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Sample records for ischemic preconditioning ip

  1. Ischemic preconditioning. Experimental facts and clinical perspective.

    PubMed

    Post, H; Heusch, G

    2002-12-01

    Brief periods of non-lethal ischemia and reperfusion render the myocardium more resistant to subsequent ischemia. This adaption occurs in a biphasic pattern: the first being active immediately and lasting for 2-3 hrs (early preconditioning), the second starting at 24 hrs until 72 hrs after the initial ischemia (delayed preconditioning) and requiring genomic activation with de novo protein synthesis. Early preconditioning is more potent than delayed preconditioning in reducing infarct size; delayed preconditioning also attenuates myocardial stunning. Early preconditioning depends on the ischemia-induced release of adenosine and opioids and, to a lesser degree, also bradykinin and prostaglandins. These molecules activate G-protein coupled receptors, initiate the activation of KATP channels and generation of oxygen radicals, and stimulate a series of protein kinases with essential roles for protein kinase C, tyrosine kinases and members of the MAP kinase family. Delayed preconditioning is triggered by a similar sequence of events, but in addition essentially depends on eNOS-derived NO. Both early and pharmacological preconditioning can be pharmacologically mimicked by exogenous adenosine, opioids, NO and activators of protein kinase C. Newly synthetized proteins associated with delayed preconditioning comprise iNOS, COX-2, manganese superoxide dismutase and possibly heat shock proteins. The final mechanism of protection by preconditioning is yet unknown; energy metabolism, KATP channels, the sodium-proton exchanger, stabilisation of the cytoskeleton and volume regulation will be discussed. For ethical reasons, evidence for ischemic preconditioning in humans is hard to provide. Clinical findings that parallel experimental ischemic preconditioning are reduced ST-segment elevation and pain during repetitive PTCA or exercise tests, a better prognosis of patients in whom myocardial infarction was preceded by angina, and reduced serum markers of myocardial necrosis after

  2. Remote ischemic preconditioning enhances fracture healing

    PubMed Central

    Çatma, Mehmet Faruk; Şeşen, Hakan; Aydın, Aytekin; Ünlü, Serhan; Demirkale, İsmail; Altay, Murat

    2015-01-01

    Purpose We hypothesized that RIP accelerates fracture healing. Methods Rats (n = 48) were used for the technique of ischemic preconditioning involved applying 35 min of intermittent pneumatic tourniquet for 7 cycles of 5 min each to the fractured hind limb. Results We observed greater callus maturity in RIP group at first week after fracture when compared to controls (p < 0,0001). The serum MDA levels demonstrated statistically lower values at the RIP group at the first week after fracture; however, there were not significant differences at 3rd and 5th weeks (p = 0.0001, p = 0.725, p = 0.271, respectively). Conclusions Greater callus maturity was obtained in RIP group. PMID:26566314

  3. Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

    PubMed

    Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

    2004-01-01

    Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion.

  4. A practical approach to remote ischemic preconditioning and ischemic preconditioning against myocardial ischemia/reperfusion injury

    PubMed Central

    Totzeck, Matthias; Hendgen-Cotta, Ulrike B.; French, Brent A.; Rassaf, Tienush

    2016-01-01

    Although urgently needed in clinical practice, a cardioprotective therapeutic approach against myocardial ischemia/ reperfusion injury remains to be established. Remote ischemic preconditioning (rIPC) and ischemic preconditioning (IPC) represent promising tools comprising three entities: the generation of a protective signal, the transfer of the signal to the target organ, and the response to the transferred signal resulting in cardioprotection. However, in light of recent scientific advances, many controversies arise regarding the efficacy of the underlying signaling. We here show methods for the generation of the signaling cascade by rIPC as well as IPC in a mouse model for in vivo myocardial ischemia/ reperfusion injury using highly reproducible approaches. This is accomplished by taking advantage of easily applicable preconditioning strategies compatible with the clinical setting. We describe methods for using laser Doppler perfusion imaging to monitor the cessation and recovery of perfusion in real time. The effects of preconditioning on cardiac function can also be assessed using ultrasound or magnetic resonance imaging approaches. On a cellular level, we confirm how tissue injury can be monitored using histological assessment of infarct size in conjunction with immunohistochemistry to assess both aspects in a single specimen. Finally, we outline, how the rIPC-associated signaling can be transferred to the target cell via conservation of the signal in the humoral (blood) compartment. This compilation of experimental protocols including a conditioning regimen comparable to the clinical setting should proof useful to both beginners and experts in the field of myocardial infarction, supplying information for the detailed procedures as well as troubleshooting guides. PMID:28066791

  5. 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

  6. Inhalational Anesthetics as Preconditioning Agents in Ischemic Brain

    PubMed Central

    Wang, Lan; Traystman, Richard J.; Murphy, Stephanie J.

    2008-01-01

    SUMMARY While many pharmacological agents have been shown to protect the brain from cerebral ischemia in animal models, none have translated successfully to human patients. One potential clinical neuroprotective strategy in humans may involve increasing the brain’s tolerance to ischemia by pre-ischemic conditioning (preconditioning). There are many methods to induce tolerance via preconditioning such as: ischemia itself, pharmacological, hypoxia, endotoxin, and others. Inhalational anesthetic agents have also been shown to result in brain preconditioning. Mechanisms responsible for brain preconditioning are many, complex, and unclear and may involve Akt activation, ATP-sensitive potassium channels, and nitric oxide, amongst many others. Anesthetics, however, may play an important and unique role as preconditioning agents, particularly during the perioperative period. PMID:17962069

  7. Molecular mechanisms of ischemic preconditioning in the kidney

    PubMed Central

    Haase, Volker H.

    2015-01-01

    More effective therapeutic strategies for the prevention and treatment of acute kidney injury (AKI) are needed to improve the high morbidity and mortality associated with this frequently encountered clinical condition. Ischemic and/or hypoxic preconditioning attenuates susceptibility to ischemic injury, which results from both oxygen and nutrient deprivation and accounts for most cases of AKI. While multiple signaling pathways have been implicated in renoprotection, this review will focus on oxygen-regulated cellular and molecular responses that enhance the kidney's tolerance to ischemia and promote renal repair. Central mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs). HIFs play a crucial role in ischemic/hypoxic preconditioning through the reprogramming of cellular energy metabolism, and by coordinating adenosine and nitric oxide signaling with antiapoptotic, oxidative stress, and immune responses. The therapeutic potential of HIF activation for the treatment and prevention of ischemic injuries will be critically examined in this review. PMID:26311114

  8. 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.

  9. Acute ischemic preconditioning of skeletal muscle prior to flap elevation augments muscle-flap survival.

    PubMed

    Carroll, C M; Carroll, S M; Overgoor, M L; Tobin, G; Barker, J H

    1997-07-01

    Ischemic preconditioning of the myocardium with repeated brief periods of ischemia and reperfusion prior to prolonged ischemia significantly reduces subsequent myocardial infarction. Following ischemic preconditioning, two "windows of opportunity" (early and late) exist, during which time prolonged ischemia can occur with reduced infarction size. The early window occurs at approximately 4 hours and the late window at 24 hours following ischemic preconditioning of the myocardium. We investigated if ischemic preconditioning of skeletal muscle prior to flap creation improved subsequent flap survival and perfusion immediately or 24 hours following ischemic preconditioning. Currently, no data exist on the utilization of ischemic preconditioning in this fashion. The animal model used was the latissimus dorsi muscle of adult male Sprague-Dawley rats. Animals were assigned to three groups, and the right or left latissimus dorsi muscle was chosen randomly in each animal. Group 1 (n = 12) was the control group, in which the entire latissimus dorsi muscle was elevated acutely without ischemic preconditioning. Group 2 (n = 8) investigated the effects of ischemic preconditioning in the early window. In this group, the latissimus dorsi muscle was elevated immediately following preconditioning. Group 3 (n = 8) investigated the effects of ischemic preconditioning in the late window, with elevation of the latissimus dorsi muscle 24 hours following ischemic preconditioning. The preconditioning regimen used in groups 2 and 3 was two 30-minute episodes of normothermic global ischemia with intervening 10-minute episodes of reperfusion. Latissimus dorsi muscle ischemia was created by occlusion of the thoracodorsal artery and vein and the intercostal perforators, after isolation of the muscle on these vessels. Muscle perfusion was assessed by a laser-Doppler perfusion imager. One week after flap elevation, muscle necrosis was quantified in all groups by means of computer-assisted digital

  10. TNFR1 mediates increased neuronal membrane EAAT3 expression after in vivo cerebral ischemic preconditioning.

    PubMed

    Pradillo, J M; Hurtado, O; Romera, C; Cárdenas, A; Fernández-Tomé, P; Alonso-Escolano, D; Lorenzo, P; Moro, M A; Lizasoain, I

    2006-01-01

    A short ischemic event (ischemic preconditioning) can result in subsequent resistance to severe ischemic injury (ischemic tolerance). Glutamate is released after ischemia and produces cell death. It has been described that after ischemic preconditioning, the release of glutamate is reduced. We have shown that an in vitro model of ischemic preconditioning produces upregulation of glutamate transporters which mediates brain tolerance. We have now decided to investigate whether ischemic preconditioning-induced glutamate transporter upregulation takes also place in vivo, its cellular localization and the mechanisms by which this upregulation is controlled. A period of 10 min of temporary middle cerebral artery occlusion was used as a model of ischemic preconditioning in rat. EAAT1, EAAT2 and EAAT3 glutamate transporters were found in brain from control animals. Ischemic preconditioning produced an up-regulation of EAAT2 and EAAT3 but not of EAAT1 expression. Ischemic preconditioning-induced increase in EAAT3 expression was reduced by the TNF-alpha converting enzyme inhibitor BB1101. Intracerebral administration of either anti-TNF-alpha antibody or of a TNFR1 antisense oligodeoxynucleotide also inhibited ischemic preconditioning-induced EAAT3 up-regulation. Immunohistochemical studies suggest that, whereas the expression of EAAT3 is located in both neuronal cytoplasm and plasma membrane, ischemic preconditioning-induced up-regulation of EAAT3 is mainly localized at the plasma membrane level. In summary, these results demonstrate that in vivo ischemic preconditioning increases the expression of EAAT2 and EAAT3 glutamate transporters the upregulation of the latter being at least partly mediated by TNF-alpha converting enzyme/TNF-alpha/TNFR1 pathway.

  11. 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

  12. Ischemic preconditioning of the muscle improves maximal exercise performance but not maximal oxygen uptake in humans.

    PubMed

    Crisafulli, Antonio; Tangianu, Flavio; Tocco, Filippo; Concu, Alberto; Mameli, Ombretta; Mulliri, Gabriele; Caria, Marcello A

    2011-08-01

    Brief episodes of nonlethal ischemia, commonly known as "ischemic preconditioning" (IP), are protective against cell injury induced by infarction. Moreover, muscle IP has been found capable of improving exercise performance. The aim of the study was the comparison of standard exercise performances carried out in normal conditions with those carried out following IP, achieved by brief muscle ischemia at rest (RIP) and after exercise (EIP). Seventeen physically active, healthy male subjects performed three incremental, randomly assigned maximal exercise tests on a cycle ergometer up to exhaustion. One was the reference (REF) test, whereas the others were performed after the RIP and EIP sessions. Total exercise time (TET), total work (TW), and maximal power output (W(max)), oxygen uptake (VO(2max)), and pulmonary ventilation (VE(max)) were assessed. Furthermore, impedance cardiography was used to measure maximal heart rate (HR(max)), stroke volume (SV(max)), and cardiac output (CO(max)). A subgroup of volunteers (n = 10) performed all-out tests to assess their anaerobic capacity. We found that both RIP and EIP protocols increased in a similar fashion TET, TW, W(max), VE(max), and HR(max) with respect to the REF test. In particular, W(max) increased by ∼ 4% in both preconditioning procedures. However, preconditioning sessions failed to increase traditionally measured variables such as VO(2max), SV(max,) CO(max), and anaerobic capacity(.) It was concluded that muscle IP improves performance without any difference between RIP and EIP procedures. The mechanism of this effect could be related to changes in fatigue perception.

  13. The effect of ischemic preconditioning on the recovery of skeletal muscle following tourniquet ischemia.

    PubMed

    Whetzel, T P; Stevenson, T R; Sharman, R B; Carlsen, R C

    1997-12-01

    It has been well documented that ischemic preconditioning limits ischemic-reperfusion injury in cardiac muscle, but the ability of ischemic preconditioning to limit skeletal muscle injury is less clear. Previous reports have emphasized the beneficial effects of ischemic preconditioning on skeletal muscle structure and capillary perfusion but have not evaluated muscle function. We investigated the morphologic and functional consequences of ischemic preconditioning, followed by a 2-hour period of tourniquet ischemia on muscles in the rat hindlimb. The 2-hour ischemia was imposed without preconditioning, or was preceded by three brief (10 minutes on/10 minutes off) preischemic conditioning intervals. We compared muscle morphology, isometric contractile function, and muscle fatigue properties in predominantly fast-twitch, tibialis anterior muscles 3 (n = 8) and 7 (n = 8) days after ischemia-reperfusion. Two hours of ischemia, followed by reperfusion, results in a 20 percent reduction of muscle mass (p < 0.05) and a 33 percent reduction in tetanic tension (p < 0.05) when compared with controls (n = 8) at 3 days. The same protocol, when preceded by ischemic preconditioning, results in similar decreases in muscle mass and contractile function. Neuromuscular transmission was also impaired in both ischemic groups 7 days after ischemia. Nerve-evoked maximum tetanic tension was 69 percent of the tension produced by direct muscle stimulation in the ischemia group and 65 percent of direct tension in the ischemic preconditioning/ischemia group. In summary, ischemic preconditioning, using the same protocol reported to be effective in limiting infarct size in porcine muscle, had no significant benefit in limiting injury or improving recovery in the ischemic rat tibialis anterior. The value of ischemic preconditioning in reducing imposed ischemic-reperfusion-induced functional deficits in skeletal muscle remains to be demonstrated.

  14. Ameliorative Effect of Recombinant Human Erythropoietin and Ischemic Preconditioning on Renal Ischemia Reperfusion Injury in Rats

    PubMed Central

    Elshiekh, Mohammed; Kadkhodaee, Mehri; Seifi, Behjat; Ranjbaran, Mina; Ahghari, Parisa

    2015-01-01

    Background: Ischemia-reperfusion (IR) injury is one of the most common causes of renal dysfunction. There is increasing evidence about the role of the reactive oxygen species (ROS) in these injuries and endogenous antioxidants seem to have an important role in decreasing the renal tissue injury. Objectives: The aim of this study was to compare the effect of recombinant human erythropoietin (EPO) and ischemic preconditioning (IPC) on renal IR injury. Materials and Methods: Twenty four male Wistar rats were allocated into four experimental groups: sham-operated, IR, EPO + IR, and IPC + IR. Rats were underwent 50 minutes bilateral ischemia followed by 24 hours reperfusion. Erythropoietin (5000 IU/kg, i.p) was administered 30 minutes before onset of ischemia. Ischemic preconditioning was performed by three cycles of 3 minutes ischemia followed by 3 minutes reperfusion. Plasma concentrations of urea and creatinine were measured. Kidney samples were taken for reactive oxidative species (ROS) measurement including superoxide dismutase (SOD) activity, glutathione (GSH) contents, and malondialdehyde (MDA) levels. Results: Compared to the sham group, IR led to renal dysfunction as evidenced by significantly higher plasma urea and creatinine. Treatment with EPO or IPC decreased urea, creatinine, and renal MDA levels and increased SOD activity and GSH contents in the kidney. Conclusions: Pretreatment with EPO and application of IPC significantly ameliorated the renal injury induced by bilateral renal IR. However, both treatments attenuated renal dysfunction and oxidative stress in kidney tissues. There were no significant differences between pretreatment with EPO or application of IPC. PMID:26866008

  15. Hyperbaric oxygen therapy and preconditioning for ischemic and hemorrhagic stroke

    PubMed Central

    Hu, Sheng-li; Feng, Hua; Xi, Guo-hua

    2016-01-01

    To date, the therapeutic methods for ischemic and hemorrhagic stroke are still limited. The lack of oxygen supply is critical for brain injury following stroke. Hyperbaric oxygen (HBO), an approach through a process in which patients breathe in 100% pure oxygen at over 101 kPa, has been shown to facilitate oxygen delivery and increase oxygen supply. Hence, HBO possesses the potentials to produce beneficial effects on stroke. Actually, accumulated basic and clinical evidences have demonstrated that HBO therapy and preconditioning could induce neuroprotective functions via different mechanisms. Nevertheless, the lack of clinical translational study limits the application of HBO. More translational studies and clinical trials are needed in the future to develop effective HBO protocols. PMID:28217297

  16. Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: Involvement of cyclooxygenases and heat shock protein 70

    PubMed Central

    Warzecha, Zygmunt; Dembinski, Artur; Ceranowicz, Piotr; Konturek, Stanislaw J; Dembinski, Marcin; Pawlik, Wieslaw W; Tomaszewska, Romana; Stachura, Jerzy; Kusnierz-Cabala, Beata; Naskalski, Jerzy W; Konturek, Peter C

    2005-01-01

    AIM: To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process. METHODS: In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg). RESULTS: IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-1β. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis. CONCLUSION: Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70. PMID:16273606

  17. 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.

  18. Cardioprotection of ischemic preconditioning in rats involves upregulating adiponectin.

    PubMed

    Wang, Hui; Wu, Wenjing; Duan, Jun; Ma, Ming; Kong, Wei; Ke, Yuannan; Li, Gang; Zheng, Jingang

    2017-02-20

    It has been reported that ischemic preconditioning (IPC) and adiponectin (APN) are cardioprotective in many cardiovascular disorders. However, whether APN mediates the effect of IPC on myocardial injury has not been elucidated. This study was conducted to investigate whether IPC affects myocardial ischemic injury by increasing APN expression. Male adult rats with cardiac knockdowns of APN and its receptors via intramyocardial small-interfering RNA injection were subjected to IPC and then myocardial infarction (MI) at 24 h post-IPC. Globular APN (gAd) was injected at 10 min before MI. APN mRNA and protein levels in myocardium as well as the plasma APN concentration were markedly high at 6 and 12 h after IPC. IPC ameliorated myocardial injury as evidenced by improved cardiac functions and a reduced infarct size. Compared with the control MI group, rats in the IPC + MI group had elevated levels of left ventricular ejection fraction and fractional shortening, and a smaller MI size (P<0.05). However, the aforementioned protective effects were ameliorated in the absence of APN and APN receptors, followed by inhibition of AMP-activated protein kinase (AMPK) phosphorylation, but reversed by gAd treatment in wild-type rats, and AMPK phosphorylation increased (P<0.05). Overall, our results suggest that the cardioprotective effects of IPC are partially due to upregulation of APN, and provide a further insight into IPC-mediated signaling effects.

  19. Ischemic Preconditioning and Placebo Intervention Improves Resistance Exercise Performance.

    PubMed

    Marocolo, Moacir; Willardson, Jeffrey M; Marocolo, Isabela C; da Mota, Gustavo Ribeiro; Simão, Roberto; Maior, Alex S

    2016-05-01

    This study evaluated the effect of ischemic preconditioning (IPC) on resistance exercise performance in the lower limbs. Thirteen men participated in a randomized crossover design that involved 3 separate sessions (IPC, PLACEBO, and control). A 12-repetition maximum (12RM) load for the leg extension exercise was assessed through test and retest sessions before the first experimental session. The IPC session consisted of 4 cycles of 5 minutes of occlusion at 220 mm Hg of pressure alternated with 5 minutes of reperfusion at 0 mm Hg for a total of 40 minutes. The PLACEBO session consisted of 4 cycles of 5 minutes of cuff administration at 20 mm Hg of pressure alternated with 5 minutes of pseudo-reperfusion at 0 mm Hg for a total of 40 minutes. The occlusion and reperfusion phases were conducted alternately between the thighs, with subjects remaining seated. No ischemic pressure was applied during the control (CON) session and subjects sat passively for 40 minutes. Eight minutes after IPC, PLACEBO, or CON, subjects performed 3 repetition maximum sets of the leg extension (2-minute rest between sets) with the predetermined 12RM load. Four minutes after the third set for each condition, blood lactate was assessed. The results showed that for the first set, the number of repetitions significantly increased for both the IPC (13.08 ± 2.11; p = 0.0036) and PLACEBO (13.15 ± 0.88; p = 0.0016) conditions, but not for the CON (11.88 ± 1.07; p > 0.99) condition. In addition, the IPC and PLACEBO conditions resulted insignificantly greater repetitions vs. the CON condition on the first set (p = 0.015; p = 0.007) and second set (p = 0.011; p = 0.019), but not on the third set (p = 0.68; p > 0.99). No difference (p = 0.465) was found in the fatigue index and lactate concentration between conditions. These results indicate that IPC and PLACEBO IPC may have small beneficial effects on repetition performance over a CON condition. Owing to potential for greater discomfort associated

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

    PubMed Central

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

    2011-01-01

    Caloric restriction (CR), resveratrol, and ischemic preconditioning (IPC) have been shown to promote protection against ischemic injury in the heart and brain, as well as in other tissues. The activity of sirtuins, which are enzymes that modulate diverse biologic processes, seems to be vital in the ability of these therapeutic modalities to prevent against cellular dysfunction and death. The protective mechanisms of the yeast Sir2 and the mammalian homolog sirtuin 1 have been extensively studied, but the involvement of other sirtuins in ischemic protection is not yet clear. We examine the roles of mammalian sirtuins in modulating protective pathways against oxidative stress, energy depletion, excitotoxicity, inflammation, DNA damage, and apoptosis. Although many of these sirtuins have not been directly implicated in ischemic protection, they may have unique roles in enhancing function and preventing against stress-mediated cellular damage and death. This review will include in-depth analyses of the roles of CR, resveratrol, and IPC in activating sirtuins and in mediating protection against ischemic damage in the heart and brain. PMID:21224864

  1. Ischemic Preconditioning Enhances Muscle Endurance during Sustained Isometric Exercise.

    PubMed

    Tanaka, D; Suga, T; Tanaka, T; Kido, K; Honjo, T; Fujita, S; Hamaoka, T; Isaka, T

    2016-07-01

    Ischemic preconditioning (IPC) enhances whole-body exercise endurance. However, it is poorly understood whether the beneficial effects originate from systemic (e. g., cardiovascular system) or peripheral (e. g., skeletal muscle) adaptations. The present study examined the effects of IPC on local muscle endurance during fatiguing isometric exercise. 12 male subjects performed sustained isometric unilateral knee-extension exercise at 20% of maximal voluntary contraction until failure. Prior to the exercise, subjects completed IPC or control (CON) treatments. During exercise trial, electromyography activity and near-infrared spectroscopy-derived deoxygenation in skeletal muscle were continuously recorded. Endurance time to task failure was significantly longer in IPC than in CON (mean±SE; 233±9 vs. 198±9 s, P<0.001). Quadriceps electromyography activity was not significantly different between IPC and CON. In contrast, deoxygenation dynamics in the quadriceps vastus lateralis muscle was significantly faster in IPC than in CON (27.1±3.4 vs. 35.0±3.6 s, P<0.01). The present study found that IPC can enhance muscular endurance during fatiguing isometric exercise. Moreover, IPC accelerated muscle deoxygenation dynamics during the exercise. Therefore, we suggest that the origin of beneficial effects of IPC on exercise performance may be the enhanced mitochondrial metabolism in skeletal muscle.

  2. Brain ischemic preconditioning is abolished by antioxidant drugs but does not up-regulate superoxide dismutase and glutathion peroxidase.

    PubMed

    Puisieux, François; Deplanque, Dominique; Bulckaen, Hélène; Maboudou, Patrice; Gelé, Patrick; Lhermitte, Michel; Lebuffe, Gilles; Bordet, Régis

    2004-11-19

    The present work examined the hypothesis that brain ischemic tolerance induced by ischemic preconditioning (IPC) is triggered by an initial oxidative stress and is associated with an increase in antioxidant enzyme activities as one end-effector of the neuroprotection. Wistar rats were preconditioned by a single 3-min occlusion of the middle cerebral artery. After a various duration of reperfusion (30 min, 24, 72 or 168 h), rats were subjected to a 60-min focal ischemia and sacrificed 24 h later. Cerebral infarcts were significantly reduced when performed during the 24- to 72-h time window after IPC. The pretreatment with the protein synthesis inhibitor, cycloheximide (1 mg/kg, i.p., 30 min prior to IPC), completely suppressed the neuroprotection. The free radical scavenger, dimethylthiourea (DMTU; 300 mg/kg, i.p., 30 min prior to IPC) and the antioxidant ebselen (10 mg/kg, oral cramming, 2 h before and 12 h after IPC) also abolished the IPC-induced protection of the brain. Nevertheless, IPC did not induce any delayed changes in antioxidant enzyme (superoxide dismutase, glutathion peroxidase) activities nor in the neuronal expression of Mn and Cu/Zn superoxide dismutase. These results indicate that an initial oxidative stress could be involved as a trigger of IPC, while antioxidant enzymes do not play a key role as end-effectors in such a neuroprotection.

  3. Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

    PubMed Central

    Aulakh, Amritpal Singh; Randhawa, Puneet Kaur; Singh, Nirmal

    2017-01-01

    Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection. PMID:28280407

  4. Remote ischemic preconditioning as treatment for non-ischemic gastrointestinal disorders: Beyond ischemia-reperfusion injury

    PubMed Central

    Camara-Lemarroy, Carlos Rodrigo

    2014-01-01

    Common gastrointestinal diseases such as radiation enteritis (RE), acute pancreatitis, inflammatory bowel diseases (IBD) and drug-induced hepatotoxicity share pathophysiological mechanisms at the molecular level, mostly involving the activation of many pathways of the immune response, ultimately leading to tissue injury. Increased oxidative stress, inflammatory cytokine release, inflammatory cell infiltration and activation and the up-regulation of inflammatory transcription factors participate in the pathophysiology of these complex entities. Treatment varies in each specific disease, but at least in the cases of RE and IBD immunosuppressors are effective. However, full therapeutic responses are not always achieved. The pathophysiology of ischemia-reperfusion (IR) injury shares many of these mechanisms. Brief and repetitive periods of ischemia in an organ or limb have been shown to protect against subsequent major IR injury in distant organs, a phenomenon called remote ischemic preconditioning (RIP). This procedure has been shown to protect the gut, pancreas and liver by modulating many of the same inflammatory mechanisms. Since RIP is safe and tolerable, and has shown to be effective in some recent clinical trials, I suggest that RIP could be used as a physiologically relevant adjunct treatment for non-ischemic gastrointestinal inflammatory conditions. PMID:24707140

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

    PubMed

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

    2013-10-22

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

  6. Effects of ischemic preconditioning in a pig model of large-for-size liver transplantation

    PubMed Central

    Leal, Antonio José Gonçalves; Tannuri, Ana Cristina Aoun; Belon, Alessandro Rodrigo; Guimarães, Raimundo Renato Nunes; Coelho, Maria Cecília Mendonça; de Oliveira Gonçalves, Josiane; Serafini, Suellen; de Melo, Evandro Sobroza; Tannuri, Uenis

    2015-01-01

    OBJECTIVE: In most cases of pediatric liver transplantation, the clinical scenario of large-for-size transplants can lead to hepatic dysfunction and a decreased blood supply to the liver graft. The objective of the present experimental investigation was to evaluate the effects of ischemic preconditioning on this clinical entity. METHODS: Eighteen pigs were divided into three groups and underwent liver transplantation: a control group, in which the weights of the donors were similar to those of the recipients, a large-for-size group, and a large-for-size + ischemic preconditioning group. Blood samples were collected from the recipients to evaluate the pH and the sodium, potassium, aspartate aminotransferase and alanine aminotransferase levels. In addition, hepatic tissue was sampled from the recipients for histological evaluation, immunohistochemical analyses to detect hepatocyte apoptosis and proliferation and molecular analyses to evaluate the gene expression of Bax (pro-apoptotic), Bcl-XL (anti-apoptotic), c-Fos and c-Jun (immediate-early genes), ischemia-reperfusion-related inflammatory cytokines (IL-1, TNF-alpha and IL-6, which is also a stimulator of hepatocyte regeneration), intracellular adhesion molecule, endothelial nitric oxide synthase (a mediator of the protective effect of ischemic preconditioning) and TGF-beta (a pro-fibrogenic cytokine). RESULTS: All animals developed acidosis. At 1 hour and 3 hours after reperfusion, the animals in the large-for-size and large-for-size + ischemic preconditioning groups had decreased serum levels of Na and increased serum levels of K and aspartate aminotransferase compared with the control group. The molecular analysis revealed higher expression of the Bax, TNF-alpha, I-CAM and TGF-beta genes in the large-for-size group compared with the control and large-for-size + ischemic preconditioning groups. Ischemic preconditioning was responsible for an increase in c-Fos, IL-1, IL-6 and e-NOS gene expression. CONCLUSION

  7. Minocycline-preconditioned neural stem cells enhance neuroprotection after ischemic stroke in rats.

    PubMed

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

    2012-03-07

    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 upregulation 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 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.

  8. Prothymosin-alpha preconditioning activates TLR4-TRIF signaling to induce protection of ischemic retina.

    PubMed

    Halder, Sebok Kumar; Matsunaga, Hayato; Ishii, Ken J; Ueda, Hiroshi

    2015-12-01

    Prothymosin-alpha protects the brain and retina from ischemic damage. Although prothymosin-alpha contributes to toll-like receptor (TLR4)-mediated immnunopotentiation against viral infection, the beneficial effects of prothymosin-alpha-TLR4 signaling in protecting against ischemia remain to be elucidated. In this study, intravitreal administration of prothymosin-alpha 48 h before induction of retinal ischemia prevented retinal cellular damage as evaluated by histology, and retinal functional deficits as evaluated by electroretinography. Prothymosin-alpha preconditioning completely prevented the ischemia-induced loss of ganglion cells with partial survival of bipolar and photoreceptor cells, but not amacrine cells, in immunohistochemistry experiments. Prothymosin-alpha treatment in the absence of ischemia caused mild activation, proliferation, and migration of retinal microglia, whereas the ischemia-induced microglial activation was inhibited by prothymosin-alpha preconditioning. All these preventive effects of prothymosin-alpha preconditioning were abolished in TLR4 knock-out mice and by pre-treatments with anti-TLR4 antibodies or minocycline, a microglial inhibitor. Prothymosin-alpha preconditioning inhibited the retinal ischemia-induced up-regulation of TLR4-related injury genes, and increased expression of TLR4-related protective genes. Furthermore, the prothymosin-alpha preconditioning-induced prevention of retinal ischemic damage was abolished in TIR-domain-containing adapter-inducing interferon-β knock-out mice, but not in myeloid differentiation primary response gene 88 knock-out mice. Taken together, the results of this study suggest that prothymosin-alpha preconditioning selectively drives TLR4-TIR-domain-containing adapter-inducing interferon-β signaling and microglia in the prevention of retinal ischemic damage. We propose the following mechanism for prothymosin-alpha (ProTα) preconditioning-induced retinal prevention against ischemia: Pro

  9. Microglia preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic rats

    PubMed Central

    Kanazawa, Masato; Miura, Minami; Toriyabe, Masafumi; Koyama, Misaki; Hatakeyama, Masahiro; Ishikawa, Masanori; Nakajima, Takashi; Onodera, Osamu; Takahashi, Tetsuya; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2017-01-01

    Cell-therapies that invoke pleiotropic mechanisms may facilitate functional recovery in stroke patients. We hypothesized that a cell therapy using microglia preconditioned by optimal oxygen-glucose deprivation (OGD) is a therapeutic strategy for ischemic stroke because optimal ischemia induces anti-inflammatory M2 microglia. We first delineated changes in angiogenesis and axonal outgrowth in the ischemic cortex using rats. We found that slight angiogenesis without axonal outgrowth were activated at the border area within the ischemic core from 7 to 14 days after ischemia. Next, we demonstrated that administration of primary microglia preconditioned by 18 hours of OGD at 7 days prompted functional recovery at 28 days after focal cerebral ischemia compared to control therapies by marked secretion of remodelling factors such as vascular endothelial growth factor, matrix metalloproteinase-9, and transforming growth factor-β polarized to M2 microglia in vitro/vivo. In conclusion, intravascular administration of M2 microglia preconditioned by optimal OGD may be a novel therapeutic strategy against ischemic stroke. PMID:28195185

  10. Renal Ischemia/Reperfusion Injury in Diabetic Rats: The Role of Local Ischemic Preconditioning

    PubMed Central

    Ozbilgin, Sule; Ozkardesler, Sevda; Akan, Mert; Boztas, Nilay; Ozbilgin, Mucahit; Ergur, Bekir Ugur; Derici, Serhan; Guneli, Mehmet Ensari; Meseri, Reci

    2016-01-01

    Background. The aim of this study was to evaluate the effects of local ischemic preconditioning using biochemical markers and histopathologically in the diabetic rat renal IR injury model. Methods. DM was induced using streptozotocin. Rats were divided into four groups: Group I, nondiabetic sham group (n = 7), Group II, diabetic sham group (n = 6), Group III, diabetic IR group (diabetic IR group, n = 6), and Group IV, diabetic IR + local ischemic preconditioning group (diabetic IR + LIPC group, n = 6). Ischemic renal injury was induced by clamping the bilateral renal artery for 45 min. 4 h following ischemia, clearance protocols were applied to assess biochemical markers and histopathologically in rat kidneys. Results. The histomorphologic total cell injury scores of the nondiabetic sham group were significantly lower than diabetic sham, diabetic IR, and diabetic IR + LIPC groups. Diabetic IR group scores were not significantly different than the diabetic sham group. But diabetic IR + LIPC group scores were significantly higher than the diabetic sham and diabetic IR groups. Conclusion. Local ischemic preconditioning does not reduce the risk of renal injury induced by ischemia/reperfusion in diabetic rat model. PMID:26925416

  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.

  12. Is delayed ischemic preconditioning as effective on running performance during a 5km time trial as acute IPC?

    PubMed

    Seeger, Joost P H; Timmers, Silvie; Ploegmakers, Danique J M; Cable, N Timothy; Hopman, Maria T E; Thijssen, Dick H J

    2017-02-01

    Ischemic preconditioning (IPC) may enhance exercise performance. Cardioprotective effects of IPC are known to re-occur 24h after the stimulus. Whether the delayed effect of IPC has similar effects as IPC on exercise performance is unknown.

  13. Progressive Evaluation of Apoptosis, Proliferation, and Angiogenesis in Fresh Rat Ovarian Autografts Under Remote Ischemic Preconditioning.

    PubMed

    Damous, Luciana Lamarão; Silva, Sônia Maria da; Carbonel, Adriana Aparecida Ferraz; Simões, Manuel de Jesus; Baracat, Edmund Chada; Montero, Edna Frasson de Souza

    2016-06-01

    This study evaluated the remote ischemic preconditioning (R-IPC) early and late repercussion on fresh ovarian transplants, aiming to assess a probable protective effect in ovarian follicular pool. Sixty Wistar EPM-1 rats were used, divided in 2 study groups: ovarian transplantation (Tx) and Tx + R-IPC, submitted to ovary transplant with or without R-IPC, respectively. These groups were subdivided according to the date for euthanasia: 4th, 7th, 14th, 21st, and 30th days of the postoperatory period. Morphology, morphometry, neoangiogenesis (vascular endothelial growth factor [VEGF]), proliferative activity (Ki-67), and apoptosis (cleaved caspase-3) were evaluated. Remote ischemic preconditioning was performed in the common iliac artery. Fresh autologous ovarian tissue was implanted integrally in the retroperitoneum. All animals showed resumption of estrous phase after ovary transplantation. Remote ischemic preconditioning attenuated the lesions progressively from the 7th day, with greater number of the immature follicles (14 days, P < .05), but didn't affect mature follicles and corpora lutea (P > .05). Immunohistochemical analyzes, taken as a whole, show that R-IPC benefic effect is more evident in the later periods of evaluation, when a greater proliferative activity (14, 21, and 30 days, P < .05) and lesser cell apoptotic activity (21 and 30 days, P < .05). The VEGF expression was similar in all times (P > .05). Remote ischemic preconditioning could have a benefic effect in the progressive evaluation of freshly grafted ovarian, especially on the latest phases of the posttransplant period. The 14th day was a landmark in the recuperation of the graft. Further investigations are necessary to determine the role of R-IPC in this scenario and its effect in frozen-thawed ovarian tissue.

  14. Xenon protects left ventricular diastolic function during acute ischemia, less than ischemic preconditioning

    PubMed Central

    Baumert, Jan-H.; Roehl, Anna B.; Funcke, Sandra; Hein, Marc

    2016-01-01

    Anesthetics modify regional left ventricular (LV) dysfunction following ischemia/reperfusion but their effects on global function in this setting are less clear. Aim of this study was to test the hypothesis that xenon would limit global LV dysfunction as caused by acute anterior wall ischemia, comparable to ischemic preconditioning. In an open-chest model under thiopental anesthesia, 30 pigs underwent 60-minute left anterior descending coronary artery occlusion, followed by 120 minutes of reperfusion. A xenon group (constant inhalation from previous to ischemia through end of reperfusion) was compared to control and ischemic preconditioning. Load-independent measures of diastolic function (end-diastolic pressure-volume relation, time constant of relaxation) and systolic function (end-systolic pressure-volume relation, preload-recruitable stroke work) were determined. Heart rate, arterial pressure, cardiac output, and arterial elastance were recorded. Data were compared in 26 pigs. Ischemia impaired global diastolic but not systolic function in control, which recovered during reperfusion. Xenon limited and preconditioning abolished diastolic dysfunction during ischemia. Arterial pressure decreased during reperfusion while arterial elastance increased. Tachycardia and antero-septal wall edema during reperfusion were observed in all groups. In spite of ischemia of 40% of LV mass, global systolic function was preserved. Deterioration in global diastolic function was limited by xenon and prevented by preconditioning. PMID:27867480

  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. Resveratrol preconditioning protects against cerebral ischemic injury via Nrf2

    PubMed Central

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

    2015-01-01

    Background and Purpose Nuclear erythroid 2 related factor 2 (Nrf2) is an astrocyte-enriched transcription factor that has previously been shown to upregulate cellular antioxidant systems in response to ischemia. While resveratrol preconditioning (RPC) has emerged as a potential neuroprotective therapy, the involvement of Nrf2 in RPC-induced neuroprotection and mitochondrial reactive oxygen species (ROS) production following cerebral ischemia remains unclear. The goal of our study was to study the contribution of Nrf2 to RPC and its effects on mitochondrial function. Methods We used rodent astrocyte cultures and an in vivo stroke model with RPC. An Nrf2 DNA-binding ELISA and protein analysis via Western blotting of downstream Nrf2 targets were performed to determine RPC-induced activation of Nrf2 in rat and mouse astrocytes. Following RPC, mitochondrial function was determined by measuring ROS production and mitochondrial respiration in both wild-type (WT) and Nrf2−/− mice. Infarct volume was measured to determine neuroprotection, while protein levels were measured by immunoblotting. Results We report that Nrf2 is activated by RPC in rodent astrocyte cultures, and that loss of Nrf2 reduced RPC-mediated neuroprotection in a mouse model of focal cerebral ischemia. In addition, we observed that wild-type and Nrf2−/− cortical mitochondria exhibited increased uncoupling and ROS production following RPC treatments, Finally, Nrf2−/− astrocytes exhibited decreased mitochondrial antioxidant expression and were unable to upregulate cellular antioxidants following RPC treatment. Conclusion Nrf2 contributes to RPC-induced neuroprotection through maintaining mitochondrial coupling and antioxidant protein expression. PMID:25908459

  17. Combined Preconditioning and Postconditioning Provides Synergistic Protection against Liver Ischemic Reperfusion Injury

    PubMed Central

    Song, Xiaoyu; Zhang, Ning; XU, Hongde; Cao, Liu; Zhang, Haipeng

    2012-01-01

    Hepatic Ischemia and Reperfusion Injury (IRI) is a major cause of liver damage during liver surgery and transplantation. Ischemic preconditioning and postconditioning are strategies that can reduce IRI. In this study, different combined types of pre- and postconditioning procedures were tested in a murine warm hepatic IRI model to evaluate their protective effects. Proanthocyanidins derived from grape seed was used before ischemia process as pharmacological preconditioning to combine with technical preconditioning and postconditioning. Three pathways related to IRI, including reactive oxygen species (ROS) generation, pro-inflammatory cytokines release and hypoxia responses were examined in hepatic IRI model. Individual and combined pre- and postconditioning protocols significantly reduce liver injury by decreasing the liver ROS and cytokine levels, as well as enhancing the hypoxia tolerance response. Our data also suggested that in addition to individual preconditioning or postconditioning, the combination of these two treatments could reduce liver ischemia/reperfusion injury more effectively by increasing the activity of ROS scavengers and antioxidants. The utilization of grape seed proanthocyanidins (GSP) could improve the oxidation resistance in combined pre- and postconditioning groups. The combined protocol also further increased the liver HIF-1 alpha protein level, but had no effect on pro-inflammatory cytokines release compared to solo treatment. PMID:22701341

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

    PubMed

    Gao, Chunlin; Cai, Ying; 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.

  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. Inhibition of CD34+ cell migration by matrix metalloproteinase-2 during acute myocardial ischemia, counteracted by ischemic preconditioning

    PubMed Central

    Lukovic, Dominika; Zlabinger, Katrin; Gugerell, Alfred; Spannbauer, Andreas; Pavo, Noemi; Mandic, Ljubica; Weidenauer, Denise T.; Kastl, Stefan; Kaun, Christoph; Posa, Aniko; Sabdyusheva Litschauer, Inna; Winkler, Johannes; Gyöngyösi, Mariann

    2017-01-01

    Background. Mobilization of bone marrow-origin CD34+ cells was investigated 3 days (3d) after acute myocardial infarction (AMI) with/without ischemic preconditioning (IP) in relation to stromal-derived factor-1 (SDF-1α)/ chemokine receptor type 4 (CXCR4) axis, to search for possible mechanisms behind insufficient cardiac repair in the first days post-AMI.  Methods. Closed-chest reperfused AMI was performed by percutaneous balloon occlusion of the mid-left anterior descending (LAD) coronary artery for 90min, followed by reperfusion in pigs. Animals were randomized to receive either IP initiated by 3x5min cycles of re-occlusion/re-flow prior to AMI (n=6) or control AMI (n=12). Blood samples were collected at baseline, 3d post-AMI, and at 1-month follow-up to analyse chemokines and mobilized CD34+ cells. To investigate the effect of acute hypoxia, SDF-1α and matrix metalloproteinase (MMP)-2 in vitro were assessed, and a migration assay of CD34+ cells toward cardiomyocytes was performed.  Results. Reperfused AMI induced significant mobilisation of CD34+ cells (baseline: 260±75 vs. 3d: 668±180; P<0.001) and secretion of MMP-2 (baseline: 291.83±53.40 vs. 3d: 369.64±72.89; P=0.011) into plasma, without affecting the SDF-1α concentration. IP led to the inhibition of MMP-2 (IP: 165.67±47.99 vs. AMI: 369.64±72.89; P=0.004) 3d post-AMI, accompanied by increased release of SDF-1α (baseline: 23.80±12.36 vs. 3d: 45.29±11.31; P=0.05) and CXCR4 (baseline: 0.59±0.16 vs. 3d: 2.06±1.42; P=0.034), with a parallel higher level of mobilisation of CD34+ cells (IP: 881±126 vs. AMI: 668±180; P=0.026), compared to non-conditioned AMI. In vitro, CD34+ cell migration toward cardiomyocytes was enhanced by SDF-1α, which was completely abolished by 90min hypoxia and co-incubation with MMP-2.  Conclusions. Non-conditioned AMI induces MMP-2 release, hampering the ischemia-induced increase in SDF-1α and CXCR4 by cleaving the SDF-1α/CXCR4 axis, with diminished mobilization of

  1. Ischemic preconditioning decreases intracellular zinc accumulation induced by oxygen-glucose deprivation in gerbil hippocampal CA1 neurons.

    PubMed

    Miyawaki, Takahiro; Yokota, Hidenori; Oguro, Keiji; Kato, Kengo; Shimazaki, Kuniko

    2004-05-27

    In normal gerbils, intracellular zinc ions ([Zn2+]i) and calcium ions ([Ca2+]i) accumulate in hippocampal CA1 neurons after global ischemia. We examined whether ischemic preconditioning modifies these changes in gerbil hippocampal slices. In normal slices, large increases in [Zn2+]i and [Ca2+]i were observed in the stratum radiatum of the CA1 area after oxygen-glucose deprivation. In preconditioned slices, there were significantly decreased peak levels of [Zn2+]i and [Ca2+]i in CA1. However, there were no differences in the peak levels of these ions in CA3 and dentate gyrus. These results suggest that modified [Zn2+]i and [Ca2+]i accumulation after an ischemic insult might be important for the mechanisms of ischemic tolerance induced by preconditioning.

  2. Translational downregulation of the noncatalytic growth factor receptor TrkB.T1 by ischemic preconditioning of primary neurons.

    PubMed

    Steinbeck, Julius A; Methner, Axel

    2005-01-01

    Short episodes of ischemia can protect neuronal cells and tissue against a subsequent lethal ischemia by a phenomenon called ischemic preconditioning. The development of this tolerance depends on protein synthesis and takes at least 1 day. It therefore seems reasonable that preconditioning leads to upregulation and translation of protective genes or posttranslational modification of pro- or antiapoptotic proteins. We recently used suppression subtractive hybridization to identify transcripts upregulated in rat primary neuronal cultures preconditioned by oxygen glucose deprivation. In this contribution, we describe the previously unknown 7-kb full-length sequence of an upregulated expressed sequence tag and show that it constitutes the 3' end of the large untranslated region of the noncatalytic "truncated" growth factor receptor TrkB.T1. TrkB.T1 is expressed most prominently in the adult brain and its mRNA was found to be 2.1-fold upregulated by ischemic preconditioning. At the protein level, however, TrkB.T1 was clearly downregulated, possibly by increased degradation in preconditioned cultures. TrKB.T1 can act as a dominant-negative inhibitor of its catalytic counterpart TrkB, which is the receptor for brain-derived neurotrophic factor (BDNF), a factor induced by ischemia that can protect from ischemia-induced neuron loss. We hypothesize that the downregulation of TrkB.T1 at the protein level can prolong BDNF-mediated protective signaling via the catalytic receptor and thus participates in the development of ischemic preconditioning.

  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. Cardiomyocyte mitochondria as targets of humoral factors released by remote ischemic preconditioning

    PubMed Central

    Gedik, Nilguen; Maciel, Leonardo; Schulte, Christiane; Skyschally, Andreas; Heusch, Gerd

    2016-01-01

    Introduction Remote ischemic preconditioning (RIPC) reduces myocardial infarct size, and protection can be transferred with plasma to other individuals, even across species. Mitochondria are the end-effectors of cardioprotection by local ischemic conditioning maneuvers. We have now analyzed mitochondrial function in response to RIPC. Material and methods Plasma from pigs undergoing placebo or RIPC (infarct size reduction by 67% in RIPC pigs compared to placebo) was transferred to isolated perfused rat hearts subjected to 30 min global ischemia followed by 120 min reperfusion for infarct size measurement. Additional experiments were terminated at 10 min reperfusion to isolate mitochondria for functional measurements. Effects of RIPC pig plasma were compared to local ischemic preconditioning (IPC) or to infusion of tumor necrosis factor α (TNF-α). Results Ischemia/reperfusion (I/R) induced an infarct of 41 ±2% of total ventricular mass. Placebo pig plasma did not affect infarct size (38 ±1, p = 0.13). The RIPC pig plasma reduced infarct size (27 ±2, p < 0.001), as did IPC (20 ±1, p < 0.001) and TNF-α (28 ±2, p < 0.001). Associated with cardioprotection, reductions of mitochondrial adenosine diphosphate (ADP)-stimulated respiration, adenosine triphosphate (ATP) production and calcium retention capacity (CRC) by I/R and placebo pig plasma were prevented by RIPC pig plasma, as they were by IPC and TNF-α. Mitochondrial reactive oxygen species production (nmol H2O2/100 µg protein) induced by I/R (272 ±34) was comparable in response to placebo pig plasma (234 ±28, p = 0.37) and was reduced by RIPC pig plasma (83 ±15, p < 0.001) as well as by IPC (78 ±21, p < 0.001) and TNF-α (125 ±42, p = 0.002). Conclusions In rat myocardium, mitochondria are an intracellular target of protection induced by humoral factors retrieved from pigs undergoing RIPC. PMID:28261301

  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. Cardiac-specific overexpression of caveolin-3 induces endogenous cardiac protection by mimicking ischemic preconditioning

    PubMed Central

    Tsutsumi, Yasuo M.; Horikawa, Yousuke T.; Jennings, Michelle M.; Kidd, Michael W.; Niesman, Ingrid R.; Yokoyama, Utako; Head, Brian P.; Hagiwara, Yasuko; Ishikawa, Yoshihiro; Miyanohara, Atsushi; Patel, Piyush M.; Insel, Paul A.; Patel, Hemal H.; Roth, David M.

    2009-01-01

    Background Caveolae, lipid-rich microdomains of the sarcolemma, localize and enrich cardiac protective signaling molecules. Caveolin-3 (Cav-3), the dominant isoform in cardiac myocytes, is a determinant of caveolae formation. We hypothesized that cardiac myocyte-specific overexpression of Cav-3 would enhance the formation of caveolae and augment cardiac protection in vivo. Methods and Results Ischemic preconditioning (IPC) in vivo increased formation of caveolae. Adenovirus for Cav-3 increased caveolar formation and phosphorylation of survival kinases in cardiac myocytes. A transgenic (TG) mouse with cardiac myocyte-specific overexpression of Cav-3 (Cav-3 OE) showed enhanced formation of caveolae on the sarcolemma. Cav-3 OE mice subjected to ischemia/reperfusion injury had a significantly reduced infarct size relative to TGneg mice. Endogenous cardiac protection in Cav-3 OE mice was similar to wild-type mice undergoing IPC; no increased protection was observed in preconditioned Cav-3 OE mice. Cav-3 knockout mice did not show endogenous protection and showed no protection in response to IPC. Cav-3 OE mouse hearts had increased basal Akt and GSK3β phosphorylation comparable to wild-type mice exposed to IPC. Wortmannin, a PI3K inhibitor, attenuated basal phosphorylation of Akt and GSK3β and blocked cardiac protection in Cav-3 OE mice. Cav-3 OE mice had improved functional recovery and reduced apoptosis at 24 h of reperfusion. Conclusion Expression of caveolin-3 is both necessary and sufficient for cardiac protection, a conclusion that unites long-standing ultrastructural and molecular observations in the ischemic heart. The current results indicate that increased expression of caveolins, apparently via actions that depend on PI3K, has the potential to protect hearts exposed to ischemia-reperfusion injury. PMID:18936328

  9. Insulin suppresses ischemic preconditioning-mediated cardioprotection through Akt-dependent mechanisms.

    PubMed

    Fullmer, Tanner M; Pei, Shaobo; Zhu, Yi; Sloan, Crystal; Manzanares, Robert; Henrie, Brandon; Pires, Karla M; Cox, James E; Abel, E Dale; Boudina, Sihem

    2013-11-01

    It is believed that the diabetic myocardium is refractory to cardioprotection by ischemic preconditioning (IPC) mainly because of impaired insulin signaling to phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB or Akt). However, human as well as animal studies have clearly showed that the hearts of type 2 diabetic humans and animals may exhibit increased signaling through PI3K-Akt but yet are resistant to cardioprotection by IPC or ischemic post-conditioning. Therefore, this study was designed to determine whether activation of insulin signaling prior to IPC is detrimental for cardioprotection and to assess the role of insulin receptors (IRs) and Akt in mediating this effect. Wild-type (WT) hearts, hearts lacking IRs or hearts expressing an active form of Akt (myrAkt1) were perfused ex vivo using a Langendorff preparation and were subjected to IPC (3cycles of 5min ischemia followed by 5min reflow before 30min no flow ischemia and then by 45min reperfusion) in the presence or absence of 1nmol/L insulin. Interestingly, whereas insulin was protective against I/R (30min no flow ischemia and 45min reperfusion), it completely abolished cardioprotection by IPC in WT hearts but not in mice lacking insulin receptors (IRs) in cardiomyocytes (CIRKO) or in all cardiac cells (TIRKO). The suppression of IPC-mediated cardioprotection was mediated through downstream signaling to Akt and Gsk3β. In addition, transgenic induction of Akt in the heart was sufficient to abrogate IPC even when insulin was absent, further confirming the involvement of Akt in insulin's suppression of cardioprotection by IPC. These data provide evidence that excessive insulin signaling to Akt is detrimental for cardioprotection by IPC and could explain the failure of the diabetic myocardium to precondition.

  10. Unraveling the role of adenosine in remote ischemic preconditioning-induced cardioprotection.

    PubMed

    Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

    2016-06-15

    Remote ischemic preconditioning (RIPC) induced by alternate cycles of preconditioning ischemia and reperfusion protects the heart against sustained ischemia-reperfusion-induced injury. This technique has been translated to clinical levels in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention and heart valve surgery. Adenosine is a master regulator of energy metabolism and reduces myocardial ischemia-reperfusion-induced injury. Furthermore, adenosine is a critical trigger as well as a mediator in RIPC-induced cardioprotection and scientists have demonstrated the role of adenosine by showing an increase in its levels in the systemic circulation during RIPC delivery. Furthermore, the blockade of cardioprotective effects of RIPC in the presence of specific adenosine receptor blockers and transgenic animals with targeted ablation of A1 receptors has also demonstrated its critical role in RIPC. The studies have shown that adenosine may elicit cardioprotection via activation of neurogenic pathway. The present review describes the possible role and mechanism of adenosine in mediating RIPC-induced cardioprotection.

  11. Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase.

    PubMed

    Wang, Feng; Yin, Jianyong; Lu, Zeyuan; Zhang, Guangyuan; Li, Junhui; Xing, Tao; Zhuang, Shougang; Wang, Niansong

    2016-07-01

    Clinical trials shows that remote ischemic preconditioning (IPC) can protect against contrast induced nephropathy (CIN) in risky patients, however, the exact mechanism is unclear. In this study, we explored whether renalase, an amine oxidase that has been previously shown to mediate reno-protection by local IPC, would also mediate the same effect elicited by remote IPC in animal model. Limb IPC was performed for 24h followed by induction of CIN. Our results indicated that limb IPC prevented renal function decline, attenuated tubular damage and reduced oxidative stress and inflammation in the kidney. All those beneficial effects were abolished by silencing of renalase with siRNA. This suggests that similar to local IPC, renalase is also critically involved in limb IPC-elicited reno-protection. Mechanistic studies showed that limb IPC increased TNFα levels in the muscle and blood, and up-regulated renalase and phosphorylated IκBα expression in the kidney. Pretreatment with TNFα antagonist or NF-κB inhibitor, largely blocked renalase expression. Besides, TNFα preconditioning increased expression of renal renalase in vivo and in vitro, and attenuated H2O2 induced apoptosis in renal tubular cells. Collectively, our results suggest that limb IPC-induced reno-protection in CIN is dependent on increased renalase expression via activation of the TNFα/NF-κB pathway.

  12. KATP channels are common mediators of ischemic and calcium preconditioning in rabbits.

    PubMed

    Kouchi, I; Murakami, T; Nawada, R; Akao, M; Sasayama, S

    1998-04-01

    Calcium preconditioning (CPC), like ischemic preconditioning (IPC), reduces myocardial infarct size in dogs and rats. ATP-sensitive potassium (KATP) channels induce cardioprotection of IPC in these animals. To determine whether KATP channels mediate both IPC and CPC, pentobarbital sodium-anesthetized rabbits received 30 min of coronary artery occlusion followed by 180 min of reperfusion. IPC was elicited by 5 min of occlusion and 10 min of reperfusion, and CPC was elicited by two cycles of 5 min of calcium infusion with an interval period of 15 min. Infarct size expressed as a percentage of the area at risk was 38 +/- 3% (mean +/- SE) in controls. IPC, CPC, and pretreatment with a KATP channel opener, cromakalim, all reduced infarct size to 13 +/- 2, 17 +/- 2, and 12 +/- 3%, respectively (P < 0.01 vs. controls). Glibenclamide, a KATP channel blocker administered 45 min (but not 20 min) before sustained ischemia, attenuated the effects of IPC and CPC (31 +/- 4 and 41 +/- 6%, respectively). Thus KATP channel activation appears to contribute to these two types of cardioprotection in rabbits.

  13. Ischemic preconditioning improves oxygen saturation and attenuates hypoxic pulmonary vasoconstriction at high altitude.

    PubMed

    Foster, Gary P; Giri, Paresh C; Rogers, Douglas M; Larson, Sophia R; Anholm, James D

    2014-06-01

    Exposure to hypoxic environments is associated with decreased arterial oxygen saturation and increased pulmonary artery pressures. Ischemic preconditioning of an extremity (IPC) is a procedure that stimulates vasoactive and inflammatory pathways that protect remote organ systems from ongoing or future ischemic injury. To test the effects of IPC on oxygen saturation and pulmonary artery pressures at high altitude, 12 healthy adult volunteers were evaluated in a randomized cross-over trial. IPC was administered utilizing a standardized protocol. IPC or placebo was administered daily for 5 days prior to ascent to altitude. All participants were evaluated twice at 4342 m altitude (placebo and IPC conditions separated by 4 weeks, randomized). The pulmonary artery systolic pressure (PASP) at 4342 m was significantly lower in the IPC condition than the placebo condition (36 ± 6.0 mmHg vs. 38.1 ± 7.6 mmHg, respectively, p = 0.035). Oxygen saturation at 4342 m was significantly higher with IPC compared to placebo (80.3 ± 8.7% vs. 75.3 ± 9.6%, respectively, p = 0.003). Prophylactic IPC treatment is associated with improved oxygen saturation and attenuation of the normal hypoxic increase in pulmonary artery pressures following ascent to high altitude.

  14. Exploring the Human Plasma Proteome for Humoral Mediators of Remote Ischemic Preconditioning - A Word of Caution

    PubMed Central

    Helgeland, Erik; Breivik, Lars Ertesvåg; Vaudel, Marc; Svendsen, Øyvind Sverre; Garberg, Hilde; Nordrehaug, Jan Erik; Berven, Frode Steingrimsen; Jonassen, Anne Kristine

    2014-01-01

    Despite major advances in early revascularization techniques, cardiovascular diseases are still the leading cause of death worldwide, and myocardial infarctions contribute heavily to this. Over the past decades, it has become apparent that reperfusion of blood to a previously ischemic area of the heart causes damage in and of itself, and that this ischemia reperfusion induced injury can be reduced by up to 50% by mechanical manipulation of the blood flow to the heart. The recent discovery of remote ischemic preconditioning (RIPC) provides a non-invasive approach of inducing this cardioprotection at a distance. Finding its endogenous mediators and their operative mode is an important step toward increasing the ischemic tolerance. The release of humoral factor(s) upon RIPC was recently demonstrated and several candidate proteins were published as possible mediators of the cardioprotection. Before clinical applicability, these potential biomarkers and their efficiency must be validated, a task made challenging by the large heterogeneity in reported data and results. Here, in an attempt to reproduce and provide more experimental data on these mediators, we conducted an unbiased in-depth analysis of the human plasma proteome before and after RIPC. From the 68 protein markers reported in the literature, only 28 could be mapped to manually reviewed (Swiss-Prot) protein sequences. 23 of them were monitored in our untargeted experiment. However, their significant regulation could not be reproducibly estimated. In fact, among the 394 plasma proteins we accurately quantified, no significant regulation could be confidently and reproducibly assessed. This indicates that it is difficult to both monitor and reproduce published data from experiments exploring for RIPC induced plasma proteomic regulations, and suggests that further work should be directed towards small humoral factors. To simplify this task, we made our proteomic dataset available via ProteomeXchange, where

  15. Ischemic preconditioning protects the brain against injury via inhibiting CaMKII-nNOS signaling pathway.

    PubMed

    Wang, Mei; Qi, Da-Shi; Zhou, Cui; Han, Dong; Li, Pei-Pei; Zhang, Fang; Zhou, Xiao-Yan; Han, Meng; Di, Jie-Hui; Ye, Jun-Song; Yu, Hong-Min; Song, Yuan-Jian; Zhang, Guang-Yi

    2016-03-01

    Although studies have shown that cerebral ischemic preconditioning (IPC) can ameliorate ischemia/reperfusion (I/R) induced brain damage, but its precise mechanisms remain unknown. Therefore, the aim of this study was to investigate the neuroprotective mechanisms of IPC against ischemic brain damage induced by cerebral I/R and to explore whether the Calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated up-regulation of nNOS ser847-phosphorylation signaling pathway contributed to the protection provided by IPC. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. The rats were pretreated with 3 min of IPC alone or KN62 (selective antagonist of CaMKII) treatment before IPC, after reperfusion for 3 days, 6 min ischemia was induced. Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. Immunoblotting was performed to measure the phosphorylation of CaMKII, nNOS, c-Jun and the expression of FasL. Immunoprecipitation was used to examine the binding between PSD95 and nNOS. The results showed that IPC could significantly protect neurons against cerebral I/R injury, furthermore, the combination of PSD95 and nNOS was increased, coinstantaneously the phosphorylation of CaMKII and nNOS (ser847) were up-regulated, however the activation of c-Jun and FasL were reduced. Conversely, KN62 treatment before IPC reversed all these effects of IPC. Taken together, the results suggest that IPC could diminish ischemic brain injury through CaMKII-mediated up-regulation of nNOS ser847-phosphorylation signaling pathway.

  16. Enhanced nitric oxide-mediated autophagy contributes to the hepatoprotective effects of ischemic preconditioning during ischemia and reperfusion.

    PubMed

    Shin, Jun-Kyu; Kang, Jung-Woo; Lee, Sun-Mee

    2016-08-31

    Ischemic preconditioning (IPC) protects against liver ischemia/reperfusion (I/R) injury. Autophagy is an essential cytoprotective system that is rapidly activated by multiple stressors. Nitric oxide (NO) acts as an inducer of IPC. We examined the impact of autophagy in liver IPC and its regulation by NO. Male C57BL/6 mice were subjected to 60 min of hepatic ischemia followed by 6 h of reperfusion. IPC was achieved for 10 min of ischemia followed by 10 min of reperfusion prior to sustained ischemia. N(ω)-Nitro-l-arginine methyl ester (L-NAME, 15 mg/kg, i.v., all NOS inhibitor) and aminoguanidine (AG, 10 mg/kg, i.v., iNOS inhibitor) were injected 10 min before IPC. SB203580 (10 mg/kg, i.p., p38 inhibitor) was injected 30 min before IPC. I/R increased serum alanine aminotransferase activity. IPC attenuated this increase, which was abolished by L-NAME, but not AG. Microtubule-associated protein-1 light chain 3-II levels increased and p62 protein levels decreased after I/R; these changes were augmented by IPC and abolished by L-NAME. I/R increased liver protein expression of autophagy-related protein (Atg)12-Atg5 complex and lysosome-associated membrane protein-2. IPC augmented the expression of these proteins, which were abolished by L-NAME, but not AG. IPC also augmented the level of phosphorylated p38 MAPK induced by I/R and this phosphorylation was abolished by L-NAME. Our findings suggest that IPC-mediated NO protects against I/R-induced liver injury by enhancing autophagic flux.

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

    PubMed Central

    2014-01-01

    Background Ischemic or volatile anesthetic preconditioning is defined as tissue protection from impending ischemic cell damage by repetitive short periods of tissue exposure to ischemia or volatile anesthetics. Objective of this study was to elucidate, if ischemic preconditioning and pharmacological preconditioning with sevoflurane have effects on muscle tissue oxygen saturation in patients undergoing surgical revascularization of the lower limb. Methods In this prospective randomized pilot study ischemic and pharmacological (sevoflurane) preconditioning was performed in 40 patients with lower limb arterial occlusive disease undergoing surgical revascularization. Sevoflurane preconditioning was performed in one group (N = 20) by repetitive application of sevoflurane for six minutes interspersed by six minutes of washout. Thereafter, ischemic preconditioning was performed in all patients (N = 40) by repetitive clamping of the femoral artery for six minutes interspersed by six minutes of reperfusion. The effect of both procedures on leg muscle tissue oxygen saturation (rSO2) was measured by near-infrared spectroscopy during both procedures and during surgery and reperfusion (INVOS® 5100C Oxymeter with Small Adult SomaSensor® SAFB-SM, Somanetics, Troy, Michigan, USA). Results Repetitive clamping and reperfusion of the femoral artery resulted in significant cyclic decrease and increase of muscle rSO2 (p < 0.0001). Pharmacological preconditioning with sevoflurane resulted in a faster and higher increase of rSO2 during postoperative reperfusion (Maximal 111% baseline ± 20 versus 103% baseline ± 14, p = 0.008) consistent with an additional effect of pharmacological preconditioning on leg perfusion. Conclusions Ischemic preconditioning of lower limb muscle tissue and pharmacological preconditioning with sevoflurane have an effect on tissue oxygenation in patients with lower limb occlusive arterial disease. Trial registration The trial has been

  18. Hypophosphorylation of Ribosomal Protein S6 is a Molecular Mechanism Underlying Ischemic Tolerance Induced by either Hibernation or Preconditioning

    PubMed Central

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

    2015-01-01

    Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions of blood flow and oxygen delivery to 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. PMID:26375300

  19. 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

  20. Threshold level of NF-kB activation in small bowel ischemic preconditioning procedure.

    PubMed

    Ferencz, A; Rácz, B; Gasz, B; Kalmár-Nagy, K; Horváth, O P; Röth, E

    2006-01-01

    Ischemic preconditioning (IPC), which is obtained by exposure to brief periods of vascular occlusion, improves organ tolerance to prolonged ischemia. The aim of this study was to evaluate the threshold level of NF-kB activation in small intestine during an IPC procedure. Various intestinal IPC were performed on 20 Wistar rats in seven groups: group I (GI, nonpreconditioned); group II (GII, 1-minute ischemia and 1-minute reperfusion); group III (GIII, two cycles of 1-minute ischemia and 1-minute reperfusion); group IV (GIV, 2-minutes ischemia and 2-minutes reperfusion); group V (GV, two cycles of 2-minute ischemia and 2-minute reperfusion); group VI (GVI, 5-minute ischemia and 10-minute reperfusion); group VII (GVII, two cycles of 5-minute ischemia and 10-minute reperfusion). Bowel biopsies were collected after laparotomy (control) as well as at 30, 60, and 120 minutes following IPC. We determined the cytoplasmic and nuclear NF-kB by a chemiluminescence-based ELISA method. Our results showed low, constant NF-kB levels in GI. In the preconditioned groups (GII-GVII), NF-kB was significantly elevated at 30 minutes following IPC (P < .05 vs control). After 1 hour, NF-kB activity decreased to the control level. However, 2 hours after IPC both forms of NF-kB were elevated significantly again, which was independent of the number of IPC cycles (P < .05 vs control). Our experiments revealed that one cycle of 1-minute ischemia and 1-minute reperfusion is a critical threshold level for NF-kB activation during small bowel IPC. Longer and more IPC cycles did not result in further elevation of NF-kB activation.

  1. Influence of ischemic preconditioning on levels of nerve growth factor, brain-derived neurotrophic factor and their high-affinity receptors in hippocampus following forebrain ischemia.

    PubMed

    Lee, Tsong-Hai; Yang, Jen-Tsung; Ko, Yu-Shien; Kato, Hiroyuki; Itoyama, Yasuto; Kogure, Kyuya

    2008-01-02

    Preconditioning of gerbil brain with a sublethal forebrain ischemia is known to protect hippocampal CA1 neurons following a subsequent lethal ischemia (the second ischemia) which usually damages neurons (ischemic tolerance). Present report using a confocal laser scanning microscope demonstrated that the hippocampal cells of sham operation gerbils contained immunofluorescent NGF and BDNF and their high-affinity receptors (TrkA and TrkB). A 2-min ischemia caused little change of these proteins (ANOVA test, P<0.05). After the second lethal ischemia, in the CA1 area with ischemic preconditioning (2-min ischemia), only BDNF but not NGF and their high-affinity receptors showed a transient reduction at 4 h (ANOVA test, P<0.01) and improved from 1 day (ANOVA test, P<0.05). In the CA1 area without ischemic preconditioning (sham operation), NGF and its high-affinity TrkA receptor showed a consistent reduction from 4 h to 7 days (ANOVA test, P<0.05); BDNF and TrkB decreased transiently from 4 h to 1 day (ANOVA test, P<0.05) but were recovered in the surviving neurons from 3 days. At 3 and 7 days after the second lethal ischemia, apoptotic cell injury could be seen in the CA1 area without ischemic preconditioning but was sparsely noted in the CA1 area with ischemic preconditioning. In the ischemia-resistant CA3 and dentate gyrus areas, only BDNF decreased significantly at 7 days in the CA3 area without ischemic preconditioning (ANOVA test, P<0.01). However, no significant change occurred in NGF, TrkA and TrkB immunofluorescence from 4 h to 7 days after the second lethal ischemia in the CA3 and dentate gyrus areas with and without ischemic preconditioning. Western blot study showed that in the hippocampal formation with ischemic preconditioning, preconditioning prevented the decline of these protein levels from 1 day to 7 days after the second lethal ischemia (ANOVA test, P>0.05). Results of this study demonstrate that ischemic preconditioning recovers the initial decline in

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

    PubMed

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

    2015-01-01

    Ischemic preconditioning (IPC) via protein kinase C epsilon (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.

  3. CpG preconditioning regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury

    PubMed Central

    Vartanian, Keri B; Mitchell, Hugh D; Stevens, Susan L; Conrad, Valerie K; McDermott, Jason E; Stenzel-Poore, Mary P

    2015-01-01

    Cytosine-phosphate-guanine (CpG) preconditioning reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms underlying genomic reprogramming are incompletely understood. MicroRNAs (miRNAs) regulate gene expression; however, their role in modulating gene responses produced by CpG preconditioning is unknown. We evaluated brain miRNA expression in response to CpG preconditioning before and after stroke using microarray. Importantly, we have data from previous gene microarrays under the same conditions, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. CpG preconditioning did not significantly alter miRNA expression before stroke, indicating that miRNA regulation is not critical for the initiation of preconditioning-induced neuroprotection. However, after stroke, differentially regulated miRNAs between CpG- and saline-treated animals associated with the upregulation of several neuroprotective genes, implicating these miRNAs in genomic reprogramming that increases neuroprotection. Statistical analysis revealed that the miRNA targets were enriched in the gene population regulated in the setting of stroke, implying that miRNAs likely orchestrate this gene expression. These data suggest that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel neuroprotective processes that reduce damage. PMID:25388675

  4. Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

    PubMed Central

    Cremers, Niels A. J.; Wever, Kimberley E.; Wong, Ronald J.; van Rheden, René E. M.; Vermeij, Eline A.; van Dam, Gooitzen M.; Carels, Carine E.; Lundvig, Ditte M. S.; Wagener, Frank A. D. T. G.

    2017-01-01

    Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luc transgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively. HO-1 promoter activity was significantly induced on the dorsal side and locally in the kidneys following RIPC treatment. Next, we investigated the origin of this RIPC-induced HO-1 promoter activity and demonstrated increased mRNA in the ligated muscle, heart and kidneys, but not in the skin. RIPC did not change HO-1 mRNA and protein levels in the wound 7 days after cutaneous injury. Both early and late RIPC did not accelerate wound closure nor affect collagen deposition. RIPC induces HO-1 expression in several organs, but not the skin, and did not improve excisional wound repair, suggesting that the skin is insensitive to RIPC-mediated protection. PMID:28218659

  5. Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial

    PubMed Central

    Walsh, Michael; Whitlock, Richard; Garg, Amit X.; Légaré, Jean-François; Duncan, Andra E.; Zimmerman, Robert; Miller, Scott; Fremes, Stephen; Kieser, Teresa; Karthikeyan, Ganesan; Chan, Matthew; Ho, Anthony; Nasr, Vivian; Vincent, Jessica; Ali, Imtiaz; Lavi, Ronit; Sessler, Daniel I.; Kramer, Robert; Gardner, Jeff; Syed, Summer; VanHelder, Tomas; Guyatt, Gordon; Rao-Melacini, Purnima; Thabane, Lehana; Devereaux, P.J.

    2016-01-01

    Background: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. Methods: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase–myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. Results: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] −0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI −0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). Interpretation: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. Trial registration: ClinicalTrials.gov, no. NCT01071265. PMID:26668200

  6. The impact of a single episode of remote ischemic preconditioning on myocardial injury after elective percutaneous coronary intervention

    PubMed Central

    Taylan, Gökay; Aktoz, Meryem; Gürlertop, Hanefi Y.; Aksoy, Yüksel; Özçelik, Fatih; Yalta, Kenan; Ekuklu, Galip

    2017-01-01

    Introduction Myocardial injury after percutaneous coronary intervention (PCI) occurs in approximately 30% of procedures, and is related to worse prognosis. Effects of remote ischemic preconditioning (RIPC) on reperfusion injury have been investigated before, yielding conflicting results. Aim To assess the impact of a single episode of RIPC on myocardial injury after elective PCI. Material and methods One hundred and four patients undergoing elective PCI, with normal baseline cardiac troponin-I (cTn-I) values, were randomized to two groups. Two patients were excluded due to data loss, and 102 patients were analyzed. Five minutes of ischemic preconditioning was delivered just before the intervention to the preconditioning group, by inflating the blood pressure cuff up to 200 mm Hg on the non-dominant arm. Postprocedural 16th hour cTn-I, ΔcTn-I (difference between the 16th h and baseline cTn-I values) and the prevalence of type 4a myocardial infarction were compared between the two groups. Results Median cTn-I values after the procedure were compared. 16th hour cTn-I was insignificantly lower in the preconditioning arm (0.026 μg/l vs. 0.045 μg/l, p = 0.186). The incidence of cTn-I elevation 5-fold above the upper reference limit (URL) (> 0.115 μg/l) was lower in the preconditioning group, but it was also not significant (21.6% vs. 11.8%, p = 0.184). Conclusions A single episode of RIPC before elective PCI demonstrated less troponin elevation but failed to show a significant effect. PMID:28344616

  7. 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

  8. Calcium-sensing receptor: a sensor and mediator of ischemic preconditioning in the heart.

    PubMed

    Sun, Junhui; Murphy, Elizabeth

    2010-11-01

    As a G protein-coupled receptor, the extracellular Ca(2+)-sensing receptor (CaSR) responds to changes not only in extracellular Ca(2+), but also to many other ligands. CaSR has been found to be expressed in the hearts and cardiovascular system. In this study, we confirmed that CaSR is expressed in mouse cardiomyocytes and showed that it is predominantly localized in caveolae. The goal of this study was to investigate whether CaSR plays a cardioprotective role in ischemic preconditioning (IPC). Hearts from C57BL/6J mice (male, 12-16 wk) were perfused in the Langendorff mode and subjected to the following treatments: 1) control perfusion; 2) perfusion with a specific CaSR antagonist, NPS2143; 3) IPC (four cycles of 5 min of global ischemia and 5 min of reperfusion); or 4) perfusion with NPS2143 before and during IPC. Following these treatments, hearts were subjected to 20 min of no-flow global ischemia and 120 min of reperfusion. Compared with control, IPC significantly improved postischemic left ventricular functional recovery and reduced infarct size. Although NPS2143 perfusion alone did not change the hemodynamic function and did not change the extent of postischemic injury, NPS2143 treatment abolished cardioprotection of IPC. Through immunoblot analysis, it was demonstrated that IPC significantly increased the levels of phosphorylated ERK1/2, AKT, and GSK-3β, which were also prevented by NPS2143 treatment. Taken together, the distribution of CaSR in caveolae along with NPS2143-blockade of IPC-induced cardioprotective signaling suggest that the activation of CaSR during IPC is cardioprotective by a process involving caveolae.

  9. Apolipoprotein A-I Is a Potential Mediator of Remote Ischemic Preconditioning

    PubMed Central

    Hibert, Pierre; Prunier-Mirebeau, Delphine; Beseme, Olivia; Chwastyniak, Maggy; Tamareille, Sophie; Lamon, Delphine; Furber, Alain; Pinet, Florence; Prunier, Fabrice

    2013-01-01

    Background Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy in clinical settings. Despite convincing evidence of the critical role played by circulating humoral mediators, their actual identities remain unknown. In this study, we aimed to identify RIPC-induced humoral mediators using a proteomic approach. Methods and Results Rats were exposed to 10-min limb ischemia followed by 5- (RIPC 5′) or 10-min (RIPC 10′) reperfusion prior to blood sampling. The control group only underwent blood sampling. Plasma samples were analyzed using surface-enhanced laser desorption and ionization - time of flight - mass spectrometry (SELDI-TOF-MS). Three protein peaks were selected for their significant increase in RIPC 10′. They were identified and confirmed as apolipoprotein A-I (ApoA-I). Additional rats were exposed to myocardial ischemia-reperfusion (I/R) and assigned to one of the following groups RIPC+myocardial infarction (MI) (10-min limb ischemia followed by 10-min reperfusion initiated 20 minutes prior to myocardial I/R), ApoA-I+MI (10 mg/kg ApoA-I injection 10 minutes before myocardial I/R), and MI (no further intervention). In comparison with untreated MI rats, RIPC reduced infarct size (52.2±3.7% in RIPC+MI vs. 64.9±2.6% in MI; p<0.05). Similarly, ApoA-I injection decreased infarct size (50.9±3.8%; p<0.05 vs. MI). Conclusions RIPC was associated with a plasmatic increase in ApoA-I. Furthermore, ApoA-I injection before myocardial I/R recapitulated the cardioprotection offered by RIPC in rats. This data suggests that ApoA-I may be a protective blood-borne factor involved in the RIPC mechanism. PMID:24155931

  10. Mechanisms underpinning protection against eccentric exercise-induced muscle damage by ischemic preconditioning.

    PubMed

    Franz, Alexander; Behringer, Michael; Nosaka, Kazunori; Buhren, Bettina Alexandra; Schrumpf, Holger; Mayer, Constantin; Zilkens, Christoph; Schumann, Moritz

    2017-01-01

    Eccentric exercise training is effective for increasing muscle mass and strength, and improving insulin sensitivity and blood lipid profiles. However, potential muscle damage symptoms such as prolonged loss of muscle function and delayed onset of muscle soreness may restrict the use of eccentric exercise, especially in clinical populations. Therefore, strategies to reduce eccentric exercise-induced muscle damage (EIMD) are necessary, and an extensive number of scientific studies have tried to identify potential intervention modalities to perform eccentric exercises without adverse effects. The present paper is based on a narrative review of current literature, and provides a novel hypothesis by which an ischemic preconditioning (IPC) of the extremities may reduce EIMD. IPC consists of an intermittent application of short-time non-lethal ischemia to an extremity (e.g. using a tourniquet) followed by reperfusion and was discovered in clinical settings in an attempt to minimize inflammatory responses induced by ischemia and ischemia-reperfusion-injury (I/R-Injury) during surgery. The present hypothesis is based on morphological and biochemical similarities in the pathophysiology of skeletal muscle damage during clinical surgery and EIMD. Even though the primary origin of stress differs between I/R-Injury and EIMD, subsequent cellular alterations characterized by an intracellular accumulation of Ca(2+), an increased production of reactive oxygen species or increased apoptotic signaling are essential elements for both. Moreover, the incipient immune response appears to be similar in I/R-Injury and EIMD, which is indicated by an infiltration of leukocytes into the damaged soft-tissue. Thus far, IPC is considered as a potential intervention strategy in the area of cardiovascular or orthopedic surgery and provides significant impact on soft-tissue protection and downregulation of undesired excessive inflammation induced by I/R-Injury. Based on the known major impact of IPC

  11. Effect of ischemic preconditioning in skeletal muscle measured by functional magnetic resonance imaging and spectroscopy: a randomized crossover trial

    PubMed Central

    2011-01-01

    Background Nuclear magnetic resonance (NMR) imaging and spectroscopy have been applied to assess skeletal muscle oxidative metabolism. Therefore, in-vivo NMR may enable the characterization of ischemia-reperfusion injury. The goal of this study was to evaluate whether NMR could detect the effects of ischemic preconditioning (IPC) in healthy subjects. Methods Twenty-three participants were included in two randomized crossover protocols in which the effects of IPC were measured by NMR and muscle force assessments. Leg ischemia was administered for 20 minutes with or without a subsequent impaired reperfusion for 5 minutes (stenosis model). IPC was administered 4 or 48 hours prior to ischemia. Changes in 31phosphate NMR spectroscopy and blood oxygen level-dependent (BOLD) signals were recorded. 3-Tesla NMR data were compared to those obtained for isometric muscular strength. Results The phosphocreatine (PCr) signal decreased robustly during ischemia and recovered rapidly during reperfusion. In contrast to PCr, the recovery of muscular strength was slow. During post-ischemic stenosis, PCr increased only slightly. The BOLD signal intensity decreased during ischemia, ischemic exercise and post-ischemic stenosis but increased during hyperemic reperfusion. IPC 4 hours prior to ischemia significantly increased the maximal PCr reperfusion signal and mitigated the peak BOLD signal during reperfusion. Conclusions Ischemic preconditioning positively influenced muscle metabolism during reperfusion; this resulted in an increase in PCr production and higher oxygen consumption, thereby mitigating the peak BOLD signal. In addition, an impairment of energy replenishment during the low-flow reperfusion was detected in this model. Thus, functional NMR is capable of characterizing changes in reperfusion and in therapeutic interventions in vivo. Trial Registration ClinicalTrials.gov: NCT00883467 PMID:21718491

  12. Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver.

    PubMed

    Duarte, Filipe V; Amorim, João A; Varela, Ana T; Teodoro, João S; Gomes, Ana P; Cunha, Rodrigo A; Palmeira, Carlos M; Rolo, Anabela P

    2016-11-15

    Although adenosine A1 receptors (A1R) have been associated to ischemic preconditioning (IPC), direct evidence for their ability to preserve mitochondrial function upon hepatic preconditioning is still missing and could represent a novel strategy to boost the quality of liver transplants. We tested if the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) prevented IPC in the liver and if the A1R agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) might afford a pharmacological preconditioning. Livers underwent a 120 min of 70% warm ischemia and 16 h of reperfusion (I/R), and the IPC group underwent a 5-min ischemic episode followed by a 10-min period of reperfusion before I/R. DPCPX or CCPA was administered intraperitoneally 2 h before IPC or I/R. The control of mitochondrial function emerged as the central element affected by IPC and controlled by endogenous A1R activation. Thus, livers from IPC- or CCPA-treated rats displayed an improved oxidative phosphorylation with higher state 3 respiratory rate, higher respiratory control ratio, increased ATP content, and decreased lag phase. IPC and CCPA also prevented the I/R-induced susceptibility to calcium-induced mitochondrial permeability transition, the rate of reactive oxygen species (ROS) generation, and the decreased mitochondrial content of phospho-Ser(9) GSK-3β. DPCPX abrogated these effects of IPC. These implicate the control of GSK-3β activity by Akt-mediated Ser(9)-GSK-3β phosphorylation preserving the efficiency of oxidative phosphorylation and ROS-mediated cell death in the ability of A1R activation to mimic IPC in the liver. In conclusion, the parallel between IPC and A1R-mediated preconditioning also paves the way to consider a putative therapeutic use of the later in liver transplants.

  13. Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts.

    PubMed Central

    Ramasamy, R; Liu, H; Anderson, S; Lundmark, J; Schaefer, S

    1995-01-01

    One or more brief periods of ischemia, termed preconditioning, dramatically limits infarct size and reduces intracellular acidosis during subsequent ischemia, potentially via enhanced sarcolemmal proton efflux mechanisms. To test the hypothesis that preconditioning increases the functional activity of sodium-dependent proton efflux pathways, isolated rat hearts were subjected to 30 min of global ischemia with or without preconditioning. Intracellular sodium (Nai) was assessed using 23Na magnetic resonance spectroscopy, and the activity of the Na-H exchanger and Na-K-2Cl cotransporter was measured by transiently exposing the hearts to an acid load (NH4Cl washout). Creatine kinase release was reduced by greater than 60% in the preconditioned hearts (P < 0.05) and was associated with improved functional recovery on reperfusion. Preconditioning increased Nai by 6.24 +/- 2.04 U, resulting in a significantly higher level of Nai before ischemia than in the control hearts. Nai increased significantly at the onset of ischemia (8.48 +/- 1.21 vs. 2.57 +/- 0.81 U, preconditioned vs. control hearts; P < 0.01). Preconditioning did not reduce Nai accumulation during ischemia, but the decline in Nai during the first 5 min of reperfusion was significantly greater in the preconditioned than in the control hearts (13.48 +/- 1.73 vs. 2.54 +/- 0.41 U; P < 0.001). Exposure of preconditioned hearts to ethylisopropylamiloride or bumetanide in the last reperfusion period limited in the increase in Nai during ischemia and reduced the beneficial effects of preconditioning. After the NH4Cl prepulse, preconditioned hearts acidified significantly more than control hearts and had significantly more rapid recovery of pH (preconditioned, delta pH = 0.35 +/- 0.04 U over 5 min; control, delta pH = 0.15 +/- 0.02 U over 5 min). This rapid pH recovery was not affected by inhibition of the Na-K-2Cl cotransporter but was abolished by inhibition of the Na-H exchanger. These results demonstrate that

  14. Electroacupuncture preconditioning attenuates ischemic brain injury by activation of the adenosine monophosphate-activated protein kinase signaling pathway

    PubMed Central

    Ran, Qiang-qiang; Chen, Huai-long; Liu, Yan-li; Yu, Hai-xia; Shi, Fei; Wang, Ming-shan

    2015-01-01

    Electroacupuncture has therapeutic effects on ischemic brain injury, but its mechanism is still poorly understood. In this study, mice were stimulated by electroacupuncture at the Baihui (GV20) acupoint for 30 minutes at 1 mA and 2/15 Hz for 5 consecutive days. A cerebral ischemia model was established by ligating the bilateral common carotid artery for 15 minutes. At 72 hours after injury, neuronal injury in the mouse hippocampus had lessened, and the number of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-positive cells reduced after electroacupuncture treatment. Moreover, expression of adenosine monophosphate-activated protein kinase α (AMPKα) and phosphorylated AMPKα was up-regulated. Intraperitoneal injection of the AMPK antagonist, compound C, suppressed this phenomenon. Our findings suggest that electroacupuncture preconditioning alleviates ischemic brain injury via AMPK activation. PMID:26330828

  15. Additive Effect on Survival of Anaesthetic Cardiac Protection and Remote Ischemic Preconditioning in Cardiac Surgery: A Bayesian Network Meta-Analysis of Randomized Trials

    PubMed Central

    Zangrillo, Alberto; Musu, Mario; Greco, Teresa; Di Prima, Ambra Licia; Matteazzi, Andrea; Testa, Valentina; Nardelli, Pasquale; Febres, Daniela; Monaco, Fabrizio; Calabrò, Maria Grazia; Ma, Jun; Finco, Gabriele; Landoni, Giovanni

    2015-01-01

    Introduction Cardioprotective properties of volatile agents and of remote ischemic preconditioning have survival effects in patients undergoing cardiac surgery. We performed a Bayesian network meta-analysis to confirm the beneficial effects of these strategies on survival in cardiac surgery, to evaluate which is the best strategy and if these strategies have additive or competitive effects. Methods Pertinent studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register (updated November 2013). A Bayesian network meta-analysis was performed. Four groups of patients were compared: total intravenous anesthesia (with or without remote ischemic preconditioning) and an anesthesia plan including volatile agents (with or without remote ischemic preconditioning). Mortality was the main investigated outcome. Results We identified 55 randomized trials published between 1991 and 2013 and including 6,921 patients undergoing cardiac surgery. The use of volatile agents (posterior mean of odds ratio = 0.50, 95% CrI 0.28–0.91) and the combination of volatile agents with remote preconditioning (posterior mean of odds ratio = 0.15, 95% CrI 0.04–0.55) were associated with a reduction in mortality when compared to total intravenous anesthesia. Posterior distribution of the probability of each treatment to be the best one, showed that the association of volatile anesthetic and remote ischemic preconditioning is the best treatment to improve short- and long-term survival after cardiac surgery, suggesting an additive effect of these two strategies. Conclusions In patients undergoing cardiac surgery, the use of volatile anesthetics and the combination of volatile agents with remote preconditioning reduce mortality when compared to TIVA and have additive effects. It is necessary to confirm these results with large, multicenter, randomized, double-blinded trials comparing these different strategies in cardiac and non-cardiac surgery, to

  16. Inhibition of Histone Deacetylase 3 (HDAC3) Mediates Ischemic Preconditioning and Protects Cortical Neurons against Ischemia in Rats

    PubMed Central

    Wu, Qimei; Zhang, Lei; Feng, Linyin

    2016-01-01

    Brain ischemic preconditioning (PC) provides vital insights into the endogenous protection against stroke. Genomic and epigenetic responses to PC condition the brain into a state of ischemic tolerance. Notably, PC induces the elevation of histone acetylation, consistent with evidence that histone deacetylase (HDAC) inhibitors protect the brain from ischemic injury. However, less is known about the specific roles of HDACs in this process. HDAC3 has been implicated in several neurodegenerative conditions. Deletion of HDAC3 confers protection against neurotoxicity and neuronal injury. Here, we hypothesized that inhibition of HDAC3 may contribute to the neuronal survival elicited by PC. To address this notion, PC and transient middle cerebral artery occlusion (MCAO) were conducted in Sprague-Dawley rats. Additionally, primary cultured cortical neurons were used to identify the modulators and effectors of HDAC3 involved in PC. We found that nuclear localization of HDAC3 was significantly reduced following PC in vivo and in vitro. Treatment with the HDAC3-specific inhibitor, RGFP966, mimicked the neuroprotective effects of PC 24 h and 7 days after MCAO, causing a reduced infarct volume and less Fluoro-Jade C staining. Improved functional outcomes were observed in the neurological score and rotarod test. We further showed that attenuated recruitment of HDAC3 to promoter regions following PC potentiates transcriptional initiation of genes including Hspa1a, Bcl2l1, and Prdx2, which may underlie the mechanism of protection. In addition, PC-activated calpains were implicated in the cleavage of HDAC3. Pretreatment with calpeptin blockaded the attenuated nuclear distribution of HDAC3 and the protective effect of PC in vivo. Collectively, these results demonstrate that the inhibition of HDAC3 preconditions the brain against ischemic insults, indicating a new approach to evoke endogenous protection against stroke. PMID:27965534

  17. Nrf2 Activation in Astrocytes Contributes to Spinal Cord Ischemic Tolerance Induced by Hyperbaric Oxygen Preconditioning

    PubMed Central

    Xu, Jiajun; Huang, Guoyang; Zhang, Kun; Sun, Jinchuan; Xu, Tao; Li, Runping

    2014-01-01

    Abstract In this study, we investigated whether nuclear factor erythroid 2-related factor 2 (Nrf2) activation in astrocytes contributes to the neuroprotection induced by a single hyperbaric oxygen preconditioning (HBO-PC) against spinal cord ischemia/reperfusion (SCIR) injury. In vivo: At 24 h after a single HBO-PC at 2.5 atmospheres absolute for 90 min, the male ICR mice underwent SCIR injury by aortic cross-clamping surgery and observed for 48 h. HBO-PC significantly improved hindlimb motor function, reduced secondary spinal cord edema, ameliorated the reactivity of spinal motor-evoked potentials, and slowed down the process of apoptosis to exert neuroprotective effects against SCIR injury. At 12 h or 24 h after HBO-PC without aortic cross-clamping surgery, Western blot, enzyme-linked immunosorbent assay, realtime-polymerase chain reaction and double-immunofluorescence staining were used to detect the Nrf2 activity of spinal cord tissue, such as mRNA level, protein content, DNA binding activity, and the expression of downstream gene, such as glutamate-cysteine ligase, γ-glutamyltransferase, multidrug resistance protein 1, which are key proteins for intracellular glutathione synthesis and transit. The Nrf2 activity and downstream genes expression were all enhanced in normal spinal cord with HBO-PC. Glutathione content of spinal cord tissue with HBO-PC significantly increased at all time points after SCIR injury. Moreover, Nrf2 overexpression mainly occurs in astrocytes. In vitro: At 24 h after HBO-PC, the primary spinal astrocyte-neuron co-cultures from ICR mouse pups were subjected to oxygen-glucose deprivation (OGD) for 90 min to simulate the ischemia-reperfusion injury. HBO-PC significantly increased the survival rate of neurons and the glutathione content in culture medium, which was mainly released from asctrocytes. Moreover, the Nrf2 activity and downstream genes expression induced by HBO-PC were mainly enhanced in astrocytes, but not in

  18. Real-Time Fluorescence Measurements of ROS and [Ca2+] in Ischemic / Reperfused Rat Hearts: Detectable Increases Occur only after Mitochondrial Pore Opening and Are Attenuated by Ischemic Preconditioning

    PubMed Central

    Rossbach, Andreas; Halestrap, Andrew P

    2016-01-01

    Mitochondrial permeability transition pore (mPTP) opening is critical for ischemia / reperfusion (I/R) injury and is associated with increased [Ca2+] and reactive oxygen species (ROS). Here we employ surface fluorescence to establish the temporal sequence of these events in beating perfused hearts subject to global I/R. A bespoke fluorimeter was used to synchronously monitor surface fluorescence and reflectance of Langendorff-perfused rat hearts at multiple wavelengths, with simultaneous measurements of hemodynamic function. Potential interference by motion artefacts and internal filtering was assessed and minimised. Re-oxidation of NAD(P)H and flavoproteins on reperfusion (detected using autofluorescence) was rapid (t0.5 < 15 s) and significantly slower following ischemic preconditioning (IP). This argues against superoxide production from reduced Complex 1 being a critical mediator of initial mPTP opening during early reperfusion. Furthermore, MitoPY1 (a mitochondria-targeted H2O2-sensitive fluorescent probe) and aconitase activity measurements failed to detect matrix ROS increases during early reperfusion. However, two different fluorescent cytosolic ROS probes did detect ROS increases after 2–3 min of reperfusion, which was shown to be after initiation of mPTP opening. Cyclosporin A (CsA) and IP attenuated these responses and reduced infarct size. [Ca2+]i (monitored with Indo-1) increased progressively during ischemia, but dropped rapidly within 90 s of reperfusion when total mitochondrial [Ca2+] was shown to be increased. These early changes in [Ca2+] were not attenuated by IP, but substantial [Ca2+] increases were observed after 2–3 min reperfusion and these were prevented by both IP and CsA. Our data suggest that the major increases in ROS and [Ca2+] detected later in reperfusion are secondary to mPTP opening. If earlier IP-sensitive changes occur that might trigger initial mPTP opening they are below our limit of detection. Rather, we suggest that IP

  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. Sex-Specific Impact of Ischemic Preconditioning on Tissue Oxygenation and Maximal Concentric Force

    PubMed Central

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

    2017-01-01

    Prior peripheral hypoxia induced via remote ischemic preconditioning (IPC) can improve physical performance in male athletes through improved O2 delivery and utilization. Since females may have an innate protective mechanism against ischemia-reperfusion injury, and since muscle metabolism during contraction differs between sexes, it is relevant to examine the impact of sex in response to IPC to determine whether it is also ergogenic in females. In a randomized, crossover, single-blind study, we investigated muscle performance, hemodynamic and O2 uptake in strength-trained males (n = 9) and females (n = 8) performing five sets of 5 maximum voluntary knee extensions on an isokinetic dynamometer, preceded by either IPC (3 × 5-min ischemia/5-min reperfusion cycles at 200 mmHg) or SHAM (20 mmHg). Changes in deoxy-hemoglobin (Δ[HHb], expressed in percentage of arterial occlusion and considered an index of O2 extraction), and total hemoglobin (Δ[THb]) concentrations of the vastus lateralis muscle were continuously monitored by near-infrared spectroscopy. The metabolic efficiency of the contractions was calculated as the average force/Δ[HHb]avg ratio. Cohen's effect sizes (ES) ± 90% confidence limits were used to estimate IPC-induced changes and sex differences. IPC increased total muscular force in males only (13.0%, ES 0.64, 0.37;0.90), and this change was greater than in females (10.4% difference, ES 0.40, 0.10;0.70). Percent force decrement was only attenuated in females (−19.8%, ES −0.38, −0.77;0.01), which was clearly different than males (sex difference: ES 0.45, −0.16;1.07). IPC also induced different changes between sexes for average muscle O2 uptake in set 2 (males: 6.4% vs. females: −16.7%, ES 0.21, −0.18;0.60), set 3 (males: 7.0% vs. females: −44.4%, ES 0.56, −0.17;1.29), set 4 (males: 9.1% vs. females: −40.2%, ES 0.51, −0.10;1.13), and set 5 (males: 10.2% vs. females: −40.4%, ES 0.52, −0.04;1.09). However, metabolic efficiency was

  1. Sex-Specific Impact of Ischemic Preconditioning on Tissue Oxygenation and Maximal Concentric Force.

    PubMed

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

    2016-01-01

    Prior peripheral hypoxia induced via remote ischemic preconditioning (IPC) can improve physical performance in male athletes through improved O2 delivery and utilization. Since females may have an innate protective mechanism against ischemia-reperfusion injury, and since muscle metabolism during contraction differs between sexes, it is relevant to examine the impact of sex in response to IPC to determine whether it is also ergogenic in females. In a randomized, crossover, single-blind study, we investigated muscle performance, hemodynamic and O2 uptake in strength-trained males (n = 9) and females (n = 8) performing five sets of 5 maximum voluntary knee extensions on an isokinetic dynamometer, preceded by either IPC (3 × 5-min ischemia/5-min reperfusion cycles at 200 mmHg) or SHAM (20 mmHg). Changes in deoxy-hemoglobin (Δ[HHb], expressed in percentage of arterial occlusion and considered an index of O2 extraction), and total hemoglobin (Δ[THb]) concentrations of the vastus lateralis muscle were continuously monitored by near-infrared spectroscopy. The metabolic efficiency of the contractions was calculated as the average force/Δ[HHb]avg ratio. Cohen's effect sizes (ES) ± 90% confidence limits were used to estimate IPC-induced changes and sex differences. IPC increased total muscular force in males only (13.0%, ES 0.64, 0.37;0.90), and this change was greater than in females (10.4% difference, ES 0.40, 0.10;0.70). Percent force decrement was only attenuated in females (-19.8%, ES -0.38, -0.77;0.01), which was clearly different than males (sex difference: ES 0.45, -0.16;1.07). IPC also induced different changes between sexes for average muscle O2 uptake in set 2 (males: 6.4% vs. females: -16.7%, ES 0.21, -0.18;0.60), set 3 (males: 7.0% vs. females: -44.4%, ES 0.56, -0.17;1.29), set 4 (males: 9.1% vs. females: -40.2%, ES 0.51, -0.10;1.13), and set 5 (males: 10.2% vs. females: -40.4%, ES 0.52, -0.04;1.09). However, metabolic efficiency was not meaningfully

  2. 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...

  3. Short-term remote ischemic preconditioning is not associated with improved blood pressure and exercise capacity in young adults.

    PubMed

    Banks, Laura; Wells, Greg D; Clarizia, Nadia A; Jean-St-Michel, Emilie; McKillop, Adam L; Redington, Andrew N; McCrindle, Brian W

    2016-08-01

    We sought to determine whether a 9-day remote ischemic preconditioning (IPC) causes improvements in exercise performance, energetics, and blood pressure. Ten participants (mean age 24 ± 4 years) had no changes in aerobic capacity (preintervention: 38 ± 10 mL/(kg·min)(-1) vs. postintervention: 38 ± 10 mL/(kg·min)(-1)), blood pressure (preintervention: 112 ± 7/66 ± 6 mm Hg vs. postintervention: 112 ± 10/62 ± 5 mm Hg), cardiac phosphocreatinine-to-adenosine-triphosphate ratio (preintervention: 2.1 ± 0.5 vs. postintervention: 2.3 ± 0.4), and postexercise skeletal muscle phosphocreatine recovery (preintervention: 34 ± 11 s vs. postintervention: 31 ± 11 s). Short-term remote IPC may be ineffective in improving these outcomes.

  4. 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

  5. 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

  6. 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

  7. Ischemic preconditioning inhibits over-expression of arginyl-tRNA synthetase gene Rars in ischemia-injured neurons.

    PubMed

    Shen, Yin; Zhao, Hong-Yang; Wang, Hai-Jun; Wang, Wen-Liang; Zhang, Li-Zhi; Fu, Rong

    2016-08-01

    The expression changes of Rars gene in ischemia-injured neurons were investigated by detecting its translational product arginyl-tRNA synthetase (ArgRS), and the inhibitory effects of ischemic preconditioning (IPC) on Rars gene were explored. Both IPC model and prolonged ischemia (PI) model were established by using the classic oxygen glucose deprivation (OGD) method. The primary cultured neurons were assigned into the following groups: the experimental group (IPC+PI group), undergoing PI after a short period of IPC; the conditional control group (PI control group), subjected to PI without IPC; blank control group, the normally cultured neurons. The Rars transcriptional activities and ArgRS expression levels were measured at different time points after re-oxygenation (3 h/6 h/12 h/24 h). Data were collected and statistically analyzed. Compared to the blank control group, the Rars activities and ArgRS levels were significantly increased in PI control group, peaking at the time point of 6 h after re-oxygenation. Rars activities and ArgRS levels were significantly lower in the experimental group than in the PI control group at different time points after re-oxygenation. PI insult can induce an escalating activity of Rars and lead to ArgRS over-expression in primary cultured neurons. IPC can inhibit the increased Rars activity and down-regulate ArgRS expression of ischemia-insulted neurons. This mechanism may confer ischemic tolerance on neurons.

  8. 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

  9. 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.

  10. 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

  11. AMPK-Regulated and Akt-Dependent Enhancement of Glucose Uptake Is Essential in Ischemic Preconditioning-Alleviated Reperfusion Injury

    PubMed Central

    Liu, Wenchong; Huang, Qichao; Yang, Weidong; Fu, Feng; Ma, Heng; Su, Hui; Wang, Haichang; Wang, Jing; Zhang, Haifeng; Gao, Feng

    2013-01-01

    Aims Ischemic preconditioning (IPC) is a potent form of endogenous protection. However, IPC-induced cardioprotective effect is significantly blunted in insulin resistance-related diseases and the underlying mechanism is unclear. This study aimed to determine the role of glucose metabolism in IPC-reduced reperfusion injury. Methods Normal or streptozotocin (STZ)-treated diabetic rats subjected to 2 cycles of 5 min ischemia/5 min reperfusion prior to myocardial ischemia (30 min)/reperfusion (3 h). Myocardial glucose uptake was determined by 18F-fluorodeoxyglucose-positron emission tomography (PET) scan and gamma-counter biodistribution assay. Results IPC exerted significant cardioprotection and markedly improved myocardial glucose uptake 1 h after reperfusion (P<0.01) as evidenced by PET images and gamma-counter biodistribution assay in ischemia/reperfused rats. Meanwhile, myocardial translocation of glucose transporter 4 (GLUT4) to plasma membrane together with myocardial Akt and AMPK phosphorylation were significantly enhanced in preconditioned hearts. Intramyocardial injection of GLUT4 siRNA markedly decreased GLUT4 expression and blocked the cardioprotection of IPC as evidence by increased myocardial infarct size. Moreover, the PI3K inhibitor wortmannin significantly inhibited activation of Akt and AMPK, reduced GLUT4 translocation, glucose uptake and ultimately, depressed IPC-induced cardioprotection. Furthermore, IPC-afforded antiapoptotic effect was markedly blunted in STZ-treated diabetic rats. Exogenous insulin supplementation significantly improved glucose uptake via co-activation of myocardial AMPK and Akt and alleviated ischemia/reperfusion injury as evidenced by reduced myocardial apoptosis and infarction size in STZ-treated rats (P<0.05). Conclusions The present study firstly examined the role of myocardial glucose metabolism during reperfusion in IPC using direct genetic modulation in vivo. Augmented glucose uptake via co-activation of myocardial AMPK

  12. Effects of preconditioning on reperfusion arrhythmias, myocardial functions, formation of free radicals, and ion shifts in isolated ischemic/reperfused rat hearts.

    PubMed

    Tosaki, A; Cordis, G A; Szerdahelyi, P; Engelman, R M; Das, D K

    1994-03-01

    The effects of preconditioning on development of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT), free radical formation, and ion shifts, particularly those of Na, K, Ca, and Mg, were studied in isolated rat heart. Hearts were randomly divided into four groups: group I, aerobically perfused time-matched controls with no preconditioning or ischemia; group II, hearts subjected to 30-min global ischemia followed by 30-min reperfusion; group III, hearts subjected to one cycle of preconditioning, consisting of 5-min global ischemia plus 10-min reperfusion, followed by 30-min global ischemia plus 30-min reperfusion; and group IV, hearts subjected to four cycles of preconditioning (5-min ischemia plus 10-min reperfusion) followed by 30-min ischemia plus 30-min reperfusion. The incidences of VF and VT were reduced from their nonpreconditioned ischemic values of 100 and 100% in group II to 83 and 92% in group III and to 33% (p < 0.05) and 41% (p < 0.05) in group IV, respectively. Maximum malondialdehyde formation, as an indirect marker of free radicals, was observed after 30-min ischemia followed by 10-min reperfusion (0.72 +/- 0.1 nmol/ml) in the nonpreconditioned ischemic group (protocol II). One and four cycles of preconditioning reduced formation of malondialdehyde from the nonpreconditioned ischemic value of 0.72 +/- 0.1 to 0.35 +/- 0.02 and 0.26 +/- 0.02 nmol/ml (p < 0.05), respectively. The same trend was observed when free radical formation was directly detected by salicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. 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

  14. Ischemic preconditioning attenuates ischemia/reperfusion injury in rat steatotic liver: role of heme oxygenase-1-mediated autophagy

    PubMed Central

    Liu, Anding; Guo, Enshuang; Yang, Jiankun; Li, Renlong; Yang, Yan; Liu, Shenpei; Hu, Jifa; Jiang, Xiaojing; Dirsch, Olaf; Dahmen, Uta; Sun, Jian; Ouyang, Mingwen

    2016-01-01

    Steatotic livers are more susceptible to ischemia/reperfusion (I/R) injury, which is ameliorated by ischemic preconditioning (IPC). Autophagy possesses protective action on liver I/R injury and declines in steatotic livers. The aim of this study was to test the hypothesis that the increased susceptibility of steatotic livers to I/R injury was associated with defective hepatic autophagy, which could be restored by IPC via heme oxygenase-1 (HO-1) signaling. Obesity and hepatic steatosis was induced using a high fat diet. Obesity impaired hepatic autophagy activity and decreased hepatic HO-1 expression. Induction of HO-1 restored autophagy activity and inhibited calpain 2 activity. Additionally, suppression of calpain 2 activity also restored autophagy activity. Mitochondrial dysfunction and hepatocellular injury were significantly increased in steatotic livers compared to lean livers in response to I/R injury. This increase in sensitivity to I/R injury was associated with defective hepatic autophagy activity in steatotic livers. IPC increased autophagy and reduced mitochondrial dysfunction and hepatocellular damage in steatotic livers following I/R injury. Furthermore, IPC increased HO-1 expression. Inhibition of HO-1 decreased the IPC-induced autophagy, increased calpain 2 activity and diminished the protective effect of IPC against I/R injury. Inhibition of calpain 2 restored autophagic defect and attenuated mitochondrial dysfunction in steatotic livers after I/R. Collectively, IPC might ameliorate steatotic liver damage and restore mitochondrial function via HO-1-mediated autophagy. PMID:27852058

  15. The endogenous mitochondrial complex II inhibitor malonate regulates mitochondrial ATP-sensitive potassium channels: implications for ischemic preconditioning.

    PubMed

    Wojtovich, Andrew P; Brookes, Paul S

    2008-01-01

    Ischemic preconditioning (IPC) affords cardioprotection against ischemia-reperfusion (IR) injury, and while the molecular mechanisms of IPC are debated, the mitochondrial ATP-sensitive K(+) channel (mK(ATP)) has emerged as a candidate effector for several IPC signaling pathways. The molecular identity of this channel is unknown, but significant pharmacologic overlap exists between mK(ATP) and mitochondrial respiratory complex II (succinate dehydrogenase). In this investigation, we utilized isolated cardiac mitochondria, Langendorff perfused hearts, and a variety of biochemical methods, to make the following observations: (i) The competitive complex II inhibitor malonate is formed in mitochondria under conditions resembling IPC. (ii) IPC leads to a reversible inhibition of complex II that has likely been missed in previous investigations due to the use of saturating concentrations of succinate. (iii) Malonate opens mK(ATP) channels even when mitochondria are respiring on complex I-linked substrates, suggesting an effect of this inhibitor on the mK(ATP) channel independent of complex II inhibition. Together, these observations suggest that complex II inhibition by endogenously formed malonate may represent an important activation pathway for mK(ATP) channels during IPC.

  16. 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

  17. 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.

  18. Co-application of ischemic preconditioning and postconditioning provides additive neuroprotection against spinal cord ischemia in rabbits.

    PubMed

    Jiang, Xiaojing; Shi, Enyi; Li, Liwen; Nakajima, Yoshiki; Sato, Shigehito

    2008-03-12

    Postconditioning can induce cardioprotection against ischemia. However, the data on postconditioning of the spinal cord is very limited. We investigated here whether co-application of ischemic preconditioning (IPC) and postconditioning can provide additive neuroprotection against prolonged spinal cord ischemia. Spinal cord ischemia was produced in rabbits by infrarenal aortic occlusion with a balloon catheter for 30 min. The four treatment groups were control (n=10): no intervention; IPC (n=10): a 5-minute aortic occlusion was performed 20 min before the prolonged ischemia; Postcon (n=10): postconditioning comprised of four cycles of 1-minute occlusion/1-minute reperfusion was applied one minute after the start of reperfusion. IPC+postcon (n=11): both IPC and postconditioning were applied. Functional evaluation with Tarlov score was performed during a 14-day observation period. Neurologic impairment was noticeably attenuated in the IPC+postcon group (compared with the control group, P<0.01, at day 1, day 2, day 7 and day 14, respectively), but not in either the IPC or Postcon group. Plasma malondialdehyde levels after reperfusion were significantly decreased to a similar extent in the IPC, Postcon and IPC+Postcon groups (compared with the control group (P<0.01). In the IPC+Postcon group, many more large motor neurons were preserved than in the control group (P<0.05) and white matter injury was also markedly attenuated as evidenced by reduction of the vacuolation area of the white matter (P<0.01) and decreased amyloid precursor protein immunoreactivity (P<0.01). From this, we conclude that the combination of IPC and postconditioning induces additive neuroprotective effects for spinal cord against ischemia and reperfusion injuries.

  19. Monocarboxylate transporter 4 plays a significant role in the neuroprotective mechanism of ischemic preconditioning in transient cerebral ischemia

    PubMed Central

    Hong, Seongkweon; Ahn, Ji Yun; Cho, Geum-Sil; Kim, In Hye; Cho, Jeong Hwi; Ahn, Ji Hyeon; Park, Joon Ha; Won, Moo-Ho; Chen, Bai Hui; Shin, Bich-Na; Tae, Hyun-Jin; Park, Seung Min; Cho, Jun Hwi; Choi, Soo Young; Lee, Jae-Chul

    2015-01-01

    Monocarboxylate transporters (MCTs), which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ischemic preconditioning (IPC) on MCT4 immunoreactivity after 5 minutes of transient cerebral ischemia in the gerbil. Animals were randomly designated to four groups (sham-operated group, ischemia only group, IPC + sham-operated group and IPC + ischemia group). A serious loss of neuron was found in the stratum pyramidale of the hippocampal CA1 region (CA1), not CA2/3, of the ischemia-only group at 5 days post-ischemia; however, in the IPC + ischemia groups, neurons in the stratum pyramidale of the CA1 were well protected. Weak MCT4 immunoreactivity was found in the stratum pyramidale of the CA1 in the sham-operated group. MCT4 immunoreactivity in the stratum pyramidale began to decrease at 2 days post-ischemia and was hardly detected at 5 days post-ischemia; at this time point, MCT4 immunoreactivity was newly expressed in astrocytes. In the IPC + sham-operated group, MCT4 immunoreactivity in the stratum pyramidale of the CA1 was increased compared with the sham-operated group, and, in the IPC + ischemia group, MCT4 immunoreactivity was also increased in the stratum pyramidale compared with the ischemia only group. Briefly, present findings show that IPC apparently protected CA1 pyramidal neurons and increased or maintained MCT4 expression in the stratum pyramidale of the CA1 after transient cerebral ischemia. Our findings suggest that MCT4 appears to play a significant role in the neuroprotective mechanism of IPC in the gerbil with transient cerebral ischemia. PMID:26692857

  20. 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.

  1. Neuroprotection of Ischemic Preconditioning is Mediated by Thioredoxin 2 in the Hippocampal CA1 Region Following a Subsequent Transient Cerebral Ischemia.

    PubMed

    Lee, Jae-Chul; Park, Joon Ha; Kim, In Hye; Cho, Geum-Sil; Ahn, Ji Hyeon; Tae, Hyun-Jin; Choi, Soo Young; Cho, Jun Hwi; Kim, Dae Won; Kwon, Young-Guen; Kang, Il Jun; Won, Moo-Ho; Kim, Young-Myeong

    2016-04-26

    Preconditioning by brief ischemic episode induces tolerance to a subsequent lethal ischemic insult, and it has been suggested that reactive oxygen species are involved in this phenomenon. Thioredoxin 2 (Trx2), a small protein with redox-regulating function, shows cytoprotective roles against oxidative stress. Here, we had focused on the role of Trx2 in ischemic preconditioning (IPC)-mediated neuroprotection against oxidative stress followed by a subsequent lethal transient cerebral ischemia. Animals used in this study were randomly assigned to six groups; sham-operated group, ischemia-operated group, IPC plus (+) sham-operated group, IPC + ischemia-operated group, IPC + auranofin (a TrxR2 inhibitor) + sham-operated group and IPC + auranofin + ischemia-operated group. IPC was subjected to a 2 minutes of sublethal transient ischemia 1 day prior to a 5 minutes of lethal transient ischemia. A significant loss of neurons was found in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) in the ischemia-operated-group 5 days after ischemia-reperfusion; in the IPC + ischemia-operated-group, pyramidal neurons in the SP were well protected. In the IPC + ischemia-operated-group, Trx2 and TrxR2 immunoreactivities in the SP and its protein level in the CA1 were not significantly changed compared with those in the sham-operated-group after ischemia-reperfusion. In addition, superoxide dismutase 2 (SOD2) expression, superoxide anion radical ( O2-) production, denatured cytochrome c expression and TUNEL-positive cells in the IPC + ischemia-operated-group were similar to those in the sham-operated-group. Conversely, the treatment of auranofin to the IPC + ischemia-operated-group significantly increased cell damage/death and abolished the IPC-induced effect on Trx2 and TrxR2 expressions. Furthermore, the inhibition of Trx2R nearly cancelled the beneficial effects of IPC on SOD2 expression, O2- production, denatured cytochrome c

  2. 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

  3. Brief anoxia preconditioning and HIF prolyl-hydroxylase inhibition enhances neuronal resistance in organotypic hippocampal slices on model of ischemic damage.

    PubMed

    Lushnikova, Iryna; Orlovsky, Maxim; Dosenko, Victor; Maistrenko, Anastasiia; Skibo, Galina

    2011-04-22

    It is well known that a brief anoxia or hypoxia episodes can render brain resistant to a subsequent ischemia. Recent investigations indicate that mechanisms of such stimulated endogenous neuroprotection are related to the family of hypoxia-inducible factors (HIF), however there are still little data available on the role of HIF family members in hippocampus-a brain structure, highly sensitive to oxygen deficiency. We have used the model of cultured hippocampal slices and single-cell quantitative RT-PCR to study HIF-1α and HIF-3α mRNA expression following triple 5-min mild anoxia, 30-min oxygen-glucose deprivation and their combination. We also tested the effects of HIF prolyl-hydroxylase inhibition with 2,4-pyridinedicarboxylic acid diethyl ester pre-treatment followed by a 30-min oxygen-glucose deprivation. It was found that neuronal damage induced by oxygen-glucose deprivation was accompanied by a significant decrease in both HIF-1α and HIF-3α mRNA levels in CA1 but not CA3 neurons. Anoxia preconditioning did not affect cell viability and HIF mRNA levels but applied before oxygen-glucose deprivation prevented neuronal damage and suppression of HIF-1α and HIF-3α mRNA expression. It was also found that effects of the prolyl-hydroxylase inhibitor were similar to anoxia preconditioning. These results suggest that anoxia preconditioning increases anti-ischemic neuronal resistance which to a certain extent correlates with the changes of HIF-1α and HIF-3α expression.

  4. The age-associated loss of ischemic preconditioning in the kidney is accompanied by mitochondrial dysfunction, increased protein acetylation and decreased autophagy

    PubMed Central

    Jankauskas, Stanislovas S.; Pevzner, Irina B.; Andrianova, Nadezda V.; Zorova, Ljubava D.; Popkov, Vasily A.; Silachev, Denis N.; Kolosova, Nataliya G.; Plotnikov, Egor Y.; Zorov, Dmitry B.

    2017-01-01

    In young rats, ischemic preconditioning (IPC), which consists of 4 cycles of ischemia and reperfusion alleviated kidney injury caused by 40-min ischemia. However,old rats lost their ability to protect the ischemic kidney by IPC. A similar aged phenotype was demonstrated in 6-month-old OXYS rats having signs of premature aging. In the kidney of old and OXYS rats, the levels of acetylated nuclear proteins were higher than in young rats, however, unlike in young rats, acetylation levels in old and OXYS rats were further increased after IPC. In contrast to Wistar rats, age-matched OXYS demonstrated no increase in lysosome abundance and LC3 content in the kidney after ischemia/reperfusion. The kidney LC3 levels were also lower in OXYS, even under basal conditions, and mitochondrial PINK1 and ubiquitin levels were higher, suggesting impaired mitophagy. The kidney mitochondria from old rats contained a population with diminished membrane potential and this fraction was expanded by IPC. Apparently, oxidative changes with aging result in the appearance of malfunctioning renal mitochondria due to a low efficiency of autophagy. Elevated protein acetylation might be a hallmark of aging which is associated with a decreased autophagy, accumulation of dysfunctional mitochondria, and loss of protection against ischemia by IPC. PMID:28294175

  5. The age-associated loss of ischemic preconditioning in the kidney is accompanied by mitochondrial dysfunction, increased protein acetylation and decreased autophagy.

    PubMed

    Jankauskas, Stanislovas S; Pevzner, Irina B; Andrianova, Nadezda V; Zorova, Ljubava D; Popkov, Vasily A; Silachev, Denis N; Kolosova, Nataliya G; Plotnikov, Egor Y; Zorov, Dmitry B

    2017-03-15

    In young rats, ischemic preconditioning (IPC), which consists of 4 cycles of ischemia and reperfusion alleviated kidney injury caused by 40-min ischemia. However,old rats lost their ability to protect the ischemic kidney by IPC. A similar aged phenotype was demonstrated in 6-month-old OXYS rats having signs of premature aging. In the kidney of old and OXYS rats, the levels of acetylated nuclear proteins were higher than in young rats, however, unlike in young rats, acetylation levels in old and OXYS rats were further increased after IPC. In contrast to Wistar rats, age-matched OXYS demonstrated no increase in lysosome abundance and LC3 content in the kidney after ischemia/reperfusion. The kidney LC3 levels were also lower in OXYS, even under basal conditions, and mitochondrial PINK1 and ubiquitin levels were higher, suggesting impaired mitophagy. The kidney mitochondria from old rats contained a population with diminished membrane potential and this fraction was expanded by IPC. Apparently, oxidative changes with aging result in the appearance of malfunctioning renal mitochondria due to a low efficiency of autophagy. Elevated protein acetylation might be a hallmark of aging which is associated with a decreased autophagy, accumulation of dysfunctional mitochondria, and loss of protection against ischemia by IPC.

  6. Neuroprotection of Ischemic Preconditioning is Mediated by Anti-inflammatory, Not Pro-inflammatory, Cytokines in the Gerbil Hippocampus Induced by a Subsequent Lethal Transient Cerebral Ischemia.

    PubMed

    Kim, Dong Won; Lee, Jae-Chul; Cho, Jeong-Hwi; Park, Joon Ha; Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Tae, Hyun-Jin; Seo, Jeong Yeol; Cho, Jun Hwi; Kang, Il Jun; Hong, Seongkweon; Kim, Young-Myeong; Won, Moo-Ho; Kim, In Hye

    2015-09-01

    Ischemic preconditioning (IPC) induced by sublethal transient cerebral ischemia could reduce neuronal damage/death following a subsequent lethal transient cerebral ischemia. We, in this study, compared expressions of interleukin (IL)-2 and tumor necrosis factor (TNF)-α as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines in the gerbil hippocampal CA1 region between animals with lethal ischemia and ones with IPC followed by lethal ischemia. In the animals with lethal ischemia, pyramidal neurons in the stratum pyramidale (SP) of the hippocampal CA1 region were dead at 5 days post-ischemia; however, IPC protected the CA1 pyramidal neurons from lethal ischemic injury. Expressions of all cytokines were significantly decreased in the SP after lethal ischemia and hardly detected in the SP at 5 days post-ischemia because the CA1 pyramidal neurons were dead. IPC increased expressions of anti-inflammatory cytokines (IL-4 and IL-13) in the stratum pyramidale of the CA1 region following no lethal ischemia (sham-operation), and the increased expressions of IL-4 and IL-13 by IPC were continuously maintained is the SP of the CA1 region after lethal ischemia. However, pro-inflammatory cytokines (IL-2 and TNF-α) in the SP of the CA1 region were similar those in the sham-operated animals with IPC, and the IL-4 and IL-13 expressions in the SP were maintained after lethal ischemia. In conclusion, this study shows that anti-inflammatory cytokines significantly increased and longer maintained by IPC and this might be closely associated with neuroprotection after lethal transient cerebral ischemia.

  7. 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

  8. 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

  9. Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p

    PubMed Central

    Ueno, Koji; Samura, Makoto; Nakamura, Tamami; Tanaka, Yuya; Takeuchi, Yuriko; Kawamura, Daichi; Takahashi, Masaya; Hosoyama, Tohru; Morikage, Noriyasu; Hamano, Kimikazu

    2016-01-01

    Ischemic preconditioning (IPC) has protective effects against ischemia-perfusion injury of organs. In the present study, we investigated the associated mechanisms after performing remote IPC (rIPC) of lower limbs by clamping abdominal aorta in mice. Subsequent experiments showed decreased damage and paralysis of lower limbs following spinal cord injury (SCI). Concomitantly, plasma vascular endothelial growth factor (VEGF) levels were increased 24 h after rIPC compared with those in sham-operated animals. In subsequent microRNA analyses, thirteen microRNAs were downregulated in exosomes 24 h after rIPC. Further studies of femoral CD34-positive bone marrow (BM) cells confirmed downregulation of these seven microRNAs 24 h after rIPC compared with those in sham-operated controls. Subsequent algorithm-based database searches suggested that two of the seven microRNAs bind to the 3′ UTR of VEGF mRNA, and following transfection into CD34-positive BM cells, anti-miR-762, and anti-miR-3072-5p inhibitors led to increased VEGF concentrations. The present data suggest that rIPC transiently increases plasma VEGF levels by downregulating miR-762 and miR-3072-5p in CD34-positive BM cells, leading to protection against organ ischemia. PMID:27905554

  10. Using the Electroretinogram to Assess Function in the Rodent Retina and the Protective Effects of Remote Limb Ischemic Preconditioning.

    PubMed

    Brandli, Alice; Stone, Jonathan

    2015-06-09

    The ERG is the sum of all retinal activity. The ERG is usually recorded from the cornea, which acts as an antenna that collects and sums signals from the retina. The ERG is a sensitive measure of changes in retinal function that are pan-retinal, but is less effective for detecting damage confined to a small area of retina. In the present work we describe how to record the 'flash' ERG, which is the potential generated when the retina is exposed to a brief light flash. We describe methods of anaesthesia, mydriasis and corneal management during recording; how to keep the retina dark adapted; electrode materials and placement; the range and calibration of stimulus energy; recording parameters and the extraction of data. We also describe a method of inducing ischemia in one limb, and how to use the ERG to assess the effects of this remote-from-the-retina ischemia on retinal function after light damage. A two-flash protocol is described which allows isolation of the cone-driven component of the dark-adapted ERG, and thereby the separation of the rod and cone components. Because it can be recorded with techniques that are minimally invasive, the ERG has been widely used in studies of the physiology, pharmacology and toxicology of the retina. We describe one example of this usefulness, in which the ERG is used to assess the function of the light-damaged retina, with and without a neuroprotective intervention; preconditioning by remote ischemia.

  11. 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.

  12. Ischemic preconditioning maintains the immunoreactivities of glucokinase and glucokinase regulatory protein in neurons of the gerbil hippocampal CA1 region following transient cerebral ischemia

    PubMed Central

    CHO, YOUNG SHIN; CHO, JUN HWI; SHIN, BICH-NA; CHO, GEUM-SIL; KIM, IN HYE; PARK, JOON HA; AHN, JI HYEON; OHK, TAEK GEUN; CHO, BYUNG-RYUL; KIM, YOUNG-MYEONG; HONG, SEONGKWEON; WON, MOO-HO; LEE, JAE-CHUL

    2015-01-01

    Glucokinase (GK) is involved in the control of blood glucose homeostasis. In the present study, the effect of ischemic preconditioning (IPC) on the immunoreactivities of GK and its regulatory protein (GKRP) following 5 min of transient cerebral ischemia was investigated in gerbils. The gerbils were randomly assigned to four groups (sham-operated group, ischemia-operated group, IPC + sham-operated group and IPC + ischemia-operated group). IPC was induced by subjecting the 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) at 5 days post-ischemia; however, in the IPC+ischemia-operated group, the neurons in the SP were well protected. Following immunohistochemical investigation, the immunoreactivities of GK and GKRP in the neurons of the SP were markedly decreased in the CA1, but not the CA2/3, from 2 days post-ischemia, and were almost undetectable in the SP 5 days post-ischemia. In the IPC + ischemia-operated group, the immunoreactivities of GK and GKRP in the SP of the CA1 were similar to those in the sham-group. In brief, the findings of the present study demonstrated that IPC notably maintained the immunoreactivities of GK and GKRP in the neurons of the SP of CA1 following ischemia-reperfusion. This indicated that GK and GKRP may be necessary for neuron survival against transient cerebral ischemia. PMID:26134272

  13. Remote Ischemic Preconditioning Enhances the Expression of Genes Encoding Antioxidant Enzymes and Endoplasmic Reticulum Stress-Related Proteins in Rat Skeletal Muscle

    PubMed Central

    Park, Ui Jun; Kim, Hyoung Tae; Cho, Won Hyun; Park, Jae Hyoung; Jung, Hye Ra; Kim, Min Young

    2016-01-01

    Purpose: Ischemic preconditioning (IPC), including remote IPC (rIPC) and direct IPC (dIPC), is a promising method to decrease ischemia-reperfusion (IR) injury. This study tested the effect of both rIPC and dIPC on the genes for antioxidant enzymes and endoplasmic reticulum (ER) stress-related proteins. Materials and Methods: Twenty rats were randomly divided into the control and study groups. In the control group (n=10), the right hind limb was sham-operated. The left hind limb (IscR) of the control group underwent IR injury without IPC. In the study group (n=10), the right hind limb received IR injury after 3 cycles of rIPC. The IscR received IR injury after 3 cycles of dIPC. Gene expression was analyzed by Quantitative real-time polymerase chain reaction from the anterior tibialis muscle. Results: The expression of the antioxidant enzyme genes including glutathione peroxidase (GPx), superoxide dismutase (SOD) 1 and catalase (CAT) were significantly reduced in IscR compared with sham treatment. In comparison with IscR, rIPC enhanced the expression of GPx, SOD2, and CAT genes. dIPC enhanced the expression of SOD2 and CAT genes. The expression of SOD2 genes was consistently higher in rIPC than in dIPC, but the difference was only significant for SOD2. The expression of genes for ER stress-related proteins tended to be reduced in IscR in comparison with sham treatment. However, the difference was only significant for C/EBP homologous protein (CHOP). In comparison with IscR, rIPC significantly up-regulated activating transcription factor 4 and CHOP, whereas dIPC up-regulated CHOP. Conclusion: Both rIPC and dIPC enhanced expression of genes for antioxidant enzymes and ER stress-related proteins. PMID:28042553

  14. 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

  15. 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.

  16. Hyperthermic preconditioning severely accelerates neuronal damage in the gerbil ischemic hippocampal dentate gyrus via decreasing SODs expressions.

    PubMed

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

    2015-11-15

    It is well known that neurons in the dentate gyrus (DG) of the hippocampus are resistant to short period of ischemia. Hyperthermia is a proven risk factor for cerebral ischemia and can produce more extensive brain damage related with mortality rates. The aim of this study was to examine the effect of hyperthermic conditioning (H) on neuronal death, gliosis and expressions of SODs as anti-oxidative enzymes in the gerbil DG following 5 min-transient cerebral ischemia. The animals were randomly assigned to 4 groups: 1) (N+sham)-group was given sham-operation with normothermia (N); 2) (N+ischemia)-group was given 5 min-transient ischemia with N; 3) (H+sham)-group was given sham-operation with H; and 4) (H+ischemia)-group was given 5 min-transient cerebral ischemia with H. H (39±0.5°C) was induced by subjecting the animals to a heating pad for 30 min before and during the operation. In the (N+ischemia)-groups, a significant neuronal death was observed in the polymorphic layer (PL) from 1 day after ischemia-reperfusion. In the (H+ischemia)-groups, neuronal death was also observed in the PL from 1day post-ischemia; the degree of the neuronal death was severer than that in the (N+ischemia)-groups. In addition, we examined the gliosis of astrocytes and microglia using anti-glial fibrillary acidic protein (GFAP) and anti- ionized calcium-binding adapter molecule 1 (Iba-1). GFAP(+) and Iba-1(+) glial cells were much more activated in the (H+ischemia)-groups than those in the (N+ischemia)-groups. On the other hand, immunoreactivities and levels of SOD1 rather than SOD2 were significantly lower in the (H+ischemia)-groups than those in the (N+ischemia)-groups. In brief, on the basis of our findings, we suggest that cerebral ischemic insult with hyperthermic conditioning brings up severer neuronal damage and gliosis in the polymorphic layer through reducing SOD1 expression rather than SOD2 expression in the DG.

  17. Pharmacologic Preconditioning: Translating the Promise

    PubMed Central

    Gidday, Jeffrey M.

    2010-01-01

    A transient, ischemia-resistant phenotype known as “ischemic tolerance” can be established in brain in a rapid or delayed fashion by a preceding noninjurious “preconditioning” stimulus. Initial preclinical studies of this phenomenon relied primarily on brief periods of ischemia or hypoxia as preconditioning stimuli, but it was later realized that many other stressors, including pharmacologic ones, are also effective. This review highlights the surprisingly wide variety of drugs now known to promote ischemic tolerance, documented and to some extent mechanistically characterized in preclinical animal models of stroke. Although considerably more experimentation is needed to thoroughly validate the ability of any currently identified preconditioning agent to protect ischemic brain, the fact that some of these drugs are already clinically approved for other indications implies that the growing enthusiasm for translational success in the field of pharmacologic preconditioning may be well justified. PMID:21197121

  18. P2Y1R-initiated, IP3R-dependent stimulation of astrocyte mitochondrial metabolism reduces and partially reverses ischemic neuronal damage in mouse

    PubMed Central

    Zheng, Wei; Talley Watts, Lora; Holstein, Deborah M; Wewer, Jimmy; Lechleiter, James D

    2013-01-01

    Glia-based neuroprotection strategies are emerging as promising new avenues to treat brain damage. We previously reported that activation of the glial-specific purinergic receptor, P2Y1R, reduces both astrocyte swelling and brain infarcts in a photothrombotic mouse model of stroke. These restorative effects were dependent on astrocyte mitochondrial metabolism. Here, we extend these findings and report that P2Y1R stimulation with the purinergic ligand 2-methylthioladenosine 5′ diphosphate (2MeSADP) reduces and partially reverses neuronal damage induced by photothrombosis. In vivo neuronal morphology was confocally imaged in transgenic mice expressing yellow fluorescent protein under the control of the Thy1 promoter. Astrocyte mitochondrial membrane potentials, monitored with the potential sensitive dye tetra-methyl rhodamine methyl ester, were depolarized after photothrombosis and subsequently repolarized when P2Y1Rs were stimulated. Mice deficient in the astrocyte-specific type 2 inositol 1,4,5 trisphosphate (IP3) receptor exhibited aggravated ischemic dendritic damage after photothrombosis. Treatment of these mice with 2MeSADP did not invoke an intracellular Ca2+ response, did not repolarize astrocyte mitochondria, and did not reduce or partially reverse neuronal lesions induced by photothrombotic stroke. These results demonstrate that IP3-Ca2+ signaling in astrocytes is not only critical for P2Y1R-enhanced protection, but suggest that IP3-Ca2+ signaling is also a key component of endogenous neuroprotection. PMID:23321785

  19. Focal cerebral ischemic tolerance and change in blood-brain barrier permeability after repetitive pure oxygen exposure preconditioning in a rodent model.

    PubMed

    Wang, Xi; Kang, Kai; Wang, Shiquan; Yao, Jianhua; Zhang, Xijing

    2016-10-01

    OBJECTIVE The goal of this study was to demonstrate that repetitive pure oxygen exposure preconditioning (O2PC) for 8 hours per day for 3 or 7 days, a practicable preconditioning for clinical use, is able to induce cerebral ischemic tolerance (IT) and further clarify the accompanying changes in the blood-brain barrier (BBB) that may be involved. METHODS A total of 68 adult male Sprague-Dawley rats and eight 1-day-old rat pups were used in this study. The adult rats were exposed to pure O2 (38 rats) 8 hours a day for 3 or 7 days or to room air (in an identical setup) for 8 hours a day for 7 days as controls (30 rats). Arterial O2 tension (PaO2) was measured in 6 rats exposed to O2 and 3 controls. Focal cerebral ischemia was elicited by middle cerebral artery occlusion (MCAO) in 37 rats, of which 21 had been exposed to pure O2 for 3 or 7 days and 16 to room air for 7 days as controls. Neurological behavior was scored with the Garcia score in 15 MCAO rats, of which 10 had been exposed to pure O2 for 3 or 7 days and 5 to room air for 7 days as controls, and cerebral infarct volumes were assessed with TTC (2,3,5-triphenyltetrazolium chloride) staining in 10 rats (5 from each group) after 7 days of exposure. Formamide-extraction method was used to detect leakage of Evans blue (EB) dye in 7 rats exposed to pure O2 for 7 days and 7 exposed to room air for 7 days. Fluorescence microscopy was used to analyze the leaked EB in the nonischemic areas of 4 rats exposed to pure O2 for 7 days and 4 exposed to room air for 7 days before MCAO and the brain of the rats that had not been subjected to MCAO. Astrocyte changes associated with O2PC were evaluated by means of fluorescence microscopy and electron microscopy in 14 rats that were exposed to the same O2 or control conditions as the MCAO rats but without MCAO. Astrocytes were also obtained from 8 rat pups and cultured; levels of AQP4 and VEGF were detected by Western blot and ELISA in cells with and without O2 treatment. RESULTS

  20. Activities of cardiac tissue matrix metalloproteinases 2 and 9 are reduced by remote ischemic preconditioning in cardiosurgical patients with cardiopulmonary bypass

    PubMed Central

    2014-01-01

    Background Transient episodes of ischemia in a remote organ or tissue (remote ischemic preconditioning, RIPC) can attenuate myocardial injury. Myocardial damage is associated with tissue remodeling and the matrix metalloproteinases 2 and 9 (MMP-2/9) are crucially involved in these events. Here we investigated the effects of RIPC on the activities of heart tissue MMP-2/9 and their correlation with serum concentrations of cardiac troponin T (cTnT), a marker for myocardial damage. Methods In cardiosurgical patients with cardiopulmonary bypass (CPB) RIPC was induced by four 5 minute cycles of upper limb ischemia/reperfusion. Cardiac tissue was obtained before as well as after CPB and serum cTnT concentrations were measured. Tissue derived from control patients (N = 17) with high cTnT concentrations (≥0.32 ng/ml) and RIPC patients (N = 18) with low cTnT (≤0.32 ng/ml) was subjected to gelatin zymography to quantify MMP-2/9 activities. Results In cardiac biopsies obtained before CPB, activities of MMP-2/9 were attenuated in the RIPC group (MMP-2: Control, 1.13 ± 0.13 a.u.; RIPC, 0.71 ± 0.12 a.u.; P < 0.05. MMP-9: Control, 1.50 ± 0.16 a.u.; RIPC, 0.87 ± 0.14 a.u.; P < 0.01), while activities of the pro-MMPs were not altered (P > 0.05). In cardiac biopsies taken after CPB activities of pro- and active MMP-2/9 were not different between the groups (P > 0.05). Spearman’s rank tests showed that MMP-2/9 activities in cardiac tissue obtained before CPB were positively correlated with postoperative cTnT serum levels (MMP-2, P = 0.016; MMP-9, P = 0.015). Conclusions Activities of MMP-2/9 in cardiac tissue obtained before CPB are attenuated by RIPC and are positively correlated with serum concentrations of cTnT. MMPs may represent potential targets for RIPC mediated cardioprotection. Trial registration ClinicalTrials.gov identifier NCT00877305. PMID:24712447

  1. 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

  2. Roles of HIF-1α, VEGF, and NF-κB in Ischemic Preconditioning-Mediated Neuroprotection of Hippocampal CA1 Pyramidal Neurons Against a Subsequent Transient Cerebral Ischemia.

    PubMed

    Lee, Jae-Chul; Tae, Hyun-Jin; Kim, In Hye; Cho, Jeong Hwi; Lee, Tae-Kyeong; Park, Joon Ha; Ahn, Ji Hyeon; Choi, Soo Young; Bai, Hui Chen; Shin, Bich-Na; Cho, Geum-Sil; Kim, Dae Won; Kang, Il Jun; Kwon, Young-Guen; Kim, Young-Myeong; Won, Moo-Ho; Bae, Eun Joo

    2016-10-26

    Ischemic preconditioning (IPC) provides neuroprotection against subsequent severe ischemic insults by specific mechanisms. We tested the hypothesis that IPC attenuates post-ischemic neuronal death in the gerbil hippocampal CA1 region (CA1) throughout hypoxia inducible factor-1α (HIF-1α) and its associated factors such as vascular endothelial growth factor (VEGF) and nuclear factor-kappa B (NF-κB). Lethal ischemia (LI) without IPC increased expressions of HIF-1α, VEGF, and p-IκB-α (/and translocation of NF-κB p65 into nucleus) in CA1 pyramidal neurons at 12 h and/or 1-day post-LI; thereafter, their expressions were decreased in the CA1 pyramidal neurons with time and newly expressed in non-pyramidal cells (pericytes), and the CA1 pyramidal neurons were dead at 5-day post-LI, and, at this point in time, their immunoreactivities were newly expressed in pericytes. In animals with IPC subjected to LI (IPC/LI)-group), CA1 pyramidal neurons were well protected, and expressions of HIF-1α, VEGF, and p-IκB-α (/and translocation of NF-κB p65 into nucleus) were significantly increased compared to the sham-group and maintained after LI. Whereas, treatment with 2ME2 (a HIF-1α inhibitor) into the IPC/LI-group did not preserve the IPC-mediated increases of HIF-1α, VEGF, and p-IκB-α (/and translocation of NF-κB p65 into nucleus) expressions and did not show IPC-mediated neuroprotection. In brief, IPC protected CA1 pyramidal neurons from LI by upregulation of HIF-1α, VEGF, and p-IκB-α expressions. This study suggests that IPC increases HIF-1α expression in CA1 pyramidal neurons, which enhances VEGF expression and NF-κB activation and that IPC may be a strategy for a therapeutic intervention of cerebral ischemic injury.

  3. Preconditioning for traumatic brain injury.

    PubMed

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

    2013-02-01

    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 preconditioning 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 future clinical situations, in which pre-TBI preconditioning could be considered.

  4. Ischemic preconditioning at a distance: altered gene expression in mouse heart and other organs following brief occlusion of the mesenteric artery.

    PubMed

    Huda, Ruksana; Chung, Dai H; Mathru, Mali

    2005-03-01

    Remote ischemic preconditionining (IPC) has been defined as a brief episode of ischemia/reperfusion in an organ that protects another remote organ from the damage induced by subsequent and prolonged ischemia. As yet, no study has been conducted with the purpose of elucidating a precise association between remote IPC and patterns of gene-transcription in cardiac tissue. In this study, using a cDNA microarray, we analyzed the gene expression profile in murine heart at 24h after brief cycles of occlusion of the superior mesenteric artery. The profile revealed that IPC induces significant levels of expression of many genes known to be associated with the stress response, redox regulation, growth and metabolism, DNA repair and other functions. The result of cDNA microarray profile from heart was also compared with those from other organs (lung, kidney and intestine). The genes identified in the expression profile may be associated with remote IPC induced late phase organ protection.

  5. 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.

  6. Delayed remote ischemic preconditioning produces an additive cardioprotection to sevoflurane postconditioning through an enhanced heme oxygenase 1 level partly via nuclear factor erythroid 2-related factor 2 nuclear translocation.

    PubMed

    Zhou, Chenghui; Li, Huatong; Yao, Yuntai; Li, Lihuan

    2014-11-01

    Although both sevoflurane postconditioning (SPoC) and delayed remote ischemic preconditioning (DRIPC) have been proved effective in various animal and human studies, the combined effect of these 2 strategies remains unclear. Therefore, this study was designed to investigate this effect and elucidate the related signal mechanisms in a Langendorff perfused rat heart model. After 30-minute balanced perfusion, isolated hearts were subjected to 30-minute ischemia followed by 60-minute reperfusion except 90-minute perfusion for control. A synergic cardioprotective effect of SPoC (3% v/v) and DRIPC (4 cycles 5-minute occlusion/5-minute reflow at the unilateral hindlimb once per day for 3 days before heart isolation) was observed with facilitated cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect was more pronounced in the combined group (6.76% ± 2.18%) than in the SPoC group (16.50% ± 4.55%, P < .001) or in the DRIPC group (10.22% ± 2.57%, P = .047). Subsequent analysis revealed that an enhanced heme oxygenase 1 (HO-1) expression, but not protein kinase B/AKt or extracellular signal-regulated kinase 1 and 2 activation, was involved in the synergic cardioprotective effect, which was further confirmed in the messenger RNA level of HO-1. Such trend was also observed in the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, an upstream regulation of HO-1. In addition, correlation analysis showed a significantly positive relationship between HO-1 expression and Nrf2 translocation (r = 0.729, P < .001). Hence, we conclude that DRIPC may produce an additive cardioprotection to SPoC through an enhanced HO-1 expression partly via Nrf2 translocation.

  7. Mitochondrial preconditioning: a potential neuroprotective strategy.

    PubMed

    Correia, Sónia C; Carvalho, Cristina; Cardoso, Susana; Santos, Renato X; Santos, Maria S; Oliveira, Catarina R; Perry, George; Zhu, Xiongwei; Smith, Mark A; Moreira, Paula I

    2010-01-01

    Mitochondria have long been known as the powerhouse of the cell. However, these organelles are also pivotal players in neuronal cell death. Mitochondrial dysfunction is a prominent feature of chronic brain disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), and cerebral ischemic stroke. Data derived from morphologic, biochemical, and molecular genetic studies indicate that mitochondria constitute a convergence point for neurodegeneration. Conversely, mitochondria have also been implicated in the neuroprotective signaling processes of preconditioning. Despite the precise molecular mechanisms underlying preconditioning-induced brain tolerance are still unclear, mitochondrial reactive oxygen species generation and mitochondrial ATP-sensitive potassium channels activation have been shown to be involved in the preconditioning phenomenon. This review intends to discuss how mitochondrial malfunction contributes to the onset and progression of cerebral ischemic stroke and AD and PD, two major neurodegenerative disorders. The role of mitochondrial mechanisms involved in the preconditioning-mediated neuroprotective events will be also discussed. Mitochondrial targeted preconditioning may represent a promising therapeutic weapon to fight neurodegeneration.

  8. 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

  9. Poly-IC preconditioning protects against cerebral and renal ischemia-reperfusion injury.

    PubMed

    Packard, Amy E B; Hedges, Jason C; Bahjat, Frances R; Stevens, Susan L; Conlin, Michael J; Salazar, Andres M; Stenzel-Poore, Mary P

    2012-02-01

    Preconditioning induces ischemic tolerance, which confers robust protection against ischemic damage. We show marked protection with polyinosinic polycytidylic acid (poly-IC) preconditioning in three models of murine ischemia-reperfusion injury. Poly-IC preconditioning induced protection against ischemia modeled in vitro in brain cortical cells and in vivo in models of brain ischemia and renal ischemia. Further, unlike other Toll-like receptor (TLR) ligands, which generally induce significant inflammatory responses, poly-IC elicits only modest systemic inflammation. Results show that poly-IC is a new powerful prophylactic treatment that offers promise as a clinical therapeutic strategy to minimize damage in patient populations at risk of ischemic injury.

  10. 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.

  11. Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning.

    PubMed

    Ren, C; Gao, X; Steinberg, G K; Zhao, H

    2008-02-19

    Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 min occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 min occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for two or three cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with three cycles of 15 min performed immediately before stroke reduced infarct size from 47.7+/-7.6% of control ischemia to 9.8+/-8.6%; at two cycles of 15 min, infarct was reduced to 24.7+/-7.3%; at two cycles of 5 min, infarct was not reduced. Delayed preconditioning with three cycles of 15 min conducted 2 days before stroke also reduced infarct to 23.0+/-10.9%, but with two cycles of 15 min it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with three cycles of 15 min performed 12 h before stroke also reduced infarct to 24.7+/-4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia.

  12. The production of hydrogen sulfide limits myocardial ischemia and reperfusion injury and contributes to the cardioprotective effects of preconditioning with endotoxin, but not ischemia in the rat.

    PubMed

    Sivarajah, A; McDonald, M C; Thiemermann, C

    2006-08-01

    We investigated whether (endogenous) hydrogen sulfide (H2S) protects the heart against myocardial ischemia and reperfusion injury. Furthermore, we investigated whether endogenous H2S is involved in the protection afforded by (1) ischemic preconditioning and (2) the second window of protection caused by endotoxin. The involvement of one of the potential (end) effectors of the cardioprotection afforded by H2S was investigated using the mitochondrial KATP channel blocker, 5-hydroxydecanoate (5-HD; 5 mg/kg). Animals were subjected to 25 min regional myocardial ischemia followed by reperfusion (2 h) and were pretreated with the H2S donor, sodium hydrosulfide (3 mg/kg i.v.). Animals were also subjected to shorter periods of myocardial ischemia (15 min) and reperfusion (2 h) and pretreated with an irreversible inhibitor of cystathionine-gamma-lyase, dl-propargylglycine (PAG; 50 mg/kg i.v.). Animals were also pretreated with PAG (50 mg/kg) and subjected to either (1) ischemic preconditioning or (2) endotoxin (1 mg/kg i.p.) 16 h before myocardial ischemia. Myocardial infarct size was determined by p-nitroblue tetrazolium staining. Administration of sodium hydrosulfide significantly reduced myocardial infarct size, and this effect was abolished by 5-HD. Administration of PAG (50 mg/kg) or 5-HD significantly increased infarct size caused by 15 min of myocardial ischemia. The delayed cardioprotection afforded by endotoxin was abolished by 5-HD or PAG. In contrast, PAG (50 mg/kg) did not affect the cardioprotective effects of ischemic preconditioning. These findings suggest that (1) endogenous H2S is produced by myocardial ischemia in sufficient amounts to limit myocardial injury and (2) the synthesis or formation of H2S by cystathionine-gamma-lyase may contribute to the second window of protection caused by endotoxin.

  13. 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.

  14. Myocardial ischemic protection in natural mammalian hibernation

    PubMed Central

    Yan, Lin; Kudej, Raymond K.; Vatner, Dorothy E.

    2015-01-01

    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

  15. 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.

  16. Effect of staged preconditioning on biochemical markers in the patients undergoing coronary artery bypass grafting.

    PubMed

    Mohammadzadeh, Alireza; Jafari, Naser; Babapoursaatlou, Behzad; Doustkami, Hossein; Hosseinian, Adallat; Hasanpour, Mohammad

    2012-01-01

    The present study has investigated the effectiveness of staged-preconditioning, in both remote and target organs. After IP the myocardial release of the biochemical markers including, creatine phosphokinase (CPK), cardiac creatine kinase (CK-MB), cardiac troponin T (cTnT) and lactate dehydrogenase (LDH) were evaluated in patients who underwent CABG, with and without staged-preconditioning. Sixty-one patients entered the study; there were 32 patients in the staged-preconditioning group and 29 patients in the control group. All patients underwent on-pump CABG using cardiopulmonary bypass (CPB) techniques. In the staged-preconditioning group, patients underwent two stages of IP on remote (upper limb) and target organs. Each stage of preconditioning was carried out by 3 cycles of ischemia and then reperfusion. Serum levels of biochemical markers were immediately measured postoperatively at 24, 48 and 72 h. Serum CK-MB, CPK and LDH levels were significantly lower in the staged-preconditioning group than in the control group. The CK-MB release in the staged-preconditioning patients reduced by 51% in comparison with controls over 72 h after CABG. These results suggest that myocardial injury was attenuated by the effect of three rounds of both remote and target organ IP.

  17. Mesenchymal stem cells preconditioned with trimetazidine promote neovascularization of hearts under hypoxia/reoxygenation injury

    PubMed Central

    Hu, Xiaowu; Yang, Junjie; Wang, Ying; Zhang, You; Ii, Masaaki; Shen, Zhenya; Hui, Jie

    2015-01-01

    Background: Cell-based angiogenesis is a promising treatment for ischemic diseases; however, survival of implanted cells is impaired by the ischemic microenvironment. In this study, mesenchymal stem cells (MSCs) for cell transplantation were preconditioned with trimetazidine (TMZ). We hypothesized that TMZ enhances the survival rate of MSCs under hypoxic stimuli through up-regulation of HIF1-α. Methods and results: Bone marrow-derived rat mesenchymal stem cells were preconditioned with 10 μM TMZ for 6 h. TMZ preconditioning of MSCs remarkably increased cell viability and the expression of HIF1-α and Bcl-2, when cells were under hypoxia/reoxygenation (H/R) stimuli. But the protective effects of TMZ were abolished after knocking down of HIF-1α. Three days after implantation of the cells into the peri-ischemic zone of rat myocardial ischemia-reperfusion (I/R) injury model, survival of the TMZ-preconditioned MSCs was high. Furthermore, capillary density and cardiac function were significantly better in the rats implanted with TMZ-preconditioned MSCs 28 days after cell injection. Conclusions: TMZ preconditioning increased the survival rate of MSCs, through up-regulation of HIF1-α, thus contributing to neovascularization and improved cardiac function of rats subjected to myocardial I/R injury. PMID:26629255

  18. The evolving concept of physiological ischemia training vs. ischemia preconditioning.

    PubMed

    Ni, Jun; Lu, Hongjian; Lu, Xiao; Jiang, Minghui; Peng, Qingyun; Ren, Caili; Xiang, Jie; Mei, Chengyao; Li, Jianan

    2015-11-01

    Ischemic heart diseases are the leading cause of death with increasing numbers of patients worldwide. Despite advances in revascularization techniques, angiogenic therapies remain highly attractive. Physiological ischemia training, which is first proposed in our laboratory, refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for about 4 weeks for the sake of triggering molecular and cellular mechanisms to promote angiogenesis and formation of collateral vessels and protect remote ischemia areas. Physiological ischemia training therapy augments angiogenesis in the ischemic myocardium by inducing differential expression of proteins involved in energy metabolism, cell migration, protein folding, and generation. It upregulates the expressions of vascular endothelial growth factor, and induces angiogenesis, protects the myocardium when infarction occurs by increasing circulating endothelial progenitor cells and enhancing their migration, which is in accordance with physical training in heart disease rehabilitation. These findings may lead to a new approach of therapeutic angiogenesis for patients with ischemic heart diseases. On the basis of the promising results in animal studies, studies were also conducted in patients with coronary artery disease without any adverse effect in vivo, indicating that physiological ischemia training therapy is a safe, effective and non-invasive angiogenic approach for cardiovascular rehabilitation. Preconditioning is considered to be the most protective intervention against myocardial ischemia-reperfusion injury to date. Physiological ischemia training is different from preconditioning. This review summarizes the preclinical and clinical data of physiological ischemia training and its difference from preconditioning.

  19. 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 ...

  20. The divergent roles of autophagy in ischemia and preconditioning

    PubMed Central

    Sheng, Rui; Qin, Zheng-hong

    2015-01-01

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

  1. Resveratrol exerts pharmacological preconditioning by activating PGC-1alpha.

    PubMed

    Tan, Lan; Yu, Jin-Tai; Guan, Hua-Shi

    2008-11-01

    Resveratrol (RSV), a polyphenol phytoalexin abundantly found in grape skins and in wines, is currently the focus of intense research as a pharmacological preconditioning agent in kidney, heart, and brain from ischemic injury. However, the exact molecular mechanism of RSV preconditioning remains obscure. The data from current studies indicate that pharmacological preconditioning with RSV were attributed to its role as intracellular antioxidant, anti-inflammatory agent, its ability to induce nitric oxide synthase (NOS) expression, its ability to induce angiogenesis, and its ability to increases sirtuin 1 (SIRT1) activity. Peroxisome proliferators-activated receptor (PPAR) gamma co-activator-1alpha (PGC-1alpha) is a member of a family of transcription coactivators that owns mitochondrial biogenesis, antioxidation, growth factor signaling regulation, and angiogenesis activities. And, almost all the signaling pathways activated by RVS involve in PGC-1alpha activity. Moreover, it has been proofed that RVS could mediate an increase PGC-1alpha activity. These significant conditions support the hypothesis that RSV exerts pharmacological preconditioning by activating PGC-1alpha. Attempts to confirm this hypothesis will provide new directions in the study of pharmaceutical preconditioning and the development of new treatment approaches for reducing the extent of ischemia/reperfusion injury.

  2. 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

  3. EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection.

    PubMed

    Olenchock, Benjamin A; Moslehi, Javid; Baik, Alan H; Davidson, Shawn M; Williams, Jeremy; Gibson, William J; Chakraborty, Abhishek A; Pierce, Kerry A; Miller, Christine M; Hanse, Eric A; Kelekar, Ameeta; Sullivan, Lucas B; Wagers, Amy J; Clish, Clary B; Vander Heiden, Matthew G; Kaelin, William G

    2016-02-25

    Ischemic preconditioning is the phenomenon whereby brief periods of sublethal ischemia protect against a subsequent, more prolonged, ischemic insult. In remote ischemic preconditioning (RIPC), ischemia to one organ protects others organs at a distance. We created mouse models to ask if inhibition of the alpha-ketoglutarate (αKG)-dependent dioxygenase Egln1, which senses oxygen and regulates the hypoxia-inducible factor (HIF) transcription factor, could suffice to mediate local and remote ischemic preconditioning. Using somatic gene deletion and a pharmacological inhibitor, we found that inhibiting Egln1 systemically or in skeletal muscles protects mice against myocardial ischemia-reperfusion (I/R) injury. Parabiosis experiments confirmed that RIPC in this latter model was mediated by a secreted factor. Egln1 loss causes accumulation of circulating αKG, which drives hepatic production and secretion of kynurenic acid (KYNA) that is necessary and sufficient to mediate cardiac ischemic protection in this setting.

  4. Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential

    PubMed Central

    Zhang, Qun; Liu, Song; Li, Tong; Yuan, Lin; Liu, Hansen; Wang, Xueer; Wang, Fuwu; Wang, Shuanglian; Hao, Aijun; Liu, Dexiang; Wang, Zhen

    2016-01-01

    Bone marrow mesenchymal stem cells (BMSCs) transplantation has shown great promises for treating various brain diseases. However, poor viability of transplanted BMSCs in injured brain has limited the therapeutic efficiency. Hypoxia-ischemic injury is one of major mechanisms underlying the survival of transplanted BMSCs. We investigated the mechanism of preconditioning of BMSCs with hydrogen sulfide (H2S), which has been proposed as a novel therapeutic strategy for hypoxia-ischemic injury. In this study, we demonstrated that preconditioning of NaHS, a H2S donor, effectively suppressed hypoxia-ischemic-induced apoptosis whereby the rise in Bax/Bcl-2 ratio. Further analyses revealed Akt and ERK1/2 pathways were involved in the protective effects of NaHS. In addition, NaHS preconditioning increased secretion of BDNF and VEGF in BMSCs. Consistent with in vitro data, transplantation of NaHS preconditioned BMSCs in vivo further enhanced the therapeutic effects of BMSCs on neuronal injury and neurological recovery, associated with increased vessel density and upregulation of BDNF and VEGF in the ischemic tissue. These findings suggest that H2S could enhance the therapeutic effects of BMSCs. The underlying mechanisms might be due to enhanced capacity of BMSCs and upregulation of protective cytokines in the hypoxia tissue. PMID:27517324

  5. 40 CFR 80.52 - Vehicle preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed...

  6. 40 CFR 80.52 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed...

  7. 40 CFR 80.52 - Vehicle preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed...

  8. 40 CFR 80.52 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed...

  9. 40 CFR 80.52 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed...

  10. 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

  11. Increased hypoxic tolerance by chemical inhibition of oxidative phosphorylation: "chemical preconditioning".

    PubMed

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

    1997-03-01

    A short ischemic episode preceding sustained ischemia is known to increase tolerance against ischemic cell death. We report early-onset long-lasting neuroprotection against in vitro hypoxia by preceding selective chemical inhibition of oxidative phosphorylation: "chemical preconditioning." The amplitude of CA1 population spikes (psap) in hippocampal slices prepared from control animals (control slices) was 31 +/- 27% (mean +/- SD) upon 45-min recovery from 15-min in vitro hypoxia. In slices prepared from animals treated in vivo with 20 mg/kg 3-nitropropionate (3-np) 1-24 h prior to slice preparation (preconditioned slices), psap improved to 90 +/- 15% (p < 0.01). Posthypoxic oxygen free radicals were reduced to 65 +/- 10% (mean +/- SD) of control in preconditioned slices (p < 0.05). Posthypoxic neuronal density improved from 52 +/- 15% (mean +/- SD) in control slices to 97 +/- 23% in preconditioned slices (p < 0.001). Glibenclamide, an antagonist at KATP-channels, partly reversed increased hypoxic tolerance. We conclude that chemical preconditioning induces early-onset long-lasting tolerance against in vitro hypoxia. Ultimately, this strategy may be applicable as a neuroprotective strategy in humans.

  12. 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

  13. Clinical Application of Preconditioning and Postconditioning to Achieve Neuroprotection

    PubMed Central

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

    2012-01-01

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

  14. 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

  15. Late cardiac preconditioning by exercise in dogs is mediated by mitochondrial potassium channels.

    PubMed

    Parra, Víctor M; Macho, Pilar; Domenech, Raúl J

    2010-09-01

    We previously showed that exercise induces myocardial preconditioning in dogs and that early preconditioning is mediated through mitochondrial adenosine triphosphate-sensitive potassium channels. We decided to study if late preconditioning by exercise is also mediated through these channels. Forty-eight dogs, surgically instrumented and trained to run daily, were randomly assigned to 4 groups: (1) Nonpreconditioned dogs: under anesthesia, the coronary artery was occluded during 1 hour and then reperfused during 4.5 hours. (2) Late preconditioned dogs: similar to group 1, but the dogs run on the treadmill for 5 periods of 5 minutes each, 24 hours before the coronary occlusion. (3) Late preconditioned dogs plus 5-hydroxydecanoate (5HD): similar to group 2, but 5HD was administered before the coronary occlusion. (4) Nonpreconditioned dogs plus 5HD: similar to group 1, but 5HD was administered before the coronary occlusion. Infarct size (percent of the risk region) decreased by effect of exercise by 56% (P < 0.05), and this effect was abolished with 5HD. 5HD by itself did not modify infarct size. Exercise did not induce myocardial ischemia, and the hemodynamics during ischemia-reperfusion period did not differ among groups. These effects were independent of changes in collateral flow to the ischemic region. We concluded that late cardiac preconditioning by exercise is mediated through mitochondrial adenosine triphosphate-sensitive potassium channels.

  16. Hypoxic preconditioning of human cardiosphere-derived cell sheets enhances cellular functions via activation of the PI3K/Akt/mTOR/HIF-1α pathway

    PubMed Central

    Tanaka, Yuya; Hosoyama, Tohru; Mikamo, Akihito; Kurazumi, Hiroshi; Nishimoto, Arata; Ueno, Koji; Shirasawa, Bungo; Hamano, Kimikazu

    2017-01-01

    Cell sheet technology is a promising therapeutic strategy for the treatment of ischemic diseases such as myocardial infarction. We recently developed a novel protocol, termed “hypoxic preconditioning,” capable of augmenting the therapeutic efficacy of cell sheets. Following this protocol, the pro-angiogenic and anti-fibrotic activity of cell sheets were enhanced by brief incubation of cell sheets under hypoxic culture conditions. However, the precise molecular mechanism underlying the hypoxic preconditioning of cell sheets is unclear. In the present study, we examined signal transducers in cell sheets to identify those responsive to hypoxic preconditioning, using cardiosphere-derived cell (CDC) sheets. We initially tested whether sheet-like structures were suitable for hypoxic preconditioning by comparing them with individual cells. Hypoxic preconditioning was more effective in sheeted cells than in individual cells. Expression of hypoxia inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) were induced upon hypoxic preconditioning of cell sheets, as was the phosphoinositide 3-kinase (PI3K)/Akt pathway. In addition, hypoxic preconditioning increased phosphorylation of epidermal growth factor receptor (EGFR) and heat shock protein 60 (HSP60) in CDC sheets. Our findings provide novel insights into the utility of hypoxic preconditioning in cell sheet-based technologies for the treatment of ischemic diseases. PMID:28337294

  17. 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.

  18. 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

  19. Hypoxic-Preconditioned Bone Marrow Stem Cell Medium Significantly Improves Outcome After Retinal Ischemia in Rats

    PubMed Central

    Roth, Steven; Dreixler, John C.; Mathew, Biji; Balyasnikova, Irina; Mann, Jacob R.; Boddapati, Venkat; Xue, Lai; Lesniak, Maciej S.

    2016-01-01

    Purpose We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina. Methods Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays. Results Eyes injected with hypoxic BMSC–conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic-preconditioned medium had 21 significantly increased protein levels compared to normoxic medium. Conclusions The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect. PMID:27367588

  20. 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

  1. 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

  2. Preconditioning Operators on Unstructured Grids

    NASA Technical Reports Server (NTRS)

    Nepomnyaschikh, S. V.

    1996-01-01

    We consider systems of mesh equations that approximate elliptic boundary value problems on arbitrary (unstructured) quasi-uniform triangulations and propose a method for constructing optimal preconditioning operators. The method is based upon two approaches: (1) the fictitious space method, i.e., the reduction of the original problem to a problem in an auxiliary (fictitious) space, and (2) the multilevel decomposition method, i.e., the construction of preconditioners by decomposing functions on hierarchical meshes. The convergence rate of the corresponding iterative process with the preconditioner obtained is independent of the mesh step. The preconditioner has an optimal computational cost: the number of arithmetic operations required for its implementation is proportional to the number of unknowns in the problem. The construction of the preconditioning operators for three dimensional problems can be done in the same way.

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

    PubMed Central

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

    2014-01-01

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

  4. Up-regulation of heme oxygenase-1 by isoflurane preconditioning during tolerance against neuronal injury induced by oxygen glucose deprivation.

    PubMed

    Li, Qifang; Zhu, Yesen; Jiang, Hong; Xu, Hui; Liu, Heping

    2008-09-01

    Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme to produce bile pigments and carbon monoxide. The HO-1 isozyme is induced by a variety of factors such as heat, heme, ischemia, and hydrogen peroxide. In recent years, mounting findings have suggested that HO-1 has a neuroprotective activity against ischemic injury. The neuroprotective role of isoflurane, a commonly used anesthetic, has been well documented, but little is known about the underlying mechanisms involved. Recently, isoflurane has been shown to up-regulate HO-1 in the liver. In this study, we show that isoflurane preconditioning promotes the survival of cultured ischemic hippocampal neurons by increasing the number of surviving neurons and their viability. Further study by reverse transcription-polymerase chain reaction and Western blot analysis showed that isoflurane preconditioning significantly increases HO-1 expression in oxygen glucose deprivation (OGD)-induced neuronal injury. Furthermore, inhibition of HO activity by tin protoporphyrin partially abolishes isoflurane preconditioning's protective effect as measured by lactate dehydrogenase release in OGD neurons. These findings indicated that the neuroprotective role of isoflurane preconditioning against OGD-induced injury might be associated with its role in up-regulating HO-1 in ischemic neurons.

  5. A precondition prover for analogy.

    PubMed

    Bledsoe, W W

    1995-01-01

    We describe here a prover PC (precondition) that normally acts as an ordinary theorem prover, but which returns a 'precondition' when it is unable to prove the given formula. If F is the formula attempted to be proved and PC returns the precondition Q, then (Q-->F) is a theorem (that PC can prove). This prover, PC, uses a proof-plan. In its simplest mode, when there is no proof-plan, it acts like ordinary abduction. We show here how this method can be used to derive certain proofs by analogy. To do this, it uses a proof-plan from a given guiding proof to help construct the proof of a similar theorem, by 'debugging' (automatically) that proof-plan. We show here the analogy proofs of a few simple example theorems and one hard pair, Ex4 and Ex4L. The given proof-plan for Ex4 is used by the system to prove automatically Ex4; and that same proof-plan is then used to prove Ex4L, during which the proof-plan is 'debugged' (automatically). These two examples are similar to two other, more difficult, theorems from the theory of resolution, namely GCR (the ground completeness of resolution) and GCLR (the ground completeness of lock resolution). GCR and GCLR have also been handled, in essence, by this system but not completed in all their details.

  6. 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.

  7. 40 CFR 1065.518 - Engine preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... engine and begin the cold soak as described in § 1065.530(a)(1). (2) Hot-start transient cycle... same ones that apply for emission testing: (1) Cold-start transient cycle. Precondition the engine by running at least one hot-start transient cycle. We will precondition your engine by running two...

  8. Hyperbaric Oxygen Preconditioning Provides Preliminary Protection Against Doxorubicin Cardiotoxicity

    PubMed Central

    Tezcan, Orhan; Karahan, Oguz; Alan, Mustafa; Ekinci, Cenap; Yavuz, Celal; Demirtas, Sinan; Ekinci, Aysun; Caliskan, Ahmet

    2017-01-01

    Background Doxorubicin (DOX) is generally recognized to have important cardiotoxic side effects. Studies are contradictory about the interaction between hyperbaric oxygen (HBO2) therapy and doxorubicin-induced cardiomyotoxicity. Recent data suggests that HBO2 therapy can lead to preconditioning of myocardium while generating oxidative stress. Herein we have investigated the effect of HBO2 therapy in a DOX-induced cardiomyocyte injury animal model. Methods Twenty-one rats were divided into three equal groups as follows: 1) Group 1 is a control group (without any intervention), used for evaluating the basal cardiac structures and determining the normal value of cardiacs and serum oxidative markers; 2) Group 2 is the doxorubicin group (single dose i.p. 20 mg/kg doxorubicin) for detecting the cardiotoxic and systemic effects of doxorubicin; 3) Group 3 is the doxorubicin and HBO2 group (100% oxygen at 2.5 atmospheric for 90 minutes, daily), for evaluating the effect of HBO2 in doxorubicin induced cardiotoxicity. At the end of the protocols, the hearts were harvested and blood samples (2 ml) were obtained. Results The doxorubicin treated animals (Group 2) had increased oxidative stress markers (both cardiac and serum) and severe cardiac injury as compared to the basal findings in the control group. Nevertheless, the highest cardiac oxidative stress index was detected in Group 3 (control vs. Group 3, p = 0.01). However, histological examination revealed that cardiac structures were well preserved in Group 3 when compared with Group 2. Conclusions Our results suggest that HBO2 preconditioning appears to be protective in the doxorubicin-induced cardiotoxicity model. Future studies are required to better elucidate the basis of this preconditioning effect of HBO2. PMID:28344418

  9. The role of HIF in cobalt-induced ischemic tolerance.

    PubMed

    Jones, S M; Novak, A E; Elliott, J P

    2013-11-12

    Understanding the endogenous survival pathways induced by ischemic tolerance may yield targets for neuroprotection from stroke. One well-studied pathway reported to be evoked by preconditioning stimuli is the transcription factor HIF (hypoxia-inducible factor). However, whether HIF induction by ischemic insults is neuroprotective or toxic is still unclear. We examined the ability of three prolyl-hydroxylase inhibitors, which induce HIF, to protect hippocampal cultures from oxygen-glucose deprivation. Hippocampal cultures were exposed to ischemic preconditioning or various concentrations of cobalt chloride, deferoxamine (DFO) or dimethyloxylalyglycine (DMOG), prior to lethal oxygen-glucose deprivation (OGD). Cell survival of neurons and astrocytes was determined with dual-label immunocytochemistry. The induction of HIF targets was assessed in mixed as well as astrocyte-enriched cultures. Ischemic preconditioning, as well as low concentrations of cobalt and DFO, enhanced the survival of neurons following OGD. However, DMOG exacerbates OGD-induced neuronal death. At low concentrations, all three prolyl-hydroxylase (PHD) inhibitors increased the survival of astrocytes. Neuroprotective concentrations of cobalt induced the transcription of the cytokine erythropoietin (EPO) in astrocyte cultures. In addition, pretreatment with recombinant human erythropoietin (rH-EPO) also protected neurons from OGD. Our data suggest that HIF-induced EPO, released from astrocytes, protects neurons from OGD. However, the three PHD inhibitors each exhibited different neuroprotective profiles at low concentrations, suggesting that not all PHD inhibitors are created equal. The protective effects at low doses is reminiscent of HIF involvement in ischemic tolerance, in which sub-lethal insults induce HIF pathways resulting in neuroprotection, whereas the high-dose toxicity suggests that over-activation of HIF is not always protective. Therefore, the choice of inhibitor and dose may determine

  10. Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury.

    PubMed

    Zhang, Yan-Bo; Guo, Zheng-Dong; Li, Mei-Yi; Li, Si-Jie; Niu, Jing-Zhong; Yang, Ming-Feng; Ji, Xun-Ming; Lv, Guo-Wei

    2015-09-01

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats.

  11. Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury

    PubMed Central

    Zhang, Yan-bo; Guo, Zheng-dong; Li, Mei-yi; Li, Si-jie; Niu, Jing-zhong; Yang, Ming-feng; Ji, Xun-ming; Lv, Guo-wei

    2015-01-01

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats. PMID:26604909

  12. H2O2 preconditioning modulates phase II enzymes through p38 MAPK and PI3K/Akt activation.

    PubMed

    Angeloni, Cristina; Motori, Elisa; Fabbri, Daniele; Malaguti, Marco; Leoncini, Emanuela; Lorenzini, Antonello; Hrelia, Silvana

    2011-06-01

    Ischemic preconditioning is a complex cardioprotective phenomenon that involves adaptive changes in cells and molecules and occurs in a biphasic pattern: an early phase after 1-2 h and a late phase after 12-24 h. While it is widely accepted that reactive oxygen species are strongly involved in triggering ischemic preconditiong, it is not clear if they play a major role in the early or late phase of preconditioning and which are the mechanisms involved. The present study was designed to investigate the mechanisms behind H(2)O(2)-induced cardioprotection in rat neonatal cardiomyocytes. We focused on antioxidant and phase II enzymes and their modulation by protein kinase signaling pathways and nuclear-factor-E(2)-related factor-1 (Nrf1) and Nrf2. H(2)O(2) preconditioning was able to counteract oxidative stress more effectively in the late than in the early phase of adaptation. In particular, H(2)O(2) preconditioning counteracted oxidative stress-induced apoptosis by decreasing caspase-3 activity, increasing Bcl2 expression and selectively increasing the expression and activity of antioxidant and phase II enzymes through Nrf1 and Nrf2 translocation to the nucleus. The downregulation of Nrf1 and Nrf2 by small interfering RNA reduced the expression level of phase II enzymes. Specific inhibitors of phosphatidylinositol 3-kinase/Akt and p38 MAPK activation partially reduced the cardioprotection elicited by H(2)O(2) preconditioning and the induction and activity of phase II enzymes. These findings demonstrate, for the first time, a key role for Nrf1, and not only for Nrf2, in the induction of phase II enzymes triggered by H(2)O(2) preconditioning.

  13. CXCL10/IP-10

    PubMed Central

    Gotsch, Francesca; Romero, Roberto; Friel, Lara; Kusanovic, Juan Pedro; Espinoza, Jimmy; Erez, Offer; Than, Nandor Gabor; Mittal, Pooja; Edwin, Samuel; Yoon, Bo Hyun; Kim, Chong Jai; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

    2008-01-01

    OBJECTIVE Interferon (IFN)-γ inducible protein, CXCL10/IP-10, is a member of the CXC chemokine family with pro-inflammatory and anti-angiogenic properties. This chemokine has been proposed to be a key link between inflammation and angiogenesis. The aim of this study was to determine whether preeclampsia and delivery of a small for gestational age (SGA) neonate are associated with changes in maternal serum concentration of CXCL10/IP-10. STUDY DESIGN This cross-sectional study included patients in the following groups: (1) non pregnant women (N=49); (2) women with normal pregnancies (N=89); (3) patients with preeclampsia (N=100); and (4) patients who delivered an SGA neonate (N=78). SGA was defined as birth weight below the 10th percentile. Maternal serum concentrations of CXCL10/IP-10 were measured by sensitive immunoassay. Non-parametric statistics were used for analysis. RESULTS (1) Patients with normal pregnancies had a significantly higher median serum concentration of CXCL10/IP-10 than non-pregnant women (median: 116.1 pg/mL, range: 40.7-1314.3 vs. median: 90.3 pg/mL, range: 49.2-214.7, respectively; p=0.002); (2) no significant correlation was found between maternal serum concentration of CXCL10/IP-10 and gestational age (between 19 and 38 weeks); (3) there were no differences in median serum CXCL10/IP-10 concentrations between patients who delivered an SGA neonate and those with normal pregnancies (median: 122.4 pg/mL, range: 37.3-693.5 vs. median: 116.1 pg/mL, range: 40.7-1314.3, respectively; p>0.05); (4) patients with preeclampsia had a higher median serum concentration of CXCL10/IP-10 than normal pregnant women (median: 156.4 pg/mL, range: 47.4-645.9 vs. median: 116.1 pg/mL, range: 40.7-1314.3, respectively; p<0.05); (5) patients with preeclampsia had a higher median concentration of CXCL10/IP-10 than those who delivered an SGA neonate (median: 156.4 pg/mL, range: 47.4-645.9 vs. median: 122.4 pg/mL, range: 37.3-693.5, respectively; p<0.05). CONCLUSIONS

  14. 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

  15. 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

  16. Ischemic Strokes (Clots)

    MedlinePlus

    ... Quiz 5 Things to Know About Stroke Ischemic Strokes (Clots) Updated:Nov 9,2016 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  17. Preconditioned characteristic boundary conditions for solution of the preconditioned Euler equations at low Mach number flows

    NASA Astrophysics Data System (ADS)

    Hejranfar, Kazem; Kamali-Moghadam, Ramin

    2012-06-01

    Preconditioned characteristic boundary conditions (BCs) are implemented at artificial boundaries for the solution of the two- and three-dimensional preconditioned Euler equations at low Mach number flows. The preconditioned compatibility equations and the corresponding characteristic variables (or the Riemann invariants) based on the characteristic forms of preconditioned Euler equations are mathematically derived for three preconditioners proposed by Eriksson, Choi and Merkle, and Turkel. A cell-centered finite volume Roe's method is used for the discretization of the preconditioned system of equations on unstructured meshes. The accuracy and performance of the preconditioned characteristic BCs applied at artificial boundaries are evaluated in comparison with the non-preconditioned characteristic BCs and the simplified BCs in computing steady low Mach number flows. The two-dimensional flow over the NACA0012 airfoil and three-dimensional flow over the hemispherical headform are computed and the results are obtained for different conditions and compared with the available numerical and experimental data. The sensitivity of the solution to the size of computational domain and the variation of the angle of attack for each type of BCs is also examined. Indications are that the preconditioned characteristic BCs implemented in the preconditioned system of Euler equations greatly enhance the convergence rate of the solution of low Mach number flows compared to the other two types of BCs.

  18. 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.

  19. Investigating the involvement of TRPV1 ion channels in remote hind limb preconditioning-induced cardioprotection in rats.

    PubMed

    Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

    2017-02-01

    Remote ischemic preconditioning (RIPC) treatment strategy is a breakthrough in the field of cardiovascular pharmacology as it has the potential to attenuate myocardial ischemia-reperfusion injury. However, the underlying intracellular pathways have not been widely explored. The present study intends to explore the possible role of TRPV1 channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 cycles in succession) was delivered by tying the blood pressure cuff at the inguinal level of the rat. The Langendorff system was used to perfuse the isolated heart and afterward was subjected to 30 min of global ischemia and 120 min of reperfusion. Sustained ischemia and, thereafter, reperfusion led to cardiac injury that was assessed in terms of infarct size, lactate dehydrogenase (LDH) release, creatine kinase (CK) release, left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), +dp/dtmax, -dp/dtmin, heart rate, rate pressure product, and coronary flow rate. The pharmacological modulators employed included capsaicin as TRPV1 agonist and capsazepine as TRPV1 antagonist. Remote hind limb preconditioning stimulus and capsaicin preconditioning (5 and 10 mg/kg) led to significant reduction in infarct size, LVEDP, LDH release, CK release, and significant improvement in LVDP, +dp/dtmax, -dp/dtmin, heart rate, rate pressure product, and coronary flow rate. However, remote hind limb preconditioning-induced cardioprotective effects were considerably abolished in the presence of capsazepine (2.5 and 5 mg/kg). This indicates that remote hind limb preconditioning stimulus possibly activates TRPV1 channels to produce cardioprotective effects.

  20. CANOPEN Controller IP Core

    NASA Astrophysics Data System (ADS)

    Caramia, Maurizio; Montagna, Mario; Furano, Gianluca; Winton, Alistair

    2010-08-01

    This paper will describe the activities performed by Thales Alenia Space Italia supported by the European Space Agency in the definition of a CAN bus interface to be used on Exomars. The final goal of this activity is the development of an IP core, to be used in a slave node, able to manage both the CAN bus Data Link and Application Layer totally in hardware. The activity has been focused on the needs of the EXOMARS mission where devices with different computational performances are all managed by the onboard computer through the CAN bus.

  1. The hyperbaric oxygen preconditioning-induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia.

    PubMed

    Ostrowski, Robert P; Graupner, Gerhart; Titova, Elena; Zhang, Jennifer; Chiu, Jeffrey; Dach, Neal; Corleone, Dalia; Tang, Jiping; Zhang, John H

    2008-01-01

    We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis. One hundred ten male Sprague-Dawley (SD) rats (300-350 g body weight) were allocated to the sham group and three other groups with 10 min of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments. We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation.

  2. Molecular chaperones and hypoxic-ischemic encephalopathy

    PubMed Central

    Hua, Cong; Ju, Wei-na; Jin, Hang; Sun, Xin; Zhao, Gang

    2017-01-01

    Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In this review, we

  3. Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain.

    PubMed

    Kawai, Hiromi; Yamashita, Toru; Ohta, Yasuyuki; Deguchi, Kentaro; Nagotani, Shoko; Zhang, Xuemei; Ikeda, Yoshio; Matsuura, Tohru; Abe, Koji

    2010-08-01

    Stroke is a major neurologic disorder. Induced pluripotent stem (iPS) cells can be produced from basically any part of patients, with high reproduction ability and pluripotency to differentiate into various types of cells, suggesting that iPS cells can provide a hopeful therapy for cell transplantation. However, transplantation of iPS cells into ischemic brain has not been reported. In this study, we showed that the iPS cells fate in a mouse model of transient middle cerebral artery occlusion (MCAO). Undifferentiated iPS cells (5 x 10(5)) were transplanted into ipsilateral striatum and cortex at 24 h after 30 mins of transient MCAO. Behavioral and histologic analyses were performed at 28 day after the cell transplantation. To our surprise, the transplanted iPS cells expanded and formed much larger tumors in mice postischemic brain than in sham-operated brain. The clinical recovery of the MCAO+iPS group was delayed as compared with the MCAO+PBS (phosphate-buffered saline) group. iPS cells formed tridermal teratoma, but could supply a great number of Dcx-positive neuroblasts and a few mature neurons in the ischemic lesion. iPS cells have a promising potential to provide neural cells after ischemic brain injury, if tumorigenesis is properly controlled.

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

    PubMed Central

    Jimenez-Mateos, Eva M.

    2015-01-01

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

  5. Time course of neuroprotection induced by in vivo normobaric hyperoxia preconditioning and angiogenesis factors

    PubMed Central

    Shahhoseini, Meisam; Bigdeli, Mohammad Reza

    2017-01-01

    Objective(s): Every year, a large number of people lose their lives due to stroke. Stroke is the second leading cause of death worldwide. Surprisingly, recent studies have shown that preconditioning with hyperoxia (HO) increases tissue tolerance to ischemia, ultimately reducing damages caused by stroke. Addressed in this study are beneficial contributions from HO preconditioning into reduced harm to be incurred by the attack, as well as its effect on the expression levels of vascular endothelial growth factor (VEGF) and endostatin. Materials and Methods: A set of experiments was conducted where a number of rats were divided into three groups. The animals in the first group received 90% oxygen for 4 hr a day, for 6 days. The second group was housed in room air and the third group was a sham (surgical stress). After 60 min of ischemia, 24 hr blood flow, neurological deficit score (NDS) and infarct volume (IV) in the group MCAO (Middle Cerebral Artery Occlusion) were investigated. Immediately following a 48 hr HO pre-treatment, sampling was performed to measure the expression levels of VEGF and endostatin. Results: Preconditioning with alternating HO led to reduced infarct volume and NDS. Moreover, pre-treatment with HO resulted in increased VEGF expression while decreasing endostatin. Conclusion: Although further studies are deemed necessary to clarify the mechanisms of ischemic tolerance, apparently, somewhat intermittent hyperoxia can be associated with positive impacts by increasing VEGF and decreasing expression of endostatin. PMID:28133527

  6. Hypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain.

    PubMed

    Ara, Jahan; Fekete, Saskia; Frank, Melissa; Golden, Jeffrey A; Pleasure, David; Valencia, Ignacio

    2011-08-01

    Preconditioning-induced ischemic tolerance has been documented in the newborn brain, however, the signaling mechanisms of this preconditioning require further elucidation. The aims of this study were to develop a hypoxic-preconditioning (PC) model of ischemic tolerance in the newborn piglet, which emulates important clinical similarities to human situation of birth asphyxia, and to characterize some of the molecular mechanisms shown to be implicated in PC-induced neuroprotection in rodent models. One day old piglets were subjected to PC (8% O2/92% N2) for 3 h and 24 h later were exposed to hypoxia-ischemia (HI) produced by a combination of hypoxia (5% FiO2) for a period of 30 min and ischemia induced by a period of hypotension (10 min of reduced mean arterial blood pressure; ≤70% of baseline). Neuropathologic analysis and unbiased stereology, conducted at 24 h, 3 and 7 days of recovery following HI, indicated a substantial reduction in the severity of brain damage in PC piglets compared to non-PC piglets (P<0.05). PC significantly increased the mRNA expression of hypoxia-inducible factor-1α (HIF-1α) and its target gene, vascular endothelial growth factor (VEGF) at 0 h, 6h, 24 h, 3 and 7 days of recovery. Immunoblot analysis demonstrated that PC resulted in HIF-1α protein stabilization and accumulation in nuclear extracts of cerebral cortex of newborn piglet brain compared to normoxic controls. Protein levels of VEGF increased in a time-dependent manner in both cortex and hippocampus following PC. Double-immunolabeling indicated that VEGF is mainly expressed in neurons, endothelial cells and astroglia. Our study demonstrates for the first time the protective efficacy of PC against hypoxic-ischemic injury in newborn piglet model, which recapitulates many pathophysiological features of asphyxiated human neonates. Furthermore, as has been shown in rodent models of preconditioning, our results suggest that PC-induced protection in neonatal piglets may involve

  7. 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.

  8. 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.

  9. Preconditioning the Helmholtz Equation for Rigid Ducts

    NASA Technical Reports Server (NTRS)

    Baumeister, Kenneth J.; Kreider, Kevin L.

    1998-01-01

    An innovative hyperbolic preconditioning technique is developed for the numerical solution of the Helmholtz equation which governs acoustic propagation in ducts. Two pseudo-time parameters are used to produce an explicit iterative finite difference scheme. This scheme eliminates the large matrix storage requirements normally associated with numerical solutions to the Helmholtz equation. The solution procedure is very fast when compared to other transient and steady methods. Optimization and an error analysis of the preconditioning factors are present. For validation, the method is applied to sound propagation in a 2D semi-infinite hard wall duct.

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

    PubMed Central

    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

  11. 40 CFR 1066.816 - Vehicle preconditioning for FTP testing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Vehicle preconditioning for FTP testing. 1066.816 Section 1066.816 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... § 1066.816 Vehicle preconditioning for FTP testing. Precondition the test vehicle before the FTP...

  12. Preconditioning matrices for Chebyshev derivative operators

    NASA Technical Reports Server (NTRS)

    Rothman, Ernest E.

    1986-01-01

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

  13. 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…

  14. Preconditioning and tolerance against cerebral ischaemia

    PubMed Central

    Dirnagl, Ulrich; Becker, Kyra; Meisel, Andreas

    2009-01-01

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

  15. Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

    PubMed

    Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F

    2014-08-22

    Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate.

  16. The role of mitochondria in protection of the heart by preconditioning

    PubMed Central

    Halestrap, Andrew P.; Clarke, Samantha J.; Khaliulin, Igor

    2007-01-01

    A prolonged period of ischaemia followed by reperfusion irreversibly damages the heart. Such reperfusion injury (RI) involves opening of the mitochondrial permeability transition pore (MPTP) under the conditions of calcium overload and oxidative stress that accompany reperfusion. Protection from MPTP opening and hence RI can be mediated by ischaemic preconditioning (IP) where the prolonged ischaemic period is preceded by one or more brief (2–5 min) cycles of ischaemia and reperfusion. Following a brief overview of the molecular characterisation and regulation of the MPTP, the proposed mechanisms by which IP reduces pore opening are reviewed including the potential roles for reactive oxygen species (ROS), protein kinase cascades, and mitochondrial potassium channels. It is proposed that IP-mediated inhibition of MPTP opening at reperfusion does not involve direct phosphorylation of mitochondrial proteins, but rather reflects diminished oxidative stress during prolonged ischaemia and reperfusion. This causes less oxidation of critical thiol groups on the MPTP that are known to sensitise pore opening to calcium. The mechanisms by which ROS levels are decreased in the IP hearts during prolonged ischaemia and reperfusion are not known, but appear to require activation of protein kinase Cε, either by receptor-mediated events or through transient increases in ROS during the IP protocol. Other signalling pathways may show cross-talk with this primary mechanism, but we suggest that a role for mitochondrial potassium channels is unlikely. The evidence for their activity in isolated mitochondria and cardiac myocytes is reviewed and the lack of specificity of the pharmacological agents used to implicate them in IP is noted. Some K+ channel openers uncouple mitochondria and others inhibit respiratory chain complexes, and their ability to produce ROS and precondition hearts is mimicked by bona fide uncouplers and respiratory chain inhibitors. IP may also provide continuing

  17. Development of an ischemic tolerance model in a PC12 cell line

    PubMed Central

    Maric, Dragan; Ruetzler, Christl; Barker, Jeffery L; Hallenbeck, John M

    2006-01-01

    Although ischemic tolerance has been described in a variety of primary cell culture systems, no similar in vitro models have been reported with any cell line. A model of ischemic preconditioning in the rat pheochromocytoma PC12 cell line is described here. When compared to nonpreconditioned cells, preexposure of PC12 cells to 6 hours of oxygen and glucose deprivation (OGD) significantly increased cell viability after 15 hours of OGD 24 hours later. Flow cytometry analysis of cells labeled with specific markers for apoptosis, Annexin V, and Hoechst 33342, and of DNA content, revealed that apoptosis is involved in OGD-induced PC12 cell death and that preconditioning of the cells mainly counteracts the effect of apoptosis. Immunocytochemistry of caspase-3, a central executioner in the apoptotic process, further confirmed the activation of apoptotic pathways in OGD-induced PC12 cell death. This model may be useful to investigate the cellular mechanisms involved in neuronal transient tolerance following ischemia. PMID:15647748

  18. 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.

  19. Condition Number Estimation of Preconditioned Matrices

    PubMed Central

    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. PMID:25816331

  20. 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

  1. Vaginal LPS changed gene transcriptional regulation response to ischemic reperfusion and increased vulnerability of fetal brain hemorrhage.

    PubMed

    Dong, Yupeng; Kimura, Yoshitaka; Ito, Takuya; Velayo, Clarissa; Sato, Takafumi; Sugibayashi, Rika; Funamoto, Kiyoe; Hitomi, Kudo; Iida, Keita; Endo, Miyuki; Sato, Naoaki; Yaegashi, Nobuo

    During pregnancy, both ischemic reperfusion and bacterial agent LPS are known risk factors for fetal brain damage. However, there is a lack of evidence to explain whether vaginal LPS affects the fetus response to ischemic reperfusion. Here we reported that there was more than 2 folds higher vulnerability of fetal brain hemorrhage response to ischemic reperfusion when mother mouse was treated with vaginal LPS. As our previously reported, ischemic reperfusion induces P53-dependent fetal brain damage was based on a molecular mechanism: the transcriptional pattern was changed from HIF-1alpha-dependent to P53-dependent immediately. In the present work, only with vaginal LPS precondition, phosphorylation of activated transcriptional factor (ATF) 2 at Thr71 appeared in response to ischemic reperfusion. Moreover, this phosphorylation was completely blocked by pre-treatment with a P53 inhibitor, pifithrin-α. We concluded that vaginal LPS precondition trigged the p53-dependent phosphorylation of ATF2 in response to ischemic reperfusion, which played an important role of increasing vulnerability to hemorrhage in fetus.

  2. 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.

  3. Lubiprostone induced ischemic colitis.

    PubMed

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

  4. 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.

  5. 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)

  6. Preconditioned minimal residual methods for Chebyshev spectral calculations

    NASA Technical Reports Server (NTRS)

    Canuto, C.; Quarteroni, A.

    1985-01-01

    The problem of preconditioning the pseudospectral Chebyshev approximation of an elliptic operator is considered. The numerical sensitiveness to variations of the coefficients of the operator are investigated for two classes of preconditioning matrices: one arising from finite differences, the other from finite elements. The preconditioned system is solved by a conjugate gradient type method, and by a Dufort-Frankel method with dynamical parameters. The methods are compared on some test problems with the Richardson method and with the minimal residual Richardson method.

  7. Preconditioning and the limit to the incompressible flow equations

    NASA Technical Reports Server (NTRS)

    Turkel, E.; Fiterman, A.; Vanleer, B.

    1993-01-01

    The use of preconditioning methods to accelerate the convergence to a steady state for both the incompressible and compressible fluid dynamic equations are considered. The relation between them for both the continuous problem and the finite difference approximation is also considered. The analysis relies on the inviscid equations. The preconditioning consists of a matrix multiplying the time derivatives. Hence, the steady state of the preconditioned system is the same as the steady state of the original system. For finite difference methods the preconditioning can change and improve the steady state solutions. An application to flow around an airfoil is presented.

  8. 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.

  9. Implicit preconditioned WENO scheme for steady viscous flow computation

    NASA Astrophysics Data System (ADS)

    Huang, Juan-Chen; Lin, Herng; Yang, Jaw-Yen

    2009-02-01

    A class of lower-upper symmetric Gauss-Seidel implicit weighted essentially nonoscillatory (WENO) schemes is developed for solving the preconditioned Navier-Stokes equations of primitive variables with Spalart-Allmaras one-equation turbulence model. The numerical flux of the present preconditioned WENO schemes consists of a first-order part and high-order part. For first-order part, we adopt the preconditioned Roe scheme and for the high-order part, we employ preconditioned WENO methods. For comparison purpose, a preconditioned TVD scheme is also given and tested. A time-derivative preconditioning algorithm is devised and a discriminant is devised for adjusting the preconditioning parameters at low Mach numbers and turning off the preconditioning at intermediate or high Mach numbers. The computations are performed for the two-dimensional lid driven cavity flow, low subsonic viscous flow over S809 airfoil, three-dimensional low speed viscous flow over 6:1 prolate spheroid, transonic flow over ONERA-M6 wing and hypersonic flow over HB-2 model. The solutions of the present algorithms are in good agreement with the experimental data. The application of the preconditioned WENO schemes to viscous flows at all speeds not only enhances the accuracy and robustness of resolving shock and discontinuities for supersonic flows, but also improves the accuracy of low Mach number flow with complicated smooth solution structures.

  10. Dynamic IP Reputation from DNS

    DTIC Science & Technology

    2016-06-21

    Dynamic IP Reputation from DNS Manos Antonakakis, Roberto Perdisci, and Wenke Lee Georgia Institute of Technology Report Documentation Page Form...Institute of Technology ,College of Computing,Atlanta,GA,30332 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS

  11. 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.

  12. 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.

  13. Fast permutation preconditioning for fractional diffusion equations.

    PubMed

    Wang, Sheng-Feng; Huang, Ting-Zhu; Gu, Xian-Ming; Luo, Wei-Hua

    2016-01-01

    In this paper, an implicit finite difference scheme with the shifted Grünwald formula, which is unconditionally stable, is used to discretize the fractional diffusion equations with constant diffusion coefficients. The coefficient matrix possesses the Toeplitz structure and the fast Toeplitz matrix-vector product can be utilized to reduce the computational complexity from [Formula: see text] to [Formula: see text], where N is the number of grid points. Two preconditioned iterative methods, named bi-conjugate gradient method for Toeplitz matrix and bi-conjugate residual method for Toeplitz matrix, are proposed to solve the relevant discretized systems. Finally, numerical experiments are reported to show the effectiveness of our preconditioners.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Review of Preconditioning Methods for Fluid Dynamics

    DTIC Science & Technology

    1992-09-01

    applies equally to all preconditioners e.g. that of Van Leer et. al. which will now be presented. The Van Leer, Lee, Roe preconditioning [55] for...a(dd an artificial viscosity. Accuracy is im1proved for low Mach number flows if the preconditioner is applied only to t lie physical convective and...w j u()s M4u’, h)t appe~var .Jtwurrral ()f C(’oII~putationial Phyisic ,". 11 Iý ( -ltrii. AX .. A .\\itinfi c 7(/Alt .1/1( 1dfr *Si/’olil nq li(o1/ itp

  19. SIMPLE MACHINE PERFUSION SIGNIFICANTLY ENHANCES HEPATOCYTE YIELDS OF ISCHEMIC AND FRESH RAT LIVERS.

    PubMed

    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 hour room temperature (20±2°C) machine perfusion protocol to treat non-premedicated livers exposed to 1 hour 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. Further, 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.

  20. 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

  1. Activation of NR2A receptors induces ischemic tolerance through CREB signaling.

    PubMed

    Terasaki, Yasukazu; Sasaki, Tsutomu; Yagita, Yoshiki; Okazaki, Shuhei; Sugiyama, Yukio; Oyama, Naoki; Omura-Matsuoka, Emi; Sakoda, Saburo; Kitagawa, Kazuo

    2010-08-01

    Previous exposure to a nonlethal ischemic insult protects the brain against subsequent harmful ischemia. N-methyl-D-aspartate (NMDA) receptors are a highly studied target of neuroprotection after ischemia. Recently, NMDA receptor subtypes were implicated in neuronal survival and death. We focused on the contribution of NR2A and cyclic-AMP response element (CRE)-binding protein (CREB) signaling to ischemic tolerance using primary cortical neurons. Ischemia in vitro was modeled by oxygen-glucose deprivation (OGD). Ischemic tolerance was induced by applying 45-mins OGD 24 h before 180-mins OGD. Sublethal OGD also induced cross-tolerance against lethal glutamate and hydrogen peroxide. After sublethal OGD, expression of phosphorylated CREB and CRE transcriptional activity were significantly increased. When CRE activity was inhibited by CREB-S133A, a mutant CREB, ischemic tolerance was abolished. Inhibiting NR2A using NVP-AAM077 attenuated preconditioning-induced neuroprotection and correlated with decreased CRE activity levels. Activating NR2A using bicuculline and 4-aminopiridine induced resistance to lethal ischemia accompanied by elevated CRE activity levels, and this effect was abolished by NVP-AAM077. Elevated brain-derived neurotrophic factor (BDNF) transcriptional activities were observed after sublethal OGD and administration of bicuculline and 4-aminopiridine. NR2A-containing NMDA receptors and CREB signaling have important functions in the induction of ischemic tolerance. This may provide potential novel therapeutic strategies to treat ischemic stroke.

  2. Ischemic Colitis Revealing Polyarteritis Nodosa

    PubMed Central

    Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.

    2013-01-01

    Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN. PMID:24382967

  3. 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. PMID:27796011

  4. Hypoxic Preconditioning Enhances the Benefit of Cardiac Progenitor-Cell Therapy for Treatment of Myocardial Infarction by Inducing CXCR4 Expression

    PubMed Central

    Tang, Yao Liang; Zhu, Wuqiang; Cheng, Min; Chen, Lijuan; Zhang, John; Sun, Tao; Kishore, Raj; Phillips, M. Ian; Losordo, Douglas W.; Qin, Gangjian

    2009-01-01

    Myocardial infarction (MI) rapidly depletes the endogenous cardiac progenitor-cell pool, and the inefficient recruitment of exogenously administered progenitor cells limits the effectiveness of cardiac-cell therapy. Recent reports indicate that interactions between the CXC chemokine stromal-cell–derived factor 1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) critically mediate the ischemia-induced recruitment of bone-marrow—derived circulating stem/progenitor cells, but the expression of CXCR4 in cardiac progenitor cells is very low. Here, we studied the influence of hypoxia on CXCR4 expression in cardiac progenitor cells, on the recruitment of intravenously administered cells to ischemic heart tissue, and on the preservation of heart function in a murine MI model. We found that hypoxic preconditioning increased CXCR4 expression in cardiosphere-derived, Lin−/c-kit+ progenitor (CLK) cells and markedly augmented CLK-cell migration (in vitro) and recruitment (in vivo) to the ischemic myocardium. Four weeks after surgically induced MI, infarct size and heart function were significantly better in mice administered hypoxia-preconditioned CLK cells than in mice treated with cells cultured under normoxic conditions. Furthermore, these effects were largely abolished by the addition of a CXCR4 inhibitor, indicating that the benefits of hypoxic preconditioning are mediated by the SDF-1/CXCR4 axis, and that therapies targeting this axis may enhance cardiac-progenitor-cell—based regenerative therapy. PMID:19407239

  5. 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... may be pushed or driven onto the test dynamometer. Acceptable cycles for preconditioning are as follows: (i) Preconditioning may consist of a 505, 866, highway, US06 or SC03 test cycles. (ii) (iii) If...

  6. 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... may be pushed or driven onto the test dynamometer. Acceptable cycles for preconditioning are as follows: (i) Preconditioning may consist of a 505, 866, highway, US06 or SC03 test cycles. (ii) (iii) If...

  7. 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... may be pushed or driven onto the test dynamometer. Acceptable cycles for preconditioning are as follows: (i) Preconditioning may consist of a 505, 866, highway, US06 or SC03 test cycles. (ii) (iii) If...

  8. 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... may be pushed or driven onto the test dynamometer. Acceptable cycles for preconditioning are as follows: (i) Preconditioning may consist of a 505, 866, highway, US06 or SC03 test cycles. (ii) (iii) If...

  9. 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... may be pushed or driven onto the test dynamometer. Acceptable cycles for preconditioning are as follows: (i) Preconditioning may consist of a 505, 866, highway, US06 or SC03 test cycles. (ii) (iii) If...

  10. A preconditioned formulation of the Cauchy-Riemann equations

    NASA Technical Reports Server (NTRS)

    Phillips, T. N.

    1983-01-01

    A preconditioning of the Cauchy-Riemann equations which results in a second-order system is described. This system is shown to have a unique solution if the boundary conditions are chosen carefully. This choice of boundary condition enables the solution of the first-order system to be retrieved. A numerical solution of the preconditioned equations is obtained by the multigrid method.

  11. 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... Test § 1066.405 Vehicle preparation and preconditioning. Prepare the vehicle for testing...

  12. Parallel Preconditioning for CFD Problems on the CM-5

    NASA Technical Reports Server (NTRS)

    Simon, Horst D.; Kremenetsky, Mark D.; Richardson, John; Lasinski, T. A. (Technical Monitor)

    1994-01-01

    Up to today, preconditioning methods on massively parallel systems have faced a major difficulty. The most successful preconditioning methods in terms of accelerating the convergence of the iterative solver such as incomplete LU factorizations are notoriously difficult to implement on parallel machines for two reasons: (1) the actual computation of the preconditioner is not very floating-point intensive, but requires a large amount of unstructured communication, and (2) the application of the preconditioning matrix in the iteration phase (i.e. triangular solves) are difficult to parallelize because of the recursive nature of the computation. Here we present a new approach to preconditioning for very large, sparse, unsymmetric, linear systems, which avoids both difficulties. We explicitly compute an approximate inverse to our original matrix. This new preconditioning matrix can be applied most efficiently for iterative methods on massively parallel machines, since the preconditioning phase involves only a matrix-vector multiplication, with possibly a dense matrix. Furthermore the actual computation of the preconditioning matrix has natural parallelism. For a problem of size n, the preconditioning matrix can be computed by solving n independent small least squares problems. The algorithm and its implementation on the Connection Machine CM-5 are discussed in detail and supported by extensive timings obtained from real problem data.

  13. 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...

  14. 40 CFR 86.532-78 - Vehicle preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 19 2013-07-01 2013-07-01 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...

  15. 40 CFR 86.532-78 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 19 2012-07-01 2012-07-01 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...

  16. 40 CFR 86.532-78 - Vehicle preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 19 2014-07-01 2014-07-01 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. The multigrid preconditioned conjugate gradient method

    NASA Technical Reports Server (NTRS)

    Tatebe, Osamu

    1993-01-01

    A multigrid preconditioned conjugate gradient method (MGCG method), which uses the multigrid method as a preconditioner of the PCG method, is proposed. The multigrid method has inherent high parallelism and improves convergence of long wavelength components, which is important in iterative methods. By using this method as a preconditioner of the PCG method, an efficient method with high parallelism and fast convergence is obtained. First, it is considered a necessary condition of the multigrid preconditioner in order to satisfy requirements of a preconditioner of the PCG method. Next numerical experiments show a behavior of the MGCG method and that the MGCG method is superior to both the ICCG method and the multigrid method in point of fast convergence and high parallelism. This fast convergence is understood in terms of the eigenvalue analysis of the preconditioned matrix. From this observation of the multigrid preconditioner, it is realized that the MGCG method converges in very few iterations and the multigrid preconditioner is a desirable preconditioner of the conjugate gradient method.

  19. Preconditioning Newton-Krylor Methods for Variably Saturated Flow

    SciTech Connect

    Woodward, C.; Jones, J

    2000-01-07

    In this paper, we compare the effectiveness of three preconditioning strategies in simulations of variably saturated flow. Using Richards' equation as our model, we solve the nonlinear system using a Newton-Krylov method. Since Krylov solvers can stagnate, resulting in slow convergence, we investigate different strategies of preconditioning the Jacobian system. Our work uses a multigrid method to solve the preconditioning systems, with three different approximations to the Jacobian matrix. One approximation lags the nonlinearities, the second results from discarding selected off-diagonal contributions, and the third matrix considered is the full Jacobian. Results indicate that although the Jacobian is more accurate, its usage as a preconditioning matrix should be limited, as it requires much more storage than the simpler approximations. Also, simply lagging the nonlinearities gives a preconditioning matrix that is almost as effective as the full Jacobian but much easier to compute.

  20. 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…

  1. Standardization efforts in IP telephony

    NASA Astrophysics Data System (ADS)

    Sengodan, Senthil; Bansal, Raj

    1999-11-01

    The recent interest in IP telephony has led to a tremendous increase of standardization activities in the area. The three main standards bodies in the area of IP telephony are the International Telecommunication Union's (ITU-T) Study Group (SG) 16, the Internet Engineering Task Force (IETF) and the European Telecommunication Standards Institute's (ETSI) TIPHON project. In addition, forums such as the International Multimedia Teleconferencing Consortium (IMTC), the Intelligent Network Forum (INF), the International Softswitch Consortium (ISC), the Electronic Computer Telephony Forum (ECTF), and the MIT's Internet Telephony Consortium (ITC) are looking into various other aspects that aim at the growth of this industry. This paper describes the main tasks (completed and in progress) undertaken by these organizations. In describing such work, an overview of the underlying technology is also provided.

  2. Ischemic optic neuropathy.

    PubMed

    Hayreh, Sohan Singh

    2009-01-01

    Ischemic optic neuropathy is one of the major causes of blindness or seriously impaired vision, yet there is disagreement as to its pathogenesis, clinical features and especially its management. This is because ischemic optic neuropathy is not one disease but a spectrum of several different types, each with its own etiology, pathogenesis, clinical features and management. They cannot be lumped together. Ischemic optic neuropathy is primarily of two types: anterior (AION) and posterior (PION), involving the optic nerve head (ONH) and the rest of the optic nerve respectively. Furthermore, both AION and PION have different subtypes. AION comprises arteritic (A-AION - due to giant cell arteritis) and, non-arteritic (NA-AION - due to causes other than giant cell arteritis); NA-AION can be further classified into classical NA-AION and incipient NA-AION. PION consists of arteritic (A-PION - due to giant cell arteritis), non-arteritic (NA-PION - due to causes other than giant cell arteritis), and surgical (a complication of several systemic surgical procedures). Thus, ischemic optic neuropathy consists of six distinct types of clinical entities. NA-AION is by far the most common type and one of the most prevalent and visually crippling diseases in the middle-aged and elderly. A-AION, though less common, is an ocular emergency and requires early diagnosis and immediate treatment with systemic high dose corticosteroids to prevent further visual loss, which is entirely preventable. Controversy exists regarding the pathogenesis, clinical features and especially management of the various types of ischemic optic neuropathy because there are multiple misconceptions about its many fundamental aspects. Recently emerging information on the various factors that influence the optic nerve circulation, and also the various systemic and local risk factors which play important roles in the development of various types of ischemic optic neuropathy have given us a better understanding of

  3. OSI and TCP/IP

    NASA Technical Reports Server (NTRS)

    Randolph, Lynwood P.

    1994-01-01

    The Open Systems Interconnection Transmission Control Protocol/Internet Protocol (OSI TCP/IP) and the Government Open Systems Interconnection Profile (GOSIP) are compared and described in terms of Federal internetworking. The organization and functions of the Federal Internetworking Requirements Panel (FIRP) are discussed and the panel's conclusions and recommendations with respect to the standards and implementation of the National Information Infrastructure (NII) are presented.

  4. Hypoxic-preconditioning enhances the regenerative capacity of neural stem/progenitors in subventricular zone of newborn piglet brain.

    PubMed

    Ara, Jahan; De Montpellier, Sybille

    2013-09-01

    Perinatal hypoxia-ischemia (HI) results in brain injury, whereas mild hypoxic episodes result in preconditioning, which can significantly reduce the vulnerability of the brain to subsequent severe hypoxia-ischemia. Hypoxic-preconditioning (PC) has been shown to enhance cell survival and differentiation of progenitor cells in the central nervous system (CNS). The purpose of this study was to determine whether pretreatment with PC prior to HI stimulates subventricular zone (SVZ) proliferation and neurogenesis in newborn piglets. One-day-old piglets were subjected to PC (8% O2/92% N2) for 3h and 24h later were exposed to HI produced by combination of hypoxia (5% FiO2) for a pre-defined period of 30min and ischemia induced by a period of 10min of hypotension. Here we demonstrate that SVZ derived neural stem/progenitor cells (NSPs) from PC, HI and PC+HI piglets proliferated as neurospheres, expressed neural progenitor and neurodevelopmental markers, and that greater proportion of the spheres generated are multipotential. Neurosphere assay revealed that preconditioning pretreatment increased the number of NSP-derived neurospheres in SVZ following HI compared to normoxic and HI controls. NSPs from preconditioned SVZ generated twice as many neurons and astrocytes in vitro. Injections with 5-Bromo-2-deoxyuridine (BrdU) after PC revealed a robust proliferative response within the SVZ that continued for one week. PC also increased neurogenesis in vivo, doublecortin positive cells with migratory profiles were observed streaming from the SVZ to striatum and neocortex. These findings show that the induction of proliferation and neurogenesis by PC might be a positive adaptation for an efficient repair and plasticity in the event of a hypoxic-ischemic insult.

  5. lschemic preconditioning in pigs: a causal role for signal transducer and activator of transcription 3.

    PubMed

    Gent, Sabine; Skyschally, Andreas; Kleinbongard, Petra; Heusch, Gerd

    2017-03-01

    Ischemic preconditioning (IPC), i.e., brief episodes of nonlethal myocardial ischemia-reperfusion (I/R) before sustained ischemia with subsequent reperfusion, reduces infarct size in all species tested so far, including humans. In rodents, the cardioprotective signal transduction causally involves an activation of Akt, ERK1/2, and STAT3. However, there are apparent species differences in the signal transduction between rodents and larger mammals such as pigs, where data on IPC's signal transduction are inconsistent for Akt and ERK1/2. The role of STAT3 has not yet been analyzed. Pigs were subjected to 60 min of left anterior descending coronary artery occlusion and 180 min of reperfusion without or with IPC (2 cycles of 3-min occlusion separated by 2 min of reperfusion 15 min before sustained I/R). Infarct size was analyzed by triphenyl tetrazolium chloride staining, and Akt, ERK1/2, and STAT3 phosphorylation was quantified in myocardial biopsies taken at baseline and early reperfusion. AG490 was used to block the STAT3 signaling pathway. IPC reduced infarct size (%area at risk; mean ± SE, I/R, 45 ± 3 vs. IPC, 18 ± 3, P < 0.05). Akt and ERK1/2 phosphorylation was increased at early reperfusion without and with IPC. In contrast, STAT3 phosphorylation at early reperfusion was only increased with IPC (%baseline; mean ± SE, I/R, 126 ± 29 vs. IPC, 408 ± 147, P < 0.05). AG490 prevented the IPC-related increase of STAT3 phosphorylation at reperfusion (%baseline; mean ± SE, 82 ± 12) and abolished IPC's cardioprotection (%area at risk; mean ± SE, 35 ± 4). In pigs, increased phosphorylation of STAT3 is causally involved, whereas Akt and ERK1/2 seem to play no role in IPC's cardioprotection.NEW & NOTEWORTHY In pig hearts in situ, ischemic preconditioning (IPC) causally involves increased phosphorylation of STAT3, whereas Akt and ERK1/2 play no role for cardioprotection. The cardioprotective signal transduction of IPC is similar to that of ischemic postconditioning

  6. Ischemia induced activation of heat shock protein 27 kinases and casein kinase 2 in the preconditioned rabbit heart.

    PubMed

    Kim, S O; Baines, C P; Critz, S D; Pelech, S L; Katz, S; Downey, J M; Cohen, M V

    1999-01-01

    Protein kinase C (PKC), p38 MAP kinase, and mitogen-activated protein kinase-activated kinases 2 and 3 (MAPKAPK2 and MAPKAPK3) have been implicated in ischemic preconditioning (PC) of the heart to reduce damage following a myocardial infarct. This study examined whether extracellular signal-regulated kinase (Erk) 1, p70 ribosomal S6 kinase (p70 S6K), casein kinase 2 (CK2), and other hsp27 kinases are also activated by PC, and if they are required for protection in rabbit hearts. CK2 and hsp27 kinase activities declined during global ischemia in control hearts, whereas PC with 5 min ischemia and 10 min reperfusion increased their activities during global ischemia. Resource Q chromatography resolved two distinct peaks of hsp27 phosphotransferase activities; the first peak (at 0.36 M NaCl) appeared to correspond to the 55-kDa MAPKAPK2. Erk1 activity was elevated in both control and PC hearts after post-ischemic reperfusion, but no change was observed in p70 S6K activity. Infarct size (measured by triphenyltetrazolium staining) in isolated rabbit hearts subjected to 30 min regional ischemia and 2 h reperfusion was 31.0+/-2.6% of the risk zone in controls and was 10.3+/-2.2% in PC hearts (p<0.001). Neither the CK2 inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) nor the Mek1/2 inhibitor PD98059 infused during ischemia blocked protection by PC. The activation of CK2 and Erk1 in ischemic preconditioned hearts appear to be epiphenomena and not required for the reduction of infarction from myocardial ischemia.

  7. 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,…

  8. Cellular and molecular neurobiology of brain preconditioning.

    PubMed

    Cadet, Jean Lud; Krasnova, Irina N

    2009-02-01

    The tolerant brain which is a consequence of adaptation to repeated nonlethal insults is accompanied by the upregulation of protective mechanisms and the downregulation of prodegenerative pathways. During the past 20 years, evidence has accumulated to suggest that protective mechanisms include increased production of chaperones, trophic factors, and other antiapoptotic proteins. In contrast, preconditioning can cause substantial dampening of the organism's metabolic state and decreased expression of proapoptotic proteins. Recent microarray analyses have also helped to document a role of several molecular pathways in the induction of the brain refractory state. The present review highlights some of these findings and suggests that a better understanding of these mechanisms will inform treatment of a number of neuropsychiatric disorders.

  9. 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.

  10. Remote ischaemic preconditioning: closer to the mechanism?

    PubMed Central

    Gleadle, Jonathan M.; Mazzone, Annette

    2016-01-01

    Brief periods of ischaemia followed by reperfusion of one tissue such as skeletal muscle can confer subsequent protection against ischaemia-induced injury in other organs such as the heart. Substantial evidence of this effect has been accrued in experimental animal models. However, the translation of this phenomenon to its use as a therapy in ischaemic disease has been largely disappointing without clear evidence of benefit in humans. Recently, innovative experimental observations have suggested that remote ischaemic preconditioning (RIPC) may be largely mediated through hypoxic inhibition of the oxygen-sensing enzyme PHD2, leading to enhanced levels of alpha-ketoglutarate and subsequent increases in circulating kynurenic acid (KYNA). These observations provide vital insights into the likely mechanisms of RIPC and a route to manipulating this mechanism towards therapeutic benefit by direct alteration of KYNA, alpha-ketoglutarate levels, PHD inhibition, or pharmacological targeting of the incompletely understood cardioprotective mechanism activated by KYNA. PMID:28163901

  11. Cellular and Molecular Neurobiology of Brain Preconditioning

    PubMed Central

    Cadet, Jean Lud; Krasnova, Irina N.

    2009-01-01

    The tolerant brain which is a consequence of adaptation to repeated non-lethal insults is accompanied by the up-regulation of protective mechanisms and the down-regulation of pro-degenerative pathways. During the past 20 years, evidence has accumulated to suggest that protective mechanisms include increased production of chaperones, trophic factors, and other anti-apoptotic proteins. In contrast, preconditioning can cause substantial dampening of the organism’s metabolic state and decreased expression of pro-apoptotic proteins. Recent microarray analyses have also helped to document a role of several molecular pathways in the induction of the brain refractory state. The present review highlights some of these findings and suggests that a better understanding of these mechanisms will inform treatment of a number of neuropsychiatric disorders. PMID:19153843

  12. Hyperbaric oxygen preconditioning attenuates postoperative cognitive impairment in aged rats.

    PubMed

    Sun, Li; Xie, Keliang; Zhang, Changsheng; Song, Rui; Zhang, Hong

    2014-06-18

    Cognitive decline after surgery in the elderly population is a major clinical problem with high morbidity. Hyperbaric oxygen (HBO) preconditioning can induce significant neuroprotection against acute neurological injury. We hypothesized that HBO preconditioning would prevent the development of postoperative cognitive impairment. Elderly male rats (20 months old) underwent stabilized tibial fracture operation under general anesthesia after HBO preconditioning (once a day for 5 days). Separate cohorts of animals were tested for cognitive function with fear conditioning and Y-maze tests, or euthanized at different times to assess the blood-brain barrier integrity, systemic and hippocampal proinflammatory cytokines, and caspase-3 activity. Animals exhibited significant cognitive impairment evidenced by a decreased percentage of freezing time and an increased number of learning trials on days 1, 3, and 7 after surgery, which were significantly prevented by HBO preconditioning. Furthermore, HBO preconditioning significantly ameliorated the increase in serum and hippocampal proinflammatory cytokines tumor necrosis factor-α, interleukin-1 β (IL-1β), IL-6, and high-mobility group protein 1 in surgery-challenged animals. Moreover, HBO preconditioning markedly improved blood-brain barrier integrity and caspase-3 activity in the hippocampus of surgery-challenged animals. These findings suggest that HBO preconditioning could significantly mitigate surgery-induced cognitive impairment, which is strongly associated with the reduction of systemic and hippocampal proinflammatory cytokines and caspase-3 activity.

  13. Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance

    PubMed Central

    Lehotský, Ján; Tothová, Barbara; Kovalská, Maria; Dobrota, Dušan; Beňová, Anna; Kalenská, Dagmar; Kaplán, Peter

    2016-01-01

    Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC) is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signaling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK) protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signaling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors leading to ischemic

  14. 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.

  15. Challenges Regarding IP Core Functional Reliability

    NASA Technical Reports Server (NTRS)

    Berg, Melanie D.; LaBel, Kenneth A.

    2017-01-01

    For many years, intellectual property (IP) cores have been incorporated into field programmable gate array (FPGA) and application specific integrated circuit (ASIC) design flows. However, the usage of large complex IP cores were limited within products that required a high level of reliability. This is no longer the case. IP core insertion has become mainstream including their use in highly reliable products. Due to limited visibility and control, challenges exist when using IP cores and subsequently compromise product reliability. We discuss challenges and suggest potential solutions to critical application IP insertion.

  16. DRESS and Ischemic Stroke.

    PubMed

    Cahyanur, Rahmat; Oktavia, Dina; Koesno, Sukamto

    2012-07-01

    DRESS (drug rash eosinophilia and systemic symptoms) is a life threatening condition characterized by skin rash, fever, leucocytosis with eosinophilia or atypical lymphocytosis, lymphadenopathy, and internal organ involvement. This case report would like to describe an interesting case of DRESS coincidence with ischemic stroke. A 38 year old woman had been admitted with skin rash and fever since four days before. Four weeks before admission she received antibiotic and multivitamin for one week. The patient looked ill, with body temperature 38.0°C. Marked physical findings were cervical lymphadenopathy and hepatomegaly. Dermatological examination finding was generalized exanthema. Laboratory evaluation showed leucocytosis, eosinophilia, and increased level of ALT and AST. During hospitalization the patient also suffered from ischemic stroke. Treatments administered in this patient were oxygen, adequate intravenous fluid, parenteral nutrition, methyl prednisolone, cethirizin bid, ranitidin bid, and antibiotic. The antibiotic treatment in this case was performed with graded challenge or test dosing.

  17. 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.

  18. Ischemic postconditioning as a novel avenue to protect against brain injury after stroke

    PubMed Central

    Zhao, Heng

    2009-01-01

    Ischemic postconditioning initially referred to a stuttering reperfusion performed immediately after reperfusion, for preventing ischemia/reperfusion injury in both myocardial and cerebral infarction. It has evolved into a concept that can be induced by a broad range of stimuli or triggers, and may even be performed as late as 6 h after focal ischemia and 2 days after transient global ischemia. The concept is thought to be derived from ischemic preconditioning or partial/gradual reperfusion, but in fact the first experiment for postconditioning was carried out much earlier than that of preconditioning or partial/gradual reperfusion, in the research on myocardial ischemia. This review first examines the protective effects and parameters of postconditioning in various cerebral ischemic models. Thereafter, it provides insights into the protective mechanisms of postconditioning associated with reperfusion injury and the Akt, mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and ATP-sensitive K+ (KATP) channel cell signaling pathways. Finally, some open issues and future challenges regarding clinical translation of postconditioning are discussed. PMID:19240739

  19. Preconditioned Minimal Residual Methods for Chebyshev Spectral Caluclations

    NASA Technical Reports Server (NTRS)

    Canuto, C.; Quarteroni, A.

    1983-01-01

    The problem of preconditioning the pseudospectral Chebyshev approximation of an elliptic operator is considered. The numerical sensitiveness to variations of the coefficients of the operator are investigated for two classes of preconditioning matrices: one arising from finite differences, the other from finite elements. The preconditioned system is solved by a conjugate gradient type method, and by a DuFort-Frankel method with dynamical parameters. The methods are compared on some test problems with the Richardson method and with the minimal residual Richardson method.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Ischaemic preconditioning reduces myocardial calcium overload in coronary-occluded pig hearts shown by continuous in vivo assessment using microdialysis.

    PubMed

    Waldenström, Anders; Ronquist, Gunnar; Aberg, Anna-Maja; Ahlström, Katarina; Hauck, Philip; Abrahamsson, Pernilla; Johansson, Göran; Biber, Björn; Haney, Michael F

    2012-03-01

    During ischaemia, ATP depletion leads to insufficient fuelling for Na(+) /K(+) ATPase, decreased electrochemical potential and increased influx of calcium ions. This study demonstrated a means to assess the effects of ischaemic preconditioning (IP) on the free intracellular Ca(2+) pool during prolonged ischaemia. In a porcine myocardial ischaemia model, microdialysis (MD) was used for sampling of metabolic and injury markers in IP and non-IP (control) groups. (45) Ca(2+) was delivered in microperfusate locally to ischaemic myocardium, with distribution and uptake assessed by (45) Ca(2+) recovery in microdialysate. Cardiomyocytes in vitro were exposed to a Ca(2+) ionophore and tested for (45) Ca(2+) uptake. An accentuated myocardial calcium ion influx (observed as an increased microdialysate (45) Ca(2+) recovery in the extracellular milieu) was noted in control pigs compared with IP pigs during ischaemia. Suspended cardiomyocytes preincubated with a Ca(2+) ionophore to increase the intracellular calcium ion pool and subsequently incubated with (45) Ca(2+) , displayed lower (45) Ca(2+) uptake in cells compared with control cells not exposed to the ionophore, corroborating the idea of a strong relationship between degree of intracellular calcium overload and microdialysate (45) Ca(2+) recovery. The ischaemic insult was differentially verified by metabolic and injury markers. We introduce an in vivo method for serial assessment of myocardial calcium overload during ischaemia, using a MD technique and (45) Ca(2+) inclusion. IP leads to relatively less calcium overload as assessed by this new method, and we interpret this to mean that reduction in calcium overload is an important part of the IP protective effect.

  5. 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

  6. Targeting TRAF3IP2 by Genetic and Interventional Approaches Inhibits Ischemia/Reperfusion-induced Myocardial Injury and Adverse Remodeling.

    PubMed

    Erikson, John M; Valente, Anthony J; Mummidi, Srinivas; Kandikattu, Hemanth Kumar; DeMarco, Vincent G; Bender, Shawn B; Fay, William P; Siebenlist, Ulrich; Chandrasekar, Bysani

    2017-02-10

    Re-establishing blood supply is the primary goal for reducing myocardial injury in subjects with ischemic heart disease. Paradoxically, reperfusion results in nitroxidative stress and a marked inflammatory response in the heart. TRAF3IP2 (TRAF3 Interacting Protein 2; previously known as CIKS or Act1) is an oxidative stress-responsive cytoplasmic adapter molecule that is an upstream regulator of both IκB kinase (IKK) and c-Jun N-terminal kinase (JNK), and an important mediator of autoimmune and inflammatory responses. Here we investigated the role of TRAF3IP2 in ischemia/reperfusion (I/R)-induced nitroxidative stress, inflammation, myocardial dysfunction, injury, and adverse remodeling. Our data show that I/R up-regulates TRAF3IP2 expression in the heart, and its gene deletion, in a conditional cardiomyocyte-specific manner, significantly attenuates I/R-induced nitroxidative stress, IKK/NF-κB and JNK/AP-1 activation, inflammatory cytokine, chemokine, and adhesion molecule expression, immune cell infiltration, myocardial injury, and contractile dysfunction. Furthermore, Traf3ip2 gene deletion blunts adverse remodeling 12 weeks post-I/R, as evidenced by reduced hypertrophy, fibrosis, and contractile dysfunction. Supporting the genetic approach, an interventional approach using ultrasound-targeted microbubble destruction-mediated delivery of phosphorothioated TRAF3IP2 antisense oligonucleotides into the LV in a clinically relevant time frame significantly inhibits TRAF3IP2 expression and myocardial injury in wild type mice post-I/R. Furthermore, ameliorating myocardial damage by targeting TRAF3IP2 appears to be more effective to inhibiting its downstream signaling intermediates NF-κB and JNK. Therefore, TRAF3IP2 could be a potential therapeutic target in ischemic heart disease.

  7. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Engines of 2 Horsepower or Less General § 183.320 Preconditioning for tests. A boat must meet the... be sealed. (f) The boat must be keel down in the water. (g) The boat must be swamped, allowing...

  8. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Engines of 2 Horsepower or Less General § 183.320 Preconditioning for tests. A boat must meet the... be sealed. (f) The boat must be keel down in the water. (g) The boat must be swamped, allowing...

  9. 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...

  10. Applying a gaming approach to IP strategy.

    PubMed

    Gasnier, Arnaud; Vandamme, Luc

    2010-02-01

    Adopting an appropriate IP strategy is an important but complex area, particularly in the pharmaceutical and biotechnology sectors, in which aspects such as regulatory submissions, high competitive activity, and public health and safety information requirements limit the amount of information that can be protected effectively through secrecy. As a result, and considering the existing time limits for patent protection, decisions on how to approach IP in these sectors must be made with knowledge of the options and consequences of IP positioning. Because of the specialized nature of IP, it is necessary to impart knowledge regarding the options and impact of IP to decision-makers, whether at the level of inventors, marketers or strategic business managers. This feature review provides some insight on IP strategy, with a focus on the use of a new 'gaming' approach for transferring the skills and understanding needed to make informed IP-related decisions; the game Patentopolis is discussed as an example of such an approach. Patentopolis involves interactive activities with IP-related business decisions, including the exploitation and enforcement of IP rights, and can be used to gain knowledge on the impact of adopting different IP strategies.

  11. 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.

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

    PubMed Central

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

    2015-01-01

    The endogenous electric field (EF)-directed migration of keratinocytes (galvanotaxis) into wounds is an essential step in wound re-epithelialization. Hypoxia, which occurs immediately after injury, acts as an early stimulus to initiate the healing process; however, the mechanisms for this effect, remain elusive. We show here that the galvanotactic migration of keratinocytes was enhanced by hypoxia preconditioning as a result of the increased directionality rather than the increased motility of keratinocytes. This enhancement was both oxygen tension- and preconditioning time-dependent, with the maximum effects achieved using 2% O2 preconditioning for 6 hours. Hypoxic preconditioning (2% O2, 6 hours) decreased the threshold voltage of galvanotaxis to < 25 mV/mm, whereas this value was between 25 and 50 mV/mm in the normal culture control. In a scratch-wound monolayer assay in which the applied EF was in the default healing direction, hypoxic preconditioning accelerated healing by 1.38-fold compared with the control conditions. Scavenging of the induced ROS by N-acetylcysteine (NAC) abolished the enhanced galvanotaxis and the accelerated healing by hypoxic preconditioning. Our data demonstrate a novel and unsuspected role of hypoxia in supporting keratinocyte galvanotaxis. Enhancing the galvanotactic response of cells might therefore be a clinically attractive approach to induce improved wound healing. PMID:25988491

  13. Myocardial Hypertrophic Preconditioning Attenuates Cardiomyocyte Hypertrophy and Slows Progression to Heart Failure Through Upregulation of S100A8/A9

    PubMed Central

    Wei, Xuan; Wu, Bing; Zhao, Jing; Zeng, Zhi; Xuan, Wanling; Cao, Shiping; Huang, Xiaobo; Asakura, Masanori; Xu, Dingli; Bin, Jianping; Kitakaze, Masafumi

    2015-01-01

    Background— Transient preceding brief ischemia provides potent cardioprotection against subsequent long ischemia, termed ischemic preconditioning. Here, we hypothesized that transient short-term hypertrophic stimulation would induce the expression of hypertrophy regression genes and render the heart resistant to subsequent hypertrophic stress, and slow the progression to heart failure, as well. Methods and Results— Cardiomyocyte hypertrophy was induced in mice by either transverse aortic constriction or an infusion of phenylephrine, and in neonatal rat ventricular cardiomyocytes by norepinephrine exposures. In the preconditioning groups, hypertrophic stimulation was provided for 1 to 7 days and then withdrawn for several days by either aortic debanding or discontinuing phenylephrine or norepinephrine treatment, followed by subsequent reexposure to the hypertrophic stimulus for the same period as in the control group. One or 6 weeks after transverse aortic constriction, the heart weight/body weight ratio was lower in the preconditioning group than in the control group, whereas the lung weight/body weight ratio was significantly decreased 6 weeks after transverse aortic constriction. Similar results were obtained in mice receiving phenylephrine infusion and neonatal rat ventricular cardiomyocytes stimulated with norepinephrine. Both mRNA and protein expression of S100A8 and S100A9 showed significant upregulation after the removal of hypertrophic stimulation and persisted for 6 weeks in response to reimposition of transverse aortic constriction. The treatment with recombinant S100A8/A9 inhibited norepinephrine-induced myocyte hypertrophy and reduced the expression of calcineurin and NFATc3, but the silencing of S100A8/A9 prevented such changes. Conclusions— Preconditioning with prohypertrophic factors exerts an antihypertrophic effect and slows the progression of heart failure, indicating the existence of the phenomenon for hypertrophic preconditioning. PMID

  14. 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.

  15. [iPS cells in dentistry].

    PubMed

    Egusa, Hiroshi

    2012-01-01

    The discovery of the induced pluripotent stem (iPS) cell technology, which enables us to produce pluripotent stem cells by introducing a few genetic factors, commands considerable attention in the field of dentistry. These iPS cells may be of particular importance for developing innovative technologies to regenerate missing jaw bones and lost teeth, and there are expectations that several types of tissue stem cells and mucosal cells in the oral area can be used as an ideal iPS cell source. We previously reported that the gingiva, which is often resected during general dental treatments and treated as biomedical waste, is a promising source of iPS cells. In this review, the current trends in iPS cell research in dentistry are outlined, and future aspects of potential applications of the iPS cell technologies to dental treatments will be discussed.

  16. Protective effects of fentanyl preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion in rats

    PubMed Central

    Xu, Q.; Li, Q.-G.; Fan, G.-R.; Liu, Q.-H.; Mi, F.-L.; Liu, B.

    2017-01-01

    We aimed to study the effect of fentanyl (Fen) preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion (I/R) in rats. A total of 120 Sprague Dawley male rats (age: 3 months) were randomly divided into: sham operation group (S group), I/R group, normal saline I/R group (NS group), and fentanyl low, middle, and high dose groups (Fen1: 2 μg/kg; Fen2: 4 μg/kg; Fen3: 6 μg/kg). Heart rate (HR), mean arterial pressure (MAP), left ventricular developed pressure (LVDP), ±dp/dtmax, malondialdehyde (MDA), superoxide dismutase (SOD) activity, creatine phosphokinase-MB (CK-MB), and cardiac troponin-I (cTnI) were measured. Myocardial ischemic (MI) area, total apoptotic myocardial cells, and protein and mRNA expressions of B-cell lymphoma 2 (Bcl-2) and Bax were detected. HR and MAP were higher, while LVDP and ±dp/dtmax were close to the base value in the Fen groups compared to those in the I/R group. Decreased MDA concentration and CK-MB value and increased SOD activity were found in the Fen groups compared to the I/R group, while cTnI concentration was significantly lower in the Fen1 and Fen2 groups (all P<0.05). Myocardial damage was less in the Fen groups compared to the I/R group and the MI areas and apoptotic indexes were significantly lower in the Fen1 and Fen2 groups (all P<0.05). Furthermore, significantly increased protein and mRNA expressions of Bcl-2, and decreased protein and mRNA expressions of Bax were found in the Fen groups compared to the I/R group (all P<0.05). Fentanyl preconditioning may suppress cardiomyocyte apoptosis induced by I/R in rats by regulating Bcl-2 and Bax. PMID:28225864

  17. Glutamate transporter type 3 mediates isoflurane preconditioning-induced acute phase of neuroprotection in mice.

    PubMed

    Li, Liaoliao; Deng, Jiao; Zuo, Zhiyi

    2013-09-01

    A pre-exposure to isoflurane reduces ischemic brain injury in rodents (isoflurane preconditioning). This neuroprotection has acute and delayed phases. Our previous in vitro studies suggest that the acute phase may involve excitatory amino acid transporters (EAATs). We determine whether this protection involves EAAT3, the major neuronal EAAT. Adult male EAAT3 knockout mice and their wild-type littermates were exposed or were not exposed to 1.5% isoflurane for 30 min. Sixty minutes later, they were subjected to a 90- or 60-min middle cerebral arterial occlusion (MCAO). Their neurological outcomes were evaluated 24h after the MCAO. In another experiment, cerebral cortex was harvested for Western blotting at 30 min after animals were exposed to 1.5% isoflurane for 30 min. Here, we showed that isoflurane reduced brain infarct volumes and improved neurological functions of wild-type mice after a 90-min MCAO. However, isoflurane pre-exposure did not change the neurological outcome of EAAT3 knockout mice no matter whether the MCAO was for 90 min or 60 min. Isoflurane increased phospho-Akt, a survival-promoting protein, in the wild-type mice but not in the EAAT3 knockout mice. The isoflurane-induced neuroprotection in the wild-type mice was abolished by LY294004, an Akt activation inhibitor. LY294004 alone did not affect the neurological outcome of the wild-type or EAAT3 knockout mice after focal brain ischemia. These results suggest that the isoflurane preconditioning-induced acute phase of neuroprotection involves EAAT3. The downstream event includes Akt activation.

  18. 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.

  19. 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.

  20. Preconditioning and postconditioning: new strategies for cardioprotection.

    PubMed

    Hausenloy, D J; Yellon, D M

    2008-06-01

    Despite optimal therapy, the morbidity and mortality of coronary heart disease (CHD) remains significant, particularly in patients with diabetes or the metabolic syndrome. New strategies for cardioprotection are therefore required to improve the clinical outcomes in patients with CHD. Ischaemic preconditioning (IPC) as a cardioprotective strategy has not fulfilled it clinical potential, primarily because of the need to intervene before the index ischaemic event, which is impossible to predict in patients presenting with an acute myocardial infarction (AMI). However, emerging studies suggest that IPC-induced protection is mediated in part by signalling transduction pathways recruited at time of myocardial reperfusion, creating the possibility of harnessing its cardioprotective potential by intervening at time of reperfusion. In this regard, the recently described phenomenon of ischaemic postconditioning (IPost) has attracted great interest, particularly as it represents an intervention, which can be applied at time of myocardial reperfusion for patients presenting with an AMI. Interestingly, the signal transduction pathways, which underlie its protection, are similar to those recruited by IPC, creating a potential common cardioprotective pathway, which can be recruited at time of myocardial reperfusion, through the use of appropriate pharmacological agents given as adjuvant therapy to current myocardial reperfusion strategies such as thrombolysis and primary percutaneous coronary intervention for patients presenting with an AMI. This article provides a brief overview of IPC and IPost and describes the common signal transduction pathway they both appear to recruit at time of myocardial reperfusion, the pharmacological manipulation of which has the potential to generate new strategies for cardioprotection.

  1. Exploring the Role of TRPV and CGRP in Adenosine Preconditioning and Remote Hind Limb Preconditioning-Induced Cardioprotection in Rats.

    PubMed

    Singh, Amritpal; Randhawa, Puneet Kaur; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2017-02-14

    The cardioprotective effects of remote hind limb preconditioning (RIPC) are well known, but mechanisms by which protection occurs still remain to be explored. Therefore, the present study was designed to investigate the role of TRPV and CGRP in adenosine and remote preconditioning-induced cardioprotection, using sumatriptan, a CGRP release inhibitor and ruthenium red, a TRPV inhibitor, in rats. For remote preconditioning, a pressure cuff was tied around the hind limb of the rat and was inflated with air up to 150 mmHg to produce ischemia in the hind limb and during reperfusion pressure was released. Four cycles of ischemia and reperfusion, each consisting of 5 min of inflation and 5 min of deflation of pressure cuff were used to produce remote limb preconditioning. An ex vivo Langendorff's isolated rat heart model was used to induce ischemia reperfusion injury by 30 min of global ischemia followed by 120 min of reperfusion. RIPC demonstrated a significant decrease in ischemia reperfusion-induced significant myocardial injury in terms of increase in LDH, CK, infarct size and decrease in LVDP, +dp/dtmax and -dp/dtmin. Moreover, pharmacological preconditioning with adenosine produced cardioprotective effects in a similar manner to RIPC. Pretreatment with sumatriptan, a CGRP release blocker, abolished RIPC and adenosine preconditioning-induced cardioprotective effects. Administration of ruthenium red, a TRPV inhibitor, also abolished adenosine preconditioning-induced cardioprotection. It may be proposed that the cardioprotective effects of adenosine and remote preconditioning are possibly mediated through activation of a TRPV channels and consequent, release of CGRP.

  2. 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.

  3. Ischemic mitral valve prolapse

    PubMed Central

    Cristiano, Spadaccio; Nenna, Antonio; Chello, Massimo

    2016-01-01

    Ischemic mitral prolapse (IMP) is a pathologic entity encountered in about one-third among the patients undergoing surgery for ischemic mitral regurgitation (IMR). IMP is generally the result of a papillary muscle injury consequent to myocardial, but the recent literature is progressively unveiling a more complex pathogenesis. The mechanisms underlying its development regards the impairment of one or more components of the mitral apparatus, which comprises the annulus, the chordae tendineae, the papillary muscle and the left ventricular wall. IMP is not only a disorder of valvular function, but also entails coexistent aspects of a geometric disturbance of the mitral valve configuration and of the left ventricular function and dimension and a correct understanding of all these aspects is crucial to guide and tailor the correct therapeutic strategy to be adopted. Localization of prolapse, anatomic features of the prolapsed leaflets and the subvalvular apparatus should be carefully evaluated as also constituting the major determinants defining patient’s outcomes. This review will summarize our current understanding of the pathophysiology and clinical evidence on IMP with a particular focus on the surgical treatment. PMID:28149574

  4. A Solution for Irregular IP Multicast Packet Flooding — For Heavy Traffic IP Multicast Communication

    NASA Astrophysics Data System (ADS)

    Misumi, Makoto; Nakagawa, Shin-Ichi; Chinen, Ken-Ichi; Shinoda, Yoichi; Yamaoka, Katsunori

    When an IP Multicast network is constructed on a switch-based network, many IP Multicast packet broadcasts are generated, and these broadcasts cause trouble for all of the other kinds of communication. To solve this problem, implementing IGMP Snooping on various switches has been proposed. However, some switches have insufficient IP Multicast packet-handling capability. This problem is also mentioned in RFC4541. In this paper, we propose the IGMP Snooping Activator (ISA) mechanism as a way to solve the IP Multicast packet-handling problem. The ISA transmits dummy IGMP Queries to maintain the IP Multicast network, and it joins the flooding IP Multicast group to activate IGMP Snooping in switches that are unable to handle IP Multicast packets. The experimental evaluation shows the effectiveness of our proposed method: the network load decreases because of the method's effective restraint of IP Multicast packet flooding.

  5. 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.

  6. Approaches for Resolving Dynamic IP Addressing.

    ERIC Educational Resources Information Center

    Foo, Schubert; Hui, Siu Cheung; Yip, See Wai; He, Yulan

    1997-01-01

    A problem with dynamic Internet protocol (IP) addressing arises when the Internet connection is through an Internet provider since the IP address is allocated only at connection time. This article examines a number of online and offline methods for resolving the problem. Suggests dynamic domain name system (DNS) and directory service look-up are…

  7. 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…

  8. SN2009ip at Very Late Times

    NASA Astrophysics Data System (ADS)

    Bigley, Andrew Christopher; Graham, Melissa Lynn

    2016-01-01

    The 2012 eruption of SN 2009ip resembled a Type IIn supernovae, dominated by emission from interaction of the ejecta with circumstellar material, but the question remains: was the 2012 outburst of SN 2009ip truly the terminal explosion of a massive star? We present time series photometric and spectroscopic data for the transient SN2009ip from 260 to 1026 days after the peak of its 2012 outburst. These data were collected at the Las Cumbres Observatory Global Telescope Network and Keck Observatory. We will show that SN 2009ip continues to decline linearly in brightness at very late epochs, analyze the evolution in flux and asymmetry of the Balmer emission lines, and investigate the geometry of the circumstellar material from the progenitor star system and the true nature of SN 2009ip.

  9. Analysis of all-optical IP routers

    NASA Astrophysics Data System (ADS)

    Tamil, Lakshman S.; Masetti, Francesco B.; McDermott, Thomas C.; Castanon, Gerardo; Ge, Andrew; Tancevski, Ljubisa

    1998-10-01

    The increased data traffic experienced today and the projected increase in the data traffic in the future demand exploration of novel approaches to IP transport such as transport of IP traffic over optics. The bimodal nature of the IP traffic short packets which are typical of transactional-style flows and large packets or bursts which are encountered in the transport of large data blocks requires, design of routers that are capable of routing packets with variable lengths efficiently. In this paper, we discuss the design aspects of such all-optical IP-switches. The broadcast and select architecture is a prime candidate for implementing optical IP routers. Construction of optical routers with buffering, wavelength conversion and multipath routing are considered. The merits and demerits of all these cases and the effect of buffer size, wavelength conversion and multiple-path routing on the blocking probability and probability of packet loss are discussed.

  10. Xenon preconditioning reduces brain damage from neonatal asphyxia in rats.

    PubMed

    Ma, Daqing; Hossain, Mahmuda; Pettet, Garry K J; Luo, Yan; Lim, Ta; Akimov, Stanislav; Sanders, Robert D; Franks, Nicholas P; Maze, Mervyn

    2006-02-01

    Xenon attenuates on-going neuronal injury in both in vitro and in vivo models of hypoxic-ischaemic injury when administered during and after the insult. In the present study, we sought to investigate whether the neuroprotective efficacy of xenon can be observed when administered before an insult, referred to as 'preconditioning'. In a neuronal-glial cell coculture, preexposure to xenon for 2 h caused a concentration-dependent reduction of lactate dehydrogenase release from cells deprived of oxygen and glucose 24 h later; xenon's preconditioning effect was abolished by cycloheximide, a protein synthesis inhibitor. Preconditioning with xenon decreased propidium iodide staining in a hippocampal slice culture model subjected to oxygen and glucose deprivation. In an in vivo model of neonatal asphyxia involving hypoxic-ischaemic injury to 7-day-old rats, preconditioning with xenon reduced infarction size when assessed 7 days after injury. Furthermore, a sustained improvement in neurologic function was also evident 30 days after injury. Phosphorylated cAMP (cyclic adenosine 3',5'-monophosphate)-response element binding protein (pCREB) was increased by xenon exposure. Also, the prosurvival proteins Bcl-2 and brain-derived neurotrophic factor were upregulated by xenon treatment. These studies provide evidence for xenon's preconditioning effect, which might be caused by a pCREB-regulated synthesis of proteins that promote survival against neuronal injury.

  11. 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.

  12. Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial

    PubMed Central

    2013-01-01

    Background Recovery after a major stroke is usually limited, but cell therapy for patients with fixed neurologic deficits is emerging. Several recent clinical trials have investigated mesenchymal stem cell (MSC) therapy for patients with ischemic stroke. We previously reported the results of a controlled trial on the application of autologous MSCs in patients with ischemic stroke with a long-term follow-up of up to 5 years (the 'STem cell Application Researches and Trials In NeuroloGy’ (STARTING) study). The results from this pilot trial are challenging, but also raise important issues. In addition, there have been recent efforts to improve the safety and efficacy of MSC therapy for stroke. Methods and design The clinical and preclinical background and the STARTING-2 study protocol are provided. The trial is a prospective, randomized, open-label, blinded-endpoint (PROBE) clinical trial. Both acute and chronic stroke patients will be selected based on clinical and radiological features and followed for 3 months after MSC treatment. The subjects will be randomized into one of two groups: (A) a MSC group (n = 40) or (B) a control group (n = 20). Autologous MSCs will be intravenously administered after ex vivo culture expansion with autologous ischemic serum obtained as early as possible, to enhance the therapeutic efficacy (ischemic preconditioning). Objective outcome measurements will be performed using multimodal MRI and detailed functional assessments by blinded observers. Discussion This trial is the first to evaluate the efficacy of MSCs in patients with ischemic stroke. The results may provide better evidence for the effectiveness of MSC therapy in patients with ischemic stroke. Trial registration This trial was registered with ClinicalTrials.gov, number NCT01716481. PMID:24083670

  13. 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

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

    PubMed Central

    Bickler, Philip E.; Fahlman, Christian S.; Gray, Jonathan; McKleroy, William; Warren, Daniel E.

    2009-01-01

    Exposure of neurons to a non-lethal hypoxic stress greatly reduces cell death during subsequent severe ischemia (hypoxic preconditioning, HPC). In organotypic cultures of rat hippocampus, we demonstrate that HPC requires inositol triphosphate (IP3) receptor-dependent Ca2+ release from the endoplasmic reticulum (ER) triggered by increased cytosolic NAD(P)H. Ca2+ chelation with intracellular BAPTA, ER Ca2+ store depletion with thapsigargin, IP3 receptor block 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 was 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. PMID:19217932

  15. [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.

  16. 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.

  17. Research report: the effects of hyperbaric oxygen preconditioning on myocardial biomarkers of cardioprotection in patients having coronary artery bypass graft surgery.

    PubMed

    Jeysen, Zivan Yogaratnam; Gerard, Laden; Levant, Guvendik; Cowen, Mike; Cale, Alex; Griffin, Steve

    2011-01-01

    We have previously conducted and reported on the primary endpoint of a clinical study which demonstrated that hyperbaric oxygen (HBO2) preconditioning consisting of two 30-minute intervals of 100% oxygen at 2.4 atmospheres absolute (ATA) prior to coronary artery bypass graft (CABG) surgery leads to an improvement in left ventricular stroke work (LVSW) 24 hours following CABG. In that study, 81 patients were randomized to treatment with HBO2 (HBO2; n = 41) or routine treatment (Control Group; n = 40) prior to surgery. The objective of this manuscript is to further report on the result of the exploratory secondary endpoints from that study, specifically the effects of HBO2 preconditioning on biomarkers of myocardial protection. Intraoperative right atrial biopsies were assessed, via an Enzyme Linked ImmunoSorbent Assay (ELISA), for the expression of eNOS and HSP72. In this study, no significant differences were observed between the groups with respect to the quantity of myocardial eNOS and HSP72. However, in the HBO2 Group, following ischemia and reperfusion, the quantities of myocardial eNOS and HSP72 were increased. This suggests that HBO2 preconditioning in this group of patients may be capable of inducing endogenous cardioprotection following ischemic reperfusion injury (IRI).

  18. 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.

  19. Cortical spreading depression-induced preconditioning in the brain

    PubMed Central

    Shen, Ping-ping; Hou, Shuai; Ma, Di; Zhao, Ming-ming; Zhu, Ming-qin; Zhang, Jing-dian; Feng, Liang-shu; Cui, Li; Feng, Jia-chun

    2016-01-01

    Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the underlying mechanism for this phenomenon remains relatively unclear. To date, numerous issues exist regarding the experimental model used to precondition the brain with cortical spreading depression, such as the administration route, concentration of potassium chloride, induction time, duration of the protection provided by the treatment, the regional distribution of the protective effect, and the types of neurons responsible for the greater tolerance. In this review, we focus on the mechanisms underlying cortical spreading depression-induced tolerance in the brain, considering excitatory neurotransmission and metabolism, nitric oxide, genomic reprogramming, inflammation, neurotropic factors, and cellular stress response. Specifically, we clarify the procedures and detailed information regarding cortical spreading depression-induced preconditioning and build a foundation for more comprehensive investigations in the field of neural regeneration and clinical application in the future. PMID:28123433

  20. 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.

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

    NASA Technical Reports Server (NTRS)

    Wong, G. S.

    1973-01-01

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

  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. 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

  4. Scalable IP switching based on optical interconnect

    NASA Astrophysics Data System (ADS)

    Luo, Zhixiang; Cao, Mingcui; Liu, Erwu

    2000-10-01

    IP traffic on the Internet and enterprise networks has been growing exponentially in the last several years, and much attention is being focused on the use of IP multicast for real-time multimedia applications. The current soft and general-purpose CPU-based routers face great stress since they have great latency and low forwarding speeds. Based on the ASICs, layer 2 switching provides high-speed packet forwarding. Integrating high-speed of Layer 2 switching with the flexibility of Layer 3 routing, Layer 3 switching (IP switching) has been put forward in order to avoid the performance bottleneck associated with Layer 3 forwarding. In this paper, we present a prototype system of a scalable IP switching based on scalable ATM switching fabric and optical interconnect. The IP switching system mainly consists of the input/output interface unit, scalable ATM switching fabric and IP control component. Optical interconnects between the input fan-out stage and the interconnect stage, also the interconnect stage and the output concentration stage provide high-speed data paths. And the interconnect stage is composed of 16 X 16 CMOS-SEED ATM switching modules. With 64 ports of OC-12 interface, the maximum throughput of the prototype system is about 20 million packets per second (MPPS) for 256 bytes average packet length, and the packet loss ratio is less than 10e-9. Benefiting from the scalable architecture and the optical interconnect, this IP switching system can easily scale to very large network size.

  5. 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

  6. Ischemic ulcers - self-care

    MedlinePlus

    ... that can cause ischemic wounds include: Diseases that cause inflammation, such as lupus High blood pressure High cholesterol levels Chronic kidney disease Blockage of the lymph vessels , which causes fluid ...

  7. 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.

  8. Hyperbaric oxygen preconditioning: a reliable option for neuroprotection

    PubMed Central

    Hu, Qin; Manaenko, Anatol; Matei, Nathanael; Guo, Zhenni; Xu, Ting; Tang, Jiping; Zhang, John H.

    2016-01-01

    Brain injury is the leading cause of death and disability worldwide and clinically there is no effective therapy for neuroprotection. Hyperbaric oxygen preconditioning (HBO-PC) has been experimentally demonstrated to be neuroprotective in several models and has shown efficiency in patients undergoing on-pump coronary artery bypass graft (CABG) surgery. Compared with other preconditioning stimuli, HBO is benign and has clinically translational potential. In this review, we will summarize the results in experimental brain injury and clinical studies, elaborate the mechanisms of HBO-PC, and discuss regimes and opinions for future interventions in acute brain injury. PMID:27826420

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 40 CFR 86.232-94 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the start of the driving cycle except when vehicle peconditioning is performed in accordance with... dynamometer and operated through one UDDS cycle. (5) For those unusual circumstances where additional... additional preconditioning shall consist of one or more driving cycles of the UDDS, as described in...

  16. 40 CFR 86.232-94 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the start of the driving cycle except when vehicle peconditioning is performed in accordance with... dynamometer and operated through one UDDS cycle. (5) For those unusual circumstances where additional... additional preconditioning shall consist of one or more driving cycles of the UDDS, as described in...

  17. 40 CFR 86.232-94 - Vehicle preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the start of the driving cycle except when vehicle peconditioning is performed in accordance with... dynamometer and operated through one UDDS cycle. (5) For those unusual circumstances where additional... additional preconditioning shall consist of one or more driving cycles of the UDDS, as described in...

  18. Preconditioning with cobalt chloride modifies pain perception in mice.

    PubMed

    Alexa, Teodora; Luca, Andrei; Dondas, Andrei; Bohotin, Catalina Roxana

    2015-04-01

    Cobalt chloride (CoCl2) modifies mitochondrial permeability and has a hypoxic-mimetic effect; thus, the compound induces tolerance to ischemia and increases resistance to a number of injury types. The aim of the present study was to investigate the effects of CoCl2 hypoxic preconditioning for three weeks on thermonociception, somatic and visceral inflammatory pain, locomotor activity and coordination in mice. A significant pronociceptive effect was observed in the hot plate and tail flick tests after one and two weeks of CoCl2 administration, respectively (P<0.001). Thermal hyperalgesia (Plantar test) was present in the first week, but recovered by the end of the experiment. Contrary to the hyperalgesic effect on thermonociception, CoCl2 hypoxic preconditioning decreased the time spent grooming the affected area in the second phase of the formalin test on the orofacial and paw models. The first phase of formalin-induced pain and the writhing test were not affected by CoCl2 preconditioning. Thus, the present study demonstrated that CoCl2 preconditioning has a dual effect on pain, and these effects should be taken into account along with the better-known neuro-, cardio- and renoprotective effects of CoCl2.

  19. 40 CFR 1066.407 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Vehicle preparation and...) AIR POLLUTION CONTROLS VEHICLE-TESTING PROCEDURES Vehicle Preparation and Running a Test § 1066.407 Vehicle preparation and preconditioning. This section describes steps to take before measuring...

  20. 40 CFR 1066.407 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Vehicle preparation and...) AIR POLLUTION CONTROLS VEHICLE-TESTING PROCEDURES Vehicle Preparation and Running a Test § 1066.407 Vehicle preparation and preconditioning. This section describes steps to take before measuring...

  1. Improvement in computational fluid dynamics through boundary verification and preconditioning

    NASA Astrophysics Data System (ADS)

    Folkner, David E.

    This thesis provides improvements to computational fluid dynamics accuracy and efficiency through two main methods: a new boundary condition verification procedure and preconditioning techniques. First, a new verification approach that addresses boundary conditions was developed. In order to apply the verification approach to a large range of arbitrary boundary conditions, it was necessary to develop unifying mathematical formulation. A framework was developed that allows for the application of Dirichlet, Neumann, and extrapolation boundary condition, or in some cases the equations of motion directly. Verification of boundary condition techniques was performed using exact solutions from canonical fluid dynamic test cases. Second, to reduce computation time and improve accuracy, preconditioning algorithms were applied via artificial dissipation schemes. A new convective upwind and split pressure (CUSP) scheme was devised and was shown to be more effective than traditional preconditioning schemes in certain scenarios. The new scheme was compared with traditional schemes for unsteady flows for which both convective and acoustic effects dominated. Both boundary conditions and preconditioning algorithms were implemented in the context of a "strand grid" solver. While not the focus of this thesis, strand grids provide automatic viscous quality meshing and are suitable for moving mesh overset problems.

  2. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Engines of More Than 2 Horsepower General § 183.220 Preconditioning for tests. A boat must meet the... be keel down in the water. (g) The boat must be swamped, allowing water to flow between the inside... flooded portion of the boat must be eliminated. (h) Water must flood the two largest air chambers and...

  3. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Engines of More Than 2 Horsepower General § 183.220 Preconditioning for tests. A boat must meet the... be keel down in the water. (g) The boat must be swamped, allowing water to flow between the inside... flooded portion of the boat must be eliminated. (h) Water must flood the two largest air chambers and...

  4. 40 CFR 86.232-94 - 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. 86.232-94... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1994 and Later Model Year Gasoline-Fueled New Light-Duty Vehicles, New Light-Duty Trucks and New...

  5. 40 CFR 86.1774-99 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 20 2012-07-01 2012-07-01 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 86.132-96 - 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. 86.132-96... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle...

  8. 40 CFR 86.1774-99 - Vehicle preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 20 2013-07-01 2013-07-01 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...

  9. 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...

  10. Protective Effect of Grape Seed Proanthocyanidins against Liver Ischemic Reperfusion Injury: Particularly in Diet-Induced Obese Mice

    PubMed Central

    Song, Xiaoyu; Xu, Hongde; Feng, Yanling; Li, Xiaoman; Lin, Meina; Cao, Liu

    2012-01-01

    Background: Hepatic ischemia and reperfusion injury (IRI) is a major complication in liver surgery, and hepatic steatosis is a primary factor aggravating cellular injury during IRI. Both pro-inflammatory cytokines and reactive oxygen species (ROS) are key mediators of hepatic IRI. Ischemic preconditioning (IpreC), remote ischemia preconditioning (RIPC) and ischemic postconditioning (IpostC) have offered protections on hepatic IRI, but all these methods have their own shortcomings. Grape seed proanthocyanidins (GSP) has a broad spectrum of pharmacological properties against oxidative stress. Thus, GSP has potential protective effects against hepatic IRI. Methods: C57BL/6 mice suffering 30mins hepatic ischemia process were sacrificed after 1h reperfusion to build murine warm hepatic IRI model. The mice were injected GSP intraperitoneally 10, 20, 40mg/kg/day for 3 weeks as pharmacological preconditioning. Obese mice fed with high-fat diet for 24 weeks before used. Three pathways related to IRI, including ROS elimination, pro-inflammatory cytokines release and hypoxia responses were examined. Results: Our data show that GSP could significantly reduce hepatic IRI by protecting hepatocyte function and increasing the activity of ROS scavengers, as well as decreasing cytokines levels. At the same time, GSP also enhance the hypoxia tolerance response. Combined GSP and postconditioning can provided synergistic protection. In the obese mice suffering hepatic IRI group, GSP was more effective than postconditioning on protecting liver against IRI, and the combined strategy was obviously superior to the solo treatment. Conclusion: GSP could protect liver against IRI: particularly in high-fat diet induced obese mice. GSP used as pharmacological preconditioning and combined with other protocols have huge potential to be used in clinical. PMID:23139633

  11. 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.

  12. Time-derivative preconditioning method for multicomponent flow

    NASA Astrophysics Data System (ADS)

    Housman, Jeffrey Allen

    A time-derivative preconditioned system of equations suitable for the numerical simulation of single component and multicomponent inviscid flows at all speeds is formulated. The system is shown to be hyperbolic in time and remain well-posed at low Mach numbers, allowing an efficient time marching solution strategy to be utilized from transonic to incompressible flow speeds. For multicomponent flow at low speed, a preconditioned nonconservative discretization scheme is described which preserves pressure and velocity equilibrium across fluid interfaces, handles sharp liquid/gas interfaces with large density ratios, while remaining well-conditioned for time marching methods. The method is then extended to transonic and supersonic flows using a hybrid conservative/nonconservative formulation which retains the pressure/velocity equilibrium property and converges to the correct weak solution when shocks are present. In order to apply the proposed model to complex flow applications, the overset grid methodology is used where the equations are transformed to a nonorthogonal curvilinear coordinate system and discretized on structured body-fitted curvilinear grids. The multicomponent model and its extension to homogeneous multiphase mixtures is discussed and the hyperbolicity of the governing equations is demonstrated. Low Mach number perturbation analysis is then performed on the system of equations and a local time-derivative preconditioning matrix is derived allowing time marching numerical methods to remain efficient at low speeds. Next, a particular time marching numerical method is presented along with three discretization schemes for the convective terms. These include a conservative preconditioned Roe type method, a nonconservative preconditioned Split Coefficient Matrix (SCM) method, and hybrid formulation which combines the conservative and nonconservative schemes using a simple switching function. A characteristic boundary treatment which includes time

  13. Review of Hydraulic Fracturing for Preconditioning in Cave Mining

    NASA Astrophysics Data System (ADS)

    He, Q.; Suorineni, F. T.; Oh, J.

    2016-12-01

    Hydraulic fracturing has been used in cave mining for preconditioning the orebody following its successful application in the oil and gas industries. In this paper, the state of the art of hydraulic fracturing as a preconditioning method in cave mining is presented. Procedures are provided on how to implement prescribed hydraulic fracturing by which effective preconditioning can be realized in any in situ stress condition. Preconditioning is effective in cave mining when an additional fracture set is introduced into the rock mass. Previous studies on cave mining hydraulic fracturing focused on field applications, hydraulic fracture growth measurement and the interaction between hydraulic fractures and natural fractures. The review in this paper reveals that the orientation of the current cave mining hydraulic fractures is dictated by and is perpendicular to the minimum in situ stress orientation. In some geotechnical conditions, these orientation-uncontrollable hydraulic fractures have limited preconditioning efficiency because they do not necessarily result in reduced fragmentation sizes and a blocky orebody through the introduction of an additional fracture set. This implies that if the minimum in situ stress orientation is vertical and favors the creation of horizontal hydraulic fractures, in a rock mass that is already dominated by horizontal joints, no additional fracture set is added to that rock mass to increase its blockiness to enable it cave. Therefore, two approaches that have the potential to create orientation-controllable hydraulic fractures in cave mining with the potential to introduce additional fracture set as desired are proposed to fill this gap. These approaches take advantage of directional hydraulic fracturing and the stress shadow effect, which can re-orientate the hydraulic fracture propagation trajectory against its theoretical predicted direction. Proppants are suggested to be introduced into the cave mining industry to enhance the

  14. 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

  15. HYPERTENSIVE-ISCHEMIC LEG ULCERS

    PubMed Central

    Farber, Eugene M.; Schmidt, Otto E. L.

    1950-01-01

    Ischemic ulcers of the leg having characteristics different from those of ordinary leg ulcers have been observed in a small number of hypertensive patients, mostly women, during the past few years. Such ulcers are usually located above the ankle. They begin with a small area of purplish discoloration at the site of slight trauma, and progress to acutely tender ulceration. In studies of tissue removed from the margin and the base of an ulcer of this kind, obliterative arteriolar sclerotic changes, ischemic-appearing connective tissue and inflammatory changes were noted. Two additional cases are reported. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:15398887

  16. [Antioxidant therapy in ischemic stroke].

    PubMed

    Suslina, Z A; Federova, T N; Maksimova, M Iu; Riasina, T V; Stvolinskiĭ, S L; Khrapova, E V; Boldyrev, A A

    2000-01-01

    The paper presents the results of investigation of emoxipin, an antioxidant synthetic drug, for treatment of patients with ischemic disorders of cerebral circulation. The drug produced a beneficial clinical effect in patients with lacunar and cardioembolic strokes of moderate severity. Therapy with emoxipin increased endogenic antioxidant activity and improved a clinical status of the patients. The protective effect of carnosine was demonstrated in experimental acute hypobaric hypoxia and cerebral ischemia in rats. The results obtained permit to recommend an inclusion of both emoxipin and carnosine in a combined treatment of ischemic disorders of cerebral circulation.

  17. Strategies for study of neuroprotection from cold-preconditioning.

    PubMed

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

    2010-09-02

    Neurological injury is a frequent cause of morbidity and mortality from general anesthesia and related surgical procedures that could be alleviated by development of effective, easy to administer and safe preconditioning treatments. We seek to define the neural immune signaling responsible for cold-preconditioning as means to identify novel targets for therapeutics development to protect brain before injury onset. Low-level pro-inflammatory mediator signaling changes over time are essential for cold-preconditioning neuroprotection. This signaling is consistent with the basic tenets of physiological conditioning hormesis, which require that irritative stimuli reach a threshold magnitude with sufficient time for adaptation to the stimuli for protection to become evident. Accordingly, delineation of the immune signaling involved in cold-preconditioning neuroprotection requires that biological systems and experimental manipulations plus technical capacities are highly reproducible and sensitive. Our approach is to use hippocampal slice cultures as an in vitro model that closely reflects their in vivo counterparts with multi-synaptic neural networks influenced by mature and quiescent macroglia/microglia. This glial state is particularly important for microglia since they are the principal source of cytokines, which are operative in the femtomolar range. Also, slice cultures can be maintained in vitro for several weeks, which is sufficient time to evoke activating stimuli and assess adaptive responses. Finally, environmental conditions can be accurately controlled using slice cultures so that cytokine signaling of cold-preconditioning can be measured, mimicked, and modulated to dissect the critical node aspects. Cytokine signaling system analyses require the use of sensitive and reproducible multiplexed techniques. We use quantitative PCR for TNF-α to screen for microglial activation followed by quantitative real-time qPCR array screening to assess tissue-wide cytokine

  18. Strategies for Study of Neuroprotection from Cold-preconditioning

    PubMed Central

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

    2010-01-01

    Neurological injury is a frequent cause of morbidity and mortality from general anesthesia and related surgical procedures that could be alleviated by development of effective, easy to administer and safe preconditioning treatments. We seek to define the neural immune signaling responsible for cold-preconditioning as means to identify novel targets for therapeutics development to protect brain before injury onset. Low-level pro-inflammatory mediator signaling changes over time are essential for cold-preconditioning neuroprotection. This signaling is consistent with the basic tenets of physiological conditioning hormesis, which require that irritative stimuli reach a threshold magnitude with sufficient time for adaptation to the stimuli for protection to become evident. Accordingly, delineation of the immune signaling involved in cold-preconditioning neuroprotection requires that biological systems and experimental manipulations plus technical capacities are highly reproducible and sensitive. Our approach is to use hippocampal slice cultures as an in vitro model that closely reflects their in vivo counterparts with multi-synaptic neural networks influenced by mature and quiescent macroglia / microglia. This glial state is particularly important for microglia since they are the principal source of cytokines, which are operative in the femtomolar range. Also, slice cultures can be maintained in vitro for several weeks, which is sufficient time to evoke activating stimuli and assess adaptive responses. Finally, environmental conditions can be accurately controlled using slice cultures so that cytokine signaling of cold-preconditioning can be measured, mimicked, and modulated to dissect the critical node aspects. Cytokine signaling system analyses require the use of sensitive and reproducible multiplexed techniques. We use quantitative PCR for TNF-α to screen for microglial activation followed by quantitative real-time qPCR array screening to assess tissue

  19. 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.

  20. IP-RFID Based Container Monitoring System

    NASA Astrophysics Data System (ADS)

    Choi, Hyung-Rim; Park, Byung-Kwon; Park, Yong-Sung; Lee, Chang-Sup; Park, Chang-Hyun

    RFID technology in container management field is considered for increasing productivity and efficiency in logistics industry. But there are a lot of problems caused by inappropriate application of RFID technology in shipping logistics. Therefore, technology development based on IP is needed for accepting diverse technology applied before and offering better service to develop container management technology involved with RFID. In this study, realtime container monitoring system using IP-RFID is designed and implemented for supplementing weakness of information gathering using existing RFID and transferring data in real time to user.

  1. Space-Based Voice over IP Networks

    NASA Technical Reports Server (NTRS)

    Nguyen, Sam P.; Okino, Clayton; Walsh, William; Clare, Loren

    2007-01-01

    In human space exploration missions (e.g. a return to the Moon and for future missions to Mars), there will be a need to provide voice communications services. In this work we focus on the performance of Voice over IP (VoIP) techniques applied to space networks, where long range latencies, simplex links, and significant bit error rates occur. Link layer and network layer overhead issues are examined. Finally, we provide some discussion on issues related to voice conferencing in the space network environment.

  2. 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.

  3. 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.

  4. Finding Chemical Reaction Paths with a Multilevel Preconditioning Protocol

    DOE PAGES

    Kale, Seyit; Sode, Olaseni; Weare, Jonathan; ...

    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

  5. 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.

  6. 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

  7. 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.

  8. HMC algorithm with multiple time scale integration and mass preconditioning

    NASA Astrophysics Data System (ADS)

    Urbach, C.; Jansen, K.; Shindler, A.; Wenger, U.

    2006-01-01

    We present a variant of the HMC algorithm with mass preconditioning (Hasenbusch acceleration) and multiple time scale integration. We have tested this variant for standard Wilson fermions at β=5.6 and at pion masses ranging from 380 to 680 MeV. We show that in this situation its performance is comparable to the recently proposed HMC variant with domain decomposition as preconditioner. We give an update of the "Berlin Wall" figure, comparing the performance of our variant of the HMC algorithm to other published performance data. Advantages of the HMC algorithm with mass preconditioning and multiple time scale integration are that it is straightforward to implement and can be used in combination with a wide variety of lattice Dirac operators.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Islet preconditioning via multimodal microfluidic modulation of intermittent hypoxia.

    PubMed

    Lo, Joe F; Wang, Yong; Blake, Alexander; Yu, Gene; Harvat, Tricia A; Jeon, Hyojin; Oberholzer, Jose; Eddington, David T

    2012-02-21

    Simultaneous stimulation of ex vivo pancreatic islets with dynamic oxygen and glucose is a critical technique for studying how hypoxia alters glucose-stimulated response, especially in transplant environments. Standard techniques using a hypoxic chamber cannot provide both oxygen and glucose modulations, while monitoring stimulus-secretion coupling factors in real-time. Using novel microfluidic device with integrated glucose and oxygen modulations, we quantified hypoxic impairment of islet response by calcium influx, mitochondrial potentials, and insulin secretion. Glucose-induced calcium response magnitude and phase were suppressed by hypoxia, while mitochondrial hyperpolarization and insulin secretion decreased in coordination. More importantly, hypoxic response was improved by preconditioning islets to intermittent hypoxia (IH, 1 min/1 min 5-21% cycling for 1 h), translating to improved insulin secretion. Moreover, blocking mitochondrial K(ATP) channels removed preconditioning benefits of IH, similar to mechanisms in preconditioned cardiomyocytes. Additionally, the multimodal device can be applied to a variety of dynamic oxygen-metabolic studies in other ex vivo tissues.

  14. Thermal Preconditioning of MIMS Type K Thermocouples to Reduce Drift

    NASA Astrophysics Data System (ADS)

    Webster, E. S.

    2017-01-01

    Type K thermocouples are the most widely used temperature sensors in industry and are often used in the convenient mineral-insulated metal-sheathed (MIMS) format. The MIMS format provides almost total immunity to oxide-related drift in the 800°C-1000°C range. However, crystalline ordering of the atomic structure causes drift in the range 200°C-600°C. Troublesomely, the effects of this ordering are reversible, leading to hysteresis in some applications. Typically, MIMS cable is subjected to a post-manufacturing high-temperature recrystallization anneal to remove cold-work and place the thermocouple in a `known state.' However, variations in the temperatures and times of these exposures can lead to variations in the `as-received state.' This study gives guidelines on the best thermal preconditioning of 3 mm MIMS Type K thermocouples in order to minimize drift and achieve the most reproducible temperature measurements. Experimental results demonstrate the consequences of using Type K MIMS thermocouples in different states, including the as-received state, after a high-temperature recrystallization anneal and after preconditioning anneals at 200°C, 300°, 400°C and and 500°C. It is also shown that meaningful calibration is possible with the use of regular preconditioning anneals.

  15. 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.

  16. 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…

  17. Is VoIP Worth It?

    ERIC Educational Resources Information Center

    Schaffhauser, Dian

    2008-01-01

    School districts have by and large had great results implementing VoIP, which has become the conduit for delivering expanded functionality, achieving greater internal control, and gaining freedom from onerous monthly phone bills. But demonstrating a financial return on what is a substantial investment can be an elusive effort. The goal of…

  18. 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…

  19. Fluoro-Jade B evidence of induced ischemic tolerance in the rat spinal cord ischemia: physiological, neurological and histopathological consequences.

    PubMed

    Orendácová, J; Ondrejcák, T; Kuchárová, K; Cízková, D; Jergová, S; Mitrusková, B; Raceková, E; Vanický, I; Marsala, J

    2005-03-01

    Fluoro-Jade B, a marker of degenerating neurons, was used to label histopathological changes in the rat spinal cord after transient ischemia and ischemic preconditioning (IPC). To characterize postischemic neurodegenerations and consequent neurological changes, a particular attention was paid to the standardization of ischemic conditions in animals of both groups. 1. The control ischemic rats were submitted to a reversible occlusion of descending aorta by insertion and subsequent inflation of a 2F Fogarty catheter for 12 min. 2. In the IPC rats, an episode of short 3 min occlusion and 30 min reperfusion preceded the 12 min ischemia. Postischemic motor function testing (ambulation and stepping) was provided repeatedly for evaluation of neurological status 2 h and 24 h after surgery and at the end of postischemic survival, i.e. after 48 h. Fluoro-Jade B staining was used to demonstrate degenerated neurons. In the control rats, neurological consequences of histopathological changes in lumbosacral spinal cord, manifested as paraplegia, were present after 12 min ischemia. Thus, numbers of degenerated Fluoro-Jade B positive cells were visible in gray matter of the most injured L(4)-S(2) spinal cord segments. Slight motor function impairment, consequential from significant decreasing in Fluoro-Jade B-positivity in the L(4)-S(2) spinal cord segments of the IPC rats, was considered the pathomorpfological evidence that IPC induces spinal cord tolerance to ischemia. Our results are consistent with the previously published silver impregnation method for histopathological demonstration of ischemic degeneration.

  20. Cross-talk of intracellular calcium stores in the response to neuronal ischemia and ischemic tolerance.

    PubMed

    Lehotský, Ján; Racay, Peter; Pavlíková, Martina; Tatarková, Zuzana; Urban, Peter; Chomová, Mária; Kovalská, Mária; Kaplán, Peter

    2009-01-01

    Ischemic/reperfusion brain injury (IRI) is a very severe event with the multiple etiopathogenesis. Ischemic preconditioning (IPC) is an important phenomenon of adaptation of CNS to subsequent ischemia. An altered cross-talk between intracellular calcium stores is presumed in the mechanisms of ischemic damage/protection. We show here that IRI leads to the inhibition of mitochondrial respiratory complexes I and IV, however due to the excess of their capacities, the mitochondrial Ca(2+) uptake rate is not significantly depressed. IPC acts at the level of both initiation and execution of IRI-induced mitochondrial apoptosis and protects from IRI-associated changes in integrity of mitochondrial membranes. IPC also activates inhibition of p53 translocation to mitochondria. Inhibition of the mitochondrial p53 pathway might thus provide a potentially important mechanism of neuronal survival after ischemic brain damage. In addition, IRI initiates a time dependent differences in endoplasmic reticular (ER) gene expression of the key UPR proteins at both the mRNA and protein levels. Moreover, gene expression of the UPR proteins is affected by preischemic treatment by the increased expression of Ca(2+) binding protein: GRP 78 and transcriptional factor ATF6 in reperfusion times. Thus, IPC exerts a role in the attenuation of ER stress response, which might be involved in the neuroprotective phenomenon of ischemic tolerance. Hippocampal cells respond to the IRI by the specific expression pattern of the secretory pathways Ca(2+) pump (SPCA1) and this pattern is affected by preischemic challenge. IPC also incompletely suppresses lipo- and protein oxidation of hippocampal membranes and leads to partial recovery of the ischemic-induced depression of SPCA activity. The data suggests the correlation of SPCA function with the role of secretory pathways (Golgi apparatus) in response to preischemic challenge. Documented functional alterations of mitochondria, ER and Golgi apparatus put

  1. 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.

  2. Hypoxic preconditioning enhances neural stem cell transplantation therapy after intracerebral hemorrhage in mice.

    PubMed

    Wakai, Takuma; Narasimhan, Purnima; Sakata, Hiroyuki; Wang, Eric; Yoshioka, Hideyuki; Kinouchi, Hiroyuki; Chan, Pak H

    2016-12-01

    Previous studies have shown that intraparenchymal transplantation of neural stem cells ameliorates neurological deficits in animals with intracerebral hemorrhage. However, hemoglobin in the host brain environment causes massive grafted cell death and reduces the effectiveness of this approach. Several studies have shown that preconditioning induced by sublethal hypoxia can markedly improve the tolerance of treated subjects to more severe insults. Therefore, we investigated whether hypoxic preconditioning enhances neural stem cell resilience to the hemorrhagic stroke environment and improves therapeutic effects in mice. To assess whether hypoxic preconditioning enhances neural stem cell survival when exposed to hemoglobin, neural stem cells were exposed to 5% hypoxia for 24 hours before exposure to hemoglobin. To study the effectiveness of hypoxic preconditioning on grafted-neural stem cell recovery, neural stem cells subjected to hypoxic preconditioning were grafted into the parenchyma 3 days after intracerebral hemorrhage. Hypoxic preconditioning significantly enhanced viability of the neural stem cells exposed to hemoglobin and increased grafted-cell survival in the intracerebral hemorrhage brain. Hypoxic preconditioning also increased neural stem cell secretion of vascular endothelial growth factor. Finally, transplanted neural stem cells with hypoxic preconditioning exhibited enhanced tissue-protective capability that accelerated behavioral recovery. Our results suggest that hypoxic preconditioning in neural stem cells improves efficacy of stem cell therapy for intracerebral hemorrhage.

  3. 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

  4. Renalase protects against ischemic AKI.

    PubMed

    Lee, H Thomas; Kim, Joo Yun; Kim, Mihwa; Wang, Peili; Tang, Lieqi; Baroni, Sara; D'Agati, Vivette D; Desir, Gary V

    2013-02-01

    Elevated levels of plasma catecholamines accompany ischemic AKI, possibly contributing the inflammatory response. Renalase, an amine oxidase secreted by the proximal tubule, degrades circulating catecholamines and reduces myocardial necrosis, suggesting that it may protect against renal ischemia reperfusion injury. Here, mice subjected to renal ischemia reperfusion injury had significantly lower levels of renalase in the plasma and kidney compared with sham-operated mice. Consistent with this, plasma NE levels increased significantly after renal ischemia reperfusion injury. Furthermore, renal tubular inflammation, necrosis, and apoptosis were more severe and plasma catecholamine levels were higher in renalase-deficient mice subjected to renal ischemia reperfusion compared with wild-type mice. Administration of recombinant human renalase reduced plasma catecholamine levels and ameliorated ischemic AKI in wild-type mice. Taken together, these data suggest that renalase protects against ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation, and that plasma renalase might be a biomarker for AKI. Recombinant renalase therapy may have potential for the prevention and treatment of AKI.

  5. Neutrophil priming by hypoxic preconditioning protects against epithelial barrier damage and enteric bacterial translocation in intestinal ischemia/reperfusion.

    PubMed

    Lu, Yen-Zhen; Wu, Chi-Chin; Huang, Yi-Chen; Huang, Ching-Ying; Yang, Chung-Yi; Lee, Tsung-Chun; Chen, Chau-Fong; Yu, Linda Chia-Hui

    2012-05-01

    Intestinal ischemia/reperfusion (I/R) induces mucosal barrier dysfunction and bacterial translocation (BT). Neutrophil-derived oxidative free radicals have been incriminated in the pathogenesis of ischemic injury in various organs, but their role in the bacteria-containing intestinal tract is debatable. Primed neutrophils are characterized by a faster and higher respiratory burst activity associated with more robust bactericidal effects on exposure to a second stimulus. Hypoxic preconditioning (HPC) attenuates ischemic injury in brain, heart, lung and kidney; no reports were found in the gut. Our aim is to investigate whether neutrophil priming by HPC protects against intestinal I/R-induced barrier damage and bacterial influx. Rats were raised in normoxia (NM) or kept in a hypobaric hypoxic chamber (380 Torr) 17 h/day for 3 weeks for HPC, followed by sham operation or intestinal I/R. Gut permeability was determined by using an ex vivo macromolecular flux assay and an in vivo magnetic resonance imaging-based method. Liver and spleen homogenates were plated for bacterial culturing. Rats raised in HPC showed diminished levels of BT, and partially improved mucosal histopathology and epithelial barrier function compared with the NM groups after intestinal I/R. Augmented cytokine-induced neutrophil chemoattractant (CINC)-1 and -3 levels and myeloperoxidase activity correlated with enhanced infiltration of neutrophils in intestines of HPC-I/R compared with NM-I/R rats. HPC alone caused blood neutrophil priming, as shown by elevated production of superoxide and hydrogen peroxide on stimulation, increased membrane translocation of cytosolic p47(phox) and p67(phox), as well as augmented bacterial-killing and phagocytotic activities. Neutrophil depletion reversed the mucosal protection by HPC, and aggravated intestinal leakiness and BT following I/R. In conclusion, neutrophil priming by HPC protects against I/R-induced BT via direct antimicrobial activity by oxidative

  6. Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic transformation by inhibiting matrix metalloproteinases in focal cerebral ischemia in rats.

    PubMed

    Soejima, Yoshiteru; Hu, Qin; Krafft, Paul R; Fujii, Mutsumi; Tang, Jiping; Zhang, John H

    2013-09-01

    Hyperglycemia dramatically aggravates brain infarct and hemorrhagic transformation (HT) after ischemic stroke. Oxidative stress and matrix metalloproteinases (MMPs) play an important role in the pathophysiology of HT. Hyperbaric oxygen preconditioning (HBO-PC) has been proved to decrease oxidative stress and has been demonstrated to be neuroprotective in experimental stroke models. The present study determined whether HBO-PC would ameliorate HT by a pre-ischemic increase of reactive oxygen species (ROS) generation, and a suppression of MMP-2 and MMP-9 in hyperglycemic middle cerebral artery occlusion (MCAO) rats. Rats were pretreated with HBO (100% O₂, 2.5 atmosphere absolutes) 1 h daily for 5 days before MCAO. Acute hyperglycemia was induced by an injection of 50% dextrose. Neurological deficits, infarction volume and hemorrhagic volume were assessed 24 h and 7 days after ischemia. ROS scavenger n-acetyl cysteine (NAC), hypoxia-inducible factor-1α (HIF-1α), inhibitor 2-methoxyestradiol (2ME2) and activator cobalt chloride (CoCl₂), and MMP inhibitor SB-3CT were administrated for mechanism study. The activity of MMP-2 and MMP-9, and the expression HIF-1α were measured. HBO-PC improved neurological deficits, and reduced hemorrhagic volume; the expression of HIF-1α was significantly decreased, and the activity of MMP-2 and MMP-9 was reduced by HBO-PC compared with vehicle group. Our results suggested that HBO-PC attenuated HT via decreasing HIF-1α and its downstream MMP-2 and MMP-9 in hyperglycemic MCAO rats.

  7. Enhancing the Classification Accuracy of IP Geolocation

    DTIC Science & Technology

    2013-10-01

    in cloud infrastructure services. For example, a Dropbox user may require their data to be hosted on servers in San Francisco, but the data’s true...location may actually be in Tennessee (see Fig. 1). Users of cloud computing deploy Virtual Machines (VM) on a cloud providers infrastructure without...datacenters, as specified by a Service Level Agreement (SLA). Cloud users can use IP geolocation to independently verify data confidentiality by

  8. Hiding Data in VoIP

    DTIC Science & Technology

    2008-12-01

    is the LACK (Lost Audio Packets Steganography ) method, which is described in the third section of this paper. Fig. 4 Steganophony...although it is an application layer steganography technique, is less complex to implement than most audio steganography algorithms. The achieved...LACK, HICCUPS and SIP-based VoIP protocols’ steganography – are briefly described. 1. INTRODUCTION The main aim of network steganography is

  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. Steps to translate preconditioning from basic research to the clinic

    PubMed Central

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

    2012-01-01

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

  11. 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.

  12. 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.

  13. Preconditioning with a decoupled rowwise ordering on the CM-5

    SciTech Connect

    Toledo, S.

    1995-12-01

    Decoupled rowwise ordering is an ordering scheme for 2-dimensional grids, which is tailored for preconditioning 5-point difference equations arising from discretizations of partial differential equations. This paper describes the ordering scheme and implementations of a conjugate gradient solver and SSOR preconditioners which use the decoupled rowwise and the red black ordering schemes on the CM-5 parallel supercomputer. The rowwise decoupled preconditioner leads to faster convergence than the red black preconditioner, and it reduces the solution time by a factor of 1.5 to 2.5 over a nonpreconditioned solver on a variety of test problems.

  14. Preconditioning methods for ideal and multiphase fluid flows

    NASA Astrophysics Data System (ADS)

    Gupta, Ashish

    The objective of this study is to develop a preconditioning method for ideal and multiphase multispecies compressible fluid flow solver using homogeneous equilibrium mixture model. The mathematical model for fluid flow going through phase change uses density and temperature in the formulation, where the density represents the multiphase mixture density. The change of phase of the fluid is then explicitly determined using the equation of state of the fluid, which only requires temperature and mixture density. The method developed is based on a finite-volume framework in which the numerical fluxes are computed using Roe's approximate Riemann solver and the modified Harten, Lax and Van-leer scheme (HLLC). All speed Roe and HLLC flux based schemes have been developed either by using preconditioning or by directly modifying dissipation to reduce the effect of acoustic speed in its numerical dissipation when Mach number decreases. Preconditioning proposed by Briley, Taylor and Whitfield, Eriksson and Turkel are studied in this research, where as low dissipation schemes proposed by Rieper and Thornber, Mosedale, Drikakis, Youngs and Williams are also considered. Various preconditioners are evaluated in terms of development, performance, accuracy and limitations in simulations at various Mach numbers. A generalized preconditioner is derived which possesses well conditioned eigensystem for multiphase multispecies flow simulations. Validation and verification of the solution procedure are carried out on several small model problems with comparison to experimental, theoretical, and other numerical results. Preconditioning methods are evaluated using three basic geometries; 1) bump in a channel 2) flow over a NACA0012 airfoil and 3) flow over a cylinder, which are then compared with theoretical and numerical results. Multiphase capabilities of the solver are evaluated in cryogenic and non-cryogenic conditions. For cryogenic conditions the solver is evaluated by predicting

  15. 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.

  16. Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways.

    PubMed

    Guan, Junhong; Du, Shaonan; Lv, Tao; Qu, Shengtao; Fu, Qiang; Yuan, Ye

    2016-01-01

    Bone morphogenetic protein (BMP)-7 mediated neuroprotective effect of cerebral ischemic preconditioning (IPC) has been studied in an ischemic animal model, but the underlying cellular mechanisms have not been clearly clarified. In this study, primary cortical neurons and the SH-SY5Y cell line were used to investigate the role of BMP-7 and its downstream signals in the neuroprotective effects of oxygen-glucose deprivation preconditioning (OGDPC). Immunocytochemistry was used to detect the expression of neurofilament in neurons. MTT and lactate dehydrogenase activity assays were used to measure the cytotoxicity. Western blot was used to detect the protein expression of BMP-7 and downstream signals. BMP inhibitor, mitogen-activated protein kinase inhibitors, Smad inhibitor and siRNA of Smad 1 were used to investigate the role of corresponding signalling pathways in the OGDPC. Results showed that OGDPC-induced overexpression of BMP-7 in primary cortical neurons and SH-SY5Y cells. Both of endogenous and exogenous BMP-7 could replicate the neuroprotective effects seen in OGDPC pretreatment. In addition, extracellular regulated protein kinases, p38 and Smad signalling pathway were found to be involved in the neuroprotective effects mediated by OGDPC via BMP-7. This study primarily reveals the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia.

  17. 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.

  18. 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…

  19. Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair.

    PubMed

    Shafiq, Muhammad; Jung, Youngmee; Kim, Soo Hyun

    2016-06-01

    Stem cells are a promising solution for the treatment of a variety of diseases. However, the limited survival and engraftment of transplanted cells due to a hostile ischemic environment is a bottleneck for effective utilization and commercialization. Within this environment, the majority of transplanted cells undergo apoptosis prior to participating in lineage differentiation and cellular integration. Therefore, in order to maximize the clinical utility of stem/progenitor cells, strategies must be employed to increase their adhesion, retention, and engraftment in vivo. Here, we reviewed key strategies that are being adopted to enhance the survival, retention, and engraftment of transplanted stem cells through the manipulation of both the stem cells and the surrounding environment. We describe how preconditioning of cells or cell manipulations strategies can enhance stem cell survival and engraftment after transplantation. We also discuss how biomaterials can enhance the function of stem cells for effective tissue regeneration. Biomaterials can incorporate or mimic extracellular function (ECM) function and enhance survival or differentiation of transplanted cells in vivo. Biomaterials can also promote angiogenesis, enhance engraftment and differentiation, and accelerate electromechanical integration of transplanted stem cells. Insight gained from this review may direct the development of future investigations and clinical trials.

  20. 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.

  1. 40 CFR 85.2218 - Preconditioned 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 idle test-EPA 91. 85.2218 Section 85.2218 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements—(1) Exhaust gas...

  2. 40 CFR 85.2218 - Preconditioned 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 idle test-EPA 91. 85.2218 Section 85.2218 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements—(1) Exhaust gas...

  3. 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 91. 85.2220 Section 85.2220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General...

  4. 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…

  5. Condition number analysis and preconditioning of the finite cell method

    NASA Astrophysics Data System (ADS)

    de Prenter, F.; Verhoosel, C. V.; van Zwieten, G. J.; van Brummelen, E. H.

    2017-04-01

    The (Isogeometric) Finite Cell Method - in which a domain is immersed in a structured background mesh - suffers from conditioning problems when cells with small volume fractions occur. In this contribution, we establish a rigorous scaling relation between the condition number of (I)FCM system matrices and the smallest cell volume fraction. Ill-conditioning stems either from basis functions being small on cells with small volume fractions, or from basis functions being nearly linearly dependent on such cells. Based on these two sources of ill-conditioning, an algebraic preconditioning technique is developed, which is referred to as Symmetric Incomplete Permuted Inverse Cholesky (SIPIC). A detailed numerical investigation of the effectivity of the SIPIC preconditioner in improving (I)FCM condition numbers and in improving the convergence speed and accuracy of iterative solvers is presented for the Poisson problem and for two- and three-dimensional problems in linear elasticity, in which Nitche's method is applied in either the normal or tangential direction. The accuracy of the preconditioned iterative solver enables mesh convergence studies of the finite cell method.

  6. 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.

  7. 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.

  8. Acupuncture for preconditioning of expectancy and/or Pavlovian extinction.

    PubMed

    Lundeberg, Thomas; Lund, Iréne

    2008-12-01

    Both specific and non-specific factors, as well as the therapist, may play a role in acupuncture therapy. Recent results suggest that verum acupuncture has specific physiological effects and that patients expectations and belief regarding a potentially beneficial treatment modulate activity in the reward and self-appraisal systems in the brain. We suggest that acupuncture treatment may partly be regarded and used as an intervention that preconditions expectancy, which results in both conditional reflexes and conditioning of expected reward and self-appraisal. If so, acupuncture should preferably be applied before the start of the specific treatment (drug or behavioural intervention which is given with the intention of achieving a specific outcome) to enhance the specific and non-specific effects. This hypothesis is further supported by the suggestions that acupuncture may be viewed as a neural stimulus that triggers Pavlovian extinction. If this is the case, acupuncture should preferably be applied repeatedly (ie in a learning process) before the start of the specific treatment to initiate the extinction of previous unpleasant associations like pain or anxiety. Our clinical data suggest that acupuncture may precondition expectancy and conditional reflexes as well as induce Pavlovian extinction. Based on the above we suggest that acupuncture should be tried (as an adjunct) before any specific therapy.

  9. Sound preconditioning therapy inhibits ototoxic hearing loss in mice.

    PubMed

    Roy, Soumen; Ryals, Matthew M; Van den Bruele, Astrid Botty; Fitzgerald, Tracy S; Cunningham, Lisa L

    2013-11-01

    Therapeutic drugs with ototoxic side effects cause significant hearing loss for thousands of patients annually. Two major classes of ototoxic drugs are cisplatin and the aminoglycoside antibiotics, both of which are toxic to mechanosensory hair cells, the receptor cells of the inner ear. A critical need exists for therapies that protect the inner ear without inhibiting the therapeutic efficacy of these drugs. The induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death and hearing loss. We hypothesized that exposure to sound that is titrated to stress the inner ear without causing permanent damage would induce HSPs in the cochlea and inhibit ototoxic drug–induced hearing loss. We developed a sound exposure protocol that induces HSPs without causing permanent hearing loss. We used this protocol in conjunction with a newly developed mouse model of cisplatin ototoxicity and found that preconditioning mouse inner ears with sound has a robust protective effect against cisplatin-induced hearing loss and hair cell death. Sound therapy also provided protection against aminoglycoside-induced hearing loss. These data indicate that sound preconditioning protects against both classes of ototoxic drugs, and they suggest that sound therapy holds promise for preventing hearing loss in patients receiving these drugs.

  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. Cell signaling in NMDA preconditioning and neuroprotection in convulsions induced by quinolinic acid.

    PubMed

    Severino, Patricia Cardoso; Muller, Gabriele do Amaral Silva; Vandresen-Filho, Samuel; Tasca, Carla Inês

    2011-10-10

    The search for novel, less invasive therapeutic strategies to treat neurodegenerative diseases has stimulated scientists to investigate the mechanisms involved in preconditioning. Preconditioning has been report to occur in many organs and tissues. In the brain, the modulation of glutamatergic transmission is an important and promising target to the use of effective neuroprotective agents. The glutamatergic excitotoxicity is a factor common to neurodegenerative diseases and acute events such as cerebral ischemia, traumatic brain injury and epilepsy. In this review we focus on the neuroprotection and preconditioning by chemical agents. Specially, chemical preconditioning models using N-methyl-d-aspartate (NMDA) pre-treatment, which has demonstrated to lead to neuroprotection against seizures and damage to neuronal tissue induced by quinolinic acid (QA). Here we attempted to gather important results obtained in the study of cellular and molecular mechanisms involved in NMDA preconditioning and neuroprotection.

  12. 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.

  13. 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.

  14. 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.

  15. Source identification of the Arctic sea ice proxy IP25

    NASA Astrophysics Data System (ADS)

    Brown, T. A.; Belt, S. T.; Tatarek, A.; Mundy, C. J.

    2014-06-01

    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.

  16. 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.

  17. Live Video and IP-TV

    NASA Astrophysics Data System (ADS)

    Merani, Maria Luisa; Saladino, Daniela

    This Chapter aims at providing a comprehensive insight into the most recent advances in the field of P2P architectures for video broadcasting, focusing on live video streaming P2P live video streaming . After introducing a classification of P2P video solutions, the first part of the Chapter provides an overview of the most interesting P2P IP-TV P2P IP-TV systems currently available over the Internet. It also concentrates on the process of data diffusion within the P2P overlay and complements this view with some measurements that highlight the most salient features of P2P architectures. The second part of the Chapter completes the view, bringing up the modeling efforts to capture the main characteristics and limits of P2P streaming systems, both analytically and numerically. The Chapter is closed by a pristine look at some challenging, open questions, with a specific emphasis on the adoption of network coding in P2P streaming solutions.

  18. 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.

  19. 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.

  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. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke

    PubMed Central

    Wang, Hailian; Li, Peiying; Xu, Na; Zhu, Ling; Cai, Mengfei; Yu, Weifeng; Gao, Yanqin

    2016-01-01

    Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms. PMID:28217291

  2. 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.

  3. Aerodynamic shape optimization using preconditioned conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Burgreen, Greg W.; Baysal, Oktay

    1993-01-01

    In an effort to further improve upon the latest advancements made in aerodynamic shape optimization procedures, a systematic study is performed to examine several current solution methodologies as applied to various aspects of the optimization procedure. It is demonstrated that preconditioned conjugate gradient-like methodologies dramatically decrease the computational efforts required for such procedures. The design problem investigated is the shape optimization of the upper and lower surfaces of an initially symmetric (NACA-012) airfoil in inviscid transonic flow and at zero degree angle-of-attack. The complete surface shape is represented using a Bezier-Bernstein polynomial. The present optimization method then automatically obtains supercritical airfoil shapes over a variety of freestream Mach numbers. Furthermore, the best optimization strategy examined resulted in a factor of 8 decrease in computational time as well as a factor of 4 decrease in memory over the most efficient strategies in current use.

  4. 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.

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

    PubMed Central

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

    2010-01-01

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

  6. 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.

  7. 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.

  8. 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.

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

    PubMed

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

    2015-03-01

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

  10. Preconditioning-induced CXCL12 upregulation minimizes leukocyte infiltration after stroke in ischemia-tolerant mice.

    PubMed

    Selvaraj, Uma Maheswari; Ortega, Sterling B; Hu, Ruilong; Gilchrist, Robert; Kong, Xiangmei; Partin, Alexander; Plautz, Erik J; Klein, Robyn S; Gidday, Jeffrey M; Stowe, Ann M

    2017-03-01

    Repetitive hypoxic preconditioning creates long-lasting, endogenous protection in a mouse model of stroke, characterized by reductions in leukocyte-endothelial adherence, inflammation, and infarct volumes. The constitutively expressed chemokine CXCL12 can be upregulated by hypoxia and limits leukocyte entry into brain parenchyma during central nervous system inflammatory autoimmune disease. We therefore hypothesized that the sustained tolerance to stroke induced by repetitive hypoxic preconditioning is mediated, in part, by long-term CXCL12 upregulation at the blood-brain barrier (BBB). In male Swiss Webster mice, repetitive hypoxic preconditioning elevated cortical CXCL12 protein levels, and the number of cortical CXCL12+ microvessels, for at least two weeks after the last hypoxic exposure. Repetitive hypoxic preconditioning-treated mice maintained more CXCL12-positive vessels than untreated controls following transient focal stroke, despite cortical decreases in CXCL12 mRNA and protein. Continuous administration of the CXCL12 receptor (CXCR4) antagonist AMD3100 for two weeks following repetitive hypoxic preconditioning countered the increase in CXCL12-positive microvessels, both prior to and following stroke. AMD3100 blocked the protective post-stroke reductions in leukocyte diapedesis, including macrophages and NK cells, and blocked the protective effect of repetitive hypoxic preconditioning on lesion volume, but had no effect on blood-brain barrier dysfunction. These data suggest that CXCL12 upregulation prior to stroke onset, and its actions following stroke, contribute to the endogenous, anti-inflammatory phenotype induced by repetitive hypoxic preconditioning.

  11. Erythropoietin: Powerful Protection of Ischemic and Post-Ischemic Brain

    PubMed Central

    Nguyen, Anh Q.; Cherry, Brandon H.; Scott, Gary F.; Ryou, Myoung-Gwi; Mallet, Robert T.

    2015-01-01

    Ischemic brain injury inflicted by stroke and cardiac arrest ranks among the leading causes of death and long-term disability in the United States. The brain consumes large amounts of metabolic substrates and oxygen to sustain its energy requirements. Consequently, the brain is exquisitely sensitive to interruptions in its blood supply, and suffers irreversible damage after 10–15 minutes of severe ischemia. Effective treatments to protect the brain from stroke and cardiac arrest have proven elusive, due to the complexities of the injury cascades ignited by ischemia and reperfusion. Although recombinant tissue plasminogen activator and therapeutic hypothermia have proven efficacious for stroke and cardiac arrest, respectively, these treatments are constrained by narrow therapeutic windows, potentially detrimental side effects and the limited availability of hypothermia equipment. Mounting evidence demonstrates the cytokine hormone erythropoietin (EPO) to be a powerful neuroprotective agent and a potential adjuvant to established therapies. Classically, EPO originating primarily in the kidneys promotes erythrocyte production by suppressing apoptosis of proerythroid progenitors in bone marrow. However, the brain is capable of producing EPO, and EPO’s membrane receptors and signaling components also are expressed in neurons and astrocytes. EPO activates signaling cascades that increase the brain’s resistance to ischemia-reperfusion stress by stabilizing mitochondrial membranes, limiting formation of reactive oxygen and nitrogen intermediates, and suppressing pro-inflammatory cytokine production and neutrophil infiltration. Collectively, these mechanisms preserve functional brain tissue and, thus, improve neurocognitive recovery from brain ischemia. This article reviews the mechanisms mediating EPO-induced brain protection, critiques the clinical utility of exogenous EPO to preserve brain threatened by ischemic stroke and cardiac arrest, and discusses the

  12. Effect of Heat Preconditioning by Microwave Hyperthermia on Human Skeletal Muscle After Eccentric Exercise

    PubMed Central

    Saga, Norio; Katamoto, Shizuo; Naito, Hisashi

    2008-01-01

    The purpose of this study was to clarify whether heat preconditioning results in less eccentric exercise-induced muscle damage and muscle soreness, and whether the repeated bout effect is enhanced by heat preconditioning prior to eccentric exercise. Nine untrained male volunteers aged 23 ± 3 years participated in this study. Heat preconditioning included treatment with a microwave hyperthermia unit (150 W, 20 min) that was randomly applied to one of the subject’s arms (MW); the other arm was used as a control (CON). One day after heat preconditioning, the subjects performed 24 maximal isokinetic eccentric contractions of the elbow flexors at 30°·s-1 (ECC1). One week after ECC1, the subjects repeated the procedure (ECC2). After each bout of exercise, maximal voluntary contraction (MVC), range of motion (ROM) of the elbow joint, upper arm circumference, blood creatine kinase (CK) activity and muscle soreness were measured. The subjects experienced both conditions at an interval of 3 weeks. MVC and ROM in the MW were significantly higher than those in the CON (p < 0.05) for ECC1; however, the heat preconditioning had no significant effect on upper arm circumference, blood CK activity, or muscle soreness following ECC1 and ECC2. Heat preconditioning may protect human skeletal muscle from eccentric exercise-induced muscle damage after a single bout of eccentric exercise but does not appear to promote the repeated bout effect after a second bout of eccentric exercise. Key pointsThere have been few studies about the effects of heat preconditioning on muscle damage caused by eccentric exercise and the repeated bout effect after a second bout of eccentric exercise.Heat preconditioning with microwave hyperthermia may attenuate eccentric exercise-induced muscle damage.Heat preconditioning does not enhance the repeated bout effect. PMID:24150151

  13. Fructose-1,6-biphosphate in rat intestinal preconditioning: involvement of nitric oxide

    PubMed Central

    Sola, A; Rosello-Catafau, J; Gelpi, E; Hotter, G

    2001-01-01

    BACKGROUND AND AIMS—Inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by nitric oxide (NO) in intestinal preconditioning could modify the rate of formation of glycolytic intermediates. Fructose-1,6-biphosphate (F16BP) is a glycolytic intermediate that protects tissue from ischaemia/reperfusion injury. We evaluated if F16BP may be endogenously accumulated as a consequence of GAPDH inhibition by NO during intestinal preconditioning in rats.
METHODS—We assessed: (1) effect of preconditioning on F16BP content; (2) effect of NO on GAPDH activity before and during sustained ischaemia; and (3) protective effect of F16BP in control, ischaemic, and preconditioned animals with or without administration of N-nitro-L-arginine methyl ester (L-NAME), NO donor, or F16BP.
RESULTS—Preconditioned rats showed a significant transient decrease in GAPDH activity and also maintained basal F16BP levels longer than ischaemic rats. L-NAME administration to preconditioned rats reversed these effects. F16BP administration to ischaemic rats decreased protein release in the perfusate. Administration of F16BP to L-NAME treated rats attenuated the harmful effect of L-NAME.
CONCLUSIONS—Our study indicates that F16BP may be endogenously accumulated in preconditioned rats as a consequence of inhibition of GAPDH by NO, and this may contribute to the protection observed in intestinal preconditioning.


Keywords: fructose-1,6-biphosphate; glyceraldehyde- 3-phosphate dehydrogenase; intestinal preconditioning; ischaemia/reperfusion injury; nitric oxide PMID:11156636

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. Design and performance evaluation of direct routing mobile IP

    NASA Astrophysics Data System (ADS)

    Jang, Jongwook; Jang, SeongHo; Kim, Kilyeun; Lee, Jung-Tae

    2001-07-01

    Mobility support on the network layer is of special importance, as the network layer holds together the huge Internet with common protocol IP. Although based on possibility different wireless or wired technologies, all nodes of the network should be able to communicate. Therefore, mobile IP (an extension of the classical IP) has been designed which enables mobility in the Internet without changing existing wired systems. However, mobile IP leaves some points unsolved. Especially, if it comes to security, efficient of the packet flow that is called triangular routing. Especially triangular routing can cause unnecessary overhead for the network. Furthermore latency can increase dramatically. This is particularly unfortunate if two communicating hosts are separated by transatlantic links. In order to this problem, many methods like IPv6 and ROMIP are proposed. But these methods have limitation. In other words, they have not compatibility because of needing modification or original IP scheme. Especially ROMIP is very complex and the overhead of control message and processing are serious. The problem of inconsistency of Binding caches may occur tool. We therefore propose and analyze the DRMIP (Direct Routing Mobile IP) which do not modify IP source needed in the sender, is compatible with IP and Mobile IP.

  1. Implementation of direct routing mobile IP for solving triangular routing

    NASA Astrophysics Data System (ADS)

    Jang, Jongwook; Jang, SeongHo; Park, Miri; Lee, Dae-bong

    2001-10-01

    Mobility support on the network layer is of special importance, as the network layer holds together the huge Internet with common protocol IP. Although based on possibility different wireless or wired technologies, all nodes of the network should be able to communicate. Therefore, mobile IP(an extension of the classical IP) has been designed which enablemobility in the Internet without changing existing wired systems. However, mobile IP leaves some points unsolved. Especially, if it comes to security, efficiency of the packet flow that is called triangular routing. Especially triangular routing can cause unnecessary overhead for the network. Furthermore latency can increase dramatically. This is particularly unfortunate if two communicating hosts are separated by transatlantic links. In order to this problem, many methods like IPv6 and ROMIP are proposed. But these methods have limitation. In other words, they have not compatibility because of needing modification of original IP scheme. Especially ROMIP is very complex and the overhead of control message and processing are serious. The problem of inconsistency of Binding caches may occur too. We therefore propose and analyze the performance of the DRMIP (Direct Routing Mobile IP) which do not modify IP source needed in the sender, is compatible with IP and Mobile IP.

  2. Ischemic brain extract increases SDF-1 expression in astrocytes through the CXCR2/miR-223/miR-27b pathway.

    PubMed

    Shin, Jin Hee; Park, Young Mi; Kim, Dong Hee; Moon, Gyeong Joon; Bang, Oh Young; Ohn, Takbum; Kim, Hyeon Ho

    2014-09-01

    Ischemic cerebral stroke is one of the leading global causes of mortality and morbidity. Ischemic preconditioning (IPC) refers to a sublethal ischemia and resulting in tolerance to subsequent severe ischemic injury. Although several pathways are reportedly involved in IPC-mediated neuroprotection, the functional role of astrocytes is not fully understood. Stromal cell-derived factor-1 (SDF-1), a CXC chemokine produced mainly in astrocytes, is a ligand for chemokine receptor CXCR4. SDF-1 is reported to play a critical role in neuroprotection after stroke by mediating the migration of neuronal progenitor cells. We hypothesized that stimuli derived from ischemic brain were involved in the protective effects of IPC. To investigate this hypothesis, the mechanism in which ischemic brain extract (IBE) induced SDF-1 expression was investigated in C6 astrocytoma cells. IBE treatment of C6 cells increased SDF-1 expression compared to that in untreated or normal brain extract (NBE)-treated cells by downregulating SDF-1 targeting miRNA, miR-27b. MiR-223 was inversely upregulated in IBE-treated cells; overexpression of miR-223 decreased the expression of miR-27b by suppressing IKKα expression. Analysis of cytokine array data revealed an IBE associated enhanced expression of CINC-1 (CXCL1) and LIX1 (CXCL5). Knockdown or inhibition of their receptor, CXCR2, abolished IBE-mediated increased expression of SDF-1. These results were confirmed in primary cultured astrocytes. Taken together, the data demonstrate that IBE-elicited signals increase SDF-1 expression through the CXCR2/miR-223/miR-27b pathway in C6 astrocytoma cells and primary astrocytes, supporting the view that increased expression of SDF-1 by ischemic insults is a possible mechanism underlying therapeutic application of IPC.

  3. 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.

  4. Preconditioned alternating direction method of multipliers for inverse problems with constraints

    NASA Astrophysics Data System (ADS)

    Jiao, Yuling; Jin, Qinian; Lu, Xiliang; Wang, Weijie

    2017-02-01

    We propose a preconditioned alternating direction method of multipliers (ADMM) to solve linear inverse problems in Hilbert spaces with constraints, where the feature of the sought solution under a linear transformation is captured by a possibly non-smooth convex function. During each iteration step, our method avoids solving large linear systems by choosing a suitable preconditioning operator. In case the data is given exactly, we prove the convergence of our preconditioned ADMM without assuming the existence of a Lagrange multiplier. In case the data is corrupted by noise, we propose a stopping rule using information on noise level and show that our preconditioned ADMM is a regularization method; we also propose a heuristic rule when the information on noise level is unavailable or unreliable and give its detailed analysis. Numerical examples are presented to test the performance of the proposed method.

  5. Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation

    PubMed Central

    Gao, Zhi-xin; Rao, Jin; Li, Yuan-hai

    2017-01-01

    Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.

  6. Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation.

    PubMed

    Gao, Zhi-Xin; Rao, Jin; Li, Yuan-Hai

    2017-02-01

    Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.

  7. 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

  8. Vascular Endothelial Growth Factor-A Is a Survival Factor for Retinal Neurons and a Critical Neuroprotectant during the Adaptive Response to Ischemic Injury

    PubMed Central

    Nishijima, Kazuaki; Ng, Yin-Shan; Zhong, Lichun; Bradley, John; Schubert, William; Jo, Nobuo; Akita, Jo; Samuelsson, Steven J.; Robinson, Gregory S.; Adamis, Anthony P.; Shima, David T.

    2007-01-01

    Vascular endothelial growth factor-A (VEGF-A) has recently been recognized as an important neuroprotectant in the central nervous system. Given its position as an anti-angiogenic target in the treatment of human diseases, understanding the extent of VEGF’s role in neural cell survival is paramount. Here, we used a model of ischemia-reperfusion injury and found that VEGF-A exposure resulted in a dose-dependent reduction in retinal neuron apoptosis. Although mechanistic studies suggested that VEGF-A-induced volumetric blood flow to the retina may be partially responsible for the neuroprotection, ex vivo retinal culture demonstrated a direct neuroprotective effect for VEGF-A. VEGF receptor-2 (VEGFR2) expression was detected in several neuronal cell layers of the retina, and functional analyses showed that VEGFR2 was involved in retinal neuroprotection. VEGF-A was also shown to be involved in the adaptive response to retinal ischemia. Ischemic preconditioning 24 hours before ischemia-reperfusion injury increased VEGF-A levels and substantially decreased the number of apoptotic retinal cells. The protective effect of ischemic preconditioning was reversed after VEGF-A inhibition. Finally, chronic inhibition of VEGF-A function in normal adult animals led to a significant loss of retinal ganglion cells yet had no observable effect on several vascular parameters. These findings have implications for both neural pathologies and ocular vascular diseases, such as diabetic retinopathy and age-related macular degeneration. PMID:17591953

  9. [Biochemical and pharmacological mechanisms of different types of hypoxic preconditioning in cerebral ischemia in mice].

    PubMed

    Kulinskiĭ, V I; Gavrilina, T V; Minakina, L N; Kovtun, V Iu

    2006-01-01

    Different types of hypoxic preconditioning (hypoxic, circulatory, hemic and tissue hypoxia) increase the tolerance to complete global cerebral ischemia at early terms (hours). Biochemico-pharmacological analysis with the use of selective agonists and antagonists showed the importance of adenosine A1-receptors and K+(ATP)-channels in the mechanisms of the neuroprotective effect and natural tolerance. The general scheme of the investigated mechanisms of different types of hypoxic preconditioning has been proposed.

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

    NASA Technical Reports Server (NTRS)

    Eleshaky, Mohammed E.; Baysal, Oktay

    1993-01-01

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

  11. Interactions of antagonists with subtypes of inositol 1,4,5-trisphosphate (IP3) receptor

    PubMed Central

    Saleem, Huma; Tovey, Stephen C; Molinski, Tedeusz F; Taylor, Colin W

    2014-01-01

    BACKGROUND AND PURPOSE Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels. Interactions of the commonly used antagonists of IP3Rs with IP3R subtypes are poorly understood. EXPERIMENTAL APPROACH IP3-evoked Ca2+ release from permeabilized DT40 cells stably expressing single subtypes of mammalian IP3R was measured using a luminal Ca2+ indicator. The effects of commonly used antagonists on IP3-evoked Ca2+ release and 3H-IP3 binding were characterized. KEY RESULTS Functional analyses showed that heparin was a competitive antagonist of all IP3R subtypes with different affinities for each (IP3R3 > IP3R1 ≥ IP3R2). This sequence did not match the affinities for heparin binding to the isolated N-terminal from each IP3R subtype. 2-aminoethoxydiphenyl borate (2-APB) and high concentrations of caffeine selectively inhibited IP3R1 without affecting IP3 binding. Neither Xestospongin C nor Xestospongin D effectively inhibited IP3-evoked Ca2+ release via any IP3R subtype. CONCLUSIONS AND IMPLICATIONS Heparin competes with IP3, but its access to the IP3-binding core is substantially hindered by additional IP3R residues. These interactions may contribute to its modest selectivity for IP3R3. Practicable concentrations of caffeine and 2-APB inhibit only IP3R1. Xestospongins do not appear to be effective antagonists of IP3Rs. PMID:24628114

  12. Ischemic brain injury in cerebral amyloid angiopathy

    PubMed Central

    van Veluw, Susanne J; Greenberg, Steven M

    2016-01-01

    Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA. PMID:25944592

  13. [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.

  14. The significance of the washout period in Preconditioning.

    PubMed

    Salie, Ruduwaan; Lochner, Amanda; Loubser, Dirk J

    2017-01-24

    Exposure of the heart to 5 min global ischaemia (I) followed by 5 min reperfusion (R) (ischaemic preconditioning, IPC) or transient Beta 2-adrenergic receptor (B2-AR) stimulation with formoterol (B2PC), followed by 5 min washout before index ischaemia, elicits cardioprotection against subsequent sustained ischaemia. Since the washout period during preconditioning is essential for subsequent cardioprotection, the aim of this study was to investigate the involvement of protein kinase A (PKA), reactive oxygen species (ROS), extracellular signal-regulated kinase (ERK), PKB/Akt, p38 MAPK and c-jun N-terminal kinase (JNK) during this period. Isolated perfused rat hearts were exposed to IPC (1x5min I / 5min R) or B2PC (1x5min Formoterol / 5min R) followed by 35 min regional ischaemia and reperfusion. Inhibitors for PKA (Rp-8CPT-cAMP)(16μM), ROS (NAC)(300μM), PKB (A-6730)(2.5μM), ERKp44/p42 (PD98,059)(10μM), p38MAPK (SB239063)(1μM) or JNK (SP600125)(10μM) were administered for 5 minutes before 5 minutes global ischaemia / 5 min reperfusion (IPC) or for 5 minutes before and during administration of formoterol ( B2PC) prior to regional ischaemia, reperfusion and infarct size (IS) determination. Hearts exposed to B2PC or IPC were freeze-clamped during the washout period for Western blots analysis of PKB, ERKp44/p42, p38MAPK and JNK. The PKA blocker abolished both B2PC and IPC, while NAC significantly increased IS of IPC but not of B2PC. Western blot analysis showed that ERKp44/p42 and PKB activation during washout after B2PC compared to IPC was significantly increased. IPC compared to B2PC showed significant p38MAPK and JNKp54/p46 activation. PKB and ERK inhibition or p38MAPK and JNK inhibition during the washout period of B2PC and IPC respectively, significantly increased IS. PKA activation before regional ischaemia is a prerequisite for cardioprotection in both B2PC and IPC. However, ROS was crucial only in IPC. Kinase activation during the washout phase of IPC and B2

  15. Effects of Thermal Preconditioning on Tissue Susceptibility to Histotripsy.

    PubMed

    Vlaisavljevich, Eli; Xu, Zhen; Arvidson, Alexa; Jin, Lifang; Roberts, William; Cain, Charles

    2015-11-01

    Histotripsy is a non-invasive ablation method that mechanically fractionates tissue by controlling acoustic cavitation. Previous work has revealed that tissue mechanical properties play a significant role in the histotripsy process, with stiffer tissues being more resistant to histotripsy-induced tissue damage. In this study, we propose a thermal pretreatment strategy to precondition tissues before histotripsy. We hypothesize that a thermal pretreatment can be used to alter tissue stiffness by modulating collagen composition, thus changing tissue susceptibility to histotripsy. More specifically, we hypothesize that tissues will soften and become more susceptible to histotripsy when preheated at ∼60°C because of collagen denaturation, but that tissues will rapidly stiffen and become less susceptible to histotripsy when preheated at ∼90°C because of collagen contraction. To test this hypothesis, a controlled temperature water bath was used to heat various ex vivo bovine tissues (tongue, artery, liver, kidney medulla, tendon and urethra). After heating, the Young's modulus of each tissue sample was measured using a tissue elastometer, and changes in tissue composition (i.e., collagen structure/density) were analyzed histologically. The susceptibility of tissues to histotripsy was investigated by treating the samples using a 750-kHz histotripsy transducer. Results revealed a decrease in stiffness and an increase in susceptibility to histotripsy for tissues (except urethra) preheated to 58°C. In contrast, preheating to 90°C increased tissue stiffness and reduced susceptibility to histotripsy for all tissues except tendon, which was significantly softened due to collagen hydrolysis into gelatin. On the basis of these results, a final set of experiments were conducted to determine the feasibility of using high-intensity focused ultrasound to provide the thermal pretreatment. Overall, the results of this study indicate the initial feasibility of a thermal

  16. Key cognitive preconditions for the evolution of language.

    PubMed

    Donald, Merlin

    2017-02-01

    Languages are socially constructed systems of expression, generated interactively in social networks, which can be assimilated by the individual brain as it develops. Languages co-evolved with culture, reflecting the changing complexity of human culture as it acquired the properties of a distributed cognitive system. Two key preconditions set the stage for the evolution of such cultures: a very general ability to rehearse and refine skills (evident early in hominin evolution in toolmaking), and the emergence of material culture as an external (to the brain) memory record that could retain and accumulate knowledge across generations. The ability to practice and rehearse skill provided immediate survival-related benefits in that it expanded the physical powers of early hominins, but the same adaptation also provided the imaginative substrate for a system of "mimetic" expression, such as found in ritual and pantomime, and in proto-words, which performed an expressive function somewhat like the home signs of deaf non-signers. The hominid brain continued to adapt to the increasing importance and complexity of culture as human interactions with material culture became more complex; above all, this entailed a gradual expansion in the integrative systems of the brain, especially those involved in the metacognitive supervision of self-performances. This supported a style of embodied mimetic imagination that improved the coordination of shared activities such as fire tending, but also in rituals and reciprocal mimetic games. The time-depth of this mimetic adaptation, and its role in both the construction and acquisition of languages, explains the importance of mimetic expression in the media, religion, and politics. Spoken language evolved out of voco-mimesis, and emerged long after the more basic abilities needed to refine skill and share intentions, probably coinciding with the common ancestor of sapient humans. Self-monitoring and self-supervised practice were necessary

  17. Paracrine repercussions of preconditioning on angiogenesis and apoptosis of endothelial cells.

    PubMed

    Raymond, Marc-André; Vigneault, Normand; Luyckx, Valerie; Hébert, Marie-Josée

    2002-02-22

    The mechanisms of cytoprotection conferred by stress preconditioning remain largely uncharacterized in endothelial cells (EC). We report that stress preconditioning of EC with serum starvation induces the release of soluble mediator(s) that confer resistance to apoptosis, increase proliferation, and enhance angiogenesis in a second set of "non-preconditioned" EC. Preconditioning was found to target specifically the mitochondrial control of apoptosis in EC with increased protein levels of Bcl-2, decreased protein levels of Bax, and decreased cytosolic release of cytochrome c. Regulators of apoptosis acting upstream and downstream of the mitochondria such as p53, cIAP-1, cIAP-2, and XIAP were not altered. Mediators classically associated with preconditioning in other cell types such as adenosine, opioids, and nitric oxide are not implicated in this cytoprotective loop. Blockade of protein kinase C-dependent signaling inhibited cytoprotection of EC. Further characterization of this paracrine pathway should provide insights into the molecular regulation of preconditioning in endothelial cells.

  18. Single low-dose lipopolysaccharide preconditioning: neuroprotective against axonal injury and modulates glial cells

    PubMed Central

    Turner, Ryan C.; Naser, Zachary J.; Lucke-Wold, Brandon P.; Logsdon, Aric F.; Vangilder, Reyna L.; Matsumoto, Rae R.; Huber, Jason D.; Rosen, Charles L.

    2017-01-01

    Aim Over 7 million traumatic brain injuries (TBI) are reported each year in the United States. However, treatments and neuroprotection following TBI are limited because secondary injury cascades are poorly understood. Lipopolysaccharide (LPS) administration before controlled cortical impact can contribute to neuroprotection. However, the underlying mechanisms and whether LPS preconditioning confers neuroprotection against closed-head injuries remains unclear. Methods The authors hypothesized that preconditioning with a low dose of LPS (0.2 mg/kg) would regulate glial reactivity and protect against diffuse axonal injury induced by weight drop. LPS was administered 7 days prior to TBI. LPS administration reduced locomotion, which recovered completely by time of injury. Results LPS preconditioning significantly reduced the post-injury gliosis response near the corpus callosum, possibly by downregulating the oncostatin M receptor. These novel findings demonstrate a protective role of LPS preconditioning against diffuse axonal injury. LPS preconditioning successfully prevented neurodegeneration near the corpus callosum, as measured by fluorojade B. Conclusion Further work is required to elucidate whether LPS preconditioning confers long-term protection against behavioral deficits and to elucidate the biochemical mechanisms responsible for LPS-induced neuroprotective effects. PMID:28164149

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

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

  20. Atorvastatin preconditioning improves the forward blood flow in the no-reflow rats.

    PubMed

    Shao, Liang; Zhang, Yong; Ma, Aiqun; Zhang, Ping; Wu, Dayin; Li, Wenzhu; Wang, Jue; Liu, Kun; Wang, Zhaohui

    2014-02-01

    Atorvastatin is not only an antilipemic but also used as an anti-inflammatory medicine in heart disease. Our working hypothesis was that atorvastatin preconditioning could improve the forward blood flow in the no-reflow rats associated with inflammation. We investigated that two doses of atorvastatin preconditioning (20 and 5 mg/kg/day) could alleviate deterioration of early cardiac diastolic function in rats with inflammation detected by echocardiography and haemodynamics. This benefit was obtained from the effect of atorvastatin preconditioning on improving forward blood flow and preserving the infarct cardiomyocytes, which was estimated by Thioflavin S and TTC staining in rats with myocardial ischemia/reperfusion. Subsequently, the improving of forward blood flow was ascribed to reduction of microthrombus in microvascular and myocardial fibrosis observed by MSB and Masson's trichrome staining with atorvastatin preconditioning. Ultimately, we found that atorvastatin preconditioning could reduce inflammation factor, such as tumor necrosis factor-α and fibrinogen-like protein 2, both in myocardial and in mononuclear cells, which probably attribute to microcirculation dysfunction in no-reflow rats detected by immunohistochemistry staining, western blot, and ELISA detection, respectively. In conclusion, atorvastatin preconditioning could alleviate deterioration of early cardiac diastolic function and improve the forward blood flow in the no-reflow rats attributing to reduction of TNF-α and fgl-2 expression.

  1. Determinants of Delayed Preconditioning Against Myocardial Stunning in Chronically-Instrumented Pigs

    PubMed Central

    2009-01-01

    To test the hypothesis that a critical stenosis prevents delayed preconditioning against stunning, studies were conducted in pigs chronically-instrumented with occluders and segment-shortening crystals. In the setting of a critical stenosis, a preconditioning stimulus of repetitive brief occlusions resulted in infarction. Thereafter, a single 10-minute occlusion was used as the preconditioning stimulus. Delayed preconditioning against stunning was documented on subsequent days by the deficit-of-function following brief repetitive occlusions. In contrast to experiments in the naïve heart, the deficit-of-function improved on the day after a single 10-minute occlusion (from 60±14 to 24±6 arbitrary units, p=0.003), and similar improvement occurred when reperfusion was performed through a critical stenosis (32±6 units, p=0.02 vs. naïve and p=0.34 vs. no stenosis). Delayed preconditioning also reduced the frequency of ventricular fibrillation, and produced a 4-fold increase in both calcium-dependent and calcium-independent NOS activity. Thus, a critical stenosis did not prevent delayed preconditioning against stunning. PMID:20160844

  2. 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.

  3. Enhanced nucleotide excision repair capacity in lung cancer cells by preconditioning with DNA-damaging agents.

    PubMed

    Choi, Ji Ye; Park, Jeong-Min; Yi, Joo Mi; Leem, Sun-Hee; Kang, Tae-Hong

    2015-09-08

    The capacity of tumor cells for nucleotide excision repair (NER) is a major determinant of the efficacy of and resistance to DNA-damaging chemotherapeutics, such as cisplatin. Here, we demonstrate that using lesion-specific monoclonal antibodies, NER capacity is enhanced in human lung cancer cells after preconditioning with DNA-damaging agents. Preconditioning of cells with a nonlethal dose of UV radiation facilitated the kinetics of subsequent cisplatin repair and vice versa. Dual-incision assay confirmed that the enhanced NER capacity was sustained for 2 days. Checkpoint activation by ATR kinase and expression of NER factors were not altered significantly by the preconditioning, whereas association of XPA, the rate-limiting factor in NER, with chromatin was accelerated. In preconditioned cells, SIRT1 expression was increased, and this resulted in a decrease in acetylated XPA. Inhibition of SIRT1 abrogated the preconditioning-induced predominant XPA binding to DNA lesions. Taking these data together, we conclude that upregulated NER capacity in preconditioned lung cancer cells is caused partly by an increased level of SIRT1, which modulates XPA sensitivity to DNA damage. This study provides some insights into the molecular mechanism of chemoresistance through acquisition of enhanced DNA repair capacity in cancer cells.

  4. Thermal preconditioning and heat-shock protein 72 preserve synaptic transmission during thermal stress.

    PubMed

    Kelty, Jonathan D; Noseworthy, Peter A; Feder, Martin E; Robertson, R Meldrum; Ramirez, Jan-Marino

    2002-01-01

    As with other tissues, exposing the mammalian CNS to nonlethal heat stress (i.e., thermal preconditioning) increases levels of heat-shock proteins (Hsps) such as Hsp70 and enhances the viability of neurons under subsequent stress. Using a medullary slice preparation from a neonatal mouse, including the site of the neural network that generates respiratory rhythm (the pre-Bötzinger complex), we show that thermal preconditioning has an additional fundamental effect, protection of synaptic function. Relative to 30 degrees C baseline, initial thermal stress (40 degrees C) greatly increased the frequency of synaptic currents recorded without pharmacological manipulation by approximately 17-fold (p < 0.01) and of miniature postsynaptic currents (mPSCs) elicited by GABA (20-fold) glutamate (10-fold), and glycine (36-fold). Thermal preconditioning (15 min at 40 degrees C) eliminated the increase in frequency of overall synaptic transmission during acute thermal stress and greatly attenuated the frequency increases of GABAergic, glutamatergic, and glycinergic mPSCs (for each, p < 0.05). Moreover, without thermal preconditioning, incubation of slices in solution containing inducible Hsp70 (Hsp72) mimicked the effect of thermal preconditioning on the stress-induced release of neurotransmitter. That preconditioning and exogenous Hsp72 can affect and preserve normal physiological function has important therapeutic implications.

  5. Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat.

    PubMed

    Feng, Yangzheng; Paul, Ian A; LeBlanc, Michael H

    2006-03-31

    Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 +/- 3.6% in vehicle pups (n = 28) to 11.9 +/- 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2alpha measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 +/- 7 pg/g in the shams (n = 6), 175 +/- 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 +/- 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity.

  6. Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat

    PubMed Central

    Feng, Yangzheng; Paul, Ian A.; LeBlanc, Michael H.

    2011-01-01

    Nicotinamide reduces ischemic brain injury in adult rats. Can similar brain protection be seen in newborn animals? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of 8% oxygen. Nicotinamide 250 or 500 mg/kg was administered i.p. 5 min after reoxygenation, with a second dose given at 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Nicotinamide 500 mg/kg reduced brain weight loss from 24.6 ± 3.6% in vehicle pups (n = 28) to 11.9 ± 2.6% in the treated pups (n = 29, P < 0.01), but treatment with 250 mg/kg did not affect brain weight. Nicotinamide 500 mg/kg also improved behavior in rotarod performance. Levels of 8-isoprostaglandin F2α measured in the cortex by enzyme immune assay 16 h after reoxygenation was 115 ± 7 pg/g in the shams (n = 6), 175 ± 17 pg/g in the 500 mg/kg nicotinamide treated (n = 7), and 320 ± 79 pg/g in the vehicle treated pups (n = 7, P < 0.05 versus sham, P < 0.05 versus nicotinamide). Nicotinamide reduced the increase in caspase-3 activity caused by hypoxic ischemia (P < 0.01). Nicotinamide reduces brain injury in the neonatal rat, possibly by reducing oxidative stress and caspase-3 activity. PMID:16533659

  7. Nitroxyl exacerbates ischemic cerebral injury and oxidative neurotoxicity.

    PubMed

    Choe, Chi-un; Lewerenz, Jan; Fischer, Gerry; Uliasz, Tracy F; Espey, Michael Graham; Hummel, Friedhelm C; King, Stephen Bruce; Schwedhelm, Edzard; Böger, Rainer H; Gerloff, Christian; Hewett, Sandra J; Magnus, Tim; Donzelli, Sonia

    2009-09-01

    Nitroxyl (HNO) donor compounds function as potent vasorelaxants, improve myocardial contractility and reduce ischemia-reperfusion injury in the cardiovascular system. With respect to the nervous system, HNO donors have been shown to attenuate NMDA receptor activity and neuronal injury, suggesting that its production may be protective against cerebral ischemic damage. Hence, we studied the effect of the classical HNO-donor, Angeli's salt (AS), on a cerebral ischemia/reperfusion injury in a mouse model of experimental stroke and on related in vitro paradigms of neurotoxicity. I.p. injection of AS (40 mumol/kg) in mice prior to middle cerebral artery occlusion exacerbated cortical infarct size and worsened the persistent neurological deficit. AS not only decreased systolic blood pressure, but also induced systemic oxidative stress in vivo indicated by increased isoprostane levels in urine and serum. In vitro, neuronal damage induced by oxygen-glucose-deprivation of mature neuronal cultures was exacerbated by AS, although there was no direct effect on glutamate excitotoxicity. Finally, AS exacerbated oxidative glutamate toxicity - that is, cell death propagated via oxidative stress in immature neurons devoid of ionotropic glutamate receptors. Taken together, our data indicate that HNO might worsen cerebral ischemia-reperfusion injury by increasing oxidative stress and decreasing brain perfusion at concentrations shown to be cardioprotective in vivo.

  8. Design methods of multilayer survivability in IP over WDM networks

    NASA Astrophysics Data System (ADS)

    Arakawa, Shin'ichi; Murata, Masayuki; Miyahara, Hideo

    2000-09-01

    IP (Internet Protocol) over WDM networks where IP packets are directly carried on the WDM network is expected to offer an infrastructure for the next generation Internet. For IP over WDM networks, a WDM protection mechanism is expected to provide a highly reliable network (i.e., robustness against the link/node failures). However, conventional IP also provides a reliability mechanism by its routing function. We thus need to treat functional partitioning or functional integration for IP over WDM networks with high reliability. In this paper, we first formulate an optimization problem for designing IP over WDM networks with protection functionalities of WDM networks, by which we can obtain IP over WDM networks with high reliability. Our formulation results in a mixed integer linear problem (MILP). However, it is known that MILP can be solved only for a small number of variables, in our case, nodes and/or wavelengths. We therefore propose two heuristic algorithms, min-hop-first and largest-traffic-first approaches in order to assign the wavelength for backup lightpath. Our results show that the min- hop-first approach takes fewer wavelengths to construct the reliable network, that is, all of lightpaths can be protected using the WDM protection mechanism. However, our largest-traffic- first approach is also a good choice in the sense that the approach can be saved the traffic volume increased at the IP router by the link failure.

  9. KChIP1: a potential modulator to GABAergic system.

    PubMed

    Xiong, Hui; Xia, Kun; Li, Benshang; Zhao, Guoping; Zhang, Zhuohua

    2009-04-01

    Compelling evidences from transgenic mice, immunoprecipitation data, gene expression analysis, and functional heterologous expression studies supported the role of Kv channel interacting proteins (KChIPs) as modulators of Kv4 (Shal) channels underlying the cardiac transient outward current and neuronal A-type current. Till now, there are four members (KChIP1-4) identified in this family. KChIP1 is expressed predominantly in brain, with relative abundance in Purkinje cells of cerebellum, the reticular thalamic nuclei, the medial habenular nuclei, the hippocampus, and striatum. Our results from in situ hybridization and immunostaining assay revealed that KChIP1 was expressed in a subpopulation of parvalbumin-positive neurons suggesting its functional relationship with the GABAergic inhibitory neurons. Moreover, results obtained from KChIP1-deficient mice showed that KChIP1 mutation did not impair survival or alter the overall brain architecture, arguing against its essential function in brain development. However, the mice bearing KChIP1 deletion showed increased susceptibility to anti-GABAergic convulsive drug pentylenetetrazole-induced seizure, indicating that KChIP1 might play pivotal roles in the GABAergic inhibitory system.

  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. Fair Scheduling for Delay-Sensitive VoIP Traffic

    NASA Astrophysics Data System (ADS)

    Ahmed, Shawish; Jiang, Xiaohong; Horiguchi, Susumu

    With the wide expansion of voice services over the IP networks (VoIP), the volume of this delay sensitive traffic is steadily growing. The current packet schedulers for IP networks meet the delay constraint of VoIP traffic by simply assigning its packets the highest priority. This technique is acceptable as long as the amount of VoIP traffic is relatively very small compared to other non-voice traffic. With the notable expansion of VoIP applications, however, the current packet schedulers will significantly sacrifice the fairness deserved by the non-voice traffic. In this paper, we extend the conventional Deficit Round-Robin (DRR) scheduler by including a packet classifier, a Token Bucket and a resource reservation scheme and propose an integrated packet scheduler architecture for the growing VoIP traffic. We demonstrate through both theoretical analysis and extensive simulation that the new architecture makes it possible for us to significantly improve the fairness to non-voice traffic while still meeting the tight delay requirement of VoIP applications.

  12. Evaluation of an Individual Placement and Support model (IPS) program.

    PubMed

    Lucca, Anna M; Henry, Alexis D; Banks, Steven; Simon, Lorna; Page, Stephanie

    2004-01-01

    While randomized clinical trials (RCTs) have helped to establish Individual Placement and Support (IPS) programs as an evidence-based practice, it is important to evaluate whether "real world" IPS programs can be implemented with fidelity and achieve outcomes comparable to programs evaluated in RCTs. The current evaluation examined retrospectively employment outcomes for go participants from an IPS-model Services for Employment and Education (SEE) program in Massachusetts over a 4.5-year period. Evaluators accessed demographic, functioning, and employment data from three sources--SEE program records/database, clinical records, and the Massachusetts Department of Mental Health Client Tracking system. Results indicate that the SEE program maintained high IPS fidelity and achieved employment outcomes comparable or superior to other SE and IPS model programs described in the literature.

  13. COPAR: A ChIP-Seq Optimal Peak Analyzer

    PubMed Central

    Wang, Xihan; Jin, Victor X.

    2017-01-01

    Sequencing data quality and peak alignment efficiency of ChIP-sequencing profiles are directly related to the reliability and reproducibility of NGS experiments. Till now, there is no tool specifically designed for optimal peak alignment estimation and quality-related genomic feature extraction for ChIP-sequencing profiles. We developed open-sourced COPAR, a user-friendly package, to statistically investigate, quantify, and visualize the optimal peak alignment and inherent genomic features using ChIP-seq data from NGS experiments. It provides a versatile perspective for biologists to perform quality-check for high-throughput experiments and optimize their experiment design. The package COPAR can process mapped ChIP-seq read file in BED format and output statistically sound results for multiple high-throughput experiments. Together with three public ChIP-seq data sets verified with the developed package, we have deposited COPAR on GitHub under a GNU GPL license. PMID:28357402

  14. COPAR: A ChIP-Seq Optimal Peak Analyzer.

    PubMed

    Tang, Binhua; Wang, Xihan; Jin, Victor X

    2017-01-01

    Sequencing data quality and peak alignment efficiency of ChIP-sequencing profiles are directly related to the reliability and reproducibility of NGS experiments. Till now, there is no tool specifically designed for optimal peak alignment estimation and quality-related genomic feature extraction for ChIP-sequencing profiles. We developed open-sourced COPAR, a user-friendly package, to statistically investigate, quantify, and visualize the optimal peak alignment and inherent genomic features using ChIP-seq data from NGS experiments. It provides a versatile perspective for biologists to perform quality-check for high-throughput experiments and optimize their experiment design. The package COPAR can process mapped ChIP-seq read file in BED format and output statistically sound results for multiple high-throughput experiments. Together with three public ChIP-seq data sets verified with the developed package, we have deposited COPAR on GitHub under a GNU GPL license.

  15. 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.

  16. Comparative Study on the Protective Effects of Salidroside and Hypoxic Preconditioning for Attenuating Anoxia-Induced Apoptosis in Pheochromocytoma (PC12) Cells

    PubMed Central

    Hu, Yao; Lv, Xiumei; Zhang, Jing; Meng, Xianli

    2016-01-01

    Background Hypoxia is an important sign that can result from body injuries or a special condition such as being at a high altitude or deep water diving. In the current studies, hypoxic preconditioning (HPC) plays a key role in reducing hypoxia-induced apoptosis. We aimed to study the pharmacologic preconditioning effects of salidroside versus those of HPC in hypoxia-/anoxia-induced apoptosis in PC12 cells (pheochromocytoma). Material/Methods PC12 cells were treated by different experimental conditions: control condition, hypoxia condition, HPC condition, low-/middle-/high-dose condition of salidroside, cyclosporine A (CsA), and oratractyloside (ATR). The cell viability, lactate dehydrogenase (LDH) activity, apoptosis, mitochondrial membrane potential (MMP), intracellular Ca2+, caspase-3 activity, and expression of Bcl-2 were detected in PC12 cells after the hypoxia treatment. Salidroside, extracted from the traditional Chinese herb Rhodiola rosea L, plays an essential role in reducing hypoxia-induced apoptosis in PC12 cells by the mitochondrial pathway. Results Salidroside decreased the apoptosis and increased the viability of hypoxia-induced PC12 cells more effectively than HPC Moreover, salidroside markedly stabilized MMP and intracellular Ca2+, reduced or inhibited LDH and caspase-3 activity, and up-regulated Bcl-2; CsA and ATR showed corresponding function. Conclusions Salidroside administration restrains apoptosis induced by hypoxia in PC12 cells. The protective effects are mediated by preservation of mitochondrial integrity and MMP to inhibit the excessive Ca2+ influx and caspase-3 activity and to promote the Bcl-2 expression, providing a potential clinical and effective therapeutic mechanism to reduce deaths from ischemic or hypoxic injury. PMID:27794583

  17. Kochen-Specker Theorem as a Precondition for Quantum Computing

    NASA Astrophysics Data System (ADS)

    Nagata, Koji; Nakamura, Tadao

    2016-12-01

    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.

  18. Positive Indian Ocean Dipole events precondition southeast Australia bushfires

    NASA Astrophysics Data System (ADS)

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

    2009-10-01

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

  19. Human sensory preconditioning in a flavor preference paradigm.

    PubMed

    Privitera, Gregory J; Mulcahey, Colleen P; Orlowski, Cassandra M

    2012-10-01

    This experiment adapted a sensory preconditioning (SPC) procedure using human participants to determine if conditioning (Cond) to one flavor (the conditioned flavor) will enhance liking for another flavor (the SPC flavor) associated with it prior to training. Participants in one of three groups (N=40 per group) consumed and rated plain or sweetened cherry and grape kool-aids in four phases. In baseline and SPC phase, ratings for a plain cherry, grape, and cherry-grape mixture were similar. In training, one flavor was sweetened (SPC+Cond and Cond Only groups) or unsweetened (SPC Only group) and ratings increased only for the flavor that was sweetened. In test, Group SPC+Cond rated the conditioned flavor and the SPC flavor as more liked and tasting sweeter. Group Cond Only rated only the conditioned flavor as more liked and tasting sweeter. Group SPC Only showed no change in ratings from baseline to test. These are the first data to show SPC learning using a flavor preference paradigm with human participants.

  20. Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats.

    PubMed

    Safari, Fereshteh; Shekarforoosh, Shahnaz; Hashemi, Tahmineh; Namvar Aghdash, Simin; Fekri, Asefeh; Safari, Fatemeh

    2016-09-27

    The aim of this study was to investigate the effect of sirtinol, as an inhibitor of sirtuin NAD-dependent histone deacetylases, on myocardial ischemia reperfusion injury following early and late ischemia preconditioning (IPC). Rats underwent sustained ischemia and reperfusion (IR) alone or proceeded by early or late IPC. Sirtinol (S) was administered before IPC. Arrhythmias were evaluated based on the Lambeth model. Infarct size (IS) was measured using triphenyltetrazolium chloride staining. The transcription level of antioxidant-coding genes was assessed by real-time PCR. In early and late IPC groups, IS and the number of arrhythmia were significantly decreased (P < 0.05 and P < 0.01 vs IR, respectively). In S + early IPC, incidences of arrhythmia and IS were not different compared with the early IPC group. However, in S + late IPC the IS was different from the late IPC group (P < 0.05). In late IPC but not early IPC, transcription levels of catalase (P < 0.01) and Mn-SOD (P < 0.05) increased, although this upregulation was not significant in the S + late IPC group. Our results are consistent with the notion that different mechanisms are responsible for early and late IPC. In addition, sirtuin NAD-dependent histone deacetylases may be implicated in late IPC-induced cardioprotection.

  1. Cerenkov luminescence tomography based on preconditioning orthogonal matching pursuit

    NASA Astrophysics Data System (ADS)

    Liu, Haixiao; Hu, Zhenhua; Wang, Kun; Tian, Jie; Yang, Xin

    2015-03-01

    Cerenkov luminescence imaging (CLI) is a novel optical imaging method and has been proved to be a potential substitute of the traditional radionuclide imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). This imaging method inherits the high sensitivity of nuclear medicine and low cost of optical molecular imaging. To obtain the depth information of the radioactive isotope, Cerenkov luminescence tomography (CLT) is established and the 3D distribution of the isotope is reconstructed. However, because of the strong absorption and scatter, the reconstruction of the CLT sources is always converted to an ill-posed linear system which is hard to be solved. In this work, the sparse nature of the light source was taken into account and the preconditioning orthogonal matching pursuit (POMP) method was established to effectively reduce the ill-posedness and obtain better reconstruction accuracy. To prove the accuracy and speed of this algorithm, a heterogeneous numerical phantom experiment and an in vivo mouse experiment were conducted. Both the simulation result and the mouse experiment showed that our reconstruction method can provide more accurate reconstruction result compared with the traditional Tikhonov regularization method and the ordinary orthogonal matching pursuit (OMP) method. Our reconstruction method will provide technical support for the biological application for Cerenkov luminescence.

  2. Prolonged preconditioning with natural honey against myocardial infarction injuries.

    PubMed

    Eteraf-Oskouei, Tahereh; Shaseb, Elnaz; Ghaffary, Saba; Najafi, Moslem

    2013-07-01

    Potential protective effects of prolonged preconditioning with natural honey against myocardial infarction were investigated. Male Wistar rats were pre-treated with honey (1%, 2% and 4%) for 45 days then their hearts were isolated and mounted on a Langendorff apparatus and perfused with a modified Krebs-Henseleit solution during 30 min regional ischemia fallowed by 120 min reperfusion. Two important indexes of ischemia-induced damage (infarction size and arrhythmias) were determined by computerized planimetry and ECG analysis, respectively. Honey (1% and 2%) reduced infarct size from 23±3.1% (control) to 9.7±2.4 and 9.5±2.3%, respectively (P<0.001). At the ischemia, honey (1%) significantly reduced (P<0.05) the number and duration of ventricular tachycardia (VT). Honey (1% and 2%) also significantly decreased number of ventricular ectopic beats (VEBs). In addition, incidence and duration of reversible ventricular fibrillation (Rev VF) were lowered by honey 2% (P<0.05). During reperfusion, honey produced significant reduction in the incidences of VT, total and Rev VF, duration and number of VT. The results showed cardioprotective effects of prolonged pre-treatment of rats with honey following myocardial infarction. Maybe, the existence of antioxidants and energy sources (glucose and fructose) in honey composition and improvement of hemodynamic functions may involve in those protective effects.

  3. 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

    2014-02-05

    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.

  4. Radionuclide imaging in ischemic stroke.

    PubMed

    Heiss, Wolf-Dieter

    2014-11-01

    Ischemic stroke is caused by interruption or significant impairment of blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphologic damage. The changes in regional cerebral blood flow and regional metabolism can be assessed by radionuclide imaging, especially SPECT and PET. SPECT and PET have broadened our understanding of flow and metabolic thresholds critical for maintenance of brain function and morphology: PET was essential in the transfer of the concept of the penumbra to clinical stroke and thereby had a great impact on developing treatment strategies. Receptor ligands can be applied as early markers of irreversible neuronal damage and can predict the size of the final infarcts, which is important for decisions on invasive therapy in large ("malignant") infarction. With SPECT and PET, the reserve capacity of the blood supply can be tested in obstructive arteriosclerosis, which is essential for planning interventions. The effect of a stroke on surrounding and contralateral primarily unaffected tissue can be investigated, helping to understand symptoms caused by disturbance in functional networks. Activation studies are useful to demonstrate alternative pathways to compensate for lesions and to test the effect of rehabilitative therapy. Radioisotope studies help to detect neuroinflammation and its effect on extension of tissue damage. Despite the limitations of broad clinical application of radionuclide imaging, this technology has a great impact on research in cerebrovascular diseases and still has various applications in the management of stroke.

  5. A highly efficient and effective motif discovery method for ChIP-seq/ChIP-chip data using positional information.

    PubMed

    Ma, Xiaotu; Kulkarni, Ashwinikumar; Zhang, Zhihua; Xuan, Zhenyu; Serfling, Robert; Zhang, Michael Q

    2012-04-01

    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.

  6. Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function

    PubMed Central

    Scherer, Paul C.; Ding, Yan; Liu, Zhiqing; Xu, Jing; Mao, Haibin; Barrow, James C.; Wei, Ning; Zheng, Ning; Snyder, Solomon H.; Rao, Feng

    2016-01-01

    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

  7. 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... Information Collection Request: 1670-NEW. SUMMARY: The Department of Homeland Security (DHS), National... received must include the words ``Department of Homeland Security'' and the docket ] number for this...

  8. 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... Information Collection Request, 1670-NEW. SUMMARY: The Department of Homeland Security (DHS), National... words ``Department of Homeland Security'' and the docket number for this action. Comments received...

  9. Downregulation of miR-181b in mouse brain following ischemic stroke induces neuroprotection against ischemic injury through targeting heat shock protein A5 and ubiquitin carboxyl-terminal hydrolase isozyme L1.

    PubMed

    Peng, Zhifeng; Li, Jiefei; Li, Yun; Yang, Xuan; Feng, Sujuan; Han, Song; Li, Junfa

    2013-10-01

    Understanding the molecular mechanism of cerebral hypoxic preconditioning (HPC)-induced endogenous neuroprotection may provide potential therapeutic targets for ischemic stroke. By using bioinformatics analysis, we found that miR-181b, one of 19 differentially expressed miRNAs, may target aconitate hydratase (ACO2), heat shock protein A5 (HSPA5), and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) among 26 changed protein kinase C isoform-specific interacting proteins in HPC mouse brain. In this study, the role of miR-181b in oxygen-glucose deprivation (OGD)-induced N2A cell ischemic injury in vitro and mouse middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury in vivo, and its regulation of ACO2, HSPA5, and UCHL1 were further determined. We found that miR-181b expression levels significantly decreased in mouse brain following MCAO and in OGD-treated N2A cells. Up- and downregulation of miR-181b by transfection of pre- or anti-miR-181b could negatively regulate HSPA5 and UCHL1 (but not ACO2) protein levels as well as N2A cell death and programmed cell death in OGD-treated N2A cells. By using a T7 promoter-driven control dual luciferase assay, we confirmed that miR-181b could bind to the 3'-untranslated rergions of HSPA5 and UCHL1 mRNAs and repress their translations. miR-181b antagomir reduced caspase-3 cleavage and neural cell loss in cerebral ischemic cortex and improved neurological deficit of mice after MCAO. In addition, HSPA5 and UCHL1 short interfering RNAs (siRNAs) blocked anti-miR-181b-mediated neuroprotection against OGD-induced N2A cell injury in vitro. These results suggest that the downregulated miR-181b induces neuroprotection against ischemic injury through negatively regulating HSPA5 and UCHL1 protein levels, providing a potential therapeutic target for ischemic stroke.

  10. Study of retinal vessel oxygen saturation in ischemic and non-ischemic branch retinal vein occlusion

    PubMed Central

    Lin, Lei-Lei; Dong, Yan-Min; Zong, Yao; Zheng, Qi-Shan; Fu, Yue; Yuan, Yong-Guang; Huang, Xia; Qian, Garrett; Gao, Qian-Ying

    2016-01-01

    AIM To explore how oxygen saturation in retinal blood vessels is altered in ischemic and non-ischemic branch retinal vein occlusion (BRVO). METHODS Fifty BRVO eyes were divided into ischemic (n=26) and non-ischemic (n=24) groups, based on fundus fluorescein angiography. Healthy individuals (n=52 and n=48, respectively) were also recruited as controls for the two groups. The mean oxygen saturations of the occluded vessels and central vessels were measured by oximetry in the BRVO and control groups. RESULTS In the ischemic BRVO group, the occluded arterioles oxygen saturation (SaO2-A, 106.0%±14.3%), instead of the occluded venule oxygen saturation (SaO2-V, 60.8%±9.4%), showed increases when compared with those in the same quadrant vessels (SaO2-A, 86.1%±16.5%) in the contralateral eyes (P<0.05). The oxygen saturations of the central vessels showed similar trends with those of the occluded vessels. In the non-ischemic BRVO group, the occluded and central SaO2-V and SaO2-A showed no significant changes. In both the ischemic and non-ischemic BRVOs, the central SaO2-A was significantly increased when compared to healthy individuals. CONCLUSION Obvious changes in the occluded and central SaO2-A were found in the ischemic BRVO group, indicating that disorders of oxygen metabolism in the arterioles may participate in the pathogenesis of ischemic BRVO. PMID:26949618

  11. [IPS an ethical paradigm for biomedical research].

    PubMed

    Gámez Escalona, José Antonio

    2013-01-01

    One of the greatest advances in molecular and cell biology was the discovery of the Induced Pluripotent Stem cells (iPS) in mice, by Shinya Yamanka and his team in 2006. The possibility that these cells can be generated also in humans opens up unexpected ways of development for biomedicine. Its main contribution is the creation of a strong protocol that takes into account three major advances in biology such as; nuclear transfer techniques, the discovery of transcription factors associated with pluripotency and the isolation of mouse embryonic stem cells. A protocol that can be easily replicated in other laboratories to have the oportunity to design tests that allow modeling of many incurable diseases, drug testing for human cells or explore the possibilities of autologous transplants of tissues or organs. Yamanaka ethical motivation to find an alternative to embryonic stem cells (ES) and prevent the destruction of embryos produced by In Vitro Fertilization techniques (IVF), has proved to be a research model, in which the intuition of the ethical principles and its application in advanced biotechnology projects, has meant the opening of a whole new way of understanding the biology of embryonic development. It is clear that development, biologically understood (puede ser también ″treated″; tratado), is not a one-way street. The possibilities to deepen into the foundations of molecular biology and genetics, along with the expectations of its clinical applications have earned Yamanka the Nobel Prize in Medicine 2012, along with another great scholar Sir John Gurdon, discoverer of nuclear transfer techniques.

  12. 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.

  13. SIP-CCME cooperation in multimedia VoIP network

    NASA Astrophysics Data System (ADS)

    Grądkowska, Magdalena; Popiel, Piotr; Sobańska, Katarzyna

    2006-10-01

    VoIP is a fast-developing technology which allows making telephone calls using a data network like the Internet. VoIP converts the voice signal from the telephone into a digital signal that travels over the Internet and then converts it back at the other end so that speaking to anyone with a regular phone number is possible. VoIP may also enable the direct calls from a computer with the use of a conventional telephone or a microphone. Some services using VoIP may only allow you to call other people using the same VoIP service, but others may allow you to call anyone who has a telephone number. First condition is a broadband Internet connection for VoIP technology to work. There are two major advantages of VOIP: lower cost and increased functionality. In the paper the integration of two networks, one with a CCME based installation and the other with a full Asterisk/SIP voicemail deployment is presented. The goal was to allow dialing between VoIP's telephony from different networks and evaluate a quality of connection with the use of certain codecs.

  14. 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

  15. 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.

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

    2013-01-01

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

  18. Forced Exercise Preconditioning Attenuates Experimental Autoimmune Neuritis by Altering Th1 Lymphocyte Composition and Egress.

    PubMed

    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.

  19. Preconditioning Techniques for a Newton-Krylov Algorithm for the Compressible Navier-Stokes Equations

    NASA Astrophysics Data System (ADS)

    Gatsis, John

    An investigation of preconditioning techniques is presented for a Newton-Krylov algorithm that is used for the computation of steady, compressible, high Reynolds number flows about airfoils. A second-order centred-difference method is used to discretize the compressible Navier-Stokes (NS) equations that govern the fluid flow. The one-equation Spalart-Allmaras turbulence model is used. The discretized equations are solved using Newton's method and the generalized minimal residual (GMRES) Krylov subspace method is used to approximately solve the linear system. These preconditioning techniques are first applied to the solution of the discretized steady convection-diffusion equation. Various orderings, iterative block incomplete LU (BILU) preconditioning and multigrid preconditioning are explored. The baseline preconditioner is a BILU factorization of a lower-order discretization of the system matrix in the Newton linearization. An ordering based on the minimum discarded fill (MDF) ordering is developed and compared to the widely popular reverse Cuthill-McKee ordering. An evolutionary algorithm is used to investigate and enhance this ordering. For the convection-diffusion equation, the MDF-based ordering performs well and RCM is superior for the NS equations. Experiments for inviscid, laminar and turbulent cases are presented to show the effectiveness of iterative BILU preconditioning in terms of reducing the number of GMRES iterations, and hence the memory requirements of the Newton-Krylov algorithm. Multigrid preconditioning also reduces the number of GMRES iterations. The framework for the iterative BILU and BILU-smoothed multigrid preconditioning algorithms is presented in detail.

  20. MACE: model based analysis of ChIP-exo

    PubMed Central

    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

    2014-01-01

    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. PMID:25249628

  1. Genetic Predisposition to Ischemic Stroke

    PubMed Central

    Kamatani, Yoichiro; Takahashi, Atsushi; Hata, Jun; Furukawa, Ryohei; Shiwa, Yuh; Yamaji, Taiki; Hara, Megumi; Tanno, Kozo; Ohmomo, Hideki; Ono, Kanako; Takashima, Naoyuki; Matsuda, Koichi; Wakai, Kenji; Sawada, Norie; Iwasaki, Motoki; Yamagishi, Kazumasa; Ago, Tetsuro; Ninomiya, Toshiharu; Fukushima, Akimune; Hozawa, Atsushi; Minegishi, Naoko; Satoh, Mamoru; Endo, Ryujin; Sasaki, Makoto; Sakata, Kiyomi; Kobayashi, Seiichiro; Ogasawara, Kuniaki; Nakamura, Motoyuki; Hitomi, Jiro; Kita, Yoshikuni; Tanaka, Keitaro; Iso, Hiroyasu; Kitazono, Takanari; Kubo, Michiaki; Tanaka, Hideo; Tsugane, Shoichiro; Kiyohara, Yutaka; Yamamoto, Masayuki; Sobue, Kenji; Shimizu, Atsushi

    2017-01-01

    Background and Purpose— The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk. Methods— We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets). Results— In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33–2.31) and 1.99 (95% confidence interval, 1.19–3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001). Conclusions— The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors. PMID:28034966

  2. Differentiation of the Infarct Core from Ischemic Penumbra within the First 4.5 Hours, Using Diffusion Tensor Imaging-Derived Metrics: A Rat Model

    PubMed Central

    Kuo, Duen-Pang; Lu, Chia-Feng; Liou, Michelle; Chen, Yung-Chieh; Chung, Hsiao-Wen

    2017-01-01

    Objective To investigate whether the diffusion tensor imaging-derived metrics are capable of differentiating the ischemic penumbra (IP) from the infarct core (IC), and determining stroke onset within the first 4.5 hours. Materials and Methods All procedures were approved by the local animal care committee. Eight of the eleven rats having permanent middle cerebral artery occlusion were included for analyses. Using a 7 tesla magnetic resonance system, the relative cerebral blood flow and apparent diffusion coefficient maps were generated to define IP and IC, half hour after surgery and then every hour, up to 6.5 hours. Relative fractional anisotropy, pure anisotropy (rq) and diffusion magnitude (rL) maps were obtained. One-way analysis of variance, receiver operating characteristic curve and nonlinear regression analyses were performed. Results The evolutions of tensor metrics were different in ischemic regions (IC and IP) and topographic subtypes (cortical, subcortical gray matter, and white matter). The rL had a significant drop of 40% at 0.5 hour, and remained stagnant up to 6.5 hours. Significant differences (p < 0.05) in rL values were found between IP, IC, and normal tissue for all topographic subtypes. Optimal rL threshold in discriminating IP from IC was about -29%. The evolution of rq showed an exponential decrease in cortical IC, from -26.9% to -47.6%; an rq reduction smaller than 44.6% can be used to predict an acute stroke onset in less than 4.5 hours. Conclusion Diffusion tensor metrics may potentially help discriminate IP from IC and determine the acute stroke age within the therapeutic time window. PMID:28246507

  3. Genomic location analysis by ChIP-Seq