation of the preconditioned Gauss-Seidel methods are presented. Numerical results are included in order to verify the performance of the methods.

  8. Hyperspectral imaging of ischemic wounds

    NASA Astrophysics Data System (ADS)

    Gnyawali, Surya C.; Elgharably, Haytham; Melvin, James; Huang, Kun; Bergdall, Valerie; Allen, David W.; Hwang, Jeeseong; Litorja, Maritoni; Shirley, Eric; Sen, Chandan K.; Xu, Ronald

    2012-03-01

    Optical imaging has the potential to achieve high spatial resolution and high functional sensitivity in wound assessment. However, clinical acceptance of many optical imaging devices is hampered by poor reproducibility, low accuracy, and lack of biological interpretation. We developed an in vivo model of ischemic flap for non-contact assessment of wound tissue functional parameters and spectral characteristics. The model was created by elevating the bipedicle skin flaps of a domestic pig from the underlying vascular bed and inhibiting graft bed reperfusion by a silastic sheet. Hyperspectral imaging was carried out on the ischemic flap model and compared with transcutaneous oxygen tension and perfusion measurements at different positions of the wound. Hyperspectral images have also been captured continuously during a post-occlusive reactive hyperemia (PORH) procedure. Tissue spectral characteristics obtained by hyperspectral imaging correlated well with cutaneous tissue oxygen tension, blood perfusion, and microscopic changes of tissue morphology. Our experiments not only demonstrated the technical feasibility for quantitative assessment of chronic wound but also provided a potential digital phantom platform for quantitative characterization and calibration of medical optical devices.

  9. Peroxisomal Biogenesis in Ischemic Brain

    PubMed Central

    Young, Jennifer M.; Nelson, Jonathan W.; Cheng, Jian; Zhang, Wenri; Mader, Sarah; Davis, Catherine M.; Morrison, Richard S.

    2015-01-01

    Abstract Aims: Peroxisomes are highly adaptable and dynamic organelles, adjusting their size, number, and enzyme composition to changing environmental and metabolic demands. We determined whether peroxisomes respond to ischemia, and whether peroxisomal biogenesis is an adaptive response to cerebral ischemia. Results: Focal cerebral ischemia induced peroxisomal biogenesis in peri-infarct neurons, which was associated with a corresponding increase in peroxisomal antioxidant enzyme catalase. Peroxisomal biogenesis was also observed in primary cultured cortical neurons subjected to ischemic insult induced by oxygen-glucose deprivation (OGD). A catalase inhibitor increased OGD-induced neuronal death. Moreover, preventing peroxisomal proliferation by knocking down dynamin-related protein 1 (Drp1) exacerbated neuronal death induced by OGD, whereas enhancing peroxisomal biogenesis pharmacologically using a peroxisome proliferator-activated receptor-alpha agonist protected against neuronal death induced by OGD. Innovation: This is the first documentation of ischemia-induced peroxisomal biogenesis in mammalian brain using a combined in vivo and in vitro approach, electron microscopy, high-resolution laser-scanning confocal microscopy, and super-resolution structured illumination microscopy. Conclusion: Our findings suggest that neurons respond to ischemic injury by increasing peroxisome biogenesis, which serves a protective function, likely mediated by enhanced antioxidant capacity of neurons. Antioxid. Redox Signal. 22, 109–120. PMID:25226217

  10. Preconditioning techniques for constrained vector potential integral equations, with application to 3-D magnetoquasistatic analysis of electronic packages

    SciTech Connect

    Kamon, M.; Phillips, J.R.

    1994-12-31

    In this paper techniques are presented for preconditioning equations generated by discretizing constrained vector integral equations associated with magnetoquasistatic analysis. Standard preconditioning approaches often fail on these problems. The authors present a specialized preconditioning technique and prove convergence bounds independent of the constraint equations and electromagnetic excitation frequency. Computational results from analyzing several electronic packaging examples are given to demonstrate that the new preconditioning approach can sometimes reduce the number of GMRES iterations by more than an order of magnitude.

  11. Research and Simulation on Application of the Mobile IP Network

    NASA Astrophysics Data System (ADS)

    Yibing, Deng; Wei, Hu; Minghui, Li; Feng, Gao; Junyi, Shen

    The paper analysed the mobile node, home agent, and foreign agent of mobile IP network firstly, some key technique, such as mobile IP network basical principle, protocol work principle, agent discovery, registration, and IP packet transmission, were discussed. Then a network simulation model was designed, validating the characteristic of mobile IP network, and some advantages, which were brought by mobile network, were testified. Finally, the conclusion is gained: mobile IP network could realize the expectation of consumer that they can communicate with others anywhere.

  12. Impact of artifact removal on ChIP quality metrics in ChIP-seq and ChIP-exo data.

    PubMed

    Carroll, Thomas S; Liang, Ziwei; Salama, Rafik; Stark, Rory; de Santiago, Ines

    2014-01-01

    With the advent of ChIP-seq multiplexing technologies and the subsequent increase in ChIP-seq throughput, the development of working standards for the quality assessment of ChIP-seq studies has received significant attention. The ENCODE consortium's large scale analysis of transcription factor binding and epigenetic marks as well as concordant work on ChIP-seq by other laboratories has established a new generation of ChIP-seq quality control measures. The use of these metrics alongside common processing steps has however not been evaluated. In this study, we investigate the effects of blacklisting and removal of duplicated reads on established metrics of ChIP-seq quality and show that the interpretation of these metrics is highly dependent on the ChIP-seq preprocessing steps applied. Further to this we perform the first investigation of the use of these metrics for ChIP-exo data and make recommendations for the adaptation of the NSC statistic to allow for the assessment of ChIP-exo efficiency.

  13. Impact of artifact removal on ChIP quality metrics in ChIP-seq and ChIP-exo data

    PubMed Central

    Carroll, Thomas S.; Liang, Ziwei; Salama, Rafik; Stark, Rory; de Santiago, Ines

    2014-01-01

    With the advent of ChIP-seq multiplexing technologies and the subsequent increase in ChIP-seq throughput, the development of working standards for the quality assessment of ChIP-seq studies has received significant attention. The ENCODE consortium's large scale analysis of transcription factor binding and epigenetic marks as well as concordant work on ChIP-seq by other laboratories has established a new generation of ChIP-seq quality control measures. The use of these metrics alongside common processing steps has however not been evaluated. In this study, we investigate the effects of blacklisting and removal of duplicated reads on established metrics of ChIP-seq quality and show that the interpretation of these metrics is highly dependent on the ChIP-seq preprocessing steps applied. Further to this we perform the first investigation of the use of these metrics for ChIP-exo data and make recommendations for the adaptation of the NSC statistic to allow for the assessment of ChIP-exo efficiency. PMID:24782889

  14. Argon Induces Protective Effects in Cardiomyocytes during the Second Window of Preconditioning

    PubMed Central

    Mayer, Britta; Soppert, Josefin; Kraemer, Sandra; Schemmel, Sabrina; Beckers, Christian; Bleilevens, Christian; Rossaint, Rolf; Coburn, Mark; Goetzenich, Andreas; Stoppe, Christian

    2016-01-01

    Increasing evidence indicates that argon has organoprotective properties. So far, the underlying mechanisms remain poorly understood. Therefore, we investigated the effect of argon preconditioning in cardiomyocytes within the first and second window of preconditioning. Primary isolated cardiomyocytes from neonatal rats were subjected to 50% argon for 1 h, and subsequently exposed to a sublethal dosage of hypoxia (<1% O2) for 5 h either within the first (0–3 h) or second window (24–48 h) of preconditioning. Subsequently, the cell viability and proliferation was measured. The argon-induced effects were assessed by evaluation of mRNA and protein expression after preconditioning. Argon preconditioning did not show any cardioprotective effects in the early window of preconditioning, whereas it leads to a significant increase of cell viability 24 h after preconditioning compared to untreated cells (p = 0.015) independent of proliferation. Argon-preconditioning significantly increased the mRNA expression of heat shock protein (HSP) B1 (HSP27) (p = 0.048), superoxide dismutase 2 (SOD2) (p = 0.001), vascular endothelial growth factor (VEGF) (p < 0.001) and inducible nitric oxide synthase (iNOS) (p = 0.001). No difference was found with respect to activation of pro-survival kinases in the early and late window of preconditioning. The findings provide the first evidence of argon-induced effects on the survival of cardiomyocytes during the second window of preconditioning, which may be mediated through the induction of HSP27, SOD2, VEGF and iNOS. PMID:27447611

  15. Argon Induces Protective Effects in Cardiomyocytes during the Second Window of Preconditioning.

    PubMed

    Mayer, Britta; Soppert, Josefin; Kraemer, Sandra; Schemmel, Sabrina; Beckers, Christian; Bleilevens, Christian; Rossaint, Rolf; Coburn, Mark; Goetzenich, Andreas; Stoppe, Christian

    2016-01-01

    Increasing evidence indicates that argon has organoprotective properties. So far, the underlying mechanisms remain poorly understood. Therefore, we investigated the effect of argon preconditioning in cardiomyocytes within the first and second window of preconditioning. Primary isolated cardiomyocytes from neonatal rats were subjected to 50% argon for 1 h, and subsequently exposed to a sublethal dosage of hypoxia (<1% O₂) for 5 h either within the first (0-3 h) or second window (24-48 h) of preconditioning. Subsequently, the cell viability and proliferation was measured. The argon-induced effects were assessed by evaluation of mRNA and protein expression after preconditioning. Argon preconditioning did not show any cardioprotective effects in the early window of preconditioning, whereas it leads to a significant increase of cell viability 24 h after preconditioning compared to untreated cells (p = 0.015) independent of proliferation. Argon-preconditioning significantly increased the mRNA expression of heat shock protein (HSP) B1 (HSP27) (p = 0.048), superoxide dismutase 2 (SOD2) (p = 0.001), vascular endothelial growth factor (VEGF) (p < 0.001) and inducible nitric oxide synthase (iNOS) (p = 0.001). No difference was found with respect to activation of pro-survival kinases in the early and late window of preconditioning. The findings provide the first evidence of argon-induced effects on the survival of cardiomyocytes during the second window of preconditioning, which may be mediated through the induction of HSP27, SOD2, VEGF and iNOS. PMID:27447611

  16. Argon Induces Protective Effects in Cardiomyocytes during the Second Window of Preconditioning.

    PubMed

    Mayer, Britta; Soppert, Josefin; Kraemer, Sandra; Schemmel, Sabrina; Beckers, Christian; Bleilevens, Christian; Rossaint, Rolf; Coburn, Mark; Goetzenich, Andreas; Stoppe, Christian

    2016-07-19

    Increasing evidence indicates that argon has organoprotective properties. So far, the underlying mechanisms remain poorly understood. Therefore, we investigated the effect of argon preconditioning in cardiomyocytes within the first and second window of preconditioning. Primary isolated cardiomyocytes from neonatal rats were subjected to 50% argon for 1 h, and subsequently exposed to a sublethal dosage of hypoxia (<1% O₂) for 5 h either within the first (0-3 h) or second window (24-48 h) of preconditioning. Subsequently, the cell viability and proliferation was measured. The argon-induced effects were assessed by evaluation of mRNA and protein expression after preconditioning. Argon preconditioning did not show any cardioprotective effects in the early window of preconditioning, whereas it leads to a significant increase of cell viability 24 h after preconditioning compared to untreated cells (p = 0.015) independent of proliferation. Argon-preconditioning significantly increased the mRNA expression of heat shock protein (HSP) B1 (HSP27) (p = 0.048), superoxide dismutase 2 (SOD2) (p = 0.001), vascular endothelial growth factor (VEGF) (p < 0.001) and inducible nitric oxide synthase (iNOS) (p = 0.001). No difference was found with respect to activation of pro-survival kinases in the early and late window of preconditioning. The findings provide the first evidence of argon-induced effects on the survival of cardiomyocytes during the second window of preconditioning, which may be mediated through the induction of HSP27, SOD2, VEGF and iNOS.

  17. IP address management : augmenting Sandia's capabilities through open source tools.

    SciTech Connect

    Nayar, R. Daniel

    2005-08-01

    Internet Protocol (IP) address management is an increasingly growing concern at Sandia National Laboratories (SNL) and the networking community as a whole. The current state of the available IP addresses indicates that they are nearly exhausted. Currently SNL doesn't have the justification to obtain more IP address space from Internet Assigned Numbers Authority (IANA). There must exist a local entity to manage and allocate IP assignments efficiently. Ongoing efforts at Sandia have been in the form of a multifunctional database application notably known as Network Information System (NWIS). NWIS is a database responsible for a multitude of network administrative services including IP address management. This study will explore the feasibility of augmenting NWIS's IP management capabilities utilizing open source tools. Modifications of existing capabilities to better allocate available IP address space are studied.

  18. Source identification of the Arctic sea ice proxy IP25.

    PubMed

    Brown, T A; Belt, S T; Tatarek, A; Mundy, C J

    2014-06-18

    Analysis of the organic geochemical biomarker IP25 in marine sediments is an established method for carrying out palaeo sea ice reconstructions for the Arctic. Such reconstructions cover timescales from decades back to the early Pleistocene, and are critical for understanding past climate conditions on Earth and for informing climate prediction models. Key attributes of IP25 include its strict association with Arctic sea ice together with its ubiquity and stability in underlying marine sediments; however, the sources of IP25 have remained undetermined. Here we report the identification of IP25 in three (or four) relatively minor (<5%) sea ice diatoms isolated from mixed assemblages collected from the Canadian Arctic. In contrast, IP25 was absent in the dominant taxa. Chemical and taxonomical investigations suggest that the IP25-containing taxa represent the majority of producers and are distributed pan-Arctic, thus establishing the widespread applicability of the IP25 proxy for palaeo Arctic sea ice reconstruction.

  19. Cell Reprogramming, IPS Limitations, and Overcoming Strategies in Dental Bioengineering

    PubMed Central

    Ibarretxe, Gaskon; Alvarez, Antonia; Cañavate, Maria-Luz; Hilario, Enrique; Aurrekoetxea, Maitane; Unda, Fernando

    2012-01-01

    The procurement of induced pluripotent stem cells, or IPS cells, from adult differentiated animal cells has the potential to revolutionize future medicine, where reprogrammed IPS cells may be used to repair disease-affected tissues on demand. The potential of IPS cell technology is tremendous, but it will be essential to improve the methodologies for IPS cell generation and to precisely evaluate each clone and subclone of IPS cells for their safety and efficacy. Additionally, the current state of knowledge on IPS cells advises that research on their regenerative properties is carried out in appropriate tissue and organ systems that permit a safe assessment of the long-term behavior of these reprogrammed cells. In the present paper, we discuss the mechanisms of cell reprogramming, current technical limitations of IPS cells for their use in human tissue engineering, and possibilities to overcome them in the particular case of dental regeneration. PMID:22690226

  20. Ischemic post-conditioning to counteract intestinal ischemia/reperfusion injury

    PubMed Central

    Guan, Yan-Fang; Pritts, Timothy A; Montrose, Marshall H

    2010-01-01

    Intestinal ischemia is a severe disorder with a variety of causes. Reperfusion is a common occurrence during treatment of acute intestinal ischemia but the injury resulting from ischemia/reperfusion (IR) may lead to even more serious complications from intestinal atrophy to multiple organ failure and death. The susceptibility of the intestine to IR-induced injury (IRI) appears from various experimental studies and clinical settings such as cardiac and major vascular surgery and organ transplantation. Whereas oxygen free radicals, activation of leukocytes, failure of microvascular perfusion, cellular acidosis and disturbance of intracellular homeostasis have been implicated as important factors in the pathogenesis of intestinal IRI, the mechanisms underlying this disorder are not well known. To date, increasing attention is being paid in animal studies to potential pre- and post-ischemia treatments that protect against intestinal IRI such as drug interference with IR-induced apoptosis and inflammation processes and ischemic pre-conditioning. However, better insight is needed into the molecular and cellular events associated with reperfusion-induced damage to develop effective clinical protection protocols to combat this disorder. In this respect, the use of ischemic post-conditioning in combination with experimentally prolonged acidosis blocking deleterious reperfusion actions may turn out to have particular clinical relevance. PMID:21607154

  1. Demonstrating a Realistic IP Mission Prototype

    NASA Technical Reports Server (NTRS)

    Rash, James; Ferrer, Arturo B.; Goodman, Nancy; Ghazi-Tehrani, Samira; Polk, Joe; Johnson, Lorin; Menke, Greg; Miller, Bill; Criscuolo, Ed; Hogie, Keith

    2003-01-01

    Flight software and hardware and realistic space communications environments were elements of recent demonstrations of the Internet Protocol (IP) mission concept in the lab. The Operating Missions as Nodes on the Internet (OMNI) Project and the Flight Software Branch at NASA/GSFC collaborated to build the prototype of a representative space mission that employed unmodified off-the-shelf Internet protocols and technologies for end-to-end communications between the spacecraft/instruments and the ground system/users. The realistic elements used in the prototype included an RF communications link simulator and components of the TRIANA mission flight software and ground support system. A web-enabled camera connected to the spacecraft computer via an Ethernet LAN represented an on-board instrument creating image data. In addition to the protocols at the link layer (HDLC), transport layer (UDP, TCP), and network (IP) layer, a reliable file delivery protocol (MDP) at the application layer enabled reliable data delivery both to and from the spacecraft. The standard Network Time Protocol (NTP) performed on-board clock synchronization with a ground time standard. The demonstrations of the prototype mission illustrated some of the advantages of using Internet standards and technologies for space missions, but also helped identify issues that must be addressed. These issues include applicability to embedded real-time systems on flight-qualified hardware, range of applicability of TCP, and liability for and maintenance of commercial off-the-shelf (COTS) products. The NASA Earth Science Technology Office (ESTO) funded the collaboration to build and demonstrate the prototype IP mission.

  2. Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke

    PubMed Central

    Geuskens, Ralph R. E. G.; Borst, Jordi; Lucas, Marit; Boers, A. M. Merel; Berkhemer, Olvert A.; Roos, Yvo B. W. E. M.; van Walderveen, Marianne A. A.; Jenniskens, Sjoerd F. M.; van Zwam, Wim H.; Dippel, Diederik W. J.; Majoie, Charles B. L. M.; Marquering, Henk A.

    2015-01-01

    Background CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up. Materials and Methods This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests. Results Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43–1.79) ml/100g (P<0.01) and 1.38 (IQR:1.15–1.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly. Conclusion For all patients a considerable region of the CTP ischemic core

  3. 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.

  4. Parallel preconditioning for the solution of nonsymmetric banded linear systems

    SciTech Connect

    Amodio, P.; Mazzia, F.

    1994-12-31

    Many computational techniques require the solution of banded linear systems. Common examples derive from the solution of partial differential equations and of boundary value problems. In particular the authors are interested in the parallel solution of block Hessemberg linear systems Gx = f, arising from the solution of ordinary differential equations by means of boundary value methods (BVMs), even if the considered preconditioning may be applied to any block banded linear system. BVMs have been extensively investigated in the last few years and their stability properties give promising results. A new class of BVMs called Reverse Adams, which are BV-A-stable for orders up to 6, and BV-A{sub 0}-stable for orders up to 9, have been studied.

  5. Can endurance exercise preconditioning prevention disuse muscle atrophy?

    PubMed Central

    Wiggs, Michael P.

    2015-01-01

    Emerging evidence suggests that exercise training can provide a level of protection against disuse muscle atrophy. Endurance exercise training imposes oxidative, metabolic, and heat stress on skeletal muscle which activates a variety of cellular signaling pathways that ultimately leads to the increased expression of proteins that have been demonstrated to protect muscle from inactivity –induced atrophy. This review will highlight the effect of exercise-induced oxidative stress on endogenous enzymatic antioxidant capacity (i.e., superoxide dismutase, glutathione peroxidase, and catalase), the role of oxidative and metabolic stress on PGC1-α, and finally highlight the effect heat stress and HSP70 induction. Finally, this review will discuss the supporting scientific evidence that these proteins can attenuate muscle atrophy through exercise preconditioning. PMID:25814955

  6. 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.

  7. In vitro synthesis and purification of PhIP-deoxyguanosine and PhIP-DNA oligomer covalent complexes

    SciTech Connect

    Freeman, J.

    1994-12-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine compound formed when meats are cooked at high temperatures. PhIP damages DNA by forming covalent complexes with DNA carcinogen. In an effort to understand how the binding of PhIP to DNA may cause cancer, it is important to characterize the structures of PhIP-damaged DNA molecules. Our HPLC data support fluorescence and {sup 32}P Post-labeling studies which indicate the formation of several species of 2{prime}deoxyguanosine-(dG) or oligodeoxynucleotide-PhIP adducts. The reaction of PhIP with dG resulted in a reddish precipitate that was likely the major adduct, N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP) adduct, with a more polar adduct fraction remaining in the supernatant. Reversed-phase HPLC analysis of the adducts in the supernatant revealed the existence of species of much shorter retention times than the dG-C8-PhIP adduct, confirming that these species are more polar than dG-C8-PhIP. At least four adducts were formed in the reaction of PhIP with DNA oligomer. HPLC analysis of the PhIP-DNA oligomer supernatant after butanol extractions revealed four unresolved peaks which spectra had maximum wavelengths between 340 and 360 nm. Though adduct peaks were not completely resolved, there was {approximately}3 minutes interval between the DNA oligomer peak and the adduct peaks. Furthermore, fluorescence emission data of the DNA oligomer-PhIP adduct solution show heterogeneous binding. The more polar PhIP adducts were fraction-collected and their structures will be solved by nuclear magnetic resonance or x-ray crystallography.

  8. Preconditioned iterative methods for inhomogeneous acoustic scattering applications

    NASA Astrophysics Data System (ADS)

    Sifuentes, Josef

    This thesis develops and analyzes efficient iterative methods for solving discretizations of the Lippmann--Schwinger integral equation for inhomogeneous acoustic scattering. Analysis and numerical illustrations of the spectral properties of the scattering problem demonstrate that a significant portion of the spectrum is approximated well on coarse grids. To exploit this, I develop a novel restarted GMRES method with adaptive deflation preconditioning based on spectral approximations on multiple grids. Much of the literature in this field is based on exact deflation, which is not feasible for most practical computations. This thesis provides an analytical framework for general approximate deflation methods and suggests a way to rigorously study a host of inexactly-applied preconditioners. Approximate deflation algorithms are implemented for scattering through thin inhomogeneities in photonic band gap problems. I also develop a short term recurrence for solving the one dimensional version of the problem that exploits the observation that the integral operator is a low rank perturbation of a self-adjoint operator. This method is based on strategies for solving Schur complement problems, and provides an alternative to a recent short term recurrence algorithm for matrices with such structure that we show to be numerically unstable for this application. The restarted GMRES method with adaptive deflation preconditioning over multiple grids, as well as the short term recurrence method for operators with low rank skew-adjoint parts, are very effective for reducing both the computational time and computer memory required to solve acoustic scattering problems. Furthermore, the methods are sufficiently general to be applicable to a wide class of problems.

  9. Evidence of the peripheral inflammatory response in patients with transient ischemic attack.

    PubMed

    Ross, Amy Miner; Hurn, Patricia; Perrin, Nancy; Wood, Lisa; Carlini, Walter; Potempa, Kathleen

    2007-01-01

    The peripheral inflammatory response, as a proxy for the acute-phase response (a known mechanism for ischemic preconditioning), and non-damage-producing transient ischemia must exist together in humans if this candidate mechanism confers ischemic tolerance. The present study was aimed at determining whether the peripheral inflammatory response (ie, elevated white blood cell, neutrophil, and monocyte counts) exists in transient ischemic attack (TIA) and stroke patients at the time of emergency room admission. The null hypothesis was tested for the variables of the peripheral inflammatory response between the mean of the laboratory normal population versus stroke and TIA patients. A retrospective review of 1041 medical records yielded 12 first-time TIA patients and 34 first-time stroke patients with no confounding evidence of other inflammatory processes. In both groups, neutrophil and monocyte percentages were significantly higher than the laboratory means (in TIA cases: neutrophils, 67.9% [12.67%], P = .001; monocytes, 8.2% [2.7%], P = .020; in stroke cases: neutrophils, 64.9% [9.1%], monocytes, 7.7% [1.6%]; both P < .001). Absolute neutrophil count was significantly higher than the laboratory mean for the stroke cases (5.13 [1.88] K/UL; P = .022). Lymphocyte percentages and absolute lymphocyte count in both groups were significantly and abnormally lower than the laboratory mean (in TIA cases, 21.7% [10.5%] and 1.4 [0.6] K/UL, respectively; in stroke cases, 24.7% [8.4%] and 1.9 [0.7] K/UL, respectively; all P

  10. Reduction of myocardial infarct size with ischemic "conditioning": physiologic and technical considerations.

    PubMed

    Przyklenk, Karin

    2013-10-01

    A wealth of evidence has revealed that the heart can be "conditioned" and rendered less vulnerable to ischemia-reperfusion injury via the upregulation of endogenous protective signaling pathways. Three distinct conditioning strategies have been identified: (1) preconditioning, the phenomenon where brief episodes of myocardial ischemia (too brief to cause cardiomyocyte death) limit necrosis caused by a subsequent sustained ischemic insult; (2) postconditioning, the concept that relief of myocardial ischemia in a staged or stuttered manner attenuates lethal ischemia-reperfusion injury; and (3) remote conditioning, or upregulation of a cardioprotective phenotype initiated by ischemia in a remote organ or tissue and "transported" to the heart. Progress has been made in defining the technical requirements and limitations of each of the 3 ischemic conditioning models (including the timing and severity of the protective stimulus), as well as elucidating the molecular mechanisms (in particular, the receptor-mediated signaling pathways) responsible for conditioning-induced myocardial protection. Moreover, phase III clinical trials are in progress, seeking to capitalize on the protection that can be achieved by postconditioning and remote conditioning, and applying these strategies in patients undergoing cardiac surgery or angioplasty for the treatment of acute myocardial infarction. There is, however, a potentially important caveat to the clinical translation of myocardial conditioning: emerging data suggest that the efficacy of ischemic conditioning is compromised in aging, diabetic, and hypertensive cohorts, the specific populations in which myocardial protection is most relevant. Successful clinical application of myocardial conditioning will therefore require an understanding of the potential confounding consequences of these comorbidities on the "conditioned" phenotype.

  11. Using IPS Magnetic Modeling to Determine Bz

    NASA Astrophysics Data System (ADS)

    Jackson, B. V.; Yu, H. S.; Hick, P. P.; Buffington, A.; Mejia-Ambriz, J. C.; Bisi, M. M.; Tokumaru, M.

    2014-12-01

    Interplanetary scintillation (IPS) observations enable remote determinations of velocity and density in the inner heliosphere while also providing forecasts of these quantities. Using the global velocities inferred from IPS, and through convection upward of magnetic fields perpendicular to a source surface produced by the Current-Sheet Source Surface (CSSS) modified potential model (Zhao and Hoeksema, J. Geophys. Res., 100, 19, 1995), global long-duration radial and tangential heliospheric field components can also be determined. In order to better include short-term transient effects and derive a value for the field normal to these components (Bn) during periods where CMEs, are present, we have tested an extension to our current 3D vector-field analysis. This extension adds closed fields from below the source surface to the CSSS model values, and when traced outward from the sub-Earth point, three magnetic field components are present. These are compared to in-situ magnetic fields measured near Earth for several periods throughout the current solar cycle from the minimum between Solar Cycle 23 and 24 up until the present. We find a significant positive correlation when using this extension to current analyses including that of the Bn field for the test cases analyzed thus far.

  12. IP-Based Video Modem Extender Requirements

    SciTech Connect

    Pierson, L G; Boorman, T M; Howe, R E

    2003-12-16

    Visualization is one of the keys to understanding large complex data sets such as those generated by the large computing resources purchased and developed by the Advanced Simulation and Computing program (aka ASCI). In order to be convenient to researchers, visualization data must be distributed to offices and large complex visualization theaters. Currently, local distribution of the visual data is accomplished by distance limited modems and RGB switches that simply do not scale to hundreds of users across the local, metropolitan, and WAN distances without incurring large costs in fiber plant installation and maintenance. Wide Area application over the DOE Complex is infeasible using these limited distance RGB extenders. On the other hand, Internet Protocols (IP) over Ethernet is a scalable well-proven technology that can distribute large volumes of data over these distances. Visual data has been distributed at lower resolutions over IP in industrial applications. This document describes requirements of the ASCI program in visual signal distribution for the purpose of identifying industrial partners willing to develop products to meet ASCI's needs.

  13. [The expression of Akt kinase in the heart ventricles under hypoxic preconditioning and myocardial remodeling].

    PubMed

    Portnichenko, A G; Lapikova-Briginskaia, T Iu; Vasilenko, M I; Portnichenko, G V; Maslov, L N; Moĭbenko, A A

    2013-01-01

    Activation of Akt-dependent mechanisms may play a significant role in the cellular response under hypoxic preconditioning and myocardial remodeling. The impact of hypoxic preconditioning, and remodeling on the expression of Akt kinase in the heart ventricles was investigated. Wistar male rats, the residents of plains or middle altitude (2100 m above sea level), were exposed to hypoxic preconditioning by "lifting" in the barochamber at the "height" of 5,600 m in 3 h. In the right and left ventricles of the heart, Akt protein expression was determined by Western blotting. It was shown, that hypoxic preconditioning causes the induction of Akt kinase in the ventricles during the period of delayed cardioprotection (1-3 days after preconditioning). Myocardial remodeling induced by chronic hypoxia in middle altitude was associated with elevated Akt expression in the myocardium, more pronounced in the left ventricle. Progression of hypoxic myocardial remodeling found in part of the animals was accompanied by a reduction of the cell hypoxic reactivity, including Akt induction in response to preconditioning. Thus, Akt kinase is involved in the mechanisms of hypoxia induced late preconditioning and myocardial remodeling in chronic hypoxia. Inhibitory regulatory mechanism was found to limit the induction of Akt in myocardium after remodeling.

  14. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats.

    PubMed

    Bakkal, B H; Gultekin, F A; Guven, B; Turkcu, U O; Bektas, S; Can, M

    2013-09-01

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  15. Rural water-supply and sanitation planning: The use of socioeconomic preconditions in project identification

    NASA Astrophysics Data System (ADS)

    Warner, Dennis B.

    1984-02-01

    Recognition of the socioeconomic preconditions for successful rural water-supply and sanitation projects in developing countries is the key to identifying a new project. Preconditions are the social, economic and technical characteristics defining the project environment. There are two basic types of preconditions: those existing at the time of the initial investigation and those induced by subsequent project activities. Successful project identification is dependent upon an accurate recognition of existing constraints and a carefully tailored package of complementary investments intended to overcome the constraints. This paper discusses the socioeconomic aspects of preconditions in the context of a five-step procedure for project identification. The procedure includes: (1) problem identification; (2) determination of socioeconomic status; (3) technology selection; (4) utilization of support conditions; and (5) benefit estimation. Although the establishment of specific preconditions should be based upon the types of projects likely to be implemented, the paper outlines a number of general relationships regarding favourable preconditions in water and sanitation planning. These relationships are used within the above five-step procedure to develop a set of general guidelines for the application of preconditions in the identification of rural water-supply and sanitation projects.

  16. Studies on effect of stress preconditioning in restrain stress-induced behavioral alterations.

    PubMed

    Kaur, Rajneet; Jaggi, Amteshwar Singh; Singh, Nirmal

    2010-02-01

    Stress preconditioning has been documented to confer on gastroprotective effects on stress-induced gastric ulcerations. However, the effects of prior exposure of stress preconditioning episodes on stress-induced behavioral changes have not been explored yet. Therefore the present study was designed to investigate the ameliorative effects of stress preconditioning in immobilization stress-induced behavioral alterations in rats. The rats were subjected to restrain stress by placing in restrainer (5.5 cm in diameter and 18 cm in length) for 3.5 h. Stress preconditioning was induced by subjecting the rats to two cycles of restraint and restrain-free periods of 15 min each. Furthermore, a similar type of stress preconditioning was induced using different time cycles of 30 and 45 min. The extent and severity of the stress-induced behavioral alterations were assessed using different behavioral tests such as hole-board test, social interaction test, open field test, and actophotometer. Restrain stress resulted in decrease in locomotor activity, frequency of head dips and rearing in hole board, line crossing and rearing in open field, and decreased following and increased avoidance in social interaction test. Stress preconditioning with two cycles of 15, 30 or 45 min respectively, did not attenuate stress-induced behavioral changes to any extent. It may be concluded that stress preconditioning does not seem to confer any protective effect in modulating restrain stress-induced behavioral alterations.

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

    PubMed

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

    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 24.9 +/- 4.4 years) were loaded to failure with a deformation rate of 1 mm/s. Half of the QT-B and the PL-B complexes underwent 200 uniaxial preconditioning cycles from 75 to 800 N at 0.5 Hz before ultimate failure loading. High-load preconditioning was made possible by the development of a highly reliable and easy-to-use cryofixation device to attach the free tendon end. PL-B complexes were more influenced by preconditioning than the QT-B complexes. Ultimate failure load, stiffness at 200 N and stiffness at 800 N were significantly higher for PL-B complexes after preconditioning, while the structural properties of QT-B complexes exhibited no significant alterations. The values of the mechanical properties like Young's modulus at 200 N and 800 N were much higher for both preconditioned specimen groups. In addition, ultimate stress was augmented by preconditioning for PL-B complexes. Hysteresis and creep effects were highest during the first few loading cycles. More than 160 cycles were needed to reach a steady state. Beyond 160 cycles there was no further creep, and hysteresis was almost constant. Creep values were 2.2% of the initial testing length for the QT-B and 3.2% of the initial testing length for the PL-B complexes. The effect of cyclic preconditioning seems to be caused by progressive fiber recruitment and by alterations of the interstitial fluid milieu.

  18. Molecular Mechanisms of Renal Ischemic Conditioning Strategies.

    PubMed

    Kierulf-Lassen, Casper; Nieuwenhuijs-Moeke, Gertrude J; Krogstrup, Nicoline V; Oltean, Mihai; Jespersen, Bente; Dor, Frank J M F

    2015-01-01

    Ischemia-reperfusion injury is the leading cause of acute kidney injury in a variety of clinical settings such as renal transplantation and hypovolemic and/or septic shock. Strategies to reduce ischemia-reperfusion injury are obviously clinically relevant. Ischemic conditioning is an inherent part of the renal defense mechanism against ischemia and can be triggered by short periods of intermittent ischemia and reperfusion. Understanding the signaling transduction pathways of renal ischemic conditioning can promote further clinical translation and pharmacological advancements in this era. This review summarizes research on the molecular mechanisms underlying both local and remote ischemic pre-, per- and postconditioning of the kidney. The different types of conditioning strategies in the kidney recruit similar powerful pro-survival mechanisms. Likewise, renal ischemic conditioning mobilizes many of the same protective signaling pathways as in other organs, but differences are recognized. PMID:26330099

  19. Novel therapeutic strategies for ischemic heart disease.

    PubMed

    Perricone, Adam J; Vander Heide, Richard S

    2014-11-01

    Despite significant advances in the physician's ability to initiate myocardial reperfusion and salvage heart tissue, ischemic heart disease remains one of the leading causes of death in the United States. Consequently, alternative therapeutic strategies have been intensively investigated, especially methods of enhancing the heart's resistance to ischemic cell death - so called "cardioprotective" interventions. However, although a great deal has been learned regarding the methods and mechanisms of cardioprotective interventions, an efficacious therapy has yet to be successfully implemented in the clinical arena. This review discusses the current understanding of cardioprotection in the context of ischemic heart disease pathophysiology, highlighting those elements of ischemic heart disease pathophysiology that have received less attention as potential targets of cardioprotective intervention.

  20. Characteristic time-stepping or local preconditioning of the Euler equations

    NASA Technical Reports Server (NTRS)

    Van Leer, Bram; Lee, Wen-Tzong; Roe, Philip L.

    1991-01-01

    A derivation is presented of a local preconditioning matrix for multidimensional Euler equations, that reduces the spread of the characteristic speeds to the lowest attainable value. Numerical experiments with this preconditioning matrix are applied to an explicit upwind discretization of the two-dimensional Euler equations, showing that this matrix significantly increases the rate of convergence to a steady solution. It is predicted that local preconditioning will also simplify convergence-acceleration boundary procedures such as the Karni (1991) procedure for the far field and the Mazaheri and Roe (1991) procedure for a solid wall.

  1. 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.

  2. Exercise and Cyclic Light Preconditioning Protect Against Light-Induced Retinal Degeneration and Evoke Similar Gene Expression Patterns.

    PubMed

    Chrenek, Micah A; Sellers, Jana T; Lawson, Eric C; Cunha, Priscila P; Johnson, Jessica L; Girardot, Preston E; Kendall, Cristina; Han, Moon K; Hanif, Adam; Ciavatta, Vincent T; Gogniat, Marissa A; Nickerson, John M; Pardue, Machelle T; Boatright, Jeffrey H

    2016-01-01

    To compare patterns of gene expression following preconditioning cyclic light rearing versus preconditioning aerobic exercise. BALB/C mice were preconditioned either by rearing in 800 lx 12:12 h cyclic light for 8 days or by running on treadmills for 9 days, exposed to toxic levels of light to cause light-induced retinal degeneration (LIRD), then sacrificed and retinal tissue harvested. Subsets of mice were maintained for an additional 2 weeks and for assessment of retinal function by electroretinogram (ERG). Both preconditioning protocols partially but significantly preserved retinal function and morphology and induced similar leukemia inhibitory factor (LIF) gene expression pattern. The data demonstrate that exercise preconditioning and cyclic light preconditioning protect photoreceptors against LIRD and evoke a similar pattern of retinal LIF gene expression. It may be that similar stress response pathways mediate the protection provided by the two preconditioning modalities.

  3. Role of phosphoinositide 3-kinase IA (PI3K-IA) activation in cardioprotection induced by ouabain preconditioning.

    PubMed

    Duan, Qiming; Madan, Namrata D; Wu, Jian; Kalisz, Jennifer; Doshi, Krunal Y; Haldar, Saptarsi M; Liu, Lijun; Pierre, Sandrine V

    2015-03-01

    Acute myocardial infarction, the clinical manifestation of ischemia-reperfusion (IR) injury, is a leading cause of death worldwide. Like ischemic preconditioning (IPC) induced by brief episodes of ischemia and reperfusion, ouabain preconditioning (OPC) mediated by Na/K-ATPase signaling protects the heart against IR injury. Class I PI3K activation is required for IPC, but its role in OPC has not been investigated. While PI3K-IB is critical to IPC, studies have suggested that ouabain signaling is PI3K-IA-specific. Hence, a pharmacological approach was used to test the hypothesis that OPC and IPC rely on distinct PI3K-I isoforms. In Langendorff-perfused mouse hearts, OPC was initiated by 4 min of ouabain 10 μM and IPC was triggered by 4 cycles of 5 min ischemia and reperfusion prior to 40 min of global ischemia and 30 min of reperfusion. Without affecting PI3K-IB, ouabain doubled PI3K-IA activity and Akt phosphorylation at Ser(473). IPC and OPC significantly preserved cardiac contractile function and tissue viability as evidenced by left ventricular developed pressure and end-diastolic pressure recovery, reduced lactate dehydrogenase release, and decreased infarct size. OPC protection was blunted by the PI3K-IA inhibitor PI-103, but not by the PI3K-IB inhibitor AS-604850. In contrast, IPC-mediated protection was not affected by PI-103 but was blocked by AS-604850, suggesting that PI3K-IA activation is required for OPC while PI3K-IB activation is needed for IPC. Mechanistically, PI3K-IA activity is required for ouabain-induced Akt activation but not PKCε translocation. However, in contrast to PKCε translocation which is critical to protection, Akt activity was not required for OPC. Further studies shall reveal the identity of the downstream targets of this new PI3K IA-dependent branch of OPC. These findings may be of clinical relevance in patients at risk for myocardial infarction with underlying diseases and/or medication that could differentially affect the

  4. Histopathologic studies of ischemic optic neuropathy.

    PubMed Central

    Knox, D L; Kerrison, J B; Green, W R

    2000-01-01

    PURPOSE: To define the histopathologic features of eyes in which a pathologic diagnosis of ischemic optic neuropathy had been made in the years 1951 through 1998. METHODS: The following data were documented: age of patient, race, sex, source of tissue, cause of death, clinical history, interval from loss of vision to death, enucleation, exenteration, and biopsy. The histopathologic criteria for diagnosis of ischemic optic neuropathy were the presence of localized ischemic edema, cavernous degeneration, or an area of atrophy located superior or inferior in the optic nerve. Cases with history of abrupt loss of vision were combined with reports from the literature to construct a time table of histopathologic features and associated conditions. RESULTS: Ischemic optic neuropathy was present in 193 eyes. There were 88 females and 65 males. The average age was 71.6 years. Ischemic edema without (early) and with (later) gitter macrophages was present in 26 (13.5%). Cavernous degeneration was present in 69 nerves (36%). Mucopolysaccharide (MPS) was present in 37 cavernous lesions 1 month or longer after loss of vision. Cavernous lesions were seen in 3 eyes in which peripapillary retinal nerve fiber layer hemorrhage had been observed prior to death. Atrophic lesions, the most common pattern, were observed in 133 optic nerves (66.8%). More than 1 ischemic lesion was seen in 38 optic nerves (19.7%). Bilateral ischemic lesions were seen in 50 (35.2%) of 142 paired eyes. CONCLUSIONS: Ischemic optic nerve lesions are initially acellular and later show macrophage infiltration. Cavernous lesions with MPS are present 4 weeks or longer after vision loss. The location of MPS posteriorly and along the internal margin suggests that MPS is produced at the edges of lesions. Progressive vision loss in ischemic optic neuropathy may be secondary to compression of intact nerve from ischemic edema and cavernous swelling, or a second ischemic lesion. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5

  5. [Stunned myocardium after acute ischemic stroke].

    PubMed

    Varela, Daniel; Díaz, Fernanda; Hlavnicka, Alejandro; Wainsztein, Néstor; Leiguarda, Ramón

    2006-01-01

    The so-called stunned myocardium, defined as transitory myocardial contractile dysfunction, has been clearly demonstrated in diverse clinical situations. However, stunned myocardium related to ischemic stroke has been poorly identified. We describe two patients with diagnosis of acute ischemic stroke who developed eletrocardiographic changes, cardiac enzyme increasing levels and myocardial dysfunction secondary to abnormal cardiac wall motion. At the same time the patients developed acute lung injury with rapid resolution, perhaps as a consequence of neurocardiogenic components.

  6. Adiposity and ischemic and hemorrhagic stroke

    PubMed Central

    Kroll, Mary E.; Green, Jane; Beral, Valerie; Sudlow, Cathie L.M.; Brown, Anna; Kirichek, Oksana; Price, Alison; Yang, TienYu Owen

    2016-01-01

    Objective: To compare associations of body mass index (BMI) with ischemic stroke and hemorrhagic stroke risk, and to review the worldwide evidence. Methods: We recruited 1.3 million previously stroke-free UK women between 1996 and 2001 (mean age 57 years [SD 5]) and followed them by record linkage for hospital admissions and deaths. We used Cox regression to estimate adjusted relative risks for ischemic and hemorrhagic (intracerebral or subarachnoid hemorrhage) stroke in relation to BMI. We conducted a meta-analysis of published findings from prospective studies on these associations. Results: During an average follow-up of 11.7 years, there were 20,549 first strokes, of which 9,993 were specified as ischemic and 5,852 as hemorrhagic. Increased BMI was associated with an increased risk of ischemic stroke (relative risk 1.21 per 5 kg/m2 BMI, 95% confidence interval 1.18–1.23, p < 0.0001) but a decreased risk of hemorrhagic stroke (relative risk 0.89 per 5 kg/m2 BMI, 0.86–0.92, p < 0.0001). The BMI-associated trends for ischemic and hemorrhagic stroke were significantly different (heterogeneity: p < 0.0001) but were not significantly different for intracerebral hemorrhage (n = 2,790) and subarachnoid hemorrhage (n = 3,062) (heterogeneity: p = 0.5). Published data from prospective studies showed consistently greater BMI-associated relative risks for ischemic than hemorrhagic stroke with most evidence (prior to this study) coming from Asian populations. Conclusions: In UK women, higher BMI is associated with increased risk of ischemic stroke but decreased risk of hemorrhagic stroke. The totality of the available published evidence suggests that BMI-associated risks are greater for ischemic than for hemorrhagic stroke. PMID:27605176

  7. Chinese Herbal Products for Ischemic Stroke.

    PubMed

    Hung, I-Ling; Hung, Yu-Chiang; Wang, Lin-Yi; Hsu, Sheng-Feng; Chen, Hsuan-Ju; Tseng, Ying-Jung; Kuo, Chun-En; Hu, Wen-Long; Li, Tsai-Chung

    2015-01-01

    Traditional Chinese herbal products (CHPs) have been described in ancient medicine systems as treatments for various stroke-associated ailments. This study is aimed to investigate the prescription patterns and combinations of CHPs for ischemic stroke in Taiwan. Prescriptions of CHPs for ischemic stroke were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan. Every prescription with a leading diagnosis of ischemic stroke made during 2000-2010 was analyzed. Descriptive statistics were applied to the pattern of co-prescriptions. Multiple logistic regression models were used to assess demographic and risk factors that are correlated with CHP use. The dataset of inpatient claims data contained information on 15,896 subjects who experienced ischemic stroke from 2000 to 2010. There was an average of 5.82 CHPs in a single prescription for subjects with ischemic stroke. Bu-yang-huan-wu-tang (BYHWT) (40.32%) was by far the most frequently prescribed formula CHP for ischemic stroke, and the most commonly used combination of two-formula-CHP was BYHWT with Shu-jin-huo-xue-tang (SJHXT) (4.40%). Dan Shen (16.50%) was the most commonly used single CHP for ischemic stroke, and the most commonly used combination of two single CHPs was Shi Chang Pua with Yuan Zhi (4.79%). We found that BYHWT and Dan Shen were the most frequently prescribed formula and single CHP for ischemic stroke, respectively. These results provide information about individualized therapy and may contribute to further pharmacologic experiments and clinical trials. PMID:26477801

  8. [Ocular ischemic syndrome--a case report].

    PubMed

    Zemba, M; Avram, Corina Ioana; Ochinciuc, Uliana; Stamate, Alina Cristina; Camburu, Raluca Lăcrămioara

    2013-01-01

    Ocular ischemic syndrome, also known as hypoperfusion/ hypotensive retinopathy or as ischemic oculopathy is a rare ocular disease determined by chronic arterial hypoperfusion through central retinal artery, posterior and anterior ciliary arteries. It is bilateral in 20% of the cases. Most often it appears due to severe occlusion of the carotid arteries (ICA, MCA>ECA), described in 1963 by Kearns and Hollenhorst. Occasionally it can be determined by the obstruction of ophtalmic artery or some arterities (Takayasu, giant cell arteritis). The risk factors are: age between 50-80 years, males (M:F = 2:1), arterial hypertension, diabetes, coronary diseases (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The case we present is of an 63 years old man known with primary arterial hypertension, hypercholesterolemia, diabetes type 2 non insulin dependent and diagnosticated with ischemic cerebral stroke and bilateral obstruction of internal carotid arteries in march 2010, who is presenting for visual impairment in both eyes. The imaging investigations show important carotid occlusion and at the ophthalmologic evaluation there are ocular hypertension and rubeosis iridis at the right eye, optic atrophy at both eyes (complete in the right eye and partial in the left eye), with superior altitudinal visual field defect in left eye. The following diagnosis was established: Chronic ocular ischemic syndrome in both eyes with Neovascular glaucoma at the right eye, Anterior ischemic optic neuropathy at the left eye and laser panphotocoagulation at the right eye was started. PMID:24386788

  9. [Ocular ischemic syndrome--a case report].

    PubMed

    Zemba, M; Avram, Corina Ioana; Ochinciuc, Uliana; Stamate, Alina Cristina; Camburu, Raluca Lăcrămioara

    2013-01-01

    Ocular ischemic syndrome, also known as hypoperfusion/ hypotensive retinopathy or as ischemic oculopathy is a rare ocular disease determined by chronic arterial hypoperfusion through central retinal artery, posterior and anterior ciliary arteries. It is bilateral in 20% of the cases. Most often it appears due to severe occlusion of the carotid arteries (ICA, MCA>ECA), described in 1963 by Kearns and Hollenhorst. Occasionally it can be determined by the obstruction of ophtalmic artery or some arterities (Takayasu, giant cell arteritis). The risk factors are: age between 50-80 years, males (M:F = 2:1), arterial hypertension, diabetes, coronary diseases (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The case we present is of an 63 years old man known with primary arterial hypertension, hypercholesterolemia, diabetes type 2 non insulin dependent and diagnosticated with ischemic cerebral stroke and bilateral obstruction of internal carotid arteries in march 2010, who is presenting for visual impairment in both eyes. The imaging investigations show important carotid occlusion and at the ophthalmologic evaluation there are ocular hypertension and rubeosis iridis at the right eye, optic atrophy at both eyes (complete in the right eye and partial in the left eye), with superior altitudinal visual field defect in left eye. The following diagnosis was established: Chronic ocular ischemic syndrome in both eyes with Neovascular glaucoma at the right eye, Anterior ischemic optic neuropathy at the left eye and laser panphotocoagulation at the right eye was started.

  10. Telemetry and Communication IP Video Player

    NASA Technical Reports Server (NTRS)

    OFarrell, Zachary L.

    2011-01-01

    Aegis Video Player is the name of the video over IP system for the Telemetry and Communications group of the Launch Services Program. Aegis' purpose is to display video streamed over a network connection to be viewed during launches. To accomplish this task, a VLC ActiveX plug-in was used in C# to provide the basic capabilities of video streaming. The program was then customized to be used during launches. The VLC plug-in can be configured programmatically to display a single stream, but for this project multiple streams needed to be accessed. To accomplish this, an easy to use, informative menu system was added to the program to enable users to quickly switch between videos. Other features were added to make the player more useful, such as watching multiple videos and watching a video in full screen.

  11. Security Research on VoIP with Watermarking

    NASA Astrophysics Data System (ADS)

    Hu, Dong; Lee, Ping

    2008-11-01

    With the wide application of VoIP, many problems have occurred. One of the problems is security. The problems with securing VoIP systems, insufficient standardization and lack of security mechanisms emerged the need for new approaches and solutions. In this paper, we propose a new security architecture for VoIP which is based on digital watermarking which is a new, flexible and powerful technology that is increasingly gaining more and more attentions. Besides known applications e.g. to solve copyright protection problems, we propose to use digital watermarking to secure not only transmitted audio but also signaling protocol that VoIP is based on.

  12. A Scalable and Practical Authentication Protocol in Mobile IP

    NASA Astrophysics Data System (ADS)

    Lee, Yong; Lee, Goo-Yeon; Kim, Hwa-Long

    Due to the proliferation of mobile devices connected to the Internet, implementing a secure and practical Mobile IP has become an important goal. A mobile IP can not work properly without authentication between the mobile node (MN), the home agent (HA) and the foreign agent (FA). In this paper, we propose a practical Mobile IP authentication protocol that uses public key cryptography only during the initial authentication. The proposed scheme is compatible with the conventional Mobile IP protocol and provides scalability against the number of MN's. We also show that the proposed protocol offers secure operation.

  13. Mig and IP-10: CXC chemokines that target lymphocytes.

    PubMed

    Farber, J M

    1997-03-01

    Mig and IP-10 are related members of the CXC subfamily of the chemokine family of cytokines. The murine Mig (MuMig), human IP-10, and the mouse homologue of IP-10, Crg-2, were all identified due to the dramatic inductions of their genes in monocytic cells treated with interferon-gamma (IFN-gamma). Studies using recombinant (r) human proteins show that, unlike most other CXC chemokines, rHuMig and rIP-10 have no activity on neutrophils but appear to target lymphocytes specifically. rHuMig and rIP-10 are active as chemotactic factors for stimulated, but not for resting, T cells. Studies done in vitro and in vivo have shown that rHuMig and rIP-10 share additional activities, including inhibition of neovascularization, inhibition of hematopoietic progenitor cells, and anti-tumor effects. rHuMig and rIP-10 show reciprocal desensitization on activated T cells and have been demonstrated to share a receptor, CXCR3. The genes for both MuMig and Crg-2 are highly expressed in multiple tissues during experimental viral and protozoan infections in mice, but their patterns of expression differ. This suggests that the Migs and IP-10/Crg-2 may play roles in host defense and that, despite their similar activities assayed in vitro, Mig and IP-10/Crg-2 may serve non-redundant functions in vivo.

  14. Machinability of IPS Empress 2 framework ceramic.

    PubMed

    Schmidt, C; Weigl, P

    2000-01-01

    Using ceramic materials for an automatic production of ceramic dentures by CAD/CAM is a challenge, because many technological, medical, and optical demands must be considered. The IPS Empress 2 framework ceramic meets most of them. This study shows the possibilities for machining this ceramic with economical parameters. The long life-time requirement for ceramic dentures requires a ductile machined surface to avoid the well-known subsurface damages of brittle materials caused by machining. Slow and rapid damage propagation begins at break outs and cracks, and limits life-time significantly. Therefore, ductile machined surfaces are an important demand for machine dental ceramics. The machining tests were performed with various parameters such as tool grain size and feed speed. Denture ceramics were machined by jig grinding on a 5-axis CNC milling machine (Maho HGF 500) with a high-speed spindle up to 120,000 rpm. The results of the wear test indicate low tool wear. With one tool, you can machine eight occlusal surfaces including roughing and finishing. One occlusal surface takes about 60 min machining time. Recommended parameters for roughing are middle diamond grain size (D107), cutting speed v(c) = 4.7 m/s, feed speed v(ft) = 1000 mm/min, depth of cut a(e) = 0.06 mm, width of contact a(p) = 0.8 mm, and for finishing ultra fine diamond grain size (D46), cutting speed v(c) = 4.7 m/s, feed speed v(ft) = 100 mm/min, depth of cut a(e) = 0.02 mm, width of contact a(p) = 0.8 mm. The results of the machining tests give a reference for using IPS Empress(R) 2 framework ceramic in CAD/CAM systems.

  15. Lessons Learned in the Design and Use of IP1 / IP2 Flexible Packaging - 13621

    SciTech Connect

    Sanchez, Mike; Reeves, Wendall; Smart, Bill

    2013-07-01

    For many years in the USA, Low Level Radioactive Waste (LLW), contaminated soils and construction debris, have been transported, interim stored, and disposed of, using IP1 / IP2 metal containers. The performance of these containers has been more than adequate, with few safety occurrences. The containers are used under the regulatory oversight of the US Department of Transportation (DOT), 49 Code of Federal Regulations (CFR). In the late 90's the introduction of flexible packaging for the transport, storage, and disposal of low level contaminated soils and construction debris was introduced. The development of flexible packaging came out of a need for a more cost effective package, for the large volumes of waste generated by the decommissioning of many of the US Department of Energy (DOE) legacy sites across the US. Flexible packaging had to be designed to handle a wide array of waste streams, including soil, gravel, construction debris, and fine particulate dust migration. The design also had to meet all of the IP1 requirements under 49CFR 173.410, and be robust enough to pass the IP2 testing 49 CFR 173.465 required for many LLW shipments. Tens of thousands of flexible packages have been safely deployed and used across the US nuclear industry as well as for hazardous non-radioactive applications, with no recorded release of radioactive materials. To ensure that flexible packages are designed properly, the manufacturer must use lessons learned over the years, and the tests performed to provide evidence that these packages are suitable for transporting low level radioactive wastes. The design and testing of flexible packaging for LLW, VLLW and other hazardous waste streams must be as strict and stringent as the design and testing of metal containers. The design should take into consideration the materials being loaded into the package, and should incorporate the right materials, and manufacturing methods, to provide a quality, safe product. Flexible packaging can be

  16. Citalopram Enhances Neurovascular Regeneration and Sensorimotor Functional Recovery after Ischemic Stroke in Mice

    PubMed Central

    Espinera, Alyssa R.; Ogle, Molly E.; Gu, Xiaohuan; Wei, Ling

    2013-01-01

    Recent clinical trials have demonstrated that treatment with selective serotonin reuptake inhibitors (SSRIs) after stroke enhances motor functional recovery; however, the underlying mechanisms remain to be further elucidated. We hypothesized that daily administration of the clinical drug citalopram would produce these functional benefits via enhancing neurovascular repair in the ischemic peri-infarct region. To test this hypothesis, focal ischemic stroke was induced in male C57/B6 mice by permanent ligation of distal branches of the middle cerebral artery to the barrel cortex and 7-min occlusion of the bilateral common carotid arteries. Citalopram (10 mg/kg, i.p.) was injected 24 hrs after stroke and daily thereafter. To label proliferating cells, bromo-deoxyuridine was injected daily beginning 3 days after stroke. Immunohistochemical and functional assays were performed to elucidate citalopram-mediated cellular and sensorimotor changes after stroke. Citalopram treatment had no significant effect on infarct formation or edema 3 days after stroke; however, citalopram-treated mice had better functional recovery than saline-treated controls 3 and 14 days after stroke in the adhesive removal test. Increased expression of brain derived neurotrophic factor was detected in the peri-infarct region 7 days after stroke in citalopram-treated animals. The number of proliferating neural progenitor cells and the distance of neuroblast migration from the sub-ventricular zone towards the ischemic cortex were significantly greater in citalopram-treated mice at 7 days after stroke. Immunohistochemical staining and co-localization analysis showed that citalopram-treated animals generated more new neurons and microvessels in the peri-infarct region 21 and 28 days after stroke. Taken together, these results suggest that citalopram promotes post-stroke sensorimotor recovery likely via enhancing neurogenesis, neural cell migration and the microvessel support in the peri-infarct region of

  17. Candesartan and glycyrrhizin ameliorate ischemic brain damage through downregulation of the TLR signaling cascade.

    PubMed

    Barakat, Waleed; Safwet, Nancy; El-Maraghy, Nabila N; Zakaria, Mohamed N M

    2014-02-01

    Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA). The current study was designed to investigate the protective effects of candesartan (0.15 mg/kg, orally) and glycyrrhizin (30 mg/kg, orally) experimentally-induced ischemic brain damage in C57BL/6 mice (middle cerebral artery occlusion, MCAO) in comparison to the effects of a standard neuroprotective drug (cerebrolysin, 7.5 mg/kg, IP). All drugs were administered 30 min before and 24h after MCAO. Both candesartan and glycyrrhizin ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in behaviour tests, reduction in brain infarction, neuronal degeneration, and leukocyte infiltration. In addition, MCAO induced a significant upregulation in the different elements of the TLR pathway including TLR-2 and TLR-4, Myd88, TRIF and IRF-3 and the downstream effectors TNF-α, IL-1β, IL-6 and NF-kB. All these changes were significantly ameliorated by treatment with candesartan and glycyrrhizin. The results of the current study represent a new indication for both candesartan and glycyrrhizin in the management of ischemic stroke with effects comparable to those of the standard neuroprotective drug cerebrolysin.

  18. 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.

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

    SciTech Connect

    Cai, Yunfeng; Bai, Zhaojun; Pask, John E.; Sukumar, N.

    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.

  20. Maintaining high-quality IP audio services in lossy IP network environments

    NASA Astrophysics Data System (ADS)

    Barton, Robert J., III; Chodura, Hartmut

    2000-07-01

    In this paper we present our research activities in the area of digital audio processing and transmission. Today's available teleconference audio solutions are lacking in flexibility, robustness and fidelity. There was a need for enhancing the quality of audio for IP-based applications to guarantee optimal services under varying conditions. Multiple tests and user evaluations have shown that a reliable audio communication toolkit is essential for any teleconference application. This paper summarizes our research activities and gives an overview of developed applications. In a first step the parameters, which influence the audio quality, were evaluated. All of these parameters have to be optimized in order to result into the best achievable quality. Therefore it was necessary to enhance existing schemes or develop new methods. Applications were developed for Internet-Telephony, broadcast of live music and spatial audio for Virtual Reality environments. This paper describes these applications and issues of delivering high quality digital audio services over lossy IP networks.

  1. Brain protection against ischemic stroke using choline as a new molecular bypass treatment

    PubMed Central

    Jin, Xin; Wang, Ru-huan; Wang, Hui; Long, Chao-liang; Wang, Hai

    2015-01-01

    Aim: To determine whether administration of choline could attenuate brain injury in a rat model of ischemic stroke and the underlying mechanisms. Methods: A rat model of ischemic stroke was established through permanent middle cerebral artery occlusion (pMCAO). After the surgery, the rats were treated with choline or choline plus the specific α7 nAChR antagonist methyllycaconitine (MLA), or with the control drug nimodipine for 10 days. The neurological deficits, brain-infarct volume, pial vessel density and the number of microvessels in the cortex were assessed. Rat brain microvascular endothelial cells (rBMECs) cultured under hypoxic conditions were used in in vitro experiments. Results: Oral administration of choline (100 or 200 mg·kg−1·d−1) or nimodipine (20 mg·kg−1·d−1) significantly improved neurological deficits, and reduced infarct volume and nerve cell loss in the ischemic cerebral cortices in pMCAO rats. Furthermore, oral administration of choline, but not nimodipine, promoted the pial arteriogenesis and cerebral-cortical capillary angiogenesis in the ischemic regions. Moreover, oral administration of choline significantly augmented pMCAO-induced increases in the expression levels of α7 nAChR, HIF-1α and VEGF in the ischemic cerebral cortices as well as in the serum levels of VEGF. Choline-induced protective effects were prevented by co-treatment with MLA (1 mg·kg−1·d−1, ip). Treatment of rBMECs cultured under hypoxic conditions in vitro with choline (1, 10 and 100 μmol/L) dose-dependently promoted the endothelial-cell proliferation, migration and tube formation, as well as VEGF secretion, which were prevented by co-treatment with MLA (1 μmol/L) or by transfection with HIF-1α siRNA. Conclusion: Choline effectively attenuates brain ischemic injury in pMCAO rats, possibly by facilitating pial arteriogenesis and cerebral-cortical capillary angiogenesis via upregulating α7 nAChR levels and inducing the expression of HIF-1α and VEGF

  2. [Reactive oxygen species are triggers and mediators of an increase in cardiac tolerance to impact of ischemia-reperfusion].

    PubMed

    Maslov, L N; Naryzhnaia, N V; Podoksenov, Iu K; Prokudina, E S; Gorbunov, A S; Zhang, I; Peĭ, Zh-M

    2015-01-01

    Reactive oxygen species (ROS) are triggers of ischemic preconditioning (IP). On the role of intracellular messengers of such cardioprotective effect of preconditioning claim: O2*, H2O2, OH*. However, we cannot exclude the possibility that other reactive oxygen metabolites also involved in the IP. Presented data suggest that IP enhances the production of ROS. The source of ROS may be mitochondrial respiratory chain and NADPH oxidase. Exogenous reactive oxygen species (O2*, H2O2) mimic the cardioprotective effect of preconditioning. Preconditioning prevents free radical damage of the heart during ischemia-reperfusion. The protective effect of IP is the consequence of reducing the production of ROS or the result of increased formation of endogenous antioxidants. Antioxidant enzymes are not involved in the protective effect of IP. Cardioprotective effect of many compounds (bradykinin, opioids, acetylcholine, phenylephrine, tumor necrosis factor-α, volatile anesthetics, protonophores, diazoxide, angiotensin II) depends on the increased production of ROS. PMID:25868322

  3. Proteomic analysis of the mice hippocampus after preconditioning induced by N-methyl-D-aspartate (NMDA).

    PubMed

    do Amaral e Silva Müller, Gabrielle; Vandresen-Filho, Samuel; Tavares, Carolina Pereira; Menegatti, Angela C O; Terenzi, Hernán; Tasca, Carla Inês; Severino, Patricia Cardoso

    2013-05-01

    Preconditioning induced by N-methyl-D-aspartate (NMDA) has been used as a therapeutic tool against later neuronal insults. NMDA preconditioning affords neuroprotection against convulsions and cellular damage induced by the NMDA receptor agonist, quinolinic acid (QA) with time-window dependence. This study aimed to evaluate the molecular alterations promoted by NMDA and to compare these alterations in different periods of time that are related to the presence or lack of neuroprotection. Putative mechanisms related to NMDA preconditioning were evaluated via a proteomic analysis by using a time-window study. After a subconvulsant and protective dose of NMDA administration mice, hippocampi were removed (1, 24 or 72 h) and total protein analyzed by 2DE gels and identified by MALDI-TOF. Differential protein expression among the time induction of NMDA preconditioning was observed. In the hippocampus of protected mice (24 h), four proteins: HSP70(B), aspartyl-tRNA synthetase, phosphatidylethanolamine binding protein and creatine kinase were found to be up-regulated. Two other proteins, HSP70(A) and V-type proton ATPase were found down-regulated. Proteomic analysis showed that the neuroprotection induced by NMDA preconditioning altered signaling pathways, cell energy maintenance and protein synthesis and processing. These events may occur in a sense to attenuate the excitotoxicity process during the activation of neuroprotection promoted by NMDA preconditioning.

  4. Synergistic effect of high-affinity binding and flow preconditioning on endothelial cell adhesion.

    PubMed

    Mathur, Anshu B; Truskey, George A; Reichert, William M

    2003-01-01

    The current study examined whether the combined introduction of high-affinity avidin-biotin bonds and fibronectin-integrin bonds (i.e., dual ligand treatment) would further augment the adhesion of flow-preconditioned endothelial cells to model substrates via contributions to the actin cytoskeleton and the formation of focal contacts. Human umbilical vein endothelial cells (HUVEC) were grown under static conditions or exposed to a flow-preconditioning regimen for 24 h. Cell retention was determined by exposure to 75 dynes/cm(2). The combination of flow preconditioning and the dual ligand treatment yielded higher cell retention under flow compared to the cells adherent via fibronectin-integrin bonds only. This increase in adhesion strength correlated with a greater focal contact area. Elongation of the HUVEC occurred after exposure to flow preconditioning; however, orientation of dual ligand adherent cells was restricted due to the presence of the high-affinity ligand. Flow-preconditioned cells showed increased stress fiber formation compared to nonconditioned cells although the stress fibers per cell for flow-preconditioned cells were the same on both the ligand systems employed. The results indicate that enhanced adhesion strength is due to a combination of increased focal contact area, stress fiber formation, and cell alignment. PMID:12483708

  5. Abdominal Surgical Incision Induces Remote Preconditioning of Trauma (RPCT) via Activation of Bradykinin Receptors (BK2R) and the Cytochrome P450 Epoxygenase Pathway in Canine Hearts

    PubMed Central

    Gross, Garrett J.; Baker, John E.; Moore, Jeannine; Falck, John R.; Nithipatikom, Kasem

    2012-01-01

    Recently, a novel observation was made in which nonischemic trauma at a site remote from the heart produced by a transverse abdominal incision resulted in a marked reduction of infarct size (IS) in the mouse heart via activation of sensory nerve fibers in the skin and subsequent activation of bradykinin 2 receptors (BK2R). This phenomenon was termed remote preconditioning of trauma (RPCT). Since RPCT may have potential clinical implications we attempted to confirm these findings in a large animal model, the dog. The epoxyeicosatrienoic acids (EETs) have also recently been shown to be antinociceptive and have been shown to mimic ischemic preconditioning (IPC) and postconditioning (POC) in dogs, therefore, we tested the role of the EETs in RPCT. Anesthetized adult mongrel dogs of either sex were subjected to 60 min of left anterior descending (LAD) coronary artery occlusion followed by 3 h of reperfusion. In all groups except the controls (no slit), a transverse slit (9 cm) was applied to the abdominal wall of the dog being careful to only slit the skin. Subsequently, 15 min after the slit the heart was subjected to the ischemia/reperfusion protocol. In the control dogs, the IS as a percent of the area at risk (AAR) was 22.5 ± 2.4%, whereas in the dogs subjected to the slit alone the IS/AAR was reduced to 9.2 ± 1.2% (*P<0.01). The BR2R blocker, HOE 140 (50 ug/kg, iv) given 10 min prior to the slit, completely abolished the protective effects of RCPT as did pretreatment with 14,15-EEZE, a putative EET receptor blocker or pretreatment with the selective EET synthesis inhibitor, MSPPOH. These results suggest that BK and the EETs share cardioprotective properties in a large animal model of RPCT. PMID:21786213

  6. ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning.

    PubMed

    Su, Chang; Sun, Fen; Cunningham, Rebecca L; Rybalchenko, Nataliya; Singh, Meharvan

    2014-01-01

    Oxidative stress has long been implicated in the pathogenesis of various neurodegenerative disorders such as Alzheimer's disease and stroke. While high levels of oxidative stress are generally associated with cell death, a slight rise of reactive oxygen species (ROS) levels can be protective by "preconditioning" cells to develop a resistance against subsequent challenges. However, the mechanisms underlying such preconditioning (PC)-induced protection are still poorly understood. Previous studies have supported a role of ERK5 (mitogen-activated protein [MAP] kinase 5) in neuroprotection and ischemic tolerance in the hippocampus. In agreement with these findings, our data suggest that ERK5 mediates both hydrogen peroxide (H2O2)-induced PC as well as nerve growth factor (NGF)-induced neuroprotection. Activation of ERK5 partially rescued pheochromocytoma PC12 cells as well as primary hippocampal neurons from H2O2-caused death, while inhibition of ERK5 abolished NGF or PC-induced protection. These results implicate ERK5 signaling as a common downstream pathway for NGF and PC. Furthermore, both NGF and PC increased the expression of the transcription factor, KLF4, which can initiate an anti-apoptotic response in various cell types. Induction of KLF4 by NGF or PC was blocked by siERK5, suggesting that ERK5 is required in this process. siKLF4 can also attenuate NGF- or PC-induced neuroprotection. Overexpression of active MEK5 or KLF4 in H2O2-stressed cells increased Bcl-2/Bax ratio and the expression of NAIP (neuronal apoptosis inhibitory protein). Taken together, our data suggest that ERK5/KLF4 cascade is a common signaling pathway shared by at least two important mechanisms by which neurons can be protected from cell death. PMID:25015774

  7. Effects of hypoxic preconditioning on synaptic ultrastructure in mice.

    PubMed

    Liu, Yi; Sun, Zhishan; Sun, Shufeng; Duan, Yunxia; Shi, Jingfei; Qi, Zhifeng; Meng, Ran; Sun, Yongxin; Zeng, Xianwei; Chui, Dehua; Ji, Xunming

    2015-01-01

    Hypoxic preconditioning (HPC) elicits resistance to more drastic subsequent insults, which potentially provide neuroprotective therapeutic strategy, but the underlying mechanisms remain to be fully elucidated. Here, we examined the effects of HPC on synaptic ultrastructure in olfactory bulb of mice. Mice underwent up to five cycles of repeated HPC treatments, and hypoxic tolerance was assessed with a standard gasp reflex assay. As expected, HPC induced an increase in tolerance time. To assess synaptic responses, Western blots were used to quantify protein levels of representative markers for glia, neuron, and synapse, and transmission electron microscopy was used to examine synaptic ultrastructure and mitochondrial density. HPC did not significantly alter the protein levels of astroglial marker (GFAP), neuron-specific markers (GAP43, Tuj-1, and OMP), synaptic number markers (synaptophysin and SNAP25) or the percentage of excitatory synapses versus inhibitory synapses. However, HPC significantly affected synaptic curvature and the percentage of synapses with presynaptic mitochondria, which showed concomitant change pattern. These findings demonstrate that HPC is associated with changes in synaptic ultrastructure. PMID:25155519

  8. Kochen-Specker Theorem as a Precondition for Quantum Computing

    NASA Astrophysics Data System (ADS)

    Nagata, Koji; Nakamura, Tadao

    2016-08-01

    We study the relation between the Kochen-Specker theorem (the KS theorem) and quantum computing. The KS theorem rules out a realistic theory of the KS type. We consider the realistic theory of the KS type that the results of measurements are either +1 or -1. We discuss an inconsistency between the realistic theory of the KS type and the controllability of quantum computing. We have to give up the controllability if we accept the realistic theory of the KS type. We discuss an inconsistency between the realistic theory of the KS type and the observability of quantum computing. We discuss the inconsistency by using the double-slit experiment as the most basic experiment in quantum mechanics. This experiment can be for an easy detector to a Pauli observable. We cannot accept the realistic theory of the KS type to simulate the double-slit experiment in a significant specific case. The realistic theory of the KS type can not depicture quantum detector. In short, we have to give up both the observability and the controllability if we accept the realistic theory of the KS type. Therefore, the KS theorem is a precondition for quantum computing, i.e., the realistic theory of the KS type should be ruled out.

  9. Linear multifrequency-grey acceleration recast for preconditioned Krylov iterations

    SciTech Connect

    Morel, Jim E. Brian Yang, T.-Y.; Warsa, James S.

    2007-11-10

    The linear multifrequency-grey acceleration (LMFGA) technique is used to accelerate the iterative convergence of multigroup thermal radiation diffusion calculations in high energy density simulations. Although it is effective and efficient in one-dimensional calculations, the LMFGA method has recently been observed to significantly degrade under certain conditions in multidimensional calculations with large discontinuities in material properties. To address this deficiency, we recast the LMFGA method in terms of a preconditioned system that is solved with a Krylov method (LMFGK). Results are presented demonstrating that the new LMFGK method always requires fewer iterations than the original LMFGA method. The reduction in iteration count increases with both the size of the time step and the inhomogeneity of the problem. However, for reasons later explained, the LMFGK method can cost more per iteration than the LMFGA method, resulting in lower but comparable efficiency in problems with small time steps and weak inhomogeneities. In problems with large time steps and strong inhomogeneities, the LMFGK method is significantly more efficient than the LMFGA method.

  10. In silico pooling of ChIP-seq control experiments.

    PubMed

    Sun, Guannan; Srinivasan, Rajini; Lopez-Anido, Camila; Hung, Holly A; Svaren, John; Keleş, Sündüz

    2014-01-01

    As next generation sequencing technologies are becoming more economical, large-scale ChIP-seq studies are enabling the investigation of the roles of transcription factor binding and epigenome on phenotypic variation. Studying such variation requires individual level ChIP-seq experiments. Standard designs for ChIP-seq experiments employ a paired control per ChIP-seq sample. Genomic coverage for control experiments is often sacrificed to increase the resources for ChIP samples. However, the quality of ChIP-enriched regions identifiable from a ChIP-seq experiment depends on the quality and the coverage of the control experiments. Insufficient coverage leads to loss of power in detecting enrichment. We investigate the effect of in silico pooling of control samples within multiple biological replicates, multiple treatment conditions, and multiple cell lines and tissues across multiple datasets with varying levels of genomic coverage. Our computational studies suggest guidelines for performing in silico pooling of control experiments. Using vast amounts of ENCODE data, we show that pairwise correlations between control samples originating from multiple biological replicates, treatments, and cell lines/tissues can be grouped into two classes representing whether or not in silico pooling leads to power gain in detecting enrichment between the ChIP and the control samples. Our findings have important implications for multiplexing samples.

  11. Research on implementation of proxy Arp in IP DSLAM

    NASA Astrophysics Data System (ADS)

    Cheng, Chuanqing; Wang, Li; Huang, Qiugen

    2005-02-01

    While the ethernet is applied more and more in public network environment and xdsl service become the most common access mode ,IP kenel DSLAM undertakes some functions such as service distribution and convergence ,security management and customer management.Facing the contradiction of the need of port isolation and the shortage of ip address,VLAN aggregation technology is applied in DSLAM.How to implement the communicatio between the two vlan but share the same ip subnet,proxy arp does this. This paper introduces how to implement proxy arp in the DSLAM. TCP/IP communication detail procedure betweent two host ,the relation of VLAN and network segment are discussed. The proxy arp model and its implementation in IP DSLAM is also expatiated in this paper and a conformance tesing is given.

  12. Computational methodology for ChIP-seq analysis

    PubMed Central

    Shin, Hyunjin; Liu, Tao; Duan, Xikun; Zhang, Yong; Liu, X. Shirley

    2015-01-01

    Chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) is a powerful technology to identify the genome-wide locations of DNA binding proteins such as transcription factors or modified histones. As more and more experimental laboratories are adopting ChIP-seq to unravel the transcriptional and epigenetic regulatory mechanisms, computational analyses of ChIP-seq also become increasingly comprehensive and sophisticated. In this article, we review current computational methodology for ChIP-seq analysis, recommend useful algorithms and workflows, and introduce quality control measures at different analytical steps. We also discuss how ChIP-seq could be integrated with other types of genomic assays, such as gene expression profiling and genome-wide association studies, to provide a more comprehensive view of gene regulatory mechanisms in important physiological and pathological processes. PMID:25741452

  13. Audio CAPTCHA for SIP-Based VoIP

    NASA Astrophysics Data System (ADS)

    Soupionis, Yannis; Tountas, George; Gritzalis, Dimitris

    Voice over IP (VoIP) introduces new ways of communication, while utilizing existing data networks to provide inexpensive voice communications worldwide as a promising alternative to the traditional PSTN telephony. SPam over Internet Telephony (SPIT) is one potential source of future annoyance in VoIP. A common way to launch a SPIT attack is the use of an automated procedure (bot), which generates calls and produces audio advertisements. In this paper, our goal is to design appropriate CAPTCHA to fight such bots. We focus on and develop audio CAPTCHA, as the audio format is more suitable for VoIP environments and we implement it in a SIP-based VoIP environment. Furthermore, we suggest and evaluate the specific attributes that audio CAPTCHA should incorporate in order to be effective, and test it against an open source bot implementation.

  14. Clusterin: a protective mediator for ischemic cardiomyocytes?

    PubMed

    Krijnen, P A J; Cillessen, S A G M; Manoe, R; Muller, A; Visser, C A; Meijer, C J L M; Musters, R J P; Hack, C E; Aarden, L A; Niessen, H W M

    2005-11-01

    We examined the relationship between clusterin and activated complement in human heart infarction and evaluated the effect of this protein on ischemic rat neonatal cardiomyoblasts (H9c2) and isolated adult ventricular rat cardiomyocytes as in vitro models of acute myocardial infarction. Clusterin protects cells by inhibiting complement and colocalizes with complement on jeopardized human cardiomyocytes after infarction. The distribution of clusterin and complement factor C3d was evaluated in the infarcted human heart. We also analyzed the protein expression of clusterin in ischemic H9c2 cells. The binding of endogenous and purified human clusterin on H9c2 cells was analyzed by flow cytometry. Furthermore, the effect of clusterin on the viability of ischemically challenged H9c2 cells and isolated adult ventricular rat cardiomyocytes was analyzed. In human myocardial infarcts, clusterin was found on scattered, morphologically viable cardiomyocytes within the infarcted area that were negative for complement. In H9c2 cells, clusterin was rapidly expressed after ischemia. Its expression was reduced after reperfusion. Clusterin bound to single annexin V-positive or annexin V and propidium iodide-positive H9c2 cells. Clusterin inhibited ischemia-induced death in H9c2 cells as well as in isolated adult ventricular rat cardiomyocytes in the absence of complement. We conclude that ischemia induces the upregulation of clusterin in ischemically challenged, but viable, cardiomyocytes. Our data suggest that clusterin protects cardiomyocytes against ischemic cell death via a complement-independent pathway.

  15. [Experimental model of ocular ischemic diseases].

    PubMed

    Kiseleva, T N; Chudin, A V

    2014-01-01

    The review presents the most common methods of modeling of retinal ischemia in vitro (chemical ischemia with iodoacetic acid, incubation of the retinal pigment epithelium cells with oligomycin, deprivation of oxygen and glucose) and in vivo (a model with increased intraocular pressure, cerebral artery occlusion, chronic ligation of the carotid arteries, photocoagulation of the retinal vessels, occlusion of the central retinal artery, endothelin-1 administration). Modeling ischemic injury in rats is the most frequently used method in studies, because the blood supply of their eyes is similar to blood flow in the human eyes. Each method has its own advantages and disadvantages. Application of methods depends on the purpose of the experimental study. Currently model of ocular ischemic disease can be obtained easily by injecting vasoconstrictive drug endothelin-1. It is the most widely used method of high intraocular pressure induced ocular ischemic damage similar to glaucoma, occlusion of central retinal artery or ophthalmic artery in human. The development of experimental models of ocular ischemic diseases and detailed investigation of mechanisms of impairment of microcirculation are useful for improve the efficiency of diagnostic and treatment of ischemic diseases of retina and optic nerve. PMID:25971134

  16. Hypothermia for hypoxic–ischemic encephalopathy

    PubMed Central

    Cotten, C Michael; Shankaran, Seetha

    2010-01-01

    Moderate to severe hypoxic–ischemic injury in newborn infants, manifested as encephalopathy immediately or within hours after birth, is associated with a high risk of either death or a lifetime with disability. In recent multicenter clinical trials, hypothermia initiated within the first 6 postnatal hours has emerged as a therapy that reduces the risk of death or impairment among infants with hypoxic–ischemic encephalopathy. Prior to hypothermia, no therapies directly targeting neonatal encephalopathy secondary to hypoxic–ischemic injury had convincing evidence of efficacy. Hypothermia therapy is now becoming increasingly available at tertiary centers. Despite the deserved enthusiasm for hypothermia, obstetric and neonatology caregivers, as well as society at large, must be reminded that in the clinical trials more than 40% of cooled infants died or survived with impairment. Although hypothermia is an evidence-based therapy, additional discoveries are needed to further improve outcome after HIE. In this article, we briefly present the epidemiology of neonatal encephalopathy due to hypoxic–ischemic injury, describe the rationale for the use of hypothermia therapy for hypoxic–ischemic encephalopathy, and present results of the clinical trials that have demonstrated the efficacy of hypothermia. We also present findings noted during and after these trials that will guide care and direct research for this devastating problem. PMID:20625441

  17. [Echocardiographic evaluation of ischemic cardiopathy].

    PubMed

    Asin Cardiel, E; Yuste, P; Señor, J; Palma, J; Martínez-Bordiu, C

    1976-01-01

    We studied a group of patients with ischemic heart disease divided into two groups: Group I coronary insufficiency. Group II myocardial infaction. We centered the work on the following aspects: analysis of the contractility; evaluation of the movement of the ventricular wall and of the septum; movement of the mitral valve; diagnosis of ventricular dyskinesias, akinesias, and hypokinesias. The patients in group I did not show significant alterations in the values of the ejection fraction and speed of circunferential shortening. The mean values of these parimeters are significantly less than the group of patients with infarcts, and 41% of these patients have EF less than 50% and Vcf less than 0.9. We did not find a correlation between these perimeters and the localization of the infarct. The velocity of the posterior ventricular wall was disminished in both groups of patients. The amplitude of movement of the posterior wall was reduced in the group of patients with infarctions. These parimeters were more altered in the posterior infarcts than in those with anterior localization and they are more an index of the state of the posterior wall than of the ventricular contractility considered overall, contary to mitral descriptions. In 3 cases of acute infarct we found paradoxical movement of the septum, which normalized itself in one patient in 6 months. In 6 other patients with old infarct we observed localized dyskinesias of the septum and of the free wall of the left ventricle. The mitral valve appears altered in a great proportion of coronary patients the most notorious characteristics being: a decrease in the EF pendent; an increase of the F index. These findings are considered in relation with the ventricular pressures and with the degree of distensibility of the left ventricle.

  18. I.P. Pavlov as a youth.

    PubMed

    Windholz, G

    1991-01-01

    Ivan P. Pavlov's youthful relations with parents and siblings, formal education, and social activities in Riazan' are described. The Pavlovs, a highly achievement-oriented family descending from a lowly serf, improved their social status by serving the Russian Orthodox Church. Pavlov, the son of a priest, studied in the 1860s at the Riazan' Ecclesiastic Seminary for priesthood. The turbulent 1860s' decade was a period of social and political reforms. Western ideas and science were introduced to Russia. The ambitious and idealistic I.P. Pavlov was influenced by popular essays written by the journalist D.I. Pisarev, the works of the German physiologist J. Moleschott, the English writer G.H. Lewes, the German zoologist C. Vogt and the physiologist M.I. Sechenov. Losing his religious faith, Pavlov abandoned the traditional goal of becoming a priest, and, convinced that science was a road to truth and progress, left Riazan' to study natural science at the University of St. Petersburg.

  19. I.P. Pavlov as a youth.

    PubMed

    Windholz, G

    1991-01-01

    Ivan P. Pavlov's youthful relations with parents and siblings, formal education, and social activities in Riazan' are described. The Pavlovs, a highly achievement-oriented family descending from a lowly serf, improved their social status by serving the Russian Orthodox Church. Pavlov, the son of a priest, studied in the 1860s at the Riazan' Ecclesiastic Seminary for priesthood. The turbulent 1860s' decade was a period of social and political reforms. Western ideas and science were introduced to Russia. The ambitious and idealistic I.P. Pavlov was influenced by popular essays written by the journalist D.I. Pisarev, the works of the German physiologist J. Moleschott, the English writer G.H. Lewes, the German zoologist C. Vogt and the physiologist M.I. Sechenov. Losing his religious faith, Pavlov abandoned the traditional goal of becoming a priest, and, convinced that science was a road to truth and progress, left Riazan' to study natural science at the University of St. Petersburg. PMID:2054299

  20. Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function.

    PubMed

    Scherer, Paul C; Ding, Yan; Liu, Zhiqing; Xu, Jing; Mao, Haibin; Barrow, James C; Wei, Ning; Zheng, Ning; Snyder, Solomon H; Rao, Feng

    2016-03-29

    The family of cullin-RING E3 Ligases (CRLs) and the constitutive photomorphogenesis 9 (COP9) signalosome (CSN) form dynamic complexes that mediate ubiquitylation of 20% of the proteome, yet regulation of their assembly/disassembly remains poorly understood. Inositol polyphosphates are highly conserved signaling molecules implicated in diverse cellular processes. We now report that inositol hexakisphosphate (IP6) is a major physiologic determinant of the CRL-CSN interface, which includes a hitherto unidentified electrostatic interaction between the N-terminal acidic tail of CSN subunit 2 (CSN2) and a conserved basic canyon on cullins. IP6, with an EC50 of 20 nM, acts as an intermolecular "glue," increasing cullin-CSN2 binding affinity by 30-fold, thereby promoting assembly of the inactive CRL-CSN complexes. The IP6 synthase, Ins(1,3,4,5,6)P5 2-kinase (IPPK/IP5K) binds to cullins. Depleting IP5K increases the percentage of neddylated, active Cul1 and Cul4A, and decreases levels of the Cul1/4A substrates p27 and p21. Besides dysregulating CRL-mediated cell proliferation and UV-induced apoptosis, IP5K depletion potentiates by 28-fold the cytotoxic effect of the neddylation inhibitor MLN4924. Thus, IP5K and IP6 are evolutionarily conserved components of the CRL-CSN system and are potential targets for cancer therapy in conjunction with MLN4924. PMID:26976604

  1. A highly efficient and effective motif discovery method for ChIP-seq/ChIP-chip data using positional information

    PubMed Central

    Ma, Xiaotu; Kulkarni, Ashwinikumar; Zhang, Zhihua; Xuan, Zhenyu; Serfling, Robert; Zhang, Michael Q.

    2012-01-01

    Identification of DNA motifs from ChIP-seq/ChIP-chip [chromatin immunoprecipitation (ChIP)] data is a powerful method for understanding the transcriptional regulatory network. However, most established methods are designed for small sample sizes and are inefficient for ChIP data. Here we propose a new k-mer occurrence model to reflect the fact that functional DNA k-mers often cluster around ChIP peak summits. With this model, we introduced a new measure to discover functional k-mers. Using simulation, we demonstrated that our method is more robust against noises in ChIP data than available methods. A novel word clustering method is also implemented to group similar k-mers into position weight matrices (PWMs). Our method was applied to a diverse set of ChIP experiments to demonstrate its high sensitivity and specificity. Importantly, our method is much faster than several other methods for large sample sizes. Thus, we have developed an efficient and effective motif discovery method for ChIP experiments. PMID:22228832

  2. Cardiac magnetic resonance determinants of functional mitral regurgitation in ischemic and non ischemic left ventricular dysfunction.

    PubMed

    Fernández-Golfín, Covadonga; De Agustin, Alberto; Manzano, M Carmen; Bustos, Ana; Sánchez, Tibisay; Pérez de Isla, Leopoldo; Fuentes, Manuel; Macaya, Carlos; Zamorano, José

    2011-04-01

    Functional mitral regurgitation (FMR) is frequent in left ventricular (LV) dilatation/dysfunction. Echocardiographic predictors of FMR are known. However, cardiac magnetic resonance (CMR) predictors of FMR have not been fully addressed. The aim of the study was to evaluate CMR mitral valve (MV) parameters associated with FMR in ischemic and non ischemic LV dysfunction. 80 patients with LV ejection fraction below 45% and/or left ventricular dilatation of ischemic and non ischemic etiology were included. Cine-MR images (steady state free-precession) were acquired in a short-axis and 4 chambers views where MV evaluation was performed. Delayed enhancement was performed as well. Significant FMR was established as more than mild MR according to the echocardiographic report. Mean age was 59 years, males 79%. FMR was detected in 20 patients (25%) Significant differences were noted in LV functional parameters and in most MV parameters according to the presence of significant FMR. However, differences were noted between ischemic and non ischemic groups. In the first, differences in most MV parameters remained significant while in the non ischemic, only systolic and diastolic interpapillary muscle distance (1.60 vs. 2.19 cm, P = 0.001; 2. 51 vs. 3.04, P = 0.008) were predictors of FMR. FMR is associated with a more severe LV dilatation/dysfunction in the overall population. CMR MV parameters are associated with the presence of significant FMR and are different between ischemic and non ischemic patients. CMR evaluation of these patients may help in risk stratification as well as in surgical candidate selection.

  3. Spectroscopic Monitoring of Kidney Tissue Ischemic Injury

    SciTech Connect

    Demos, S G; Fitzgerald, J T; Michalopoulou, A P; Troppmann, C

    2004-03-11

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  4. Resilience in Patients with Ischemic Heart Disease

    PubMed Central

    de Lemos, Conceição Maria Martins; Moraes, David William; Pellanda, Lucia Campos

    2016-01-01

    Background Resilience is a psychosocial factor associated with clinical outcomes in chronic diseases. The relationship between this protective factor and certain diseases, such heart diseases, is still under-explored. Objective The present study sought to investigate the frequency of resilience in individuals with ischemic heart disease. Method This was a cross-sectional study with 133 patients of both genders, aged between 35 and 65 years, treated at Rio Grande do Sul Cardiology Institute - Cardiology University Foundation, with a diagnosis of ischemic heart disease during the study period. Sixty-seven patients had a history of acute myocardial infarction. The individuals were interviewed and evaluated by the Wagnild & Young resilience scale and a sociodemographic questionnaire. Results Eighty-one percent of patients were classified as resilient according to the scale. Conclusion In the sample studied, resilience was identified in high proportion among patients with ischemic heart disease. PMID:26815312

  5. Cerebrovascular arteriopathy (arteriosclerosis) and ischemic childhood stroke.

    PubMed

    Daniels, S R; Bates, S; Lukin, R R; Benton, C; Third, J; Glueck, C J

    1982-01-01

    The aim of this report is to describe the intracranial cerebrovascular abnormalities and clinical status of 8 children who had familial lipoprotein disorders and evidence of thromboembolic cerebrovascular disease. Six of the 8 children had low levels of plasma high density lipoprotein cholesterol, two had high triglyceride levels, and all came from kindreds characterized by familial lipoprotein abnormalities and premature cardio- and/or cerebrovascular atherosclerosis. Vascular occlusion, irregularities of the arterial lumen, beading, tortuosity, and evidence of collateralization were consistently noted. We speculate that cerebrovascular arteriosclerosis in pediatric ischemic stroke victims who have familial lipoprotein abnormalities may be related to lipoprotein-mediated endothelial damage and thrombosis formation, or to the failure to restore endothelial cells' integrity following damage. The apparent association of lipoproteins and strokes in children and their families merits further exploration, particularly when assessing cerebral angiograms in pediatric ischemic stroke victims. In children with unexplained ischemic cerebrovascular accidents, the diagnostic possibility of occlusive arteriosclerosis with thrombosis must be entertained.

  6. [Vascular brain lesions and ischemic heart disease].

    PubMed

    Levin, G Z

    1979-01-01

    The role of essential hypertension in the pathogenesis of cerebral vessel disorders (not only hemorrhagic, but also ischemic) is greater than in the pathogenesis of the heart ischemic disease. An analysis of the evidences left by ancient doctors, when compared with statistical data of our time, gives one grounds to believe that cerebral hemorrhages have been a rather common disease, at least, since the time of the antique civilization of Greece and Rome, whereas ischemic heart disease has become a widespread disease among the population of the developed countries only in our time. This makes it possible to assume that the role of essential hypertension and that of atherosclerosis are not equal in the "diseases of civilization", if the diseases of today's developed society are meant.

  7. The association of migraine with ischemic stroke.

    PubMed

    Kurth, Tobias

    2010-03-01

    Migraine is a common, chronic-intermittent primary headache disorder affecting mostly women. The migraine pathophysiology involves both the neuronal and vascular systems, and in some patients, transient neurologic symptoms occur, which are known as migraine aura. A large body of literature supports an association between migraine and ischemic stroke, which is apparent mostly in young women with migraine with aura. Further increased risks have been observed particularly in smokers and women who use oral contraceptives. The vast majority of individual studies, as well as a recent meta-analysis, did not find an association between migraine without aura and ischemic stroke. Although there are several hypotheses about potential biological mechanisms linking migraine with aura to ischemic stroke, the precise causes remain unclear. Because the absolute risk of stroke is considerably low in patients with migraine, the vast majority of migraine patients will not experience a stroke event because of the migraine.

  8. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  9. 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.

  10. Forced Exercise Preconditioning Attenuates Experimental Autoimmune Neuritis by Altering Th1 Lymphocyte Composition and Egress

    PubMed Central

    Calik, Michael W.; Shankarappa, Sahadev A.; Langert, Kelly A.; Stubbs, Evan B.

    2015-01-01

    A short-term exposure to moderately intense physical exercise affords a novel measure of protection against autoimmune-mediated peripheral nerve injury. Here, we investigated the mechanism by which forced exercise attenuates the development and progression of experimental autoimmune neuritis (EAN), an established animal model of Guillain–Barré syndrome. Adult male Lewis rats remained sedentary (control) or were preconditioned with forced exercise (1.2 km/day × 3 weeks) prior to P2-antigen induction of EAN. Sedentary rats developed a monophasic course of EAN beginning on postimmunization day 12.3 ± 0.2 and reaching peak severity on day 17.0 ± 0.3 (N = 12). By comparison, forced-exercise preconditioned rats exhibited a similar monophasic course but with significant (p < .05) reduction of disease severity. Analysis of popliteal lymph nodes revealed a protective effect of exercise preconditioning on leukocyte composition and egress. Compared with sedentary controls, forced exercise preconditioning promoted a sustained twofold retention of P2-antigen responsive leukocytes. The percentage distribution of pro-inflammatory (Th1) lymphocytes retained in the nodes from sedentary EAN rats (5.1 ± 0.9%) was significantly greater than that present in nodes from forced-exercise preconditioned EAN rats (2.9 ± 0.6%) or from adjuvant controls (2.0 ± 0.3%). In contrast, the percentage of anti-inflammatory (Th2) lymphocytes (7–10%) and that of cytotoxic T lymphocytes (∼20%) remained unaltered by forced exercise preconditioning. These data do not support an exercise-inducible shift in Th1:Th2 cell bias. Rather, preconditioning with forced exercise elicits a sustained attenuation of EAN severity, in part, by altering the composition and egress of autoreactive proinflammatory (Th1) lymphocytes from draining lymph nodes. PMID:26186926

  11. Meclizine Preconditioning Protects the Kidney Against Ischemia-Reperfusion Injury.

    PubMed

    Kishi, Seiji; Campanholle, Gabriela; Gohil, Vishal M; Perocchi, Fabiana; Brooks, Craig R; Morizane, Ryuji; Sabbisetti, Venkata; Ichimura, Takaharu; Mootha, Vamsi K; Bonventre, Joseph V

    2015-09-01

    Global or local ischemia contributes to the pathogenesis of acute kidney injury (AKI). Currently there are no specific therapies to prevent AKI. Potentiation of glycolytic metabolism and attenuation of mitochondrial respiration may decrease cell injury and reduce reactive oxygen species generation from the mitochondria. Meclizine, an over-the-counter anti-nausea and -dizziness drug, was identified in a 'nutrient-sensitized' chemical screen. Pretreatment with 100 mg/kg of meclizine, 17 h prior to ischemia protected mice from IRI. Serum creatinine levels at 24 h after IRI were 0.13 ± 0.06 mg/dl (sham, n = 3), 1.59 ± 0.10 mg/dl (vehicle, n = 8) and 0.89 ± 0.11 mg/dl (meclizine, n = 8). Kidney injury was significantly decreased in meclizine treated mice compared with vehicle group (p < 0.001). Protection was also seen when meclizine was administered 24 h prior to ischemia. Meclizine reduced inflammation, mitochondrial oxygen consumption, oxidative stress, mitochondrial fragmentation, and tubular injury. Meclizine preconditioned kidney tubular epithelial cells, exposed to blockade of glycolytic and oxidative metabolism with 2-deoxyglucose and NaCN, had reduced LDH and cytochrome c release. Meclizine upregulated glycolysis in glucose-containing media and reduced cellular ATP levels in galactose-containing media. Meclizine inhibited the Kennedy pathway and caused rapid accumulation of phosphoethanolamine. Phosphoethanolamine recapitulated meclizine-induced protection both in vitro and in vivo. PMID:26501107

  12. Glaciations in response to climate variations preconditioned by evolving topography.

    PubMed

    Pedersen, Vivi Kathrine; Egholm, David Lundbek

    2013-01-10

    Landscapes modified by glacial erosion show a distinct distribution of surface area with elevation (hypsometry). In particular, the height of these regions is influenced by climatic gradients controlling the altitude where glacial and periglacial processes are the most active, and as a result, surface area is focused just below the snowline altitude. Yet the effect of this distinct glacial hypsometric signature on glacial extent and therefore on continued glacial erosion has not previously been examined. Here we show how this topographic configuration influences the climatic sensitivity of Alpine glaciers, and how the development of a glacial hypsometric distribution influences the intensity of glaciations on timescales of more than a few glacial cycles. We find that the relationship between variations in climate and the resulting variation in areal extent of glaciation changes drastically with the degree of glacial modification in the landscape. First, in landscapes with novel glaciations, a nearly linear relationship between climate and glacial area exists. Second, in previously glaciated landscapes with extensive area at a similar elevation, highly nonlinear and rapid glacial expansions occur with minimal climate forcing, once the snowline reaches the hypsometric maximum. Our results also show that erosion associated with glaciations before the mid-Pleistocene transition at around 950,000 years ago probably preconditioned the landscape--producing glacial landforms and hypsometric maxima--such that ongoing cooling led to a significant change in glacial extent and erosion, resulting in more extensive glaciations and valley deepening in the late Pleistocene epoch. We thus provide a mechanism that explains previous observations from exposure dating and low-temperature thermochronology in the European Alps, and suggest that there is a strong topographic control on the most recent Quaternary period glaciations.

  13. Analysis and modeling of neural processes underlying sensory preconditioning.

    PubMed

    Matsumoto, Yukihisa; Hirashima, Daisuke; Mizunami, Makoto

    2013-03-01

    Sensory preconditioning (SPC) is a procedure to demonstrate learning to associate between relatively neutral sensory stimuli in the absence of an external reinforcing stimulus, the underlying neural mechanisms of which have remained obscure. We address basic questions about neural processes underlying SPC, including whether neurons that mediate reward or punishment signals in reinforcement learning participate in association between neutral sensory stimuli. In crickets, we have suggested that octopaminergic (OA-ergic) or dopaminergic (DA-ergic) neurons participate in memory acquisition and retrieval in appetitive or aversive conditioning, respectively. Crickets that had been trained to associate an odor (CS2) with a visual pattern (CS1) (phase 1) and then to associate CS1 with water reward or quinine punishment (phase 2) exhibited a significantly increased or decreased preference for CS2 that had never been paired with the US, demonstrating successful SPC. Injection of an OA or DA receptor antagonist at different phases of the SPC training and testing showed that OA-ergic or DA-ergic neurons do not participate in learning of CS2-CS1 association in phase 1, but that OA-ergic neurons participate in learning in phase 2 and memory retrieval after appetitive SPC training. We also obtained evidence suggesting that association between CS2 and US, which should underlie conditioned response of crickets to CS2, is formed in phase 2, contrary to the standard theory of SPC assuming that it occurs in the final test. We propose models of SPC to account for these findings, by extending our model of classical conditioning.

  14. Analysis and modeling of neural processes underlying sensory preconditioning.

    PubMed

    Matsumoto, Yukihisa; Hirashima, Daisuke; Mizunami, Makoto

    2013-03-01

    Sensory preconditioning (SPC) is a procedure to demonstrate learning to associate between relatively neutral sensory stimuli in the absence of an external reinforcing stimulus, the underlying neural mechanisms of which have remained obscure. We address basic questions about neural processes underlying SPC, including whether neurons that mediate reward or punishment signals in reinforcement learning participate in association between neutral sensory stimuli. In crickets, we have suggested that octopaminergic (OA-ergic) or dopaminergic (DA-ergic) neurons participate in memory acquisition and retrieval in appetitive or aversive conditioning, respectively. Crickets that had been trained to associate an odor (CS2) with a visual pattern (CS1) (phase 1) and then to associate CS1 with water reward or quinine punishment (phase 2) exhibited a significantly increased or decreased preference for CS2 that had never been paired with the US, demonstrating successful SPC. Injection of an OA or DA receptor antagonist at different phases of the SPC training and testing showed that OA-ergic or DA-ergic neurons do not participate in learning of CS2-CS1 association in phase 1, but that OA-ergic neurons participate in learning in phase 2 and memory retrieval after appetitive SPC training. We also obtained evidence suggesting that association between CS2 and US, which should underlie conditioned response of crickets to CS2, is formed in phase 2, contrary to the standard theory of SPC assuming that it occurs in the final test. We propose models of SPC to account for these findings, by extending our model of classical conditioning. PMID:23380289

  15. Meclizine Preconditioning Protects the Kidney Against Ischemia–Reperfusion Injury

    PubMed Central

    Kishi, Seiji; Campanholle, Gabriela; Gohil, Vishal M.; Perocchi, Fabiana; Brooks, Craig R.; Morizane, Ryuji; Sabbisetti, Venkata; Ichimura, Takaharu; Mootha, Vamsi K.; Bonventre, Joseph V.

    2015-01-01

    Global or local ischemia contributes to the pathogenesis of acute kidney injury (AKI). Currently there are no specific therapies to prevent AKI. Potentiation of glycolytic metabolism and attenuation of mitochondrial respiration may decrease cell injury and reduce reactive oxygen species generation from the mitochondria. Meclizine, an over-the-counter anti-nausea and -dizziness drug, was identified in a ‘nutrient-sensitized’ chemical screen. Pretreatment with 100 mg/kg of meclizine, 17 h prior to ischemia protected mice from IRI. Serum creatinine levels at 24 h after IRI were 0.13 ± 0.06 mg/dl (sham, n = 3), 1.59 ± 0.10 mg/dl (vehicle, n = 8) and 0.89 ± 0.11 mg/dl (meclizine, n = 8). Kidney injury was significantly decreased in meclizine treated mice compared with vehicle group (p < 0.001). Protection was also seen when meclizine was administered 24 h prior to ischemia. Meclizine reduced inflammation, mitochondrial oxygen consumption, oxidative stress, mitochondrial fragmentation, and tubular injury. Meclizine preconditioned kidney tubular epithelial cells, exposed to blockade of glycolytic and oxidative metabolism with 2-deoxyglucose and NaCN, had reduced LDH and cytochrome c release. Meclizine upregulated glycolysis in glucose-containing media and reduced cellular ATP levels in galactose-containing media. Meclizine inhibited the Kennedy pathway and caused rapid accumulation of phosphoethanolamine. Phosphoethanolamine recapitulated meclizine-induced protection both in vitro and in vivo. PMID:26501107

  16. Meclizine Preconditioning Protects the Kidney Against Ischemia-Reperfusion Injury.

    PubMed

    Kishi, Seiji; Campanholle, Gabriela; Gohil, Vishal M; Perocchi, Fabiana; Brooks, Craig R; Morizane, Ryuji; Sabbisetti, Venkata; Ichimura, Takaharu; Mootha, Vamsi K; Bonventre, Joseph V

    2015-09-01

    Global or local ischemia contributes to the pathogenesis of acute kidney injury (AKI). Currently there are no specific therapies to prevent AKI. Potentiation of glycolytic metabolism and attenuation of mitochondrial respiration may decrease cell injury and reduce reactive oxygen species generation from the mitochondria. Meclizine, an over-the-counter anti-nausea and -dizziness drug, was identified in a 'nutrient-sensitized' chemical screen. Pretreatment with 100 mg/kg of meclizine, 17 h prior to ischemia protected mice from IRI. Serum creatinine levels at 24 h after IRI were 0.13 ± 0.06 mg/dl (sham, n = 3), 1.59 ± 0.10 mg/dl (vehicle, n = 8) and 0.89 ± 0.11 mg/dl (meclizine, n = 8). Kidney injury was significantly decreased in meclizine treated mice compared with vehicle group (p < 0.001). Protection was also seen when meclizine was administered 24 h prior to ischemia. Meclizine reduced inflammation, mitochondrial oxygen consumption, oxidative stress, mitochondrial fragmentation, and tubular injury. Meclizine preconditioned kidney tubular epithelial cells, exposed to blockade of glycolytic and oxidative metabolism with 2-deoxyglucose and NaCN, had reduced LDH and cytochrome c release. Meclizine upregulated glycolysis in glucose-containing media and reduced cellular ATP levels in galactose-containing media. Meclizine inhibited the Kennedy pathway and caused rapid accumulation of phosphoethanolamine. Phosphoethanolamine recapitulated meclizine-induced protection both in vitro and in vivo.

  17. Glaciations in response to climate variations preconditioned by evolving topography.

    PubMed

    Pedersen, Vivi Kathrine; Egholm, David Lundbek

    2013-01-10

    Landscapes modified by glacial erosion show a distinct distribution of surface area with elevation (hypsometry). In particular, the height of these regions is influenced by climatic gradients controlling the altitude where glacial and periglacial processes are the most active, and as a result, surface area is focused just below the snowline altitude. Yet the effect of this distinct glacial hypsometric signature on glacial extent and therefore on continued glacial erosion has not previously been examined. Here we show how this topographic configuration influences the climatic sensitivity of Alpine glaciers, and how the development of a glacial hypsometric distribution influences the intensity of glaciations on timescales of more than a few glacial cycles. We find that the relationship between variations in climate and the resulting variation in areal extent of glaciation changes drastically with the degree of glacial modification in the landscape. First, in landscapes with novel glaciations, a nearly linear relationship between climate and glacial area exists. Second, in previously glaciated landscapes with extensive area at a similar elevation, highly nonlinear and rapid glacial expansions occur with minimal climate forcing, once the snowline reaches the hypsometric maximum. Our results also show that erosion associated with glaciations before the mid-Pleistocene transition at around 950,000 years ago probably preconditioned the landscape--producing glacial landforms and hypsometric maxima--such that ongoing cooling led to a significant change in glacial extent and erosion, resulting in more extensive glaciations and valley deepening in the late Pleistocene epoch. We thus provide a mechanism that explains previous observations from exposure dating and low-temperature thermochronology in the European Alps, and suggest that there is a strong topographic control on the most recent Quaternary period glaciations. PMID:23302860

  18. Human amniotic fluid stem cell preconditioning improves their regenerative potential.

    PubMed

    Rota, Cinzia; Imberti, Barbara; Pozzobon, Michela; Piccoli, Martina; De Coppi, Paolo; Atala, Anthony; Gagliardini, Elena; Xinaris, Christodoulos; Benedetti, Valentina; Fabricio, Aline S C; Squarcina, Elisa; Abbate, Mauro; Benigni, Ariela; Remuzzi, Giuseppe; Morigi, Marina

    2012-07-20

    Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell-derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line-derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning.

  19. Human Amniotic Fluid Stem Cell Preconditioning Improves Their Regenerative Potential

    PubMed Central

    Rota, Cinzia; Imberti, Barbara; Pozzobon, Michela; Piccoli, Martina; De Coppi, Paolo; Atala, Anthony; Gagliardini, Elena; Xinaris, Christodoulos; Benedetti, Valentina; Fabricio, Aline S.C.; Squarcina, Elisa; Abbate, Mauro; Benigni, Ariela; Remuzzi, Giuseppe

    2012-01-01

    Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell–derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line–derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning. PMID:22066606

  20. 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.

  1. Neural Stem Cells and Ischemic Brain

    PubMed Central

    Zhang, Zhenggang; Chopp, Michael

    2016-01-01

    Stroke activates neural stem cells in the ventricular-subventricular zone (V/SVZ) of the lateral ventricle, which increases neuroblasts and oligodendrocyte progenitor cells (OPCs). Within the ischemic brain, neural stem cells, neuroblasts and OPCs appear to actively communicate with cerebral endothelial cells and other brain parenchymal cells to mediate ischemic brain repair; however, stroke-induced neurogenesis unlikely plays any significant roles in neuronal replacement. In this mini-review, we will discuss recent findings how intercellular communications between stroke-induced neurogenesis and oligodendrogenesis and brain parenchymal cells could potentially facilitate brain repair processes. PMID:27488979

  2. Ischemic Gastropathic Ulcer Mimics Gastric Cancer

    PubMed Central

    Daher, Saleh; Lahav, Ziv; Rmeileh, Ayman Abu; Mizrahi, Meir

    2016-01-01

    Gastric ulcer due to mesenteric ischemia is a rare clinical finding. As a result, few reports of ischemic gastric ulcers have been reported in the literature. The diagnosis of ischemic gastropathy is seldom considered in patients presenting with abdominal pain and gastric ulcers. In this case report, we describe a patient with increasing abdominal pain, weight loss, and gastric ulcers, who underwent extensive medical evaluation and whose symptoms were resistant to medical interventions. Finally he was diagnosed with chronic mesenteric ischemia, and his clinical and endoscopic abnormalities resolved after surgical revascularization of both the superior mesenteric artery and the celiac trunk. PMID:27579191

  3. IP3 receptors regulate vascular smooth muscle contractility and hypertension

    PubMed Central

    Lin, Qingsong; Zhao, Guiling; Fang, Xi; Peng, Xiaohong; Tang, Huayuan; Wang, Hong; Jing, Ran; Liu, Jie; Ouyang, Kunfu

    2016-01-01

    Inositol 1, 4, 5-trisphosphate receptor–mediated (IP3R-mediated) calcium (Ca2+) release has been proposed to play an important role in regulating vascular smooth muscle cell (VSMC) contraction for decades. However, whether and how IP3R regulates blood pressure in vivo remains unclear. To address these questions, we have generated a smooth muscle–specific IP3R triple-knockout (smTKO) mouse model using a tamoxifen-inducible system. In this study, the role of IP3R-mediated Ca2+ release in adult VSMCs on aortic vascular contractility and blood pressure was assessed following tamoxifen induction. We demonstrated that deletion of IP3Rs significantly reduced aortic contractile responses to vasoconstrictors, including phenylephrine, U46619, serotonin, and endothelin 1. Deletion of IP3Rs also dramatically reduced the phosphorylation of MLC20 and MYPT1 induced by U46619. Furthermore, although the basal blood pressure of smTKO mice remained similar to that of wild-type controls, the increase in systolic blood pressure upon chronic infusion of angiotensin II was significantly attenuated in smTKO mice. Taken together, our results demonstrate an important role for IP3R-mediated Ca2+ release in VSMCs in regulating vascular contractility and hypertension. PMID:27777977

  4. Reviewing ChIPS, The Chandra Imaging and Plotting System

    NASA Astrophysics Data System (ADS)

    Miller, J.; Burke, D. J.; Evans, I. N.; Evans, J. D.; McLaughlin, W.

    2015-09-01

    The Chandra Imaging and Plotting System (ChIPS) is a 2D plotting system designed to allow users to easily create, manipulate, and produce publication quality visualizations. ChIPS has a simple but very powerful interactive interface that allows users to dynamically modify the contents and layout of their plots quickly and efficiently, with the results of any changes being immediately visible. ChIPS allows users to construct their plots fully interactively, and then save the final plot commands as a Python script. This bypasses the need to iteratively edit and rerun the script when developing the plot. Features such as undo and redo commands allow users to easily step backwards and forwards through previous commands, while the ability so save ChIPS sessions in a platform-independent state file allows the session to be restored at any time, even on another machine. Because ChIPS offers a Python interface, users can analyze their data using the broad array of modules offered in Python, and visualize the information in ChIPS at the same time. In this paper we explore the design decisions behind the development of ChIPS and some of the lessons learned along the way.

  5. A decentralized software bus based on IP multicas ting

    NASA Technical Reports Server (NTRS)

    Callahan, John R.; Montgomery, Todd

    1995-01-01

    We describe decentralized reconfigurable implementation of a conference management system based on the low-level Internet Protocol (IP) multicasting protocol. IP multicasting allows low-cost, world-wide, two-way transmission of data between large numbers of conferencing participants through the Multicasting Backbone (MBone). Each conference is structured as a software bus -- a messaging system that provides a run-time interconnection model that acts as a separate agent (i.e., the bus) for routing, queuing, and delivering messages between distributed programs. Unlike the client-server interconnection model, the software bus model provides a level of indirection that enhances the flexibility and reconfigurability of a distributed system. Current software bus implementations like POLYLITH, however, rely on a centralized bus process and point-to-point protocols (i.e., TCP/IP) to route, queue, and deliver messages. We implement a software bus called the MULTIBUS that relies on a separate process only for routing and uses a reliable IP multicasting protocol for delivery of messages. The use of multicasting means that interconnections are independent of IP machine addresses. This approach allows reconfiguration of bus participants during system execution without notifying other participants of new IP addresses. The use of IP multicasting also permits an economy of scale in the number of participants. We describe the MULITIBUS protocol elements and show how our implementation performs better than centralized bus implementations.

  6. MACE: model based analysis of ChIP-exo.

    PubMed

    Wang, Liguo; Chen, Junsheng; Wang, Chen; Uusküla-Reimand, Liis; Chen, Kaifu; Medina-Rivera, Alejandra; Young, Edwin J; Zimmermann, Michael T; Yan, Huihuang; Sun, Zhifu; Zhang, Yuji; Wu, Stephen T; Huang, Haojie; Wilson, Michael D; Kocher, Jean-Pierre A; Li, Wei

    2014-11-10

    Understanding the role of a given transcription factor (TF) in regulating gene expression requires precise mapping of its binding sites in the genome. Chromatin immunoprecipitation-exo, an emerging technique using λ exonuclease to digest TF unbound DNA after ChIP, is designed to reveal transcription factor binding site (TFBS) boundaries with near-single nucleotide resolution. Although ChIP-exo promises deeper insights into transcription regulation, no dedicated bioinformatics tool exists to leverage its advantages. Most ChIP-seq and ChIP-chip analytic methods are not tailored for ChIP-exo, and thus cannot take full advantage of high-resolution ChIP-exo data. Here we describe a novel analysis framework, termed MACE (model-based analysis of ChIP-exo) dedicated to ChIP-exo data analysis. The MACE workflow consists of four steps: (i) sequencing data normalization and bias correction; (ii) signal consolidation and noise reduction; (iii) single-nucleotide resolution border peak detection using the Chebyshev Inequality and (iv) border matching using the Gale-Shapley stable matching algorithm. When applied to published human CTCF, yeast Reb1 and our own mouse ONECUT1/HNF6 ChIP-exo data, MACE is able to define TFBSs with high sensitivity, specificity and spatial resolution, as evidenced by multiple criteria including motif enrichment, sequence conservation, direct sequence pileup, nucleosome positioning and open chromatin states. In addition, we show that the fundamental advance of MACE is the identification of two boundaries of a TFBS with high resolution, whereas other methods only report a single location of the same event. The two boundaries help elucidate the in vivo binding structure of a given TF, e.g. whether the TF may bind as dimers or in a complex with other co-factors.

  7. Preconditioning of Microglia by α-Synuclein Strongly Affects the Response Induced by Toll-like Receptor (TLR) Stimulation

    PubMed Central

    Gonzalez-Rey, Elena; Lachaud, Christian C.; Guilliams, Tim; Fernandez-Montesinos, Rafael; Benitez-Rondan, Alicia; Robledo, Gema; Hmadcha, Abdelkrim; Delgado, Mario; Dobson, Christopher M.; Pozo, David

    2013-01-01

    In recent years, it has become accepted that α-synuclein (αSyn) has a key role in the microglia-mediated neuroinflammation, which accompanies the development of Parkinson’s disease and other related disorders, such as Dementia with Lewy Bodies and Alzheimer’s disease. Nevertheless, the cellular and molecular mechanisms underlying its pathological actions, especially in the sporadic forms of the diseases, are not completely understood. Intriguingly, several epidemiological and animal model studies have revealed a link between certain microbial infections and the onset or progression of sporadic forms of these neurodegenerative disorders. In this work, we have characterized the effect of toll-like receptor (TLR) stimulation on primary murine microglial cultures and analysed the impact of priming cells with extracellular wild-type (Wt) αSyn on the subsequent TLR stimulation of cells with a set of TLR ligands. By assaying key interleukins and chemokines we report that specific stimuli, in particular Pam3Csk4 (Pam3) and single-stranded RNA40 (ssRNA), can differentially affect the TLR2/1- and TLR7-mediated responses of microglia when pre-conditioned with αSyn by augmenting IL-6, MCP-1/CCL2 or IP-10/CXCL10 secretion levels. Furthermore, we report a skewing of αSyn-primed microglia stimulated with ssRNA (TLR7) or Pam3 (TLR2/1) towards intermediate but at the same time differential, M1/M2 phenotypes. Finally, we show that the levels and intracellular location of activated caspase-3 protein change significantly in αSyn-primed microglia after stimulation with these particular TLR agonists. Overall, we report a remarkable impact of non-aggregated αSyn pre-sensitization of microglia on TLR-mediated immunity, a phenomenon that could contribute to triggering the onset of sporadic α-synuclein-related neuropathologies. PMID:24236103

  8. Application of Mobile-ip to Space and Aeronautical Networks

    NASA Technical Reports Server (NTRS)

    Leung, Kent; Shell, Dan; Ivancic, William D.; Stewart, David H.; Bell, Terry L.; Kachmar, Brian A.

    2001-01-01

    The National Aeronautics and Space Administration (NASA) is interested in applying mobile Internet protocol (mobile-ip) technologies to its space and aeronautics programs. In particular, mobile-ip will play a major role in the Advanced Aeronautic Transportation Technology (AAT-F), the Weather Information Communication (WINCOMM), and the Small Aircraft Transportation System (SATS) aeronautics programs. This paper describes mobile-ip and mobile routers--in particular, the features, capabilities, and initial performance of the mobile router are presented. The application of mobile-router technology to NASA's space and aeronautics programs is also discussed.

  9. Actuator development for the Instrument Pointing System (IPS)

    NASA Technical Reports Server (NTRS)

    Suttner, K.

    1984-01-01

    The mechanisms of the instrument pointing system (IPS) are described. Particular emphasis is placed on the actuators which are necessary for operating the IPS. The actuators are described as follows: (1) two linear actuators that clamp the gimbals down during ascent and descent; (2) two linear actuators that attach the payload to the IPS during the mission, and release it into the payload clamps; (3) one rotational actuator that opens and closes the payload clamps; and (4) three identical drive units that represent the three orthogonal gimbal axes and are the prime movers for pointing. Design features, manufacturing problems, test performance, and results are presented.

  10. Heliospheric Tomography from IPS Data at 140 MHz

    NASA Astrophysics Data System (ADS)

    Mejia-Ambriz, J. C.; Jackson, B. V.; Gonzalez-Esparza, A.; Buffington, A.

    2014-12-01

    Interplanetary scintillation (IPS) from radio telescopes provides data to study density and velocity evolution of the solar wind and heliospheric disturbances. A tomography program developed at the University of California, San Diego, makes 3D reconstructions and forecasts of the inner heliosphere dynamics from IPS results. For the first time we incorporate 140 MHz IPS results from the MEXican Array Radio Telescope (MEXART) into the tomography program. We show that MEXART data complement observations from other radio-systems located at different longitudes, thus providing more complete heliospheric coverage.

  11. Pharmacologic preconditioning with berberine attenuating ischemia-induced apoptosis and promoting autophagy in neuron.

    PubMed

    Zhang, Qichun; Bian, Huimin; Guo, Liwei; Zhu, Huaxu

    2016-01-01

    Pharmacologic preconditioning is an intriguing and emerging approach adopted to prevent injury of ischemia/reperfusion. Neuroprotection is the cardinal effect of these pleiotropic actions of berberine. Here we investigated that whether berberine could acts as a preconditioning stimuli contributing to attenuate hypoxia-induced neurons death as well. Male Sprague-Dawley rats of middle cerebral artery occlusion (MCAO) and rat primary cortical neurons undergoing oxygen and glucose deprivation (OGD) were preconditioned with berberine (40 mg/kg, for 24 h in vivo, and 10(-6) mol/L, for 2 h in vitro, respectively). The neurological deficits and cerebral water contents of MCAO rats were evaluated. The autophagy and apoptosis were further determined in primary neurons in vitro. Berberine preconditioning (BP) was then shown to ameliorate the neurological deficits, decrease cerebral water content and promote neurogenesis of MCAO rats. Decreased LDH release from OGD-treated neurons was observed via BP, which was blocked by LY294002 (20 µmol/L), GSK690693 (10 µmol/L), or YC-1 (25 µmol/L). Furthermore, BP stimulated autophagy and inhibited apoptosis via modulated the autophagy-associated proteins LC 3, Beclin-1 and p62, and apoptosis-modulating proteins caspase 3, caspase 8, caspase 9, PARP and BCL-2/Bax. In conclusion, berberine acts as a stimulus of preconditioning that exhibits neuroprotection via promoting autophagy and decreasing anoxia-induced apoptosis. PMID:27158406

  12. Gauss-Newton inspired preconditioned optimization in large deformation diffeomorphic metric mapping.

    PubMed

    Hernandez, Monica

    2014-10-21

    In this work, we propose a novel preconditioned optimization method in the paradigm of Large Deformation Diffeomorphic Metric Mapping (LDDMM). The preconditioned update scheme is formulated for the non-stationary and the stationary parameterizations of diffeomorphisms, yielding three different LDDMM methods. The preconditioning matrices are inspired in the Hessian approximation used in Gauss-Newton method. The derivatives are computed using Frechet differentials. Thus, optimization is performed in a Sobolev space, in contrast to optimization in L(2) commonly used in non-rigid registration literature. The proposed LDDMM methods have been evaluated and compared with their respective implementations of gradient descent optimization. Evaluation has been performed using real and simulated images from the Non-rigid Image Registration Evaluation Project (NIREP). The experiments conducted in this work reported that our preconditioned LDDMM methods achieved a performance similar or superior to well-established-in-literature gradient descent non-stationary LDDMM in the great majority of cases. Moreover, preconditioned optimization showed a substantial reduction in the execution time with an affordable increase of the memory usage per iteration. Additional experiments reported that optimization using Frechet differentials should be preferable to optimization using L(2) differentials.

  13. Pharmacologic preconditioning with berberine attenuating ischemia-induced apoptosis and promoting autophagy in neuron

    PubMed Central

    Zhang, Qichun; Bian, Huimin; Guo, Liwei; Zhu, Huaxu

    2016-01-01

    Pharmacologic preconditioning is an intriguing and emerging approach adopted to prevent injury of ischemia/reperfusion. Neuroprotection is the cardinal effect of these pleiotropic actions of berberine. Here we investigated that whether berberine could acts as a preconditioning stimuli contributing to attenuate hypoxia-induced neurons death as well. Male Sprague-Dawley rats of middle cerebral artery occlusion (MCAO) and rat primary cortical neurons undergoing oxygen and glucose deprivation (OGD) were preconditioned with berberine (40 mg/kg, for 24 h in vivo, and 10-6 mol/L, for 2 h in vitro, respectively). The neurological deficits and cerebral water contents of MCAO rats were evaluated. The autophagy and apoptosis were further determined in primary neurons in vitro. Berberine preconditioning (BP) was then shown to ameliorate the neurological deficits, decrease cerebral water content and promote neurogenesis of MCAO rats. Decreased LDH release from OGD-treated neurons was observed via BP, which was blocked by LY294002 (20 µmol/L), GSK690693 (10 µmol/L), or YC-1 (25 µmol/L). Furthermore, BP stimulated autophagy and inhibited apoptosis via modulated the autophagy-associated proteins LC 3, Beclin-1 and p62, and apoptosis-modulating proteins caspase 3, caspase 8, caspase 9, PARP and BCL-2/Bax. In conclusion, berberine acts as a stimulus of preconditioning that exhibits neuroprotection via promoting autophagy and decreasing anoxia-induced apoptosis. PMID:27158406

  14. Remote ischemic perconditioning attenuates ischemia/reperfusion-induced downregulation of AQP2 in rat kidney.

    PubMed

    Kristensen, Marie Louise V; Kierulf-Lassen, Casper; Nielsen, Per Mose; Krag, Søren; Birn, Henrik; Nejsum, Lene N; Nørregaard, Rikke

    2016-07-01

    Renal ischemia/reperfusion (I/R) can lead to impaired urine concentration ability and increased fractional excretion of sodium (FeNa). Local ischemic preconditioning improves renal water and sodium handling after I/R injury. Here, we investigate whether remote ischemic perconditioning (rIPeC) prevents dysregulation of renal water and salt handling in response to I/R injury and mechanisms that may be involved. Rats were subjected to right nephrectomy and randomized into a sham group or an I/R group. In the I/R group, rats were subjected to 37 min of renal ischemia and 3 days of reperfusion. rIPeC was applied to the abdominal aorta. Blood and urine were collected on day 3 postoperatively for clearance studies. The expression of aquaporins (AQPs) and the sodium transporter Na-K-ATPase were analyzed using immunoblotting and immunohistochemistry. I/R injury resulted in polyuria, increased FeNa, and decreased urine osmolality compared to sham rats. rIPeC attenuated the increase in FeNa and the decrease in urine osmolality. Expression of AQP1, AQP2, phosphorylated AQP2 (pAQP2), and Na-K-ATPase was downregulated in I/R rats. rIPeC attenuated the reductions in AQP2 and pAQP2 expression. Immunohistochemistry revealed decreased labeling of Na-K-ATPase in the outer medulla in I/R kidneys compared to kidneys from sham and I/R + rIPeC rats. After renal ischemia, the expression of Na-K-ATPase was substantially reduced in the outer medullary thick ascending limb. In conclusion, our data suggest that rIPeC might prevent dysregulation of renal water and salt handling via regulation of AQP2 expression and phosphorylation as well as via regulation of Na-K-ATPase expression in I/R rat kidneys. PMID:27405971

  15. An overview of antithrombotics in ischemic stroke.

    PubMed

    Schweickert, Patricia A; Gaughen, John R; Kreitel, Elizabeth M; Shephard, Timothy J; Solenski, Nina J; Jensen, Mary E

    2016-06-19

    The use of antithrombotic medications is an important component of ischemic stroke treatment and prevention. This article reviews the evidence for best practices for antithrombotic use in stroke with focused discussion on the specific agents used to treat and prevent stroke. PMID:27153001

  16. Gene Therapy For Ischemic Heart Disease

    PubMed Central

    Lavu, Madhav; Gundewar, Susheel; Lefer, David J.

    2010-01-01

    Current pharmacologic therapy for ischemic heart disease suffers multiple limitations such as compliance issues and side effects of medications. Revascularization procedures often end with need for repeat procedures. Patients remain symptomatic despite maximal medical therapy. Gene therapy offers an attractive alternative to current pharmacologic therapies and may be beneficial in refractory disease. Gene therapy with isoforms of growth factors such as VEGF, FGF and HGF induces angiogenesis, decreases apoptosis and leads to protection in the ischemic heart. Stem cell therapy augmented with gene therapy used for myogenesis has proven to be beneficial in numerous animal models of myocardial ischemia. Gene therapy coding for antioxidants, eNOS, HSP, mitogen-activated protein kinase and numerous other anti apoptotic proteins have demonstrated significant cardioprotection in animal models. Clinical trials have demonstrated safety in humans apart from symptomatic and objective improvements in cardiac function. Current research efforts are aimed at refining various gene transfection techniques and regulation of gene expression in vivo in the heart and circulation to improve clinical outcomes in patients that suffer from ischemic heart disease. In this review article we will attempt to summarize the current state of both preclinical and clinical studies of gene therapy to combat myocardial ischemic disease. PMID:20600100

  17. Systemic corticosteroids in nonarteritic ischemic optic neuropathy

    PubMed Central

    Al-Zubidi, Nagham; Zhang, Jason; Spitze, Arielle; Lee, Andrew G

    2014-01-01

    Nonarteritic ischemic optic neuropathy (NAION) is one of the most prevalent optic nerve disorders seen in ophthalmic practice. The role of corticosteroid therapy in NAION remains a highly controversial area of debate in ophthalmology. This brief review will provide an overview of the current clinical evidence on this topic as well as some comment on the medical debate. PMID:25449939

  18. Preconditioning with Associated Blocking of Ca2+ Inflow Alleviates Hypoxia-Induced Damage to Pancreatic β-Cells

    PubMed Central

    Ma, Zuheng; Moruzzi, Noah; Catrina, Sergiu-Bogdan; Hals, Ingrid; Oberholzer, José

    2013-01-01

    Objective Beta cells of pancreatic islets are susceptible to functional deficits and damage by hypoxia. Here we aimed to characterize such effects and to test for and pharmacological means to alleviate a negative impact of hypoxia. Methods and Design Rat and human pancreatic islets were subjected to 5.5 h of hypoxia after which functional and viability parameters were measured subsequent to the hypoxic period and/or following a 22 h re-oxygenation period. Preconditioning with diazoxide or other agents was usually done during a 22 h period prior to hypoxia. Results Insulin contents decreased by 23% after 5.5 h of hypoxia and by 61% after a re-oxygenation period. Preconditioning with diazoxide time-dependently alleviated these hypoxia effects in rat and human islets. Hypoxia reduced proinsulin biosynthesis (3H-leucine incorporation into proinsulin) by 35%. Preconditioning counteracted this decrease by 91%. Preconditioning reduced hypoxia-induced necrosis by 40%, attenuated lowering of proteins of mitochondrial complexes I–IV and enhanced stimulation of HIF-1-alpha and phosphorylated AMPK proteins. Preconditioning by diazoxide was abolished by co-exposure to tolbutamide or elevated potassium (i.e. conditions which increase Ca2+ inflow). Preconditioning with nifedipine, a calcium channel blocker, partly reproduced effects of diazoxide. Both diazoxide and nifedipine moderately reduced basal glucose oxidation whereas glucose-induced oxygen consumption (tested with diazoxide) was unaffected. Preconditioning with diaxoxide enhanced insulin contents in transplants of rat islets to non-diabetic rats and lowered hyperglycemia vs. non-preconditioned islets in streptozotocin-diabetic rats. Preconditioning of human islet transplants lowered hyperglycemia in streptozotocin-diabetic nude mice. Conclusions 1) Prior blocking of Ca2+ inflow associates with lesser hypoxia-induced damage, 2) preconditioning affects basal mitochondrial metabolism and accelerates activation of hypoxia

  19. Research on the Changes to the Lipid/Polymer Membrane Used in the Acidic Bitterness Sensor Caused by Preconditioning.

    PubMed

    Harada, Yuhei; Noda, Junpei; Yatabe, Rui; Ikezaki, Hidekazu; Toko, Kiyoshi

    2016-01-01

    A taste sensor that uses lipid/polymer membranes can evaluate aftertastes felt by humans using Change in membrane Potential caused by Adsorption (CPA) measurements. The sensor membrane for evaluating bitterness, which is caused by acidic bitter substances such as iso-alpha acid contained in beer, needs an immersion process in monosodium glutamate (MSG) solution, called "MSG preconditioning". However, what happens to the lipid/polymer membrane during MSG preconditioning is not clear. Therefore, we carried out three experiments to investigate the changes in the lipid/polymer membrane caused by the MSG preconditioning, i.e., measurements of the taste sensor, measurements of the amount of the bitterness substance adsorbed onto the membrane and measurements of the contact angle of the membrane surface. The CPA values increased as the preconditioning process progressed, and became stable after 3 d of preconditioning. The response potentials to the reference solution showed the same tendency of the CPA value change during the preconditioning period. The contact angle of the lipid/polymer membrane surface decreased after 7 d of MSG preconditioning; in short, the surface of the lipid/polymer membrane became hydrophilic during MSG preconditioning. The amount of adsorbed iso-alpha acid was increased until 5 d preconditioning, and then it decreased. In this study, we revealed that the CPA values increased with the progress of MSG preconditioning in spite of the decrease of the amount of iso-alpha acid adsorbed onto the lipid/polymer membrane, and it was indicated that the CPA values increase because the sensor sensitivity was improved by the MSG preconditioning. PMID:26891299

  20. IPS Classic. Science, art and nature: a case report.

    PubMed

    Culp, L; Roach, R R

    1995-01-01

    The ceramo-metal restoration still forms the backbone of modern restorative dentistry, despite many new systems. This article discusses a unique ceramo-metal system, its advantages, and clinical and technical applications; teamwork between the dentist and the technician is emphasized. IPS Classic (Ivoclar Williams) is a ceramic system with several exclusive features. It encompasses Color Visions, a computer-generated shade system, and the IPS Impulse modifier system allows the ceramist unlimited creativity in color development.

  1. Design and implementation of an integrated IP telephone gateway

    NASA Astrophysics Data System (ADS)

    Huang, Yongfeng; Feng, Dan; Zhang, Jiangling

    1999-08-01

    A new idea of design on an Integrated IP Telephone Gateway is stated in this paper. Some key techniques are analyzed and discussed in detail. A Centered Echo Chancellor based on TMS320C6201 DSP is implemented, and many optimization methods for voice compression code are concluded to enhance the performance of the gateway. Finally, the performance parameters of the Integrated IP Telephony Gateway are summarized in this paper.

  2. A simulation of the IPS variations from a magnetohydrodynamical simulation

    NASA Technical Reports Server (NTRS)

    Tappin, S. J.; Dryer, M.; Han, S. M.; Wu, S. T.

    1987-01-01

    Calculations of the variations of interplanetary scintillation (IPS) from a disturbance simulated by a 3-D magnetohydrodynamical (MHD) model of the solar wind are presented. The simulated maps are compared with observations and it is found that the MHD model reproduces the qualitative features of observed disturbances. The disturbance produced by the MHD simulation is found to correspond in strength with the weakest disturbance which can be reliably detected by existing single station IPS observations.

  3. Reprogramming therapeutics: iPS cell prospects for neurodegenerative disease.

    PubMed

    Abeliovich, Asa; Doege, Claudia A

    2009-02-12

    The recent description of somatic cell reprogramming to an embryonic stem (ES) cell-like phenotype, termed induced pluripotent stem (iPS) cell technology, presents an exciting potential venue toward cell-based therapeutics and disease models for neurodegenerative disorders. Two recent studies (Dimos et al. and Ebert et al.) describe the initial characterization of neurodegenerative disease patient-derived iPS cell cultures as proof of concept for the utility of this technology.

  4. Cerebrospinal fluid may mediate CNS ischemic injury

    PubMed Central

    Wang, Yanming F; Gwathmey, Judith K; Zhang, Guorong; Soriano, Sulpicio G; He, Shunli; Wang, Yanguang

    2005-01-01

    Background The central nervous system (CNS) is extremely vulnerable to ischemic injury. The details underlying this susceptibility are not completely understood. Since the CNS is surrounded by cerebrospinal fluid (CSF) that contains a low concentration of plasma protein, we examined the effect of changing the CSF in the evolution of CNS injury during ischemic insult. Methods Lumbar spinal cord ischemia was induced in rabbits by cross-clamping the descending abdominal aorta for 1 h, 2 h or 3 h followed by 7 d of reperfusion. Prior to ischemia, rabbits were subjected to the following procedures; 1) CSF depletion, 2) CSF replenishment at 0 mmHg intracranial pressure (ICP), and 3) replacement of CSF with 8% albumin- or 1% gelatin-modified artificial CSF, respectively. Motor function of the hind limbs and histopathological changes of the spinal cord were scored. Post-ischemic microcirculation of the spinal cord was visualized by fluorescein isothiocyanate (FITC) albumin. Results The severity of histopathological damage paralleled the neurological deficit scores. Paraplegia and associated histopathological changes were accompanied by a clear post-ischemic deficit in blood perfusion. Spinal cord ischemia for 1 h resulted in permanent paraplegia in the control group. Depletion of the CSF significantly prevented paraplegia. CSF replenishment with the ICP reduced to 0 mmHg, did not prevent paraplegia. Replacement of CSF with albumin- or gelatin-modified artificial CSF prevented paraplegia in rabbits even when the ICP was maintained at 10–15 mmHg. Conclusion We conclude that the presence of normal CSF may contribute to the vulnerability of the spinal cord to ischemic injury. Depletion of the CSF or replacement of the CSF with an albumin- or gelatin-modified artificial CSF can be neuroprotective. PMID:16174300

  5. Wide-field fluorescence molecular tomography with compressive sensing based preconditioning

    PubMed Central

    Yao, Ruoyang; Pian, Qi; Intes, Xavier

    2015-01-01

    Wide-field optical tomography based on structured light illumination and detection strategies enables efficient tomographic imaging of large tissues at very fast acquisition speeds. However, the optical inverse problem based on such instrumental approach is still ill-conditioned. Herein, we investigate the benefit of employing compressive sensing-based preconditioning to wide-field structured illumination and detection approaches. We assess the performances of Fluorescence Molecular Tomography (FMT) when using such preconditioning methods both in silico and with experimental data. Additionally, we demonstrate that such methodology could be used to select the subset of patterns that provides optimal reconstruction performances. Lastly, we compare preconditioning data collected using a normal base that offers good experimental SNR against that directly acquired with optimal designed base. An experimental phantom study is provided to validate the proposed technique. PMID:26713202

  6. 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.

  7. Prenatal cocaine exposure induces deficits in Pavlovian conditioning and sensory preconditioning among infant rat pups.

    PubMed

    Heyser, C J; Chen, W J; Miller, J; Spear, N E; Spear, L P

    1990-12-01

    Offspring derived from Sprague-Dawley dams that received daily subcutaneous injection of 40 mg/kg.3 cc-1 cocaine hydrochloride (C40) or saline (LC) from Gestational Days 8-20 were tested for first-order Pavlovian conditioning and sensory preconditioning at Postnatal Days 8 (P8), P12, and P21. Although C40 dams gained significantly less weight than LC dams, pup body weights did not differ between the two groups. Significant sensory preconditioning was obtained at P8 and P12 (but not at P21) in LC offspring, confirming previous reports of decline in performance in this task during ontogeny. In contrast, C40 offspring failed to exhibit sensory preconditioning at any test age. In addition, C40 pups tested at P8 did not display significant first-order conditioning. Taken together these results suggest a more general deficit in cognitive functioning rather than a delay in cognitive development in prenatally cocaine-exposed offspring.

  8. Preconditioning for the Navier-Stokes equations with finite-rate chemistry

    NASA Technical Reports Server (NTRS)

    Godfrey, Andrew G.; Walters, Robert W.; Van Leer, Bram

    1993-01-01

    The preconditioning procedure for generalized finite-rate chemistry and the proper preconditioning for the one-dimensional Navier-Stokes equations are presented. Eigenvalue stiffness is resolved and convergence-rate acceleration is demonstrated over the entire Mach-number range from the incompressible to the hypersonic. Specific benefits are realized at low and transonic flow speeds. The extended preconditioning matrix accounts for thermal and chemical non-equilibrium and its implementation is explained for both explicit and implicit time marching. The effect of higher-order spatial accuracy and various flux splittings is investigated. Numerical analysis reveals the possible theoretical improvements from using proconditioning at all Mach numbers. Numerical results confirm the expectations from the numerical analysis. Representative test cases include flows with previously troublesome embedded high-condition-number regions.

  9. Analysis of a Lipid/Polymer Membrane for Bitterness Sensing with a Preconditioning Process

    PubMed Central

    Yatabe, Rui; Noda, Junpei; Tahara, Yusuke; Naito, Yoshinobu; Ikezaki, Hidekazu; Toko, Kiyoshi

    2015-01-01

    It is possible to evaluate the taste of foods or medicines using a taste sensor. The taste sensor converts information on taste into an electrical signal using several lipid/polymer membranes. A lipid/polymer membrane for bitterness sensing can evaluate aftertaste after immersion in monosodium glutamate (MSG), which is called “preconditioning”. However, we have not yet analyzed the change in the surface structure of the membrane as a result of preconditioning. Thus, we analyzed the change in the surface by performing contact angle and surface zeta potential measurements, Fourier transform infrared spectroscopy (FTIR), X-ray photon spectroscopy (XPS) and gas cluster ion beam time-of-flight secondary ion mass spectrometry (GCIB-TOF-SIMS). After preconditioning, the concentrations of MSG and tetradodecylammonium bromide (TDAB), contained in the lipid membrane were found to be higher in the surface region than in the bulk region. The effect of preconditioning was revealed by the above analysis methods. PMID:26404301

  10. Nitroglycerine and sodium trioxodinitrate: from the discovery to the preconditioning effect.

    PubMed

    Pagliaro, Pasquale; Gattullo, Donatella; Penna, Claudia

    2013-10-01

    The history began in the 19th century with Ascanio Sobrero (1812-1888), the discoverer of glycerol trinitrate (nitroglycerine, NTG), and with Angelo Angeli (1864-1931), the discoverer of sodium trioxodinitrate (Angeli's salt). It is likely that Angeli and Sobrero never met, but their two histories will join each other more than a century later. In fact, it has been discovered that both NTG and Angeli's salt are able to induce a preconditioning effect. As NTG has a long history as an antianginal drug its newly discovered property as a preconditioning agent has also been tested in humans. Angeli's salt properties as a preconditioning and inotropic agent have only been tested in animals so far.

  11. Wide-field fluorescence molecular tomography with compressive sensing based preconditioning.

    PubMed

    Yao, Ruoyang; Pian, Qi; Intes, Xavier

    2015-12-01

    Wide-field optical tomography based on structured light illumination and detection strategies enables efficient tomographic imaging of large tissues at very fast acquisition speeds. However, the optical inverse problem based on such instrumental approach is still ill-conditioned. Herein, we investigate the benefit of employing compressive sensing-based preconditioning to wide-field structured illumination and detection approaches. We assess the performances of Fluorescence Molecular Tomography (FMT) when using such preconditioning methods both in silico and with experimental data. Additionally, we demonstrate that such methodology could be used to select the subset of patterns that provides optimal reconstruction performances. Lastly, we compare preconditioning data collected using a normal base that offers good experimental SNR against that directly acquired with optimal designed base. An experimental phantom study is provided to validate the proposed technique.

  12. [Application for Lifestyle disease by iPS cells technologies].

    PubMed

    Takashima, Yasuhiro

    2016-03-01

    Currently it is less advanced to understand the pathology of lifestyle disease by using iPS cells because there is partly less direct connection between life style disease and iPS cells. So much more scientists focus on regenerative medicine such as beta cells therapy using iPS cells technologies. It will be indeed a powerful tool to generate beta cells from iPS cells as even in type2 diabetes patients, hyposecretion of insulin from beta cells in pancreas is one of causes. Another reason is complexity of the pathology of life style disease. There are a lot of reasons to cause lifestyle disease. Lifestyle diseases include cancer, chronic liver disease, Type 2 diabetes, heart disease, metabolic syndrome, chronic renal failure, stroke, and obesity. Since obesity is one of major causes of lifestyle diseases, we want to focus on adipogenesis from iPS cells in this review. We analysed and established the differentiation protocol into adipocytes from mouse ES cells and human iPS cells. The other point in this review is the starting pluripotent cells for differentiation. Quality of pluripotent stem cells are one of most critical factors to succeed in getting well-differentiated cells. Recently, we have developed new naive human pluripotent stem cells (PSC),"Reset cells". Naive PSC have more similar to human epibast cells than conventional human PSC. They will be more ideal cells for differentiation because of their hypomethylated status and earlier stage of development. PMID:26923982

  13. [Application for Lifestyle disease by iPS cells technologies].

    PubMed

    Takashima, Yasuhiro

    2016-03-01

    Currently it is less advanced to understand the pathology of lifestyle disease by using iPS cells because there is partly less direct connection between life style disease and iPS cells. So much more scientists focus on regenerative medicine such as beta cells therapy using iPS cells technologies. It will be indeed a powerful tool to generate beta cells from iPS cells as even in type2 diabetes patients, hyposecretion of insulin from beta cells in pancreas is one of causes. Another reason is complexity of the pathology of life style disease. There are a lot of reasons to cause lifestyle disease. Lifestyle diseases include cancer, chronic liver disease, Type 2 diabetes, heart disease, metabolic syndrome, chronic renal failure, stroke, and obesity. Since obesity is one of major causes of lifestyle diseases, we want to focus on adipogenesis from iPS cells in this review. We analysed and established the differentiation protocol into adipocytes from mouse ES cells and human iPS cells. The other point in this review is the starting pluripotent cells for differentiation. Quality of pluripotent stem cells are one of most critical factors to succeed in getting well-differentiated cells. Recently, we have developed new naive human pluripotent stem cells (PSC),"Reset cells". Naive PSC have more similar to human epibast cells than conventional human PSC. They will be more ideal cells for differentiation because of their hypomethylated status and earlier stage of development.

  14. 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.

  15. Sensory preconditioning, the Espinet effect, and Heider's balance theory: note on animal reasoning of event relations.

    PubMed

    Nakajima, Sadahiko

    2005-06-01

    Sensory preconditioning and the Espinet effect illustrate that animals can reason about event relations. In sensory preconditioning, a combination of positive A-B and B-C relations yields a positive A-C relation. In the Espinet effect, a combination of a negative A-B relation and a positive B-C relation yields a negative A-C relation. Using analogies of Heider's balance theory of human attitudes, we predict that nonhuman animals would also infer a positive A-C relation from negative A-B and B-C relations.

  16. Propulsion-related flowfields using the preconditioned Navier-Stokes equations

    NASA Technical Reports Server (NTRS)

    Venkateswaran, S.; Weiss, J. M.; Merkle, C. L.; Choi, Y.-H.

    1992-01-01

    A previous time-derivative preconditioning procedure for solving the Navier-Stokes is extended to the chemical species equations. The scheme is implemented using both the implicit ADI and the explicit Runge-Kutta algorithms. A new definition for time-step is proposed to enable grid-independent convergence. Several examples of both reacting and non-reacting propulsion-related flowfields are considered. In all cases, convergence that is superior to conventional methods is demonstrated. Accuracy is verified using the example of a backward facing step. These results demonstrate that preconditioning can enhance the capability of density-based methods over a wide range of Mach and Reynolds numbers.

  17. Preconditioning for the Navier-Stokes equations with finite-rate chemistry

    NASA Technical Reports Server (NTRS)

    Godfrey, Andrew G.

    1993-01-01

    The extension of Van Leer's preconditioning procedure to generalized finite-rate chemistry is discussed. Application to viscous flow is begun with the proper preconditioning matrix for the one-dimensional Navier-Stokes equations. Eigenvalue stiffness is resolved and convergence-rate acceleration is demonstrated over the entire Mach-number range from nearly stagnant flow to hypersonic. Specific benefits are realized at the low and transonic flow speeds typical of complete propulsion-system simulations. The extended preconditioning matrix necessarily accounts for both thermal and chemical nonequilibrium. Numerical analysis reveals the possible theoretical improvements from using a preconditioner for all Mach number regimes. Numerical results confirm the expectations from the numerical analysis. Representative test cases include flows with previously troublesome embedded high-condition-number areas. Van Leer, Lee, and Roe recently developed an optimal, analytic preconditioning technique to reduce eigenvalue stiffness over the full Mach-number range. By multiplying the flux-balance residual with the preconditioning matrix, the acoustic wave speeds are scaled so that all waves propagate at the same rate, an essential property to eliminate inherent eigenvalue stiffness. This session discusses a synthesis of the thermochemical nonequilibrium flux-splitting developed by Grossman and Cinnella and the characteristic wave preconditioning of Van Leer into a powerful tool for implicitly solving two and three-dimensional flows with generalized finite-rate chemistry. For finite-rate chemistry, the state vector of unknowns is variable in length. Therefore, the preconditioning matrix extended to generalized finite-rate chemistry must accommodate a flexible system of moving waves. Fortunately, no new kind of wave appears in the system. The only existing waves are entropy and vorticity waves, which move with the fluid, and acoustic waves, which propagate in Mach number dependent

  18. Preconditioned upwind methods to solve 3-D incompressible Navier-Stokes equations for viscous flows

    NASA Technical Reports Server (NTRS)

    Hsu, C.-H.; Chen, Y.-M.; Liu, C. H.

    1990-01-01

    A computational method for calculating low-speed viscous flowfields is developed. The method uses the implicit upwind-relaxation finite-difference algorithm with a nonsingular eigensystem to solve the preconditioned, three-dimensional, incompressible Navier-Stokes equations in curvilinear coordinates. The technique of local time stepping is incorporated to accelerate the rate of convergence to a steady-state solution. An extensive study of optimizing the preconditioned system is carried out for two viscous flow problems. Computed results are compared with analytical solutions and experimental data.

  19. SUR1-Associated Mechanisms Are Not Involved in Ischemic Optic Neuropathy 1 Day Post-Injury

    PubMed Central

    Nicholson, James D.; Guo, Yan; Bernstein, Steven L.

    2016-01-01

    Ischemia-reperfusion injury after central nervous system (CNS) injury presents a major health care challenge with few promising treatments. Recently, it has become possible to reduce edema after CNS injury by antagonizing a sulfonylurea receptor 1 (SUR1) regulated ion channel expressed after injury. SUR1 upregulation after injury is a necessary precondition for the formation of this channel, and has been implicated in white matter injury after clinical spinal cord trauma. Glibenclamide, an SUR1 antagonist, appears to have neuroprotective effect against cerebral stroke in an open-label small clinical trial and great effectiveness in reducing damage after varied experimental CNS injury models. Despite its importance in CNS injuries, SUR1 upregulation appears to play no part in rodent anterior ischemic optic neuropathy (rAION) injury as tested by real-time PCR and immunohistochemical staining of rAION-injured rat optic nerve (ON). Furthermore, the SUR1 antagonist glibenclamide administered immediately after rAION injury provided no protection to proximal ON microvasculature 1 day post-injury but may reduce optic nerve head edema in a manner unrelated to ON SUR1 expression. Our results suggest that there may be fundamental differences between rAION optic nerve ischemia and other CNS white matter injuries where SUR1 appears to play a role. PMID:27560494

  20. SUR1-Associated Mechanisms Are Not Involved in Ischemic Optic Neuropathy 1 Day Post-Injury.

    PubMed

    Nicholson, James D; Guo, Yan; Bernstein, Steven L

    2016-01-01

    Ischemia-reperfusion injury after central nervous system (CNS) injury presents a major health care challenge with few promising treatments. Recently, it has become possible to reduce edema after CNS injury by antagonizing a sulfonylurea receptor 1 (SUR1) regulated ion channel expressed after injury. SUR1 upregulation after injury is a necessary precondition for the formation of this channel, and has been implicated in white matter injury after clinical spinal cord trauma. Glibenclamide, an SUR1 antagonist, appears to have neuroprotective effect against cerebral stroke in an open-label small clinical trial and great effectiveness in reducing damage after varied experimental CNS injury models. Despite its importance in CNS injuries, SUR1 upregulation appears to play no part in rodent anterior ischemic optic neuropathy (rAION) injury as tested by real-time PCR and immunohistochemical staining of rAION-injured rat optic nerve (ON). Furthermore, the SUR1 antagonist glibenclamide administered immediately after rAION injury provided no protection to proximal ON microvasculature 1 day post-injury but may reduce optic nerve head edema in a manner unrelated to ON SUR1 expression. Our results suggest that there may be fundamental differences between rAION optic nerve ischemia and other CNS white matter injuries where SUR1 appears to play a role.