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Sample records for ischemic preconditioning ip

  1. The neuroprotective mechanism of brain ischemic preconditioning

    PubMed Central

    Liu, Xiao-qian; Sheng, Rui; Qin, Zheng-hong

    2009-01-01

    Brain ischemia is one of the most common causes of death and the leading cause of adult disability in the world. Brain ischemic preconditioning (BIP) refers to a transient, sublethal ischemia which results in tolerance to later, otherwise lethal, cerebral ischemia. Many attempts have been made to understand the molecular and cellular mechanisms underlying the neuroprotection offered by ischemic preconditioning. Many studies have shown that neuroprotective mechanisms may involve a series of molecular regulatory pathways including activation of the N-methyl-D-aspartate (NMDA) and adenosine receptors; activation of intracellular signaling pathways such as mitogen activated protein kinases (MAPK) and other protein kinases; upregulation of Bcl-2 and heat shock proteins (HSPs); and activation of the ubiquitin-proteasome pathway and the autophagic-lysosomal pathway. A better understanding of the processes that lead to cell death after stroke as well as of the endogenous neuroprotective mechanisms by which BIP protects against brain ischemic insults could help to develop new therapeutic strategies for this devastating neurological disease. The purpose of the present review is to summarize the neuroprotective mechanisms of BIP and to discuss the possibility of mimicking ischemic preconditioning as a new strategy for preventive treatment of ischemia. PMID:19617892

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

    PubMed Central

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

    2016-01-01

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

  3. 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

  4. Role of Trimetazidine in Ischemic Preconditioning in Patients With Symptomatic Coronary Artery Disease

    PubMed Central

    Costa, Leandro M.A.; Rezende, Paulo C.; Garcia, Rosa M.R.; Uchida, Augusto H.; Seguro, Luis Fernando B.C.; Scudeler, Thiago L.; Bocchi, Edimar A.; Krieger, Jose E.; Hueb, Whady; Ramires, Jos Antonio F.; Filho, Roberto Kalil

    2015-01-01

    Abstract Ischemic preconditioning (IP) is a powerful cardioprotective cellular mechanism that has been related to the warm-up phenomenon or walk-through angina, and has been documented through the use of sequential exercise tests (ETs). It is known that several drugs, for example, cromokalim, pinacidil, adenosine, and nicorandil, can interfere with the cellular pathways of IP. The purpose of this article is to report the effect of the anti-ischemic agent trimetazidine (TMZ) on IP in symptomatic coronary artery disease (CAD) patients. We conducted a prospective study evaluating IP by the analysis of ischemic parameters in 2 sequential ETs. In phase I, without TMZ, patients underwent ET1 and ET2 with a 30-minute interval between them. In phase II, after 1 week of TMZ 35?mg twice daily, all patients underwent 2 consecutive ETs (ET3 and ET4). IP was considered present when the time to 1.0-mm segment ST on electrocardiogram deviation (T-1.0?mm) and rate pressure product (RPP) were greater in the second of 2 tests. The improvement in T-1.0?mm and RPP were compared in the 2 phases: without TMZ and after 1-week TMZ to assess the action of such drug in myocardial protective mechanisms. ETs were analyzed by 2 independent cardiologists. From 135 CAD patients screened, 96 met inclusion criteria and 62 completed the study protocol. Forty patients manifested IP by demonstrating an improvement in T-1.0?mm in ET2 compared with ET1, without the use of any drugs (phase I). In phase II, after 1-week TMZ, 26 patients (65%) did not show any incremental result in ischemic parameters in ET4 compared with ET3. Furthermore, of these patients, 8 (20%) had IP blockage. In this study, TMZ did not add any benefit to IP in patients with stable symptomatic CAD. PMID:26287407

  5. Protective effect of nitric oxide induced by ischemic preconditioning on reperfusion injury of rat liver graft

    PubMed Central

    Gong, Jian-Ping; Tu, Bing; Wang, Wei; Peng, Yong; Li, Shou-Bai; Yan, Lu-Nan

    2004-01-01

    AIM: Ischemic preconditioning (IP) is a brief ischemic episode, which confers a state of protection against the subsequent long-term ischemia-reperfusion injuries. However, little is known regarding the use of IP before the sustained cold storage and liver transplantation. The present study was designed to evaluate the protective effect of IP on the long-term preservation of liver graft and the prolonged anhepatic-phase injury. METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation. All livers underwent 10 min of ischemia followed by 10 min of reperfusion before harvest. Rat liver transplantation was performed with the portal vein clamped for 25 min. Tolerance of transplanted liver to the reperfusion injury and liver damage were investigated. The changes in adenosine concentration in hepatic tissue and those of nitric oxide (NO) and tumor necrosis factor (TNF) in serum were also assessed. RESULTS: Recipients with IP significantly improved their one-week survival rate and liver function, they had increased levels of circulating NO and hepatic adenosine, and a reduced level of serum TNF, as compared to controls. Histological changes indicating hepatic injuries appeared improved in the IP group compared with those in control group. The protective effect of IP was also obtained by administration of adenosine, while blockage of the NO pathway using N?-nitro-L-arginine methyl ester abolished the protective effect of IP. CONCLUSION: IP appears to have a protective effect on the long-term preservation of liver graft and the prolonged anhepatic-phase injuries. NO may be involved in this process. PMID:14695772

  6. Role of ischemic preconditioning in hepatic ischemia-reperfusion injury

    PubMed Central

    Boyko, Valeriy V.; Tyshchenko, Oleksandr M.; Skoryi, Denys I.; Kozlova, Tatiana V.; Gorgol, Natalia I.; Volchenko, Igor V.

    2014-01-01

    Background Investigation into less traumatic method of vascular occlusion during liver resection is the actual problem in hepatic surgery because of high level of complications such as liver failure. In this connection, the goal of our study was to determine the optimal model of vascular clamping. The research showed that vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique. Methods Forty white giant rabbits were divided randomly into four groups (n=10 in each group). In group I we used continuous Pringle maneuver by 30 min. In group II we used intermittent Pringle maneuver: 15 min of clamping/5 min of unclamping (reperfusion)/15 min of clamping. In group III we used intermittent Pringle maneuver with ischemic precondition: 5 min of ischemia/5 min of reperfusion, 10 min of ischemia/5 min of reperfusion/15 min of ischemia. Group IV (control group) is without hepatic ischemia. All animals were performed a liver biopsy at the end of the surgery. Five rabbits from each group underwent re-laparotomy on day 3 after surgery with biopsy samples being taken for studying reparative processes in liver parenchyma. Results Results of morphometric analysis were the best to illustrate different level of liver injury in the groups. Thus, there were 95.5% damaged hepatocytes after vascular occlusion in hepatic preparations in group I, 70.3% damaged hepatocytes in group II, and 42.3% damaged hepatocytes in group III. There were 5.3% damaged hepatocytes in the control group. Conclusions Vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique that does not involve major structural injuries and functional disorders in the remnant liver. Thus, it is amenable to translation into clinical practice and may improve outcomes in liver resection with inflow vascular occlusion. PMID:25202694

  7. 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 enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in normal mouse heart. IPC preserves the integrity of TJ structure and function that are vulnerable to IR injury.

  8. 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

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

    PubMed

    Lalonde, Franois; 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. PMID:25068802

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

    PubMed

    Brandli, Alice

    2015-01-01

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

  11. Concepts of hypoxic NO signaling in remote ischemic preconditioning

    PubMed Central

    Totzeck, Matthias; Hendgen-Cotta, Ulrike; Rassaf, Tienush

    2015-01-01

    Acute coronary syndromes remain a leading single cause of death worldwide. Therapeutic strategies to treat cardiomyocyte threatening ischemia/reperfusion injury are urgently needed. Remote ischemic preconditioning (rIPC) applied by brief ischemic episodes to heart-distant organs has been tested in several clinical studies, and the major body of evidence points to beneficial effects of rIPC for patients. The underlying signaling, however, remains incompletely understood. This relates particularly to the mechanism by which the protective signal is transferred from the remote site to the target organ. Many pathways have been forwarded but none can explain the protective effects completely. In light of recent experimental studies, we here outline the current knowledge relating to the generation of the protective signal in the remote organ, the signal transfer to the target organ and the transduction of the transferred signal into cardioprotection. The majority of studies favors a humoral factor that activates cardiomyocyte downstream signaling - receptor-dependent and independently. Cellular targets include deleterious calcium (Ca2+) signaling, reactive oxygen species, mitochondrial function and structure, and cellular apoptosis and necrosis. Following an outline of the existing evidence, we will furthermore characterize the existing knowledge and discuss future perspectives with particular emphasis on the interaction between the recently discovered hypoxic nitrite-nitric oxide signaling in rIPC. This refers to the protective role of nitrite, which can be activated endogenously using rIPC and which then contributes to cardioprotection by rIPC. PMID:26516418

  12. Concepts of hypoxic NO signaling in remote ischemic preconditioning.

    PubMed

    Totzeck, Matthias; Hendgen-Cotta, Ulrike; Rassaf, Tienush

    2015-10-26

    Acute coronary syndromes remain a leading single cause of death worldwide. Therapeutic strategies to treat cardiomyocyte threatening ischemia/reperfusion injury are urgently needed. Remote ischemic preconditioning (rIPC) applied by brief ischemic episodes to heart-distant organs has been tested in several clinical studies, and the major body of evidence points to beneficial effects of rIPC for patients. The underlying signaling, however, remains incompletely understood. This relates particularly to the mechanism by which the protective signal is transferred from the remote site to the target organ. Many pathways have been forwarded but none can explain the protective effects completely. In light of recent experimental studies, we here outline the current knowledge relating to the generation of the protective signal in the remote organ, the signal transfer to the target organ and the transduction of the transferred signal into cardioprotection. The majority of studies favors a humoral factor that activates cardiomyocyte downstream signaling - receptor-dependent and independently. Cellular targets include deleterious calcium (Ca(2+)) signaling, reactive oxygen species, mitochondrial function and structure, and cellular apoptosis and necrosis. Following an outline of the existing evidence, we will furthermore characterize the existing knowledge and discuss future perspectives with particular emphasis on the interaction between the recently discovered hypoxic nitrite-nitric oxide signaling in rIPC. This refers to the protective role of nitrite, which can be activated endogenously using rIPC and which then contributes to cardioprotection by rIPC. PMID:26516418

  13. Remote ischemic preconditioning for kidney protection: GSK3?-centric insights into the mechanism of action.

    PubMed

    Liu, Zhangsuo; Gong, Rujun

    2015-11-01

    Preventing acute kidney injury (AKI) in high-risk patients following medical interventions is a paramount challenge for clinical practice. Recent data from animal experiments and clinical trials indicate that remote ischemic preconditioning, represented by limb ischemic preconditioning, confers a protective action on the kidney. Ischemic preconditioning is effective in reducing the risk for AKI following cardiovascular interventions and the use of iodinated radiocontrast media. Nevertheless, the underlying mechanisms for this protective effect are elusive. A protective signal is conveyed from the remote site undergoing ischemic preconditioning, such as the limb, to target organs, such as the kidney, by multiple potential communication pathways, which may involve humoral, neuronal, and systemic mechanisms. Diverse transmitting pathways trigger a variety of signaling cascades, including the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, all of which converge on glycogen synthase kinase 3? (GSK3?). Inhibition of GSK3? subsequent to ischemic preconditioning reinforces the Nrf2-mediated antioxidant defense, diminishes the nuclear factor-?B-dependent proinflammatory response, and exerts prosurvival effects ensuing from the desensitized mitochondria permeability transition. Thus, therapeutic targeting of GSK3? by ischemic preconditioning or by pharmacologic preconditioning with existing US Food and Drug Administration-approved drugs having GSK3?-inhibitory activities might represent a pragmatic and cost-effective adjuvant strategy for kidney protection and prophylaxis against AKI. PMID:26271146

  14. Behavioral evaluation of ischemic damage to CA1 hippocampal neurons: effects of preconditioning.

    PubMed

    Duszczyk, Ma?gorzata; Ziembowicz, Apolonia; Gadamski, Roman; Lazarewicz, Jerzy W

    2006-01-01

    In Mongolian gerbils, global forebrain ischemia induces enhanced locomotor activity and the disruption of nest building immediately after the insult, followed by damage to hippocampal neurons developing 3 days later. Preconditioning by a brief episode of sublethal ischemia induces the protection of CA1 hippocampal neurons against a lethal ischemic insult. We examined how preconditioning with 2-min ischemia affects disturbances in the nest building behavior and locomotor activity induced by the injurious 3-min ischemia. Morphological examination confirmed that preconditioning significantly reduced neuronal damage in CA1 evoked by injurious ischemia. Behavioral studies demonstrated that preconditioning reduced the locomotor hyperactivity and latency in nest building after test ischemia, in comparison to sham or naive animals. The results indicate that the nest building test and measurement of locomotor activity may be used for an early in vivo prediction of the extent of ischemic brain damage and tolerance induced by ischemic preconditioning. PMID:17265693

  15. Peripheral Vascular Disease as Remote Ischemic Preconditioning for Acute Stroke

    PubMed Central

    Connolly, Mark; Bilgin-Freiert, Arzu; Ellingson, Benjamin; Dusick, Joshua R.; Liebeskind, David; Saver, Jeff; Gonzalez, Nestor R.

    2013-01-01

    Obectives Remote ischemic preconditioning (RIPC) is a powerful endogenous mechanism whereby a brief period of ischemia is capable of protecting remote tissues from subsequent ischemic insult. While this phenomenon has been extensively studied in the heart and brain in animal models, little work has been done to explore the effects of RIPC in human patients with acute cerebral ischemia. This study investigates whether chronic peripheral hypoperfusion, in the form of pre-existing arterial peripheral vascular disease (PVD) that has not been surgically treated, is capable of inducing neuroprotective effects for acute ischemic stroke. Methods Individuals with PVD who had not undergone prior surgical treatment were identified from a registry of stroke patients. A control group within the same database was identified by matching patient’s demographics and risk factors. The two groups were compared in terms of outcome by NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), mortality, and volume of infarcted tissue at presentation and at discharge. Results The matching algorithm identified 26 pairs of PVD-control patients (9 pairs were female and 17 pairs were male). Age range was 20 to 93 years (mean 73). The PVD group was found to have significantly lower NIHSS scores at admission (NIHSS ≤ 4: PVD 47.1%, Control 4.35%, p < 0.003), significantly more favorable outcomes at discharge (mRS ≤ 2: PVD 30.8%, Control 3.84%, p < 0.012), and a significantly lower mortality rate (PVD 26.9%, Control 57.7% p=0.024). Mean acute stroke volume at admission and at discharge were significantly lower for the PVD group (Admission: PVD 39.6mL, Control 148.3mL, p < 0.005 and Discharge: PVD 111.7mL, Control 275mL, p < 0.001). Conclusion Chronic limb hypoperfusion induced by PVD can potentially produce a neuroprotective effect in acute ischemic stroke. This effect resembles the neuroprotection induced by RIPC in preclinical models. PMID:23958050

  16. Changes in the NPY immunoreactivity in gerbil hippocampus after hypoxic and ischemic preconditioning.

    PubMed

    Duszczyk, Malgorzata; Ziembowicz, Apolonia; Gadamski, Roman; Wieronska, Joanna M; Smialowska, Maria; Lazarewicz, Jerzy W

    2009-02-01

    Preconditioning with sublethal ischemia or hypoxia may reduce the high susceptibility of CA1 pyramidal neurons to ischemic injury. In this study, we tested the hypothesis that enhanced level of neuropeptide Y (NPY) might play a role in the mechanisms responsible for this induced tolerance. Changes in NPY immunoreactivity in the hippocampal formation of preconditioned Mongolian gerbils were compared with the level of tolerance to test ischemia. Tolerance was induced by preconditioning with 2-min of ischemia or with three trials of mild hypobaric hypoxia (360 Torr, 2 h), separated by 24 h, that were completed 48 h before the 3-min test ischemia. The number of NPY-positive neurons in the gerbil hippocampal formation was assessed 2, 4 and 7 days after preconditioning. Survival of the CA1 pyramidal neurons was examined 14 days after the insult. Our experiments demonstrated that ischemic and hypoxic preconditioning produced equal attenuation of the damage evoked by 3-min ischemia, although the pattern of NPY immunoreactivity in the hippocampus differed. Preconditioning ischemia resulted in a 20% rise in the number of NPY-positive neurons 2 days later that disappeared 4 days after the ischemic episode, while mild hypobaric hypoxia induced a twofold increase in the number of NPY-positive neurons that lasted for at least 7 days. Although induced tolerance to ischemia 2 days after ischemic or hypoxic preconditioning was accompanied by increased immunoreactivity of NPY, there was no correlation between its intensity and the level of neuroprotection. PMID:19012964

  17. Transient inhibition of glucose uptake mimics ischemic preconditioning by salvaging ischemic myocardium in the rabbit heart.

    PubMed

    Goto, M; Tsuchida, A; Liu, Y; Cohen, M V; Downey, J M

    1995-09-01

    The aim of this study was to test whether transient inhibition of glucose uptake could precondition the rabbit heart. Rabbit hearts experienced 30 min regional ischemia followed by either 120 min (isolated heart protocol) or 180 min (in situ protocol) reperfusion. Infarct size was determined by tetrazolium staining. In isolated heart experiments, 15 min perfusion with glucose-free Krebs buffer starting 30 min prior to ischemia significantly limited infarct size to 9.9 +/- 2.6% of the risk zone as compared with 29.4 +/- 1.7% infarction in controls. This protection could be blocked (30.8 +/- 3.4%) by polymyxin B (50 microM), a protein kinase C inhibitor, but not by 8-(p-sulfophenyl)theophylline, an adenosine receptor inhibitor, suggesting the mechanism was similar to that of ischemic preconditioning but without involvement of adenosine receptors. Pyruvate and acetate inhibit glucose uptake without incurring a metabolic deficit. When 20 mM pyruvate or 1 mM acetate was added to the glucose-containing buffer for 15 min prior to ischemia, protection was evident (12.0 +/- 3.0% and 10.0 +/- 3.7% infarction, respectively). However, when acetate (1 mM) was present in the perfusate throughout the experiment, neither omission of glucose nor addition of pyruvate caused protection (26.1 +/- 2.2% and 28.9 +/- 4.7% infarction, respectively). Furthermore, when in situ hearts which preferably utilize lipid substrates were treated with pyruvate (2 g/kg i.v. 20 min before ischemia), infarct size was 40.3 +/- 3.0%, which did not differ from that in untreated hearts (38.6 +/- 3.2%). Hence transient inhibition of glucose uptake can precondition the heart, but only if other substrates which are utilized in preference to glucose are absent. PMID:8523449

  18. Protective Effect of Ischemic Preconditioning on Cold Preservation and Reperfusion Injury Associated With Rat Intestinal Transplantation

    PubMed Central

    Sola, Anna; De Oca, Javier; Gonzlez, Rosario; Prats, Neus; Rosell-Catafau, Joan; Gelp, Emilio; Jaurrieta, Eduardo; Hotter, Georgina

    2001-01-01

    Objective To define the protective effect of ischemic preconditioning on cold ischemia and reperfusion injury associated with intestinal transplantation, and the role of nitric oxide in this process. Summary Background Data Ischemia/reperfusion injury continues to be a significant obstacle in small bowel transplantation. Preconditioning is a mechanism that protects against this injury. Methods To study the capacity of preconditioning to prevent cold ischemia-associated injury and the inflammatory response associated with intestinal transplantation, the authors studied a control group of animals, cold ischemia groups with or without previous preconditioning and with or without previous administration of L-NAME or NONOS, and intestinal transplantation groups with or without previous preconditioning and with or without previous administration of L-NAME or NONOS. Results Histologic findings and the release of lactate dehydrogenase into the preservation solution showed that preconditioning protects against cold ischemic preservation-associated injury. Preconditioning also prevented the inflammatory response associated with intestinal transplantation, measured by the above parameters and by neutrophil recruitment in the intestine. Inhibition of nitric oxide eliminates the protective effect. Conclusions Preconditioning protects the intestinal grafts from cold preservation and reperfusion injury in the rat intestinal transplantation model. Nitric oxide is involved in this protection. PMID:11420489

  19. Ischemic Preconditioning Affects Long-Term Cell Fate through DNA DamageRelated Molecular Signaling and Altered Proliferation

    PubMed Central

    Kapoor, Sorabh; Berishvili, Ekaterine; Bandi, Sriram; Gupta, Sanjeev

    2015-01-01

    Despite the potential of ischemic preconditioning for organ protection, long-term effects in terms of molecular processes and cell fates are ill defined. We determined consequences of hepatic ischemic preconditioning in rats, including cell transplantation assays. Ischemic preconditioning induced persistent alterations; for example, after 5 days liver histology was normal, but ?-glutamyl transpeptidase expression was observed, with altered antioxidant enzyme content, lipid peroxidation, and oxidative DNA adducts. Nonetheless, ischemic preconditioning partially protected from toxic liver injury. Similarly, primary hepatocytes from donor livers preconditioned with ischemia exhibited undesirably altered antioxidant enzyme content and lipid peroxidation, but better withstood insults. However, donor hepatocytes from livers preconditioned with ischemia did not engraft better than hepatocytes from control livers. Moreover, proliferation of hepatocytes from donor livers preconditioned with ischemia decreased under liver repopulation conditions. Hepatocytes from donor livers preconditioned with ischemia showed oxidative DNA damage with expression of genes involved in MAPK signaling that impose G1/S and G2/M checkpoint restrictions, including p38 MAPKregulated or ERK-1/2regulated cell-cycle genes such as FOS, MAPK8, MYC, various cyclins, CDKN2A, CDKN2B, TP53, and RB1. Thus, although ischemic preconditioning allowed hepatocytes to better withstand secondary insults, accompanying DNA damage and molecular events simultaneously impaired their proliferation capacity over the long term. Mitigation of ischemic preconditioninginduced DNA damage and deleterious molecular perturbations holds promise for advancing clinical applications. PMID:25128377

  20. Resistance of the myocardium to ischemia and the efficacy of ischemic preconditioning in experimental diabetes mellitus.

    PubMed

    Galagudza, M M; Nekrasova, M K; Syrenskii, A V; Nifontov, E M

    2007-06-01

    Data on the influences of diabetes mellitus on the severity of ischemic damage to the myocardium are contradictory. We report here experiments using a model based on in vivo myocardial infarcts resulting from coronary occlusion to study the resistance of the myocardium in rats with alloxan-induced insulin-dependent diabetes mellitus to prolonged ischemia, along with studies of the infarct-limiting efficacy of ischemic preconditioning. The results showed that after diabetes mellitus for six weeks, the relative size of infarcts was significantly less than in controls (39.8 +/- 8.8 and 62.3 +/- 6.6% of the size of the anatomical risk zone respectively, p < 0.01). In addition, animals with diabetes mellitus developed ischemic ventricular tachyarrhythmia significantly less often than controls. A single episode of ischemic preconditioning in animals with diabetes mellitus had a less marked infarct-limiting effect than the same procedure in controls. Thus, these data support the existence of an endogenous cardioprotective phenotype (metabolic preconditioning) in experimental diabetes. On the other hand, the efficacy of ischemic preconditioning was sharply decreased in diabetes. PMID:17505800

  1. 3?phosphoinositide-dependent kinase-1 is essential for ischemic preconditioning of the myocardium

    PubMed Central

    Budas, Grant R.; Sukhodub, Andrey; Alessi, Dario R.; Jovanovi?, Aleksandar

    2007-01-01

    Brief periods of ischemia and reperfusion that precede sustained ischemia lead to a reduction in myocardial infarct size. This phenomenon, known as ischemic preconditioning, is mediated by signaling pathway(s) that are yet to be fully defined. 3?-phosphoinositide-dependent kinase-1 (PDK1) has been implicated in numerous cellular processes. However, the involvement of PDK1 in preconditioning has yet to be elucidated. Studying PDK1 is not as straightforward as it is for the majority of kinases, due to the lack of a specific inhibitor of PDK1. Therefore, we have taken advantage of PDK1 hypomorphic mutant mice with reduced expression of PDK1 to study the role of PDK1 in preconditioning. Whole heart and single cell models of preconditioning demonstrated that the hearts and cardiac cells from PDK1 hypomorphic mice could not be preconditioned. The cardioprotective effect of PDK1 was not related to the effect that preconditioning has on sarcolemmal membrane action potential as revealed by di-8-ANEPPS, a sarcolemmal-potential sensitive dye, and laser confocal microscopy. In contrast, experiments with JC-1, a mitochondrial membrane potential-sensitive dye, has demonstrated that intact PDK1 levels were required for preconditioning-mediated regulation of mitochondrial membrane potential. Western blotting combined with functional experiments have shown that intact PDK1 levels were required for preconditioning-induced phosphorylation of protein kinase B (PKB), glycogen synthase kinase-3? (GSK-3?), and cardioprotection. We conclude that PDK1 mediates preconditioning in the heart by regulating activating PKB-GSK-3? to regulate mitochondrial but not sarcolemmal membrane potential. 3?phosphoinositide-dependent kinase-1 (PDK1) is essential for ischemic preconditioning of the myocardium. PMID:17077284

  2. Protein kinase C-dependent activation of P44/42 mitogen-activated protein kinase and heat shock protein 70 in signal transduction during hepatocyte ischemic preconditioning

    PubMed Central

    Gao, Yi; Shan, Yu-Qiang; Pan, Ming-Xin; Wang, Yu; Tang, Li-Jun; Li, Hao; Zhang, Zhi

    2004-01-01

    AIM: To investigate the significance of protein kinase C (PKC), P44/42 mitogen-activated protein kinase (MAPKs) and heat shock protein (HSP)70 signal transduction during hepatocyte ischemic preconditioning. METHODS: In this study we used an in vitro ischemic preconditioning (IP) model for hepatocytes and an in vivo model for rat liver to investigate the significance of protein kinase C (PKC), P44/42 mitogen-activated protein kinase (P44/42 MAPKs) and heat shock protein 70 (HSP70) signal transduction in IP. Through a normal liver cell hypoxic preconditioning (HP) model in which cultured normal liver cells were subjected to 3 cycles of 5 min of incubation under hypoxic conditions followed by 5 min of reoxygenation and subsequently exposed to hypoxia and reoxygenation for 6 h and 9 h respectively. PKC inhibitor, activator and MEK inhibitor were utilized to analyze the phosphorylation of PKC, the expression of P44/42 MAPKs and HSP70. Viability and cellular ultrastructure were also observed. By using rat liver as an in vivo model of liver preconditioning (3 cycles of 10-min occlusion and 10-min reperfusion), in vivo phosphorylation of PKC and P44/42MAPKs, HSP70 expression were further analyzed. AST/ALT concentration, cellular structure and ultrastruture were also observed. All the data were statistically analyzed. RESULTS: Similar results were obtained in both in vivo and in vitro IP models. Compared with the control without IP (or HP), the phosphorylation of PKC and P44/42 MAPKs and the expression of HSP70 were obviously increased in IP (or HP) treated model in which cytoprotection could be found. The effects of preconditioning were mimicked by stimulating PKC with 4? phorobol-12-myristate13-acetate (PMA). Conversely, inhibiting PKC with chelerythrine abolished the protection given by preconditioning. PD98059, inhibitor of MEK (the upstream kinase of P44/42MAPKs), also reverted the cytoprotection exerted by preconditioning. CONCLUSION: The results demonstrate that preconditioning induces a rapid activation of P44/42MAPKs and PKC activation plays a pivotal role in the activation of P44/42 MAPKs pathway that participates in the preservation of liver cells. HSP expression is regulated by signals in PKC dependent P44/ 42 MAPKs pathway. PMID:15052686

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-10-22

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

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

    PubMed Central

    Leal, Antonio Jos Gonalves; Tannuri, Ana Cristina Aoun; Belon, Alessandro Rodrigo; Guimares, Raimundo Renato Nunes; Coelho, Maria Ceclia Mendona; de Oliveira Gonalves, 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: Ischemia-reperfusion injury in this model of large-for-size liver transplantation could be partially attenuated by ischemic preconditioning. PMID:25789522

  6. Neuronal K(ATP) channels mediate hypoxic preconditioning and reduce subsequent neonatal hypoxic-ischemic brain injury.

    PubMed

    Sun, Hong-Shuo; Xu, Baofeng; Chen, Wenliang; Xiao, Aijiao; Turlova, Ekaterina; Alibraham, Ammar; Barszczyk, Andrew; Bae, Christine Y J; Quan, Yi; Liu, Baosong; Pei, Lin; Sun, Christopher L F; Deurloo, Marielle; Feng, Zhong-Ping

    2015-01-01

    Neonatal hypoxic-ischemic brain injury and its related illness hypoxic-ischemic encephalopathy (HIE) are major causes of nervous system damage and neurological morbidity in children. Hypoxic preconditioning (HPC) is known to be neuroprotective in cerebral ischemic brain injury. K(ATP) channels are involved in ischemic preconditioning in the heart; however the involvement of neuronal K(ATP) channels in HPC in the brain has not been fully investigated. In this study, we investigated the role of HPC in hypoxia-ischemia (HI)-induced brain injury in postnatal seven-day-old (P7) CD1 mouse pups. Specifically, TTC (2,3,5-triphenyltetrazolium chloride) staining was used to assess the infarct volume, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling) to detect apoptotic cells, Western blots to evaluate protein level, and patch-clamp recordings to measure K(ATP) channel current activities. Behavioral tests were performed to assess the functional recovery after hypoxic-ischemic insults. We found that hypoxic preconditioning reduced infarct volume, decreased the number of TUNEL-positive cells, and improved neurobehavioral functional recovery in neonatal mice following hypoxic-ischemic insults. Pre-treatment with a K(ATP) channel blocker, tolbutamide, inhibited hypoxic preconditioning-induced neuroprotection and augmented neurodegeneration following hypoxic-ischemic injury. Pre-treatment with a K(ATP) channel opener, diazoxide, reduced infarct volume and mimicked hypoxic preconditioning-induced neuroprotection. Hypoxic preconditioning induced upregulation of the protein level of the Kir6.2 isoform and enhanced current activities of K(ATP) channels. Hypoxic preconditioning restored the HI-reduced PKC and pAkt levels, and reduced caspase-3 level, while tolbutamide inhibited the effects of hypoxic preconditioning. We conclude that K(ATP) channels are involved in hypoxic preconditioning-induced neuroprotection in neonatal hypoxic-ischemic brain injury. K(ATP) channel openers may therefore have therapeutic effects in neonatal hypoxic-ischemic brain injury. PMID:25448006

  7. Effects of glycogen depletion on ischemic injury in isolated rat hearts: insights into preconditioning.

    PubMed

    Schaefer, S; Carr, L J; Prussel, E; Ramasamy, R

    1995-03-01

    Limitation of myocardial injury and infarction has been demonstrated by interventions such as ischemic preconditioning or the use of pyruvate as a substrate, which reduces glycogen content before, and acidosis during, ischemia. An isolated perfused rat heart model of global ischemia was employed to test the hypothesis that glycogen depletion reduces ischemic injury as measured by creatine kinase release. 31P-nuclear magnetic resonance spectroscopy was used to measure high-energy phosphates (ATP and phosphocreatine), phosphomonoesters (PME), and intracellular pH. Compared with control glucose-perfused hearts with normal glycogen content (1.49 +/- 0.13 mg Glc/g wet wt), glycogen-depleted pyruvate, ischemic preconditioned, and glycogen-depleted glucose hearts all had reduced glycogen content before ischemia (0.62 +/- 0.16, 0.81 +/- 0.10, and 0.67 +/- 0.12 mg Glc/g wet wt, respectively; P = 0.003) and significantly higher pH at the end of ischemia (5.85 +/- 0.02, 6.33 +/- 0.06, 6.24 +/- 0.04, and 6.12 +/- 0.02 in control, glycogen-depleted pyruvate, preconditioned, and glycogen-depleted glucose-perfused hearts, respectively; P < 0.01), although acidification during the initial phase of ischemia was differentially affected by the three interventions. Glycogen-depleted pyruvate and preconditioned hearts had reduced PME accumulation, greater recovery of function and phosphocreatine, and lower creatine kinase release on reperfusion, whereas glycogen-depleted glucose-perfused hearts were similar to control hearts. In summary, glycogen depletion by these three methods limits the fall in pH during global ischemia, although glycogen depletion in the absence of preconditioning does not limit ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7900892

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

    PubMed

    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

  9. 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

  10. Ischemic preconditioning and infarct mass: the effect of hypercholesterolemia and endothelial dysfunction.

    PubMed

    Jung, O; Jung, W; Malinski, T; Wiemer, G; Schoelkens, B A; Linz, W

    2000-02-01

    In an experimental model of atherosclerosis we investigated whether rabbits fed an atherogenic diet (0.25% cholesterol, 3% coconut oil) develop endothelial dysfunction accompanied with increased infarct mass compared to normal fed rabbits and, whether hypercholesterolemia would interfere with the beneficial outcome of ischemic preconditioning observed in normal rabbits. After four weeks on either a normal or an atherogenic diet, New Zealand White rabbits (n=7 in each group) were subjected to 30 min of myocardial ischemia by occlusion of a branch of the left anterior descending coronary artery (LAD) followed by 2 hours of reperfusion (infarct studies). For ischemic preconditioning experiments, LAD was additionally occluded twice for 5 min followed by 10 min reperfusion before the long-lasting (30 min) ischemia. Infarct mass was evaluated by triphenyl-tetrazolium staining. Besides the assessment of aortic endothelium-dependent function and NO-release, aortic and cardiac vessels were inspected for atherosclerotic lesions. Total cholesterol serum levels in rabbits on an atherogenic diet were significantly higher (15.3+/-2.7 mmol/L) than those on a standard diet (0.65+/-0.08 mmol/L). The aortas and heart vessels were without any histological evidence of atherosclerosis, whereas endothelial dysfunction and significantly reduced calcium-ionophore stimulated endothelial NO-release were found in isolated aortic rings of hypercholesterolemic animals. Rabbits on a standard diet showed an infarct mass (related to the area at risk) of 41+/-33%, which was reduced to 21+/-2% by ischemic preconditioning (49% decrease, p<0.05). In rabbits on an atherogenic diet, infarct mass was significantly increased to 63+/-3% (52% increase versus standard diet). Interestingly, hypercholesterolemia did not affect the beneficial influence of ischemic preconditioning; infarct mass (21+/-3%, p<0.05 vs hypercholesterolemia) was similar to rabbits on a standard diet with ischemic preconditioning. Our results show that experimental hypercholesterolemia increases infarct mass in nonpreconditioned hearts but it does not interfere with the reduction of infarct mass elicited by preconditioning. This may suggest that NO produced by the endothelium is not a prime factor in the cardioprotective mechanism of preconditioning. PMID:10744357

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

    PubMed Central

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

    2015-01-01

    Ischemic preconditioning represents an important adaptation mechanism of CNS, which results in its increased tolerance to the lethal cerebral ischemia. The molecular mechanisms responsible for the induction and maintenance of ischemic tolerance in the brain are complex and not yet completely clarified. In the last 10?years, great attention has been devoted to unravel the intracellular pathways activated by preconditioning and responsible for the establishing of the tolerant phenotype. Indeed, recent papers have been published supporting the hypothesis that mitochondria might act as master regulators of preconditioning-triggered endogenous neuroprotection due to their ability to control cytosolic calcium homeostasis. More interestingly, the demonstration that functional alterations in the ability of mitochondria and endoplasmic reticulum (ER) managing calcium homeostasis during ischemia, opened a new line of research focused to the role played by mitochondria and ER cross-talk in the pathogenesis of cerebral ischemia in order to identify new molecular mechanisms involved in the ischemic tolerance. In line with these findings and considering that the expression of the three isoforms of the sodium calcium exchanger (NCX), NCX1, NCX2, and NCX3, mainly responsible for the regulation of Ca2+ homeostasis, was reduced during cerebral ischemia, it was investigated whether these proteins might play a role in neuroprotection induced by ischemic tolerance. In this review, evidence supporting the involvement of ER and mitochondria interaction within the preconditioning paradigm will be provided. In particular, the key role played by NCXs in the regulation of Ca2+-homeostasis at the different subcellular compartments will be discussed as new molecular mechanism proposed for the establishing of ischemic tolerant phenotype. PMID:26074868

  12. 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 6weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4cycles of ischemic preconditioning (IPC), then 30min of ischemia followed by 120min 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?M) perfused during reperfusion for 120min, 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?M), perfused during reperfusion 2min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion. PMID:25743572

  13. 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. PMID:26089545

  14. Acute bioenergetic intervention or pharmacological preconditioning protects neuron against ischemic injury

    PubMed Central

    Liu, Shimin; Zhen, Gehua; Li, Rung-chi; Dor, Sylvain

    2013-01-01

    Although acute ischemic stroke has high mortality and morbidity rate but yet still has very limited treatment. In this study we have tested the concept of neuron protection by acute bioenergetic intervention or by pharmacological preconditioning with natural antioxidants. Adenosine triphosphate (ATP), pentobarbital, and suramin were encapsulated in pH-sensitive liposomes and used as bioenergy stabilizer. We induced ATP depletion model by incubating cells with media added with ATP-depleting agents for 2 hours. Treatment with bioenergy stabilizer started 10-min post inducing of ATP-depletion. The acute treatment with bioenergy stabilizer significantly increased cell viability in neuro-2a cells. In searching for a pharmacological preconditioning candidate for reducing ischemic injury, we tested cocoa-derived flavanols using bilateral common carotid artery occlusion (BCCAO). We pretreated mice with cocoa-derived flavanols (75 mg/kg) or water orally for 7 days and subjected mice for 12 minutes BCCAO. At 7 days post-ischemia, the number of surviving hippocampal CA1 neurons was significantly higher in the treated mice than in the water-treated controls. The protection from cocoa-derived flavanols was found associated with increased total antioxidant capacity in the brain. Our results indicate that for reducing acute ischemic injury bioenergetic intervention using advanced drug delivery tools is conceptually feasible, and for reducing reperfusion related secondary injury pharmacological preconditioning may provide significant protection. PMID:24285991

  15. Proteomic analysis of the hippocampus in nave and ischemic-preconditioned rat.

    PubMed

    Nakajima, Takayuki; Hata, Ryusuke; Kondo, Tomohiro; Takenaka, Shigeo

    2015-11-15

    The hippocampus exhibits regional differences in vulnerability to ischemia, wherein pyramidal cells in the CA1 region are vulnerable to ischemia while pyramidal cells in the CA3 region and granule cells in the dentate gyrus (DG) region are relatively ischemia resistant. However, pyramidal cells in the CA1 region reportedly exhibit ischemic tolerance following exposure to a brief non-lethal period of ischemia known as ischemic preconditioning. In this study, we used proteomic analysis to examine the difference in protein expression between nave rat CA1 and CA3/DG regions, as well as the altered protein expression in the CA1 region after 3min of ischemic preconditioning. Proteomic analysis identified ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), glutathione S-transferase ?5 (GST?5), glutamine synthetase (GS), and dynamin-1 as proteins with differential expression levels in nave CA1 and CA3/DG regions. The difference in expression levels of GST?5 and GS between these two regions was further confirmed by western blot. Our analysis also identified aconitase2, ?-tubulin, protein-l-isoaspartate O-methiltransferase (PIMT), and voltage-dependent anion channel 1 (VDCA1) as proteins with down-regulated expression levels in the CA1 region following 3min ischemic preconditioning. The decrease in the expression of aconitase2 was also confirmed by western blot and immunohistochemical staining. The present results suggest that GST?5 and GS may be associated with ischemia-resistance in the CA3/DG region and that aconitase2 may play a part in the ischemic tolerance in the CA1 region. PMID:26342941

  16. Protection of cardiac mitochondria by diazoxide and protein kinase C: Implications for ischemic preconditioning

    PubMed Central

    Korge, Paavo; Honda, Henry M.; Weiss, James N.

    2002-01-01

    Mitochondrial ATP-sensitive K (mitoKATP) channels play a central role in protecting the heart from injury in ischemic preconditioning. In isolated mitochondria exposed to elevated extramitochondrial Ca, Pi, and anoxia to simulate ischemic conditions, the selective mitoKATP channel agonist diazoxide (2550 ?M) potently reduced mitochondrial injury by preventing both the mitochondrial permeability transition (MPT) and cytochrome c loss from the intermembrane space. Both effects were blocked completely by the selective mitoKATP antagonist 5-hydroxydecanoate. The protective effect against Ca-induced MPT was most evident under conditions in which the ability of electron transport to support membrane potential (??m) was decreased and inner membrane leakiness was increased moderately. Under these conditions, mitoKATP channel activity strongly regulated ??m, and diazoxide prevented MPT by inhibiting the driving force for Ca uptake. Phorbol 12-myristate 13-acetate mimicked the protective effects of diazoxide, unless 5-hydroxydecanoate was present, indicating that protein kinase C activation also protects mitochondria by activating mitoKATP channels. Because ??m recovery ultimately is required for heart functional recovery, these results may explain how mitoKATP channel activation mimics ischemic preconditioning by protecting mitochondria as they pass through a critical vulnerability window during ischemia/reperfusion. PMID:11867760

  17. 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

  18. Remote Ischemic Preconditioning and Renoprotection: From Myth to a Novel Therapeutic Option?

    PubMed Central

    Nia, Amir M.; Caglayan, Evren; Er, Fikret

    2014-01-01

    There is currently no effective prophylactic regimen available to prevent contrast-induced AKI (CI-AKI), a frequent and life-threatening complication after cardiac catheterization. Therefore, novel treatment strategies are required to decrease CI-AKI incidence and to improve clinical outcomes in these patients. Remote ischemic preconditioning (rIPC), defined as transient brief episodes of ischemia at a remote site before a subsequent prolonged ischemia/reperfusion injury of the target organ, is an adaptational response that protects against ischemic and reperfusion insult. Indeed, several studies demonstrated the tissue-protective effects of rIPC in various target organs, including the kidneys. In this regard, rIPC may offer a novel noninvasive and virtually cost-free treatment strategy for decreasing CI-AKI incidence. This review evaluates the current experimental and clinical evidence for rIPC as a potential renoprotective strategy, and discusses the underlying mechanisms and key areas for future research. PMID:24309187

  19. 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. PMID:26509376

  20. Using hormetic strategies to improve ischemic preconditioning and postconditioning against stroke.

    PubMed

    Zhao, Heng; Joo, Sungpil; Xie, Weiying; Ji, Xunming

    2013-01-01

    Both ischemic preconditioning (IPreC) and ischemic postconditioning (IPostC) trigger endogenous neuroprotective mechanisms in cerebral ischemia. IPreC is defined as a brief ischemia that protects against a subsequent severe ischemia, while IPostC refers to a series of brief cerebral blood vessel occlusions performed at reperfusion following an ischemic event. Hormesis describes a biphasic dose-response relationship in toxicology, where a low dose of toxicant stimulates and a high dose inhibits biological responses. In general, any minor stress will stimulate a biological system to generate an adaptive response; in most cases, if not all, such an adaptive response to a minor stress is beneficial to the biological system. Proponents of hormesis suggest that this effect is independent of any models, either in vivo or in vitro, from animal, plant, fungi, yeast, to bacteria, by any measurement of end points, survival ratio or time, growth, tissue repair, life span, cognition, learning and memory. In this review, we examine whether IPreC and IPostC are actually sub-forms of hormesis and whether quantitative hormetic strategies can be used to study IPreC and IPostC. By integrating the concepts of IPreC and IPostC with hormesis, we aim to broaden the avenues leading to clinical translation of IPreC and IPostC in stroke treatment. PMID:23750305

  1. 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...

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

    PubMed

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

    2015-11-01

    A pilot randomized controlled trial that evaluated the effect of remote ischemic preconditioning (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed. PMID:26574485

  3. CBF changes associated with focal ischemic preconditioning in the spontaneously hypertensive rat.

    PubMed

    Zhao, Liang; Nowak, Thaddeus S

    2006-09-01

    Experimental stroke models exhibit robust protection after prior preconditioning (PC) insults. This study comprehensively examined cerebral blood flow (CBF) responses to permanent middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats preconditioned by noninjurious transient focal ischemia, using [(14)C]iodoantipyrine autoradiography at varied occlusion intervals. Preconditioning was produced by 10-min occlusion of the MCA and ipsilateral common carotid artery under halothane anesthesia. These vessels were permanently coagulated 24 h later in naïve, PC, and sham-operated rats. Infarct volumes were determined from hematoxylin-eosin-stained frozen sections after 1 or 3 days. Edema-corrected infarct volume was reduced from 127+/-21 in naïve rats to 101+/-31 and 52+/-28 mm(3) in sham and PC groups, respectively, at 1 day, with similar results at 3 days. All animals exhibited a consistent CBF threshold for infarction (approximately 30 mL/100 g/min). Tissue volumes below this threshold were identical in naïve and PC groups after 15-min occlusion. However, by 3 h the volume of ischemic cortex decreased in the PC group but remained unchanged in naïve rats, predicting final infarct volumes. Cerebral blood flow recovery was confirmed in brains of individual rats evaluated by repeated laser Doppler perfusion imaging during the same 3-h interval. Modest sham protection correlated with better-maintained global perfusion, detectable also in the contralateral cortex, apparently reflecting the PC effects of prior anesthesia. These results establish that timely reperfusion of penumbra, achieved by synergistic mechanisms, is a primary determinant of PC-induced protection in experimental stroke. PMID:16407854

  4. Remote ischemic preconditioning to reduce contrast-induced nephropathy: study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Despite the increasing use of pre- and posthydration protocols and low-osmolar instead of high-osmolar iodine-containing contrast media, the incidence of contrast-induced nephropathy (CIN) is still significant. There is evidence that contrast media cause ischemia-reperfusion injury of the medulla. Remote ischemic preconditioning (RIPC) is a non-invasive, safe, and low-cost method to reduce ischemia-reperfusion injury. Methods The RIPCIN study is a multicenter, single-blinded, randomized controlled trial in which 76 patients at risk of CIN will receive standard hydration combined with RIPC or hydration with sham preconditioning. RIPC will be applied by four cycles of 5min ischemia and 5min reperfusion of the forearm by inflating a blood pressure cuff at 50mmHg above the actual systolic pressure. The primary outcome measure will be the change in serum creatinine from baseline to 48 to 72h after contrast administration. Discussion A recent pilot study reported that RIPC reduced the incidence of CIN after coronary angioplasty. The unusual high incidence of CIN in this study is of concern and limits its generalizability. Therefore, we propose a randomized controlled trial to study whether RIPC reduces contrast-induced kidney injury in patients at risk for CIN according to the Dutch guidelines. Trial registration Current Controlled Trials ISRCTN76496973 PMID:24721127

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

    PubMed Central

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

    2014-01-01

    Despite major advances in early revascularization techniques, cardiovascular diseases are still the leading cause of death worldwide, and myocardial infarctions contribute heavily to this. Over the past decades, it has become apparent that reperfusion of blood to a previously ischemic area of the heart causes damage in and of itself, and that this ischemia reperfusion induced injury can be reduced by up to 50% by mechanical manipulation of the blood flow to the heart. The recent discovery of remote ischemic preconditioning (RIPC) provides a non-invasive approach of inducing this cardioprotection at a distance. Finding its endogenous mediators and their operative mode is an important step toward increasing the ischemic tolerance. The release of humoral factor(s) upon RIPC was recently demonstrated and several candidate proteins were published as possible mediators of the cardioprotection. Before clinical applicability, these potential biomarkers and their efficiency must be validated, a task made challenging by the large heterogeneity in reported data and results. Here, in an attempt to reproduce and provide more experimental data on these mediators, we conducted an unbiased in-depth analysis of the human plasma proteome before and after RIPC. From the 68 protein markers reported in the literature, only 28 could be mapped to manually reviewed (Swiss-Prot) protein sequences. 23 of them were monitored in our untargeted experiment. However, their significant regulation could not be reproducibly estimated. In fact, among the 394 plasma proteins we accurately quantified, no significant regulation could be confidently and reproducibly assessed. This indicates that it is difficult to both monitor and reproduce published data from experiments exploring for RIPC induced plasma proteomic regulations, and suggests that further work should be directed towards small humoral factors. To simplify this task, we made our proteomic dataset available via ProteomeXchange, where scientists can mine for novel potential targets. PMID:25333471

  6. Bone morphogenic protein-7 contributes to cerebral ischemic preconditioning induced-ischemic tolerance by activating p38 mitogen-activated protein kinase signaling pathway.

    PubMed

    Guan, Junhong; Li, Han; Lv, Tao; Chen, Duo; Yuan, Ye; Qu, Shengtao

    2014-08-01

    Cerebral ischemic preconditioning (IPC), which refers to a transient and noninjurious ischemia is able to induce tolerance against the subsequent lethal ischemia, including ischemic stroke. We have previously reported that bone morphogenic protein-7 (BMP-7) contributes to the neuroprotective effects of IPC-induced ischemic tolerance, and thus ameliorates the following ischemia/reperfusion (I/R) injury in rats. Consequently, in the present study, we continued to explore the underlying regulatory mechanisms involved in BMP-7-mediated cerebral IPC in the rat model of ischemic tolerance. Male Wistar rats were preconditioned by 15-min middle cerebral artery occlusion (MCAO). After 2-day reperfusion, these animals were subjected to prolonged MCAO for 2h. Our results showed that the phosphorylated p38 mitogen-activated protein kinase (MAPK) paralleling to BMP-7 was up-regulated by IPC in rat brain. Inactivation of p38 MAPK by pretreatment of SB203580, a p38 MAPK-specific suppressor, weakened the protective effect of IPC on CA1 neurons. Moreover, the enhanced phosphorylation of p38 MAPK induced by IPC was attenuated when the endogenous BMP-7 was inhibited by BMP-7 antagonist noggin. Besides, blockade of p38 MAPK signal transduction pathway via SB203580 abrogated the protective effects of exogenous BMP-7 against cerebral infraction. These present findings suggest that BMP-7 contributes to cerebral IPC-induced ischemic tolerance via activating p38 MAPK signaling pathway. PMID:24682853

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

    PubMed Central

    2014-01-01

    Background Stroke is accompanied by a distinguished inflammatory reaction that is initiated by the infiltration of immunocytes, expression of cytokines, and other inflammatory mediators. As natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the innate immune system, we investigated the mechanism of NK cells-induced brain injuries after cerebral ischemia and the chemotactic effect of IP-10 simultaneously. Methods NK cells infiltration, interferon-gamma (IFN-γ) and IP-10 expression were detected by immunohistochemistry, immunofluorescence, PCR and flow cytometry in human and C57/BL6 wild type mouse ischemic brain tissues. The ischemia area was detected via 2,3,5-triphenyltetrazolium chloride staining. CXCR3 mean fluorescence intensity of isolated NK cells was measured by flow cytometry. The neuronal injury made by NK cells was examined via apoptosis experiment. The chemotactic of IP-10 was detected by migration and permeability assays. Results In human ischemic brain tissue, infiltrations of NK cells were observed and reached a peak at 2 to 5 days. In a permanent middle cerebral artery occlusion (pMCAO) model, infiltration of NK cells into the ischemic infarct region reached their highest levels 12 hours after ischemia. IFN-γ-positive NK cells and levels of the chemokine IP-10 were also detected within the ischemic region, from 6 hours up to 4 days after pMCAO was performed, and IFN-γ levels decreased after NK cells depletion in vivo. Co-culture experiments of neural cells with NK cells also showed that neural necrosis was induced via IFN-γ. In parallel experiments with IP-10, the presence of CXCR3 indicates that NK cells were affected by IP-10 via CXCR3, and the effect was dose-dependent. After IP-10 depletion in vivo, NK cells decreased. In migration assays and permeability experiments, disintegration of the blood–brain barrier (BBB) was observed following the addition of NK cells. Moreover, in the presence of IP-10 this injury was aggravated. Conclusions All findings support the hypothesis that NK cells participate in cerebral ischemia and promote neural cells necrosis via IFN-γ. Moreover, IP-10 intensifies injury to the BBB by NK cells via CXCR3. PMID:24742325

  8. 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 invitro 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 preconditioning paradigm. We therefore propose 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, via a suppression of protein synthesis and/or energy consumption. PMID:26375300

  9. Preconditioning effect of (S)-3,5-dihydroxyphenylglycine on ischemic injury in middle cerebral artery occluded Sprague-Dawley rats.

    PubMed

    Nik Ramli, Nik Nasihah; Omar, Nursyazwani; Husin, Andrean; Ismail, Zalina; Siran, Rosfaiizah

    2015-02-19

    Glutamate receptors are the integral cellular components associated with excitotoxicity mechanism induced by the ischemic cascade events. Therefore the glutamate receptors have become the major molecular targets of neuroprotective agents in stroke researches. Recent studies have demonstrated that a Group I metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) preconditioning elicits neuroprotection in the hippocampal slice cultures exposed to toxic level of N-methyl-d-aspartate (NMDA). We further investigated the preconditioning effects of (S)-3,5-DHPG on acute ischemic stroke rats. One 10 or 100?M of (S)-3,5-DHPG was administered intrathecally to Sprague-Dawley adult male rats, 2h prior to induction of acute ischemic stroke by middle cerebral artery occlusion (MCAO). After 24h, neurological deficits were evaluated by modified stroke severity scores and grid-walking test. All rats were sacrificed and infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining. The serum level of neuron-specific enolase (NSE) of each rat was analyzed by enzyme-linked immunosorbent assay (ELISA). One and 10?M of (S)-3,5-DHPG preconditioning in the stroke rats showed significant improvements in motor impairment (P<0.01), reduction in the infarct volume (P<0.01) and reduction in the NSE serum level (P<0.01) compared to the control stroke rats. We conclude that 1 and 10?M (S)-3,5-DHPG preconditioning induced protective effects against acute ischemic insult in vivo. PMID:25562631

  10. Ischemic Preconditioning Increases the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat

    PubMed Central

    Serafn, Anna; Rosell-Catafau, Joan; Prats, Neus; Xaus, Carme; Gelp, Emilio; Peralta, Carmen

    2002-01-01

    Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether preconditioning, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic preconditioning reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of preconditioning. Thus, ischemic preconditioning could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation. PMID:12163383

  11. Limb Ischemic Preconditioning Protects Endothelium from Oxidative Stress by Enhancing Nrf2 Translocation and Upregulating Expression of Antioxidases

    PubMed Central

    Chen, Min; Zhang, Mingsheng; Zhang, Xuanping; Li, Jie; Wang, Yan; Fan, Yanying; Shi, Ruizan

    2015-01-01

    Remote ischemic preconditioning is often performed by limb ischemic preconditioning (LIPC), which has been demonstrated to be beneficial to various cells, including endothelial cells. The mechanisms underlying the protection have not been well clarified. The present study was designed to observe the effects of sera derived from rats after LIPC on human umbilical vein endothelial cells (HUVECs) injured by hydrogen peroxide (H2O2) -induced oxidative stress and explore the involvement of redox state in the protection. Incubation with 1 mM H2O2 for 2 h induced a significant reduction in HUVECs viability with increased production of malondialdehyde (MDA) and reactive oxygen species (ROS). Preincubation with early preconditioning serum (EPS) or delayed preconditioning serum (DPS) derived from rats subjected to LIPC alleviated these changes. Both EPS and DPS increased the nuclear translocation of transcription factor nuclear factor E2-related factor 2 (Nrf2) and the expression of antioxidases. The protective effects of EPS and DPS were blocked neither by MEK/ERK inhibitors U0126 nor by PI3K/Akt inhibitors LY294002. In conclusion, the present study provides the evidence that LIPC protects the HUVECs from H2O2-induced injury by, at least partially, enhancement of Nrf2 translocation and upregulation of antioxidases via signaling pathways independent of MEK/ERK and PI3K/Akt. PMID:26029932

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

    PubMed

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

    2016-01-01

    Although the amount of evidence demonstrating the beneficial effects of ischemic preconditioning (IPC) on exercise performance is increasing, conclusions about its efficacy cannot yet be drawn. Therefore, the purposes of this review were to determine the effect of IPC on exercise performance and identify the effects of different IPC procedures, exercise types, and subject characteristics on exercise performance. The analysis comprised 19 relevant studies from 2000 to 2015, 15 of which were included in the meta-analyses. Effect sizes (ES) were calculated as the standardized mean difference. Overall, IPC had a small beneficial effect on exercise performance (ES = 0.43; 90% confidence interval [CI], 0.28 to 0.51). The largest ES were found for aerobic (ES = 0.51; 90% CI, 0.35 to 0.67) and anaerobic (ES = 0.23; 90% CI, -0.12 to 0.58) exercise. In contrast, an unclear effect was observed in power and sprint performance (ES = 0.16; 90% CI, -0.20 to 0.52). In conclusion, IPC can effectively enhance aerobic and anaerobic exercise performance. PMID:26218309

  13. Ischemic pre-conditioning in deceased donor liver transplantation: a prospective randomized clinical trial.

    PubMed

    Amador, A; Grande, L; Mart, J; Deulofeu, R; Miquel, R; Sol, A; Rodriguez-Laiz, G; Ferrer, J; Fondevila, C; Charco, R; Fuster, J; Hotter, G; Garca-Valdecasas, J C

    2007-09-01

    To assess the immediate and long-term effects of ischemic preconditioning (IPC) in deceased donor. liver transplantation (LT), we designed a prospective, randomized controlled trial involving 60 donors: control group (CTL, n = 30) or study group (IPC, n = 30). IPC was induced by 10-min hiliar clamping immediately before recovery of organs. Clinical data and blood and liver samples were obtained in the donor and in the recipient for measurements. IPC significantly improved biochemical markers of liver cell function such as uric acid, hyaluronic acid and Hypoxia-Induced Factor-1 alpha (HIF-1 alpha) levels. Moreover, the degree of apoptosis was significantly lower in the IPC group. On clinical basis, IPC significantly improved the serum aspartate aminotransferase (AST) levels and reduced the need for reoperation in the postoperative period. Moreover, the incidence of primary nonfunction (PNF) was lower in the IPC group, but did not achieve statistical significance. We conclude that 10-min IPC protects against I/R injury in deceased donor LT. PMID:17697262

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Remote ischemic preconditioning (RIPre) can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG) surgery were assigned randomly to a RIPre group (n=20) or coronary heart disease (CHD) group (n=20). Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD), CD34+ monocyte count, and endothelial nitric oxide synthase (eNOS expression). Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.52.4 vs 4.94.2%, P<0.05) and significantly reduced troponin after CABG surgery (0.720.31 and 1.640.19, P<0.05). RIPre activated STAT-3 and increased CD34+ endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells. PMID:25923462

  16. Impact of ischemic preconditioning on ischemia-reperfusion injury of the rat sciatic nerve

    PubMed Central

    Dong, Shuanghai; Cao, Yun; Li, Haoqing; Tian, Jiwei; Yi, Chengqing; Sang, Weilin

    2015-01-01

    The aim of this study was to assess the preventive effects of ischemic preconditioning (IPC) on ischemia-reperfusion (IR) injury in the sciatic nerve of the rat hind limb. This study included two experiments. For Experiment 1, 40 Sprague-Dawley (SD) rats were randomly divided into 4 equal groups that received different IPC treatments prior to IR. Serum concentrations of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) were assessed following reperfusion. Furthermore, we tested the electrophysiological response and ultrastructural changes in the ipsilateral sciatic nerve after IR. After determining the best IPC protocol for protection, we performed a second experiment with 30 SD rats randomly divided into 3 equal groups. Each group underwent 1, 2, or 3 IPC cycles before prolonged ischemia and reperfusion. The same analyses as in Experiment 1 were performed. In Experiment 1, the AST, LDH, and MDA concentrations were decreased in all IPC groups compared with the control group. Concentration of these enzymes showed decreases with increasing IPC cycle number in Experiment 2; however, the difference between 2 and 3 cycles of IPC did not reach significance. Conversely, SOD activity increased in the rapid and delayed groups, and with increasing cycles of IPC. The electrophysiological test showed a decrease in amplitude and increase in conduction velocity with increasing IPC cycles. Moreover, ultrastructural damage decreased with increasing IPC cycles. IPC protected against IR injury in the peripheral nerves. This effect was positively correlated with the number of IPC cycles. PMID:26629140

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

    PubMed

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

    2015-09-01

    The acute effect of ischemic preconditioning (IPC) on the maximal performance in the 100-m freestyle event was studied in recreational swimmers. 15 swimmers (21.03.2?years) participated in a random crossover model on 3 different days (control [CON], IPC or SHAM), separated by 3-5 days. IPC consisted of 4 cycles of 5-min occlusion (220?mmHg)/5-min reperfusion in each arm, and the SHAM protocol was similar to IPC but with only 20?mmHg during the occlusion phase. The subjects were informed that both maneuvers (IPC and SHAM) would improve their performance. After IPC, CON or SHAM, the volunteers performed a maximal 100-m time trial. IPC improved performance (p=0.036) compared to CON. SHAM performance was only better than CON (p=0.059) as a tendency but did not differ from IPC performance. The individual response of the subjects to the different maneuvers was very heterogeneous. We conclude that IPC may improve performance in recreational swimmers, but this improvement could mainly be a placebo effect. PMID:26058479

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

    PubMed Central

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

    2015-01-01

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

  19. 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

  20. Protective effect of pharmacological preconditioning of total flavones of abelmoschl manihot on cerebral ischemic reperfusion injury in rats.

    PubMed

    Wen, Ji-Yue; Chen, Zhi-Wu

    2007-01-01

    The present study was to investigate the effect of pharmacological preconditioning of total flavones of abelmoschl manihot (TFA) on cerebral ischemic reperfusion injury in rats. Rat cerebral ischemia/reperfusion injury was induced by occluding the right middle cerebral artery (MCA). The infarct size was determined by staining with 2,3,5-triphenyl tetrazalium chloride (TTC). The serum malonaldehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) levels were measured by using spectrophotometry; Inducible NO synthase (iNOS) mRNA expression was detected by RT-PCR method. The percentage of cerebral infarction volume was 28.1 +/- 0.8 in the model group, while TFA or nimodipine (Nim) pretreatment 36 hours prior to the ischemic insult significantly decreased the infarction volume. Increases of serum LDH activity and MDA level were observed after ischemia/reperfusion, but these changes were inhibited in rats pretreated with either TFA (20, 40, 80, 160 mg/kg) or Nim, indicating a delayed protective effect of TFA preconditioning on cerebral ischemic reperfusion injury. In addition, the serum NO level and the cerebral iNOS mRNA were up-regulated, suggesting a possible mechanism for the protective effect of TFA pretreatment on cerebral ischemic reperfusion injury. PMID:17708631

  1. Extracellular Adenosine Formation by Ecto-5-Nucleotidase (CD73) Is No Essential Trigger for Early Phase Ischemic Preconditioning

    PubMed Central

    2015-01-01

    Background Adenosine is a powerful trigger for ischemic preconditioning (IPC). Myocardial ischemia induces intracellular and extracellular ATP degradation to adenosine, which then activates adenosine receptors and elicits cardioprotection. Conventionally extracellular adenosine formation by ecto-5-nucleotidase (CD73) during ischemia was thought to be negligible compared to the massive intracellular production, but controversial reports in the past demand further evaluation. In this study we evaluated the relevance of ecto-5-nucleotidase (CD73) for infarct size reduction by ischemic preconditioning in in vitro and in vivo mouse models of myocardial infarction, comparing CD73-/- and wild type (WT) mice. Methods and Results 3x5 minutes of IPC induced equal cardioprotection in isolated saline perfused hearts of wild type (WT) and CD73-/- mice, reducing control infarct sizes after 20 minutes of ischemia and 90 minutes of reperfusion from 46 6.3% (WT) and 56.1 7.6% (CD73-/-) to 26.8 4.7% (WT) and 25.6 4.7% (CD73-/-). Coronary venous adenosine levels measured after IPC stimuli by high-pressure liquid chromatography showed no differences between WT and CD73-/- hearts. Pharmacological preconditioning of WT hearts with adenosine, given at the measured venous concentration, was evenly cardioprotective as conventional IPC. In vivo, 4x5 minutes of IPC reduced control infarct sizes of 45.3 8.9% (WT) and 40.5 8% (CD73-/-) to 26.3 8% (WT) and 22.6 6.6% (CD73-/-) respectively, eliciting again equal cardioprotection. The extent of IPC-induced cardioprotection in male and female mice was identical. Conclusion The infarct size limiting effects of IPC in the mouse heart in vitro and in vivo are not significantly affected by genetic inactivation of CD73. The ecto-5-nucleotidase derived extracellular formation of adenosine does not contribute substantially to adenosines well known cardioprotective effect in early phase ischemic preconditioning. PMID:26261991

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

    PubMed

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

    2015-10-01

    Protection of intestinal graft mucosa during cold preservation is still an unmet need in clinical practice, thus affecting the success of transplantation. The present study investigates the ability of two ischemic preconditioning (IPC) procedures to limit cold preservation injury. Three groups of Sprague-Dawley rats were recruited (n=11 each) as follows: the short IPC (SIPC) performed through 4 cycles of mesenteric ischemia of 4 min each followed by 10 min of reperfusion, the long IPC (LIPC) obtained by 2 ischemic cycles of 12 min each followed by 10 min of reperfusion, and the control group (C) without IPC. Grafts were then stored in cold histidine-tryptophan-ketoglutarate solution and samples were taken at 0, 3, 6 and 9 h lasting preservation. Both IPC groups showed an advanced degree of preservation with delayed development of graft mucosa damage, mainly in the crypt region. At the beginning of preservation, the graft mucosa in both IPC groups showed lower degree of mucosal injury index (MII) by 50% in comparison with C group. Specifically, a significant improvement of MII was observed after 3h of preservation in the LIPC group (p<0.05) in comparison with untreated C grafts. Significant atrophy of the intestinal mucosa in C group was found after 3h of preservation (p<0.01), in SIPC group the progress of atrophy was delayed to 6 h (p<0.001), and in LIPC group only moderate decrease in that was found. A parallel increase of laminin expression with the MII rate after 6 and 9h of preservation in comparison with the level at time 0 was observed in all grafts (p<0.001 and p<0.01, respectively). In both IPC groups the apoptotic cell (AC) rate was significantly reduced at the beginning of cold preservation (p<0.05 both). Moreover, in both the SIPC and C groups, the progressive increase in MII rate connected with AC rate decrease was due to a predominance of necrosis. By contrast in the LIPC group, after an increase of nearly 50% in the AC rate at the 3rd hour, its level remained fairly constant during the further 6 h of preservation, thus probably preventing necrosis and improving graft viability. PMID:26123930

  3. Ischemic Preconditioning Preserves Mitochondrial Membrane Potential and Limits Reactive Oxygen Species Production

    PubMed Central

    Quarrie, Ricardo; Lee, Daniel S.; Steinbaugh, Gregory; Cramer, Brandon; Erdahl, Warren; Pfeiffer, Douglas R.; Zweier, Jay L.; Crestanello, Juan A.

    2012-01-01

    Background Mitochondrial superoxide radical (O2?) production increases after cardiac ischemia-reperfusion (IR). Ischemic preconditioning (IPC) preserves mitochondrial function and attenuates O2? production, but the mechanism is unknown. Mitochondrial membrane potential (m??) is known to affect O2? production; mitochondrial depolarization decreases O2? formation. We examined the relationship between O2? production and m?? during IR and IPC. Materials/Methods Rat hearts were subjected to Control or IPC. Mitochondria were isolated at end-equilibration (End EQ), end-ischemia (End I) and end-reperfusion (End RP). m?? was measured using a tetraphenylphosphonium electrode. Mitochondrial O2? production was measured by electron paramagnetic resonance (EPR) using DMPO spin trap. Cytochrome c levels were measured using high pressure liquid chromatography. Results IPC preserved m?? at End I (?1565 vs. ?1316 mV, p<0.001) and End RP (?1682 vs. ?1552 mV, p<0.05). At End RP, IPC attenuated O2? production (2527221 vs. 3523250 AU/mg protein, p<0.05). IPC preserved cytochrome c levels (35114 vs. 26916 picomoles/mg protein, p<0.05) at End RP, and decreased mitochondrial cristae disruption (104 vs. 337%, p<0.05) and amorphous density formation (184 vs. 281%, p<0.05). Conclusion We conclude that IPC preserves m??, possibly by limiting disruption of mitochondrial inner membrane. IPC also decreases mitochondrial O2? production and preserves mitochondrial ultrastructure after IR. While it was previously held that slight decreases in m?? decrease O2? production, our results indicate that preservation of m?? is associated with decreased O2? and preservation of cardiac function in IPC. These findings indicate that the mechanism of IPC may not involve m?? depolarization, but rather preservation of mitochondrial electrochemical potential. PMID:22763215

  4. Effect of Remote Ischemic Preconditioning on Platelet Activation Induced by Coronary Procedures.

    PubMed

    Lanza, Gaetano Antonio; Stazi, Alessandra; Villano, Angelo; Torrini, Flavia; Milo, Maria; Laurito, Marianna; Flego, Davide; Aurigemma, Cristina; Liuzzo, Giovanna; Crea, Filippo

    2016-02-01

    In this study, we aim to assess whether remote ischemic preconditioning (RIPC) reduces platelet activation during coronary angiography (CA) and/or percutaneous coronary interventions. We studied 30 patients who underwent CA because of a suspect of stable angina. Patients were randomized to RIPC (3 short episodes of forearm ischemia) or sham RIPC (controls) before the procedure. Blood samples were collected at baseline, at the end of the procedure, and 24 hours later. Monocyte-platelet aggregate (MPA) formation and platelet CD41 in the MPA gate and CD41 and CD62 expression in the platelet gate were assessed by flow cytometry, in the absence and in the presence of adenosine diphosphate (ADP) stimulation. A significant increase in platelet activation occurred during the invasive procedure in controls, which persisted at 24 hours. However, compared with controls, RIPC group showed no or a lower increase in platelet variables, including MPA formation (p <0.0001) and CD41 (p = 0.002) in the MPA gate and CD41 (p <0.0001) and CD62 (p = 0.002) in the platelet gate. ADP increased platelet activation at baseline, but did not further increase platelet reactivity during the invasive procedure in either groups. Percutaneous coronary interventions, performed in 10 patients (6 in the RIPC group and 4 in controls), did not have any further significant effect on platelet activation and reactivity compared with CA alone. In conclusion, RIPC reduces platelet activation occurring during CA. In contrast, no effects were observed on platelet response to ADP stimulation, probably related to the administration of an ADP antagonist in all patients. PMID:26739396

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

    PubMed

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

    2015-11-01

    This study investigated the effects of ischemic preconditioning (IPC) on the ratings of perceived exertion (RPE), surface electromyography, and pulmonary oxygen uptake (V?o2) onset kinetics during cycling until exhaustion at the peak power output attained during an incremental test. A group of 12 recreationally trained cyclists volunteered for this study. After determination of peak power output during an incremental test, they were randomly subjected on different days to a performance protocol preceded by intermittent bilateral cuff pressure inflation to 220 mmHg (IPC) or 20 mmHg (control). To increase data reliability, the performance visits were replicated, also in a random manner. There was an 8.0% improvement in performance after IPC (control: 303 s, IPC 327 s, factor SDs of /1.13, P = 0.01). This change was followed by a 2.9% increase in peak V?o2 (control: 3.95 l/min, IPC: 4.06 l/min, factor SDs of /1.15, P = 0.04), owing to a higher amplitude of the slow component of the V?o2 kinetics (control: 0.45 l/min, IPC: 0.63 l/min, factor SDs of /2.21, P = 0.05). There was also an attenuation in the rate of increase in RPE (P = 0.01) and a progressive increase in the myoelectrical activity of the vastus lateralis muscle (P = 0.04). Furthermore, the changes in peak V?o2 (r = 0.73, P = 0.007) and the amplitude of the slow component (r = 0.79, P = 0.002) largely correlated with performance improvement. These findings provide a link between improved aerobic metabolism and enhanced severe-intensity cycling performance after IPC. Furthermore, the delayed exhaustion after IPC under lower RPE and higher skeletal muscle activation suggest they have a role on the ergogenic effects of IPC on endurance performance. PMID:26359484

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

    PubMed Central

    Murphy, Elizabeth

    2010-01-01

    As a G protein-coupled receptor, the extracellular Ca2+-sensing receptor (CaSR) responds to changes not only in extracellular Ca2+, 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, 1216 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-3?, 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. PMID:20833954

  7. 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?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) PMID:23051145

  8. 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 ? (AMPK?) and phosphorylated AMPK? 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

  9. The remote ischemic preconditioning algorithm: effect of number of cycles, cycle duration and effector organ mass on efficacy of protection.

    PubMed

    Johnsen, Jacob; Pryds, Kasper; Salman, Rasha; Lfgren, Bo; Kristiansen, Steen Buus; Btker, Hans Erik

    2016-03-01

    Remote ischemic preconditioning (rIPC), induced by cycles of transient limb ischemia and reperfusion (IR), is cardioprotective. The optimal rIPC-algorithm is not established. We investigated the effect of cycle numbers and ischemia duration within each rIPC-cycle and the influence of effector organ mass on the efficacy of cardioprotection. Furthermore, the duration of the early phase of protection by rIPC was investigated. Using a tourniquet tightened at the inguinal level, we subjected C57Bl/6NTac mice to intermittent hind-limb ischemia and reperfusion. The rIPC-protocols consisted of (I) two, four, six or eight cycles, (II) 2, 5 or 10min of ischemia in each cycle, (III) single or two hind-limb occlusions and (IV) 0.5, 1.5, 2.0 or 2.5h intervals from rIPC to index cardiac ischemia. All rIPC algorithms were followed by 5min of reperfusion. The hearts were subsequently exposed to 25min of global ischemia and 60min of reperfusion in an ex vivo Langendorff model. Cardioprotection was evaluated by infarct size and post-ischemic hemodynamic recovery. Four to six rIPC cycles yielded significant cardioprotection with no further protection by eight cycles. Ischemic cycles lasting 2min offered the same protection as cycles of 5min ischemia, whereas prolonged cycles lasting 10min abrogated protection. One and two hind-limb preconditioning were equally protective. In our mouse model, the duration of protection by rIPC was 1.5h. These findings indicate that the number and duration of cycles rather than the tissue mass exposed to rIPC determines the efficacy of rIPC. PMID:26768477

  10. Glyburide enhancement of lactate production in ischemic heart is modified by preconditioning: an in vivo experimental study in pigs by microdialysis technique.

    PubMed

    Wikstrm, B G; Ronquist, G; Waldenstrm, A

    1996-05-01

    The concentrations of lactate, pyruvate, and adenosine, together with some of their derivatives, were determined in microdialysates from 12 pig hearts, 6 of which were subjected to preconditioning and 40 min of ischemia (index ischemia) and 6 of which were subjected to only 40 min of index ischemia. Two microdialysis probes were inserted in ischemic myocardium. Glyburide (10 mu M) in a modified isotonic Krebs-Ringer phosphate buffer was administered through one of the probes and plain isotonic phosphate buffer was administered through the other. Accordingly, the experimental setup permitted us to study the metabolic effects of glyburide on ischemic myocardium constituting two groups that were either preconditioned or unpreconditioned. The preconditioning effect was validated with area at risk and infarction area measurements in 12 other pigs. We noted no functional differences between the groups. In the unpreconditioned group glyburide infusion resulted in enhanced 60% lactate production during index ischemia. However, preconditioning attenuated the enhancing effect of glyburide on lactate production. The interplay between the effects of glyburide and preconditioning on ischemic myocardium is suggested to be dependent on the different modes of action on the K(+)(ATP) channel. PMID:8859930

  11. Ischemic preconditioning protects hippocampal pyramidal neurons from transient ischemic injury via the attenuation of oxidative damage through upregulating heme oxygenase-1.

    PubMed

    Lee, Jae-Chul; Kim, In Hye; Park, Joon Ha; Ahn, Ji Hyeon; Cho, Jeong-Hwi; Cho, Geum-Sil; Tae, Hyun-Jin; Chen, Bai Hui; Yan, Bing Chun; Yoo, Ki-Yeon; Choi, Jung Hoon; Lee, Choong Hyun; Hwang, In Koo; Cho, Jun Hwi; Kwon, Young-Guen; Kim, Young-Myeong; Won, Moo-Ho

    2015-02-01

    Ischemic preconditioning (IPC) provides neuroprotection against subsequent severe ischemic injury by activating specific mechanisms. In this study, we tested the hypothesis that IPC attenuates postischemic neuronal death via heme oxygenase-1 (HO-1). Animals used in this study were randomly assigned to 4 groups; sham-operated group, ischemia-operated group, IPC plus (+) sham-operated group and IPC+ischemia-operated group. IPC was induced by subjecting gerbils to 2min of ischemia followed by 1 day of recovery. A significant loss of neurons was observed in pyramidal neurons of the hippocampal CA1 region (CA1) in the ischemia-operated groups at 5 days postischemia. In the IPC+ischemia-operated groups, CA1 pyramidal neurons were well protected. The level of HO-1 protein and its activity increased significantly in the CA1 of the IPC+sham-operated group, and the level and activity was maintained in all the time after ischemia-reperfusion compared with the ischemia-operated groups. HO-1 immunoreactivity was induced in the CA1 pyramidal neurons in both IPC+sham-operated- and IPC+ischemia-operated groups. We also found that levels or immunoreactivities of superoxide anion, 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal were significantly decreased in the CA1 of both IPC+sham-operated- and IPC+ischemia-operated groups. Whereas, treatment with zinc protoporphyrin IX (a HO-1 inhibitor) into the IPC+ischemia-operated groups did not preserve the IPC-mediated increase of HO-1 and lost beneficial effects of IPC by inhibiting ischemia-induced DNA damage and lipid peroxidation. In brief, IPC protects CA1 pyramidal neurons from ischemic injury by upregulating HO-1, and we suggest that the enhancement of HO-1 expression by IPC may be a legitimate strategy for a therapeutic intervention of cerebral ischemic damage. PMID:25483558

  12. 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...

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

    PubMed Central

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

    2015-01-01

    Background Ischemic preconditioning (IPC) of the heart is a protective strategy in which a brief ischemic stimulus immediately before a lethal ischemic episode potently limits infarct size. Although very promising in animal models of myocardial infarction, IPC has not yet been successfully translated to benefit for patients. Objective To appraise all preclinical evidence on IPC for myocardial infarction and identify factors hampering translation. Methods and results Using systematic review and meta-analysis, we identified 503 animal studies reporting infarct size data from 785 comparisons between IPC-treated and control animals. Overall, IPC reduced myocardial infarction by 24.6% [95%CI 23.5, 25.6]. Subgroup analysis showed that IPC efficacy was reduced in comorbid animals and non-rodents. Efficacy was highest in studies using 23 IPC cycles applied <45 minutes before myocardial infarction. Local and remote IPC were equally effective. Reporting of study quality indicators was low: randomization, blinding and a sample size calculation were reported in 49%, 11% and 2% of publications, respectively. Conclusions Translation of IPC to the clinical setting may be hampered by the observed differences between the animals used in preclinical IPC studies and the patient population, regarding comorbidity, sex and age. Furthermore, the IPC protocols currently used in clinical trials could be optimized in terms of timing and the number of ischemic cycles applied. In order to inform future clinical trials successfully, future preclinical studies on IPC should aim to maximize both internal and external validity, since poor methodological quality may limit the value of the preclinical evidence. PMID:26580958

  14. Remote ischemic precondition prevents radial artery endothelial dysfunction induced by ischemia and reperfusion based on a cyclooxygenase-2-dependent mechanism

    PubMed Central

    Liu, Zhen-Bing; Yang, Wen-Xia; Fu, Xiang-Hua; Zhao, Lin-Feng; Gao, Jun-Ling

    2015-01-01

    Ischemic preconditioning (IPC) and remote ischemic precondition (RIPC) are resistance to ischemia-reperfusion (IR) injury. They have common protective mechanism. Cyclooxygenase (COX)-2 participate in the mechanism of IPC. So, the purpose of this study was to determine whether RIPC protects endothelial function of radial artery in human against IR and whether COX-2 involves in this effect. Endothelial IR injury was induced by arm ischemia (20 min) and reperfusion. Flow-mediated dilation (FMD) of the radial artery was measured before and after IR. RIPC (three 5-min cycles of ischemia of the contralateral arm) was applied immediately and 24 h before IR. All volunteers received the COX-2 inhibitor celecoxib (200 mg orally twice daily) for 5 days. On day 6, all subjects experienced the same studies as described. FMD was reduced by IR without administration of RIPC (P<0.0001). RIPC prevent this impairment of FMD immediately (P=NS) and at 24 h (P=NS). Nevertheless, the COX-2 inhibiter abolished protective effect of RIPC at 24 h (P=NS), but not immediately (P=0.001). After administration of the COX-2 inhibiter, post-IR FMD after RIPC performed immediately had significant increase than after RIPC performed at 24 h (P=0.001) and without administration of RIPC (P=0.003). The COX-2 inhibiter made post-IR FMD evidently decrease after RIPC performed at 24 h (P=0.002). RIPC prevents radial artery endothelial dysfunction induced by IR. This protective effect of RIPC in the late phase is mediated by a COX-2-dependent mechanism. PMID:26885023

  15. Renoprotective Mechanism of Remote Ischemic Preconditioning Based on Transcriptomic Analysis in a Porcine Renal Ischemia Reperfusion Injury Model

    PubMed Central

    Kim, Sook Young; Cho, Young In; Lee, Kwang Suk; Kim, Kwang Hyun; Yang, Seung Choul; Han, Woong Kyu

    2015-01-01

    Ischemic preconditioning (IPC) is a well-known phenomenon in which tissues are exposed to a brief period of ischemia prior to a longer ischemic event. This technique produces tissue tolerance to ischemia reperfusion injury (IRI). Currently, IPCs mechanism of action is poorly understood. Using a porcine single kidney model, we performed remote IPC with renal IRI and evaluated the IPC mechanism of action. Following left nephrectomy, 15 female Yorkshire pigs were divided into three groups: no IPC and 90 minutes of warm ischemia (control), remote IPC immediately followed by 90 minutes of warm ischemia (rIPCe), and remote IPC with 90 minutes of warm ischemia performed 24 hours later (rIPCl). Differential gene expression analysis was performed using a porcine-specific microarray. The microarray analysis of porcine renal tissues identified 1,053 differentially expressed probes in preconditioned pigs. Among these, 179 genes had altered expression in both the rIPCe and rIPCl groups. The genes were largely related to oxidation reduction, apoptosis, and inflammatory response. In the rIPCl group, an additional 848 genes had altered expression levels. These genes were primarily related to immune response and inflammation, including those coding for cytokines and cytokine receptors and those that play roles in the complement system and coagulation cascade. In the complement system, the membrane attack complex was determined to be sublytic, because it colocalized with phosphorylated extracellular signal-regulated kinase. Furthermore, alpha 2 macroglobulin, tissue plasminogen activator, uterine plasmin trypsin inhibitor, and arginase-1 mRNA levels were elevated in the rIPCl group. These findings indicate that remote IPC produces renoprotective effects through multiple mechanisms, and these effects develop over a long timeframe rather than immediately following IPC. PMID:26489007

  16. 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

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

    PubMed

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

    2015-05-01

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

  18. Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C2H2 zinc finger protein

    PubMed Central

    Han, D.; Zhang, C.; Fan, W.J.; Pan, W.J.; Feng, D.M.; Qu, S.L.; Jiang, Z.S.

    2014-01-01

    Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C2H2 motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element. PMID:25493376

  19. Neuroprotective gene expression profiles in ischemic cortical cultures preconditioned with IGF-1 or bFGF.

    PubMed

    Yoshida, Erin; Atkinson, Trevor G; Chakravarthy, Balu

    2004-11-24

    The mechanisms underlying growth factor preconditioning of neurons are only partially elucidated, and no studies have been conducted in this area using a gene profiling approach. We used cDNA microarrays to compare the transcriptional profiles of cells preconditioned either with insulin-like growth factor I (IGF-1) or basic fibroblast growth factor (bFGF), to identify differentially regulated genes that may function in growth factor signaling, response to oxygen-glucose deprivation (OGD), and most importantly, cell survival. Primary rat cortical cultures were treated with bFGF or IGF-1 for 2, 24, or 24 h followed by OGD for 90 min, and compared with cells that were subject to OGD without growth factor pretreatment. Although the majority of surveyed genes were unchanged in all experimental treatments, 175 genes (10% of the cDNAs on the chip) were found to be differentially regulated in at least one of the treatment conditions. Hierarchical clustering of these 175 genes was used to identify four expression clusters: IGF-1 regulated, bFGF regulated, OGD regulated, and putative neuroprotective genes. Further analysis using realtime RT-PCR confirmed that we had identified genes that are regulated by single growth factors, as well as several more that are co-regulated by both IGF-1 and bFGF. These genes can influence neuronal survival by affecting diverse pathways such as growth factor signal transduction (CD44, DTR, DUSP6, EPS8, IGFBP3), DNA repair and transcription (FOXJ1), metabolic homeostasis (RASA1, SHMT2), cytoskeletal stability (MSN, MAPT) and cholesterol biosynthesis (FDFT1, FDPS). PMID:15530650

  20. Hypoxia-inducible factor 1 transcriptional activity in endothelial cells is required for acute phase cardioprotection induced by ischemic preconditioning.

    PubMed

    Sarkar, Kakali; Cai, Zheqing; Gupta, Rigu; Parajuli, Nirmal; Fox-Talbot, Karen; Darshan, Medha S; Gonzalez, Frank J; Semenza, Gregg L

    2012-06-26

    Infarction occurs when myocardial perfusion is interrupted for prolonged periods of time. Short episodes of ischemia and reperfusion protect against tissue injury when the heart is subjected to a subsequent prolonged ischemic episode, a phenomenon known as ischemic preconditioning (IPC). Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates adaptive responses to hypoxia/ischemia and is required for IPC. In this study, we performed a cellular and molecular characterization of the role of HIF-1 in IPC. We analyzed mice with knockout of HIF-1? or HIF-1? in Tie2(+) lineage cells, which include bone marrow (BM) and vascular endothelial cells, compared with control littermates. Hearts were subjected to 30 min of ischemia and 120 min of reperfusion, either as ex vivo Langendorff preparations or by in situ occlusion of the left anterior descending artery. The IPC stimulus consisted of two cycles of 5-min ischemia and 5-min reperfusion. Mice lacking HIF-1? or HIF-1? in Tie2(+) lineage cells showed complete absence of protection induced by IPC, whereas significant protection was induced by adenosine infusion. Treatment of mice with a HIF-1 inhibitor (digoxin or acriflavine) 4 h before Langendorff perfusion resulted in loss of IPC, as did administration of acriflavine directly into the perfusate immediately before IPC. We conclude that HIF-1 activity in endothelial cells is required for acute IPC. Expression and dimerization of the HIF-1? and HIF-1? subunits is required, suggesting that the heterodimer is functioning as a transcriptional activator, despite the acute nature of the response. PMID:22699503

  1. 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 57 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 57 days after surgery (p?=?0.753). The summarized Z score showed a trend to more cognitive decline in the control group (2.165.30) compared to the RIPC group (1.144.02; 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 (0.191.94) g/L vs. 0.48 (0.071.84) g/L] and 24 hours after surgery [0.36 (0.141.89) g/L vs. 0.26 (0.070.90) g/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

  2. Ischemic preconditioning does not improve peak exercise capacity at sea level or simulated high altitude in trained male cyclists.

    PubMed

    Hittinger, Elizabeth A; Maher, Jennifer L; Nash, Mark S; Perry, Arlette C; Signorile, Joseph F; Kressler, Jochen; Jacobs, Kevin A

    2015-01-01

    Ischemic preconditioning (IPC) may improve blood flow and oxygen delivery to tissues, including skeletal muscle, and has the potential to improve intense aerobic exercise performance, especially that which results in arterial hypoxemia. The aim of the study was to determine the effects of IPC of the legs on peak exercise capacity (W(peak)), submaximal and peak cardiovascular hemodynamics, and peripheral capillary oxygen saturation (SpO2) in trained males at sea level (SL) and simulated high altitude (HA; 13.3% FIO2, ? 3650 m). Fifteen highly trained male cyclists and triathletes completed 2 W(peak) tests (SL and HA) and 4 experimental exercise trials (10 min at 55% altitude-specific W(peak) then increasing by 30 W every 2 min until exhaustion) with and without IPC. HA resulted in significant arterial hypoxemia during exercise compared with SL (73% 6% vs. 93% 4% SpO2, p < 0.001) that was associated with 21% lower W(peak) values. IPC did not significantly improve W(peak) at SL or HA. Additionally, IPC failed to improve cardiovascular hemodynamics or SpO2 during submaximal exercise or at W(peak). In conclusion, IPC performed 45 min prior to exercise does not improve W(peak) or systemic oxygen delivery during submaximal or peak exercise at SL or HA. Future studies must examine the influence of IPC on local factors, such as working limb blood flow, oxygen delivery, and arteriovenous oxygen difference as well as whether the effectiveness of IPC is altered by the volume of muscle made ischemic, the timing prior to exercise, and high altitude acclimatization. PMID:25474566

  3. Review and meta-analysis of randomized controlled clinical trials of remote ischemic preconditioning in cardiovascular surgery.

    PubMed

    Takagi, Hisato; Manabe, Hideaki; Kawai, Norikazu; Goto, Shin-Nosuke; Umemoto, Takuya

    2008-12-01

    To determine whether remote ischemic preconditioning (RIPC) is beneficial for patients who undergo cardiovascular surgery (CVS), a systematic review and meta-analysis of randomized controlled clinical trials of RIPC for the prevention of myocardial injury in CVS was performed. All prospective randomized controlled clinical trials of RIPC versus control that enrolled patients who underwent CVS were identified using a 2-level search strategy. First, a public-domain database (Medline) was searched using a Web-based search engine (PubMed). Second, relevant studies were identified through a manual search of secondary sources, including references of initially identified reports and a search of reviews and commentaries. The search identified 4 prospective randomized controlled clinical trials of RIPC versus control that enrolled patients who underwent CVS. In total, this meta-analysis included data on 184 patients who underwent CVS randomized to RIPC or control. Pooled analysis of the 4 trials demonstrated a statistically significant reduction in biomarkers of myocardial injury with RIPC relative to control (standardized mean difference -0.81, 95% confidence interval -1.29 to -0.33, p = 0.0010). In conclusion, the present study, the first systematic review and meta-analysis of randomized controlled clinical trials, demonstrated a statistically significant benefit of RIPC over control for reduction in biomarkers of myocardial injury in CVS patients. PMID:19026301

  4. A Sphingosine Kinase Form 2 Knockout Sensitizes Mouse Myocardium to Ischemia/Reoxygenation Injury and Diminishes Responsiveness to Ischemic Preconditioning

    PubMed Central

    Vessey, Donald A.; Li, Luyi; Jin, Zhu-Qiu; Kelley, Michael; Honbo, Norman; Zhang, Jianqing; Karliner, Joel S.

    2011-01-01

    Sphingosine kinase (SphK) exhibits two isoforms, SphK1 and SphK2. Both forms catalyze the synthesis of sphingosine 1-phosphate (S1P), a sphingolipid involved in ischemic preconditioning (IPC). Since the ratio of SphK1?:?SphK2 changes dramatically with aging, it is important to assess the role of SphK2 in IR injury and IPC. Langendorff mouse hearts were subjected to IR (30?min equilibration, 50?min global ischemia, and 40?min reperfusion). IPC consisted of 2?min of ischemia and 2?min of reperfusion for two cycles. At baseline, there were no differences in left ventricular developed pressure (LVDP), ?dP/dtmax, and heart rate between SphK2 null (KO) and wild-type (WT) hearts. In KO hearts, SphK2 activity was undetectable, and SphK1 activity was unchanged compared to WT. Total SphK activity was reduced by 53%. SphK2 KO hearts subjected to IR exhibited significantly more cardiac damage (37 1% infarct size) compared with WT (28 1% infarct size); postischemic recovery of LVDP was lower in KO hearts. IPC exerted cardioprotection in WT hearts. The protective effect of IPC against IR was diminished in KO hearts which had much higher infarction sizes (35 2%) compared to the IPC/IR group in control hearts (12 1%). Western analysis revealed that KO hearts had substantial levels of phosphorylated p38 which could predispose the heart to IR injury. Thus, deletion of the SphK2 gene sensitizes the myocardium to IR injury and diminishes the protective effect of IPC. PMID:21904650

  5. Effect of Remote Ischemic Preconditioning on Phosphorylated Protein Signaling in Children Undergoing Tetralogy of Fallot Repair: A Randomized Controlled Trial

    PubMed Central

    Pepe, Salvatore; Liaw, Norman Y.; Hepponstall, Michele; Sheeran, Freya L.; Yong, Matthew S.; d'Udekem, Yves; Cheung, Michael M.; Konstantinov, Igor E.

    2013-01-01

    Background Our previous randomized controlled trial demonstrated cardiorespiratory protection by remote ischemic preconditioning (RIPC) in children before cardiac surgery. However, the impact of RIPC on myocardial prosurvival intracellular signaling remains unknown in cyanosis. RIPC may augment phosphorylated protein signaling in myocardium and circulating leukocytes during tetralogy of Fallot (ToF) repair. Methods and Results Children (n=40) undergoing ToF repair were double?blind randomized to RIPC (n=11 boys, 9 girls) or control (sham RIPC: n=9 boys, 11 girls). Blood samples were taken before, immediately after, and 24 hours after cardiopulmonary bypass. Resected right ventricular outflow tract muscle and leukocytes were processed for protein expression and mitochondrial respiration. There was no difference in age (7.13.4 versus 7.13.4 months), weight (7.71.8 versus 7.51.9 kg), or bypass or aortic cross?clamp times between the groups (control versus RIPC, meanSD). No differences were seen between the groups for an increase in the ratio of phosphorylated to total protein for protein kinase B, p38 mitogen activated protein kinase, signal transducer and activator of transcription 3, glycogen synthase kinase 3?, heat shock protein 27, Connexin43, or markers associated with promotion of necrosis (serum cardiac troponin I), apoptosis (Bax, Bcl?2), and autophagy (Parkin, Beclin?1, LC3B). A high proportion of total proteins were in phosphorylated form in control and RIPC myocardium. In leukocytes, mitochondrial respiration and assessed protein levels did not differ between groups. Conclusions In patients with cyanotic heart disease, a high proportion of proteins are in phosphorylated form. RIPC does not further enhance phosphorylated protein signaling in myocardium or circulating leukocytes in children undergoing ToF repair. Clinical Trial Registration URL: (http://www.anzctr.org.au/trial_view.aspx?id=335613. Unique identifier: Australian New Zealand Clinical Trials Registry number ACTRN12610000496011. PMID:23666460

  6. Transcriptome Analysis of Renal Ischemia/Reperfusion Injury and Its Modulation by Ischemic Pre-Conditioning or Hemin Treatment

    PubMed Central

    Amano, Mariane Tami; Gonalves, Giselle Martins; Hyane, Meire Ioshie; Cenedeze, Marcos Antonio; Renesto, Paulo Guilherme; Pacheco-Silva, Alvaro; Moreira-Filho, Carlos Alberto; Cmara, Niels Olsen Saraiva

    2012-01-01

    Ischemia/reperfusion injury (IRI) is a leading cause of acute renal failure. The definition of the molecular mechanisms involved in renal IRI and counter protection promoted by ischemic pre-conditioning (IPC) or Hemin treatment is an important milestone that needs to be accomplished in this research area. We examined, through an oligonucleotide microarray protocol, the renal differential transcriptome profiles of mice submitted to IRI, IPC and Hemin treatment. After identifying the profiles of differentially expressed genes observed for each comparison, we carried out functional enrichment analysis to reveal transcripts putatively involved in potential relevant biological processes and signaling pathways. The most relevant processes found in these comparisons were stress, apoptosis, cell differentiation, angiogenesis, focal adhesion, ECM-receptor interaction, ion transport, angiogenesis, mitosis and cell cycle, inflammatory response, olfactory transduction and regulation of actin cytoskeleton. In addition, the most important overrepresented pathways were MAPK, ErbB, JAK/STAT, Toll and Nod like receptors, Angiotensin II, Arachidonic acid metabolism, Wnt and coagulation cascade. Also, new insights were gained about the underlying protection mechanisms against renal IRI promoted by IPC and Hemin treatment. Venn diagram analysis allowed us to uncover common and exclusively differentially expressed genes between these two protective maneuvers, underscoring potential common and exclusive biological functions regulated in each case. In summary, IPC exclusively regulated the expression of genes belonging to stress, protein modification and apoptosis, highlighting the role of IPC in controlling exacerbated stress response. Treatment with the Hmox1 inducer Hemin, in turn, exclusively regulated the expression of genes associated with cell differentiation, metabolic pathways, cell cycle, mitosis, development, regulation of actin cytoskeleton and arachidonic acid metabolism, suggesting a pleiotropic effect for Hemin. These findings improve the biological understanding of how the kidney behaves after IRI. They also illustrate some possible underlying molecular mechanisms involved in kidney protection observed with IPC or Hemin treatment maneuvers. PMID:23166714

  7. Characterization of acute ischemia?related physiological responses associated with remote ischemic preconditioning: a randomized controlled, crossover human study

    PubMed Central

    Sharma, Vikram; Cunniffe, Brian; Verma, Amit P.; Cardinale, Marco; Yellon, Derek

    2014-01-01

    Abstract Remote Ischemic Preconditioning (RIPC) is emerging as a new noninvasive intervention that has the potential to protect a number of organs against ischemiareperfusion (IR) injury. The standard protocols normally used to deliver RIPC involve a number of cycles of inflation of a blood pressure (BP) cuff on the arm and/or leg to an inflation pressure of 200 mmHg followed by cuff deflation for a short period of time. There is little evidence to support what limb (upper or lower) or cuff inflation pressures are most effective to deliver this intervention without causing undue discomfort/pain in nonanesthetized humans. In this preliminary study, a doseresponse assessment was performed using a range of cuff inflation pressures (140, 160, and 180 mmHg) to induce limb ischemia in upper and lower limbs. Physiological changes in the occluded limb and any pain/discomfort associated with RIPC with each cuff inflation pressure were determined. Results showed that ischemia can be induced in the upper limb at much lower cuff inflation pressures compared with the standard 200 mmHg pressure generally used for RIPC, provided the cuff inflation pressure is ~30 mmHg higher than the resting systolic BP. In the lower limb, a higher inflation pressure, (~55 mmHg > resting systolic BP), is required to induce ischemia. Cyclical changes in capillary blood O2, CO2, and lactate levels during the RIPC stimulus were observed. RIPC at higher cuff inflation pressures of 160 and 180 mmHg was better tolerated in the upper limb. In summary, limb ischemia for RIPC can be more easily induced at lower pressures and is much better tolerated in the upper limb in young healthy individuals. However, whether benefits of RIPC can also be derived with protocols delivered to the upper limb using lower cuff inflation pressures and with lesser discomfort compared to the lower limb, remains to be investigated. PMID:25413320

  8. Transcriptome analysis of renal ischemia/reperfusion injury and its modulation by ischemic pre-conditioning or hemin treatment.

    PubMed

    Correa-Costa, Matheus; Azevedo, Htylas; Amano, Mariane Tami; Gonalves, Giselle Martins; Hyane, Meire Ioshie; Cenedeze, Marcos Antonio; Renesto, Paulo Guilherme; Pacheco-Silva, Alvaro; Moreira-Filho, Carlos Alberto; Cmara, Niels Olsen Saraiva

    2012-01-01

    Ischemia/reperfusion injury (IRI) is a leading cause of acute renal failure. The definition of the molecular mechanisms involved in renal IRI and counter protection promoted by ischemic pre-conditioning (IPC) or Hemin treatment is an important milestone that needs to be accomplished in this research area. We examined, through an oligonucleotide microarray protocol, the renal differential transcriptome profiles of mice submitted to IRI, IPC and Hemin treatment. After identifying the profiles of differentially expressed genes observed for each comparison, we carried out functional enrichment analysis to reveal transcripts putatively involved in potential relevant biological processes and signaling pathways. The most relevant processes found in these comparisons were stress, apoptosis, cell differentiation, angiogenesis, focal adhesion, ECM-receptor interaction, ion transport, angiogenesis, mitosis and cell cycle, inflammatory response, olfactory transduction and regulation of actin cytoskeleton. In addition, the most important overrepresented pathways were MAPK, ErbB, JAK/STAT, Toll and Nod like receptors, Angiotensin II, Arachidonic acid metabolism, Wnt and coagulation cascade. Also, new insights were gained about the underlying protection mechanisms against renal IRI promoted by IPC and Hemin treatment. Venn diagram analysis allowed us to uncover common and exclusively differentially expressed genes between these two protective maneuvers, underscoring potential common and exclusive biological functions regulated in each case. In summary, IPC exclusively regulated the expression of genes belonging to stress, protein modification and apoptosis, highlighting the role of IPC in controlling exacerbated stress response. Treatment with the Hmox1 inducer Hemin, in turn, exclusively regulated the expression of genes associated with cell differentiation, metabolic pathways, cell cycle, mitosis, development, regulation of actin cytoskeleton and arachidonic acid metabolism, suggesting a pleiotropic effect for Hemin. These findings improve the biological understanding of how the kidney behaves after IRI. They also illustrate some possible underlying molecular mechanisms involved in kidney protection observed with IPC or Hemin treatment maneuvers. PMID:23166714

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

    PubMed

    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

    2015-10-01

    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

  10. Ischemic preconditioning accelerates muscle deoxygenation dynamics and enhances exercise endurance during the work-to-work test

    PubMed Central

    Kido, Kohei; Suga, Tadashi; Tanaka, Daichi; Honjo, Toyoyuki; Homma, Toshiyuki; Fujita, Satoshi; Hamaoka, Takafumi; Isaka, Tadao

    2015-01-01

    Ischemic preconditioning (IPC) improves maximal exercise performance. However, the potential mechanism(s) underlying the beneficial effects of IPC remain unknown. The dynamics of pulmonary oxygen uptake (VO2) and muscle deoxygenation during exercise is frequently used for assessing O2 supply and extraction. Thus, this study examined the effects of IPC on systemic and local O2 dynamics during the incremental step transitions from low- to moderate- and from moderate- to severe-intensity exercise. Fifteen healthy, male subjects were instructed to perform the work-to-work cycling exercise test, which was preceded by the control (no occlusion) or IPC (3 × 5 min, bilateral leg occlusion at >300 mmHg) treatments. The work-to-work test was performed by gradually increasing the exercise intensity as follows: low intensity at 30 W for 3 min, moderate intensity at 90% of the gas exchange threshold (GET) for 4 min, and severe intensity at 70% of the difference between the GET and VO2 peak until exhaustion. During the exercise test, the breath-by-breath pulmonary VO2 and near-infrared spectroscopy-derived muscle deoxygenation were continuously recorded. Exercise endurance during severe-intensity exercise was significantly enhanced by IPC. There were no significant differences in pulmonary VO2 dynamics between treatments. In contrast, muscle deoxygenation dynamics in the step transition from low- to moderate-intensity was significantly faster in IPC than in CON (27.2 ± 2.9 vs. 19.8 ± 0.9 sec, P < 0.05). The present findings showed that IPC accelerated muscle deoxygenation dynamics in moderate-intensity exercise and enhanced severe-intensity exercise endurance during work-to-work test. The IPC-induced effects may result from mitochondrial activation in skeletal muscle, as indicated by the accelerated O2 extraction. PMID:25952936

  11. 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

  12. Remote ischemic preconditioning with a specialized protocol activates the non-neuronal cardiac cholinergic system and increases ATP content in the heart.

    PubMed

    Oikawa, Shino; Mano, Asuka; Takahashi, Rina; Kakinuma, Yoshihiko

    2015-11-01

    Ischemic preconditioning (IPC) renders the targeted organ resistant to prolonged ischemic insults, leading to organoprotection. Among several means to achieve IPC, we reported that remote ischemic preconditioning (RIPC) activates the non-neuronal cardiac cholinergic system (NNCCS) to accelerate de novo ACh synthesis in cardiomyocytes. In the current study, we aimed to optimize a specific protocol to most efficiently activate NNCCS using RIPC. In this study, we elucidated that the protocol with 3 min of ischemia repeated three times increased cardiac ChAT expression (139.2 0.4%; P < 0.05) as well as ACh (14.2 2.0 10(-8) M; P< 0.05) and ATP content (2.13 0.19 ?mol/g tissue; P < 0.05) in the heart. Moreover, in the specific protocol, several characteristic responses against energy starvation and for obtaining adequate energy were observed; therefore, it is suggested that RIPC evokes a robust response by the heart to activate NNCCS through the modification of energy metabolism. PMID:26072685

  13. Response of secretory pathways Ca(2+) ATPase gene expression to hyperhomocysteinemia and/or ischemic preconditioning in rat cerebral cortex and hippocampus.

    PubMed

    Pavlikova, Martina; Kovalska, Maria; Tatarkova, Zuzana; Sivonova-Kmetova, Monika; Kaplan, Peter; Lehotsky, Jan

    2011-01-01

    The study determines whether hyperhomocysteinemia (risk factor of brain ischemia) alone or in combination with ischemic preconditioning (IPC) affects the ischemia-induced changes in gene expression of secretory pathways Ca(2+)-ATPase (SPCA1). Hyperhomocysteinemia was induced by subcutaneous administration of homocysteine (Hcy; 0.45 µmol/g body weight) twice a day at 8 h intervals for 14 days. Rats were preconditioned by 5 min ischemia and 2 days later, 15 min of global forebrain ischemia was induced by four vessel occlusion. We observed that hyperhomocysteinemia significantly decreased the level of SPCA1 mRNA in the cortex. Pre-ischemic challenge was noticeable in both brain areas. In the cortex, pre-ischemia in Hcy group led to the abrupt stimulation of the mRNA expression by 249% within the Hcy ischemic group and by 321% in the Hcy control. Values further exceeded those observed in the naive control. In the hippocampus, the differences between naive and Hcy groups were not observed. IPC initiated elevation of mRNA expression to 159% (p < 0.05) of control with Hcy and to 131% (p < 0.01) of ischemia with Hcy, respectively. Documented response of SPCA gene to IPC in hyperhomocysteinemic group might suggest a correlation of SPCA expression consistent with the role of cross-talks between intracellular Ca(2+) stores including secretory pathways in the tolerance phenomenon. PMID:21869453

  14. Near infrared spectroscopy (NIRS) to assess the effects of local ischemic preconditioning in the muscle of healthy volunteers and critically ill patients.

    PubMed

    Orbegozo Corts, Diego; Puflea, Florin; De Backer, Daniel; Creteur, Jacques; Vincent, Jean-Louis

    2015-11-01

    Near-infrared spectroscopy (NIRS) permits non-invasive evaluation of tissue oxygen saturation (StO2). A vascular occlusion test (VOT) produces transient controlled ischemia similar to that used in ischemic preconditioning. We hypothesized that we could evaluate local responses to ischemic preconditioning by performing repeated VOTs and observing the changes in different NIRS VOT-derived variables. In healthy volunteers (n=20), four VOTs were performed at 30-min intervals on one day and, in a second group (n=21), two VOTs with time intervals of 5, 15 or 30min were performed on 3 separate days. Two cohorts of patients, one with circulatory shock (n=23) and a hemodynamically stable group (n=20), were also studied, repeating the VOT twice with a 5-min interval. In the 1-day volunteers, there was a median decrease of 15 (6-21)% in the Desc slope (StO2 decrease during VOT) after the second VOT, but no significant change in the Asc slope (StO2 increase after VOT). In the 3-day volunteers, the Desc slope also decreased, regardless of the time interval between VOTs. There was no overall decrease in the Desc slope in either patient cohort with repeated VOTs but there was marked individual patient variability. Patients in whom the Desc slope decreased had less organ dysfunction at admission, required less norepinephrine (0.00 vs 0.08mcg/kg/min, p=0.02), less frequently had sepsis (12 vs 50%, p=0.02) and had a lower mortality (6 vs 39%, p=0.03) compared to those in whom it did not decrease. Repeated NIRS VOT can non-invasively assess the local effects of ischemic preconditioning in the muscle. PMID:26265192

  15. 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

  16. 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 neurological dysfunction with improved survival by activation of the K(ATP) channel. PMID:25122082

  17. Remote ischemic preconditioning of cardiomyocytes inhibits the mitochondrial permeability transition pore independently of reduced calcium?loading or sarcKATP channel activation

    PubMed Central

    Turrell, Helen E.; Thaitirarot, Chokanan; Crumbie, Hayley; Rodrigo, Glenn

    2014-01-01

    Abstract Ischemic preconditioning (IPC) inhibits Ca2+?loading during ischemia which contributes to cardioprotection by inhibiting mechanical injury due to hypercontracture and biochemical injury through mitochondrial permeability transition (MPT) pores during reperfusion. However, whether remote?IPC reduced Ca2+?loading during ischemia and its subsequent involvement in inhibiting MPT pore formation during reperfusion has not been directly shown. We have developed a cellular model of remote IPC to look at the impact of remote conditioning on Ca2+?regulation and MPT pore opening during simulated ischemia and reperfusion, using fluorescence microscopy. Ventricular cardiomyocytes were isolated from control rat hearts, hearts preconditioned with three cycles of ischemia/reperfusion or nave myocytes remotely conditioned with effluent collected from preconditioned hearts. Both conventional?IPC and remote?IPC reduced the loss of Ca2+?homeostasis and contractile function following reenergization of metabolically inhibited cells and protected myocytes against ischemia/reperfusion injury. However, only conventional?IPC reduced the Ca2+?loading during metabolic inhibition and this was independent of any change in sarcKATP channel activity but was associated with a reduction in Na+?loading, reflecting a decrease in Na/H exchanger activity. Remote?IPC delayed opening of the MPT pores in response to ROS, which was dependent on PKC? and NOS?signaling. These data show that remote?IPC inhibits MPT pore opening to a similar degree as conventional IPC, however, the contribution of MPT pore inhibition to protection against reperfusion injury is independent of Ca2+?loading in remote IPC. We suggest that inhibition of the MPT pore and not Ca2+?loading is the common link in cardioprotection between conventional and remote IPC. PMID:25428953

  18. Acute inhibition of monoamine oxidase and ischemic preconditioning in isolated rat hearts: interference with postischemic functional recovery but no effect on infarct size reduction.

    PubMed

    D?nil?, Maria D; Privistirescu, Andreea I; Mirica, Silvia N; Sturza, Adrian; Ordodi, Valentin; Noveanu, Lavinia; Duicu, Oana M; Muntean, Danina M

    2015-09-01

    Monoamine oxidases (MAOs) have recently emerged as important mitochondrial sources of oxidative stress in the cardiovascular system. Generation of reactive oxygen species during the brief episodes of ischemic preconditioning (IPC) is responsible for the cardioprotection at reperfusion. The aim of this study was to assess the effects of two MAO inhibitors (clorgyline and pargyline) on the IPC-related protection in isolated rat hearts. Animals subjected to 30 min global ischemia and 120 min reperfusion were assigned to the following groups: (i) Control, no additional intervention; (ii) IPC, 3 cycles of 5 min ischemia and 5 min reperfusion before the index ischemia; (iii) IPC-clorgyline, IPC protocol bracketed for 5 min with clorgyline (50 ?mol/L); (iv) IPC-pargyline, IPC protocol bracketed for 5 min with pargyline (0.5 mmol/L). The postischemic functional recovery was assessed by the left ventricular developed pressure (LVDP) and the indices of contractility (+dLVP/dt max) and relaxation (-dLVP/dt max). Infarct size (IS) was quantified by TTC staining. In both genders, IPC significantly improved functional recovery that was further enhanced in the presence of either clorgyline or pargyline. IS reduction was comparable among all the preconditioned groups, regardless of the presence of MAO inhibitors. In isolated rat hearts, acute inhibition of MAOs potentiates the IPC-induced postischemic functional recovery without interfering with the anti-necrotic protection. PMID:26322912

  19. Remote limb ischemic preconditioning (rIPC) activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in renal ischemia/reperfusion injury.

    PubMed

    Hussein, Abdelaziz M; Harraz, Ahmed M; Awadalla, Amira; Barakat, Nashwa; Khater, Shery; Shokeir, Ahmed A

    2016-01-01

    The mechanisms underlying the renoprotective effect for remote limb ischemic preconditioning (rIPC) against renal ischemia/reperfusion injury need further elucidation. In our work, one hundred and twenty male Sprague Dawley rats were randomized into 3 groups; sham, I/R group (left renal 45 min ischemia) and rIPC (as I/R group with 3 cycles of left femoral ischemic PC just before renal ischemia). Rats were sacrificed at 2 h, 24 h, 48 h and 7 days. Serum creatinine and urea were measured at the baseline and endpoints. Also, histopathological examination and assessment of the expression of inflammatory cytokines e.g. TNF-α, IL-1β and ICAM-1 and antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 in left kidney were done by the end of experiment. The results of this study demonstrated that, rIPC caused significant improvement in serum creatinine and BUN levels and in the expression of antioxidant genes and Bcl-2 antiapoptotic gene with significant attenuation of pro-inflammatory cytokines and histopathological damage score at all-time points compared to I/R group (p ≤ 0.05). In conclusion, inhibition of inflammatory cytokine (TNF-α, IL-1β and ICAM-1) formation and activation of antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 could be possible underlying mechanisms for the renoprotective effect of rIPC. PMID:26612920

  20. Ischemic preconditioning protects neurons from damage and maintains the immunoreactivity of kynurenic acid in the gerbil hippocampal CA1 region following transient cerebral ischemia

    PubMed Central

    LEE, JAE-CHUL; TAE, HYUN-JIN; CHO, GEUM-SIL; KIM, IN HYE; AHN, JI HYEON; PARK, JOON HA; CHEN, BAI HUI; CHO, JEONG-HWI; SHIN, BICH NA; CHO, JUN HWI; BAE, EUN JOO; PARK, JINSEU; KIM, YOUNG-MYEONG; CHOI, SOO YOUNG; WON, MOO-HO

    2015-01-01

    Pyramidal neurons in region I of hippocampus proper (CA1) are particularly vulnerable to excitotoxic processes following transient forebrain ischemia. Kynurenic acid (KYNA) is a small molecule derived from tryptophan when this amino acid is metabolized through the kynurenine pathway. In the present study, we examined the effects of ischemic preconditioning (IPC) on the immunoreactivity and protein levels of KYNA following 5 min of transient forebrain ischemia in gerbils. The animals were randomly assigned to 4 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, we observed a significant loss of pyramidal neurons in the CA1 stratum pyramidale (SP) at 5 days post-ischemia; however, in the IPC + ischemia-operated group, the pyramidal neurons were well protected. KYNA immunoreactivity in the SP of the ischemia-operated group was significantly altered following ischemia-reperfusion and was very low 5 days following ischemia-reperfusion. In the IPC + ischemia-operated group, however, KYNA immunoreactivity was constitutively detected in the SP of the CA1 region after the ischemic insult. We also found that the alteration pattern of the KYNA protein level in the CA1 region following ischemia was generally similar to the immunohistochemical changes observed. In brief, our findings demonstrated that IPC maintained and even increased KYNA immunoreactivity in the SP of the CA1 region following ischemia-reperfusion. The data from the present study thus indicate that the enhancement of KYNA expression by IPC may be necessary for neuronal survival following transient ischemic injury. PMID:25872573

  1. Ischemic preconditioning protects neurons from damage and maintains the immunoreactivity of kynurenic acid in the gerbil hippocampal CA1 region following transient cerebral ischemia.

    PubMed

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

    2015-06-01

    Pyramidal neurons in region I of hippocampus proper (CA1) are particularly vulnerable to excitotoxic processes following transient forebrain ischemia. Kynurenic acid (KYNA) is a small molecule derived from tryptophan when this amino acid is metabolized through the kynurenine pathway. In the present study, we examined the effects of ischemic preconditioning (IPC) on the immunoreactivity and protein levels of KYNA following 5 min of transient forebrain ischemia in gerbils. The animals were randomly assigned to 4 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, we observed a significant loss of pyramidal neurons in the CA1 stratum pyramidale (SP) at 5 days post-ischemia; however, in the IPC + ischemia-operated group, the pyramidal neurons were well protected. KYNA immunoreactivity in the SP of the ischemia-operated group was significantly altered following ischemia-reperfusion and was very low 5 days following ischemia-reperfusion. In the IPC + ischemia-operated group, however, KYNA immunoreactivity was constitutively detected in the SP of the CA1 region after the ischemic insult. We also found that the alteration pattern of the KYNA protein level in the CA1 region following ischemia was generally similar to the immunohistochemical changes observed. In brief, our findings demonstrated that IPC maintained and even increased KYNA immunoreactivity in the SP of the CA1 region following ischemia-reperfusion. The data from the present study thus indicate that the enhancement of KYNA expression by IPC may be necessary for neuronal survival following transient ischemic injury. PMID:25872573

  2. [MIMICKING ISCHEMIC PRECONDITIONING PHENOMENON THROUGH THE IMPACT ON THE CANNABINOID RECEPTORS: ROLE OF PROTEIN KINASE AND NO-SYNTHASE].

    PubMed

    Lishmanov, Yu B; Maslov, L N; Krylatov, A V; Khaliulin, I G

    2015-08-01

    It was established that CB 1-receptors stimulation mimic preconditioning phenomena. Since the cardioprotective effect of cannabinoid HU-210 is occurred both in the experiments in vivo and in the experiments in vitro there are reasons to believe that the protective effect of HU-210 is me- diated via an activation of cardiac CB1-receptors. It is established that the cardioprotective effect of cannabinoid HU-2 10 is depends upon a stimulation ofprotein kinase C whereas NO-synthase is not involved in protective impact of CB1-receptor stimulation. PMID:26591586

  3. 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)-? 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 5days 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 5days 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-?) 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. PMID:26290267

  4. Effect of Remote Ischemic Preconditioning on Acute Kidney Injury in Nondiabetic Patients Undergoing Coronary Artery Bypass Graft Surgery: A Secondary Analysis of 2 Small Randomized Trials

    PubMed Central

    Venugopal, Vinod; Laing, Chris M.; Ludman, Andrew; Yellon, Derek M.; Hausenloy, Derek

    2010-01-01

    Background Novel treatment strategies are required to reduce the development of acute kidney injury (AKI) in patients undergoing cardiac surgery. In this respect, remote ischemic preconditioning (RIPC), a phenomenon in which transient nonlethal ischemia applied to an organ or tissue protects another organ or tissue from subsequent lethal ischemic injury, is a potential renoprotective strategy. Study Design Secondary analysis of 2 randomized trials. Setting & Participants 78 consenting selected nondiabetic patients in a university teaching hospital undergoing elective coronary artery bypass graft (CABG) surgery recruited to 2 previously reported randomized studies. Intervention RIPC consisted of three 5-minute cycles of right forearm ischemia, induced by inflating a blood pressure cuff on the upper arm to 200 mm Hg, with an intervening 5 minutes of reperfusion, during which time the cuff was deflated. The control consisted of placing an uninflated cuff on the arm for 30 minutes. Outcomes AKI measured using Acute Kidney Injury Network (AKIN) criteria, duration of hospital stay, in-hospital and 30-day mortality. Results Numbers of participants with AKI stages 1, 2, and 3 were 1 (3%), 3 (8%), and 0 in the intervention group compared with 10 (25%), 0, and 0 in the control group, respectively (P = 0.005). The decrease in AKI was independent of the effect of concomitant aortic valve replacement and cross-clamp times, which were distributed unevenly between the 2 groups. Limitations Retrospective analysis of data. More patients in the RIPC group underwent concomitant aortic valve replacement with CABG; although we have corrected statistically for this imbalance, it remains an important confounding variable. Conclusions RIPC induced using transient forearm ischemia decreased the incidence of AKI in nondiabetic patients undergoing elective CABG surgery in this retrospective analysis. A large prospective clinical trial is required to study this effect and clinical outcomes in patients undergoing cardiac surgery. PMID:20974511

  5. Time-dependent profiles of microRNA expression induced by ischemic preconditioning in the gerbil hippocampus.

    PubMed

    Sun, Miao; Yamashita, Toru; Shang, Jingwei; Liu, Ning; Deguchi, Kentaro; Feng, Juan; Abe, Koji

    2015-01-01

    MicroRNAs (miRNAs) are critically important in both normal neuronal development and neurological diseases. Although cerebral ischemia has been shown to alter the miRNA profiles of rats, the role of miRNA in the cornu ammonis 1 region of the gerbil hippocampus under ischemic tolerance has not been studied. In the present study, Mongolian gerbils were subjected to one or three times the nonlethal dose of 2-min transient common carotid artery occlusion (tCCAO). miRNA microarray technology detected 251 miRNAs and the expression of seven of these in terms of ischemic tolerance. They were compared at different time points: 1 day, 7 days, 1 month, and 6 months. mmu-miR-15a-5p, related to neurogenesis, showed increased expression after one dose of 2-min tCCAO and was much higher after three doses. An increase in sha-miR-24 and oan-let-7b-3p, related to transactivation response DNA-binding protein (TDP43), was observed after one dose of 2-min tCCAO, but the peak was accelerated to an earlier period of reperfusion after three doses. In contrast, mmu-miR-125b-5p and mmu-miR-132-5p, related to fused in sarcoma/translocated in liposarcoma (FUS/TLS), showed similar increases at both doses. mmu-miR-181c-5p and mmu-miR-378a-5p, related to heat shock protein 70 (HSP70), also showed accelerated expression after three doses. This data set provides new insight about miRNA expression during neurogenesis, and related to TDP43, FUS/TLS, and HSP70, which may be useful when pursuing further studies on the possible use of miRNAs as biomarkers in cerebral ischemic tolerance and neuroregeneration. PMID:25646661

  6. Isoflurane preconditioning provides neuroprotection against stroke by regulating the expression of the TLR4 signalling pathway to alleviate microglial activation

    PubMed Central

    Sun, Meiyan; Deng, Bin; Zhao, Xiaoyong; Gao, Changjun; Yang, Lu; Zhao, Hui; Yu, Daihua; Zhang, Feng; Xu, Lixian; Chen, Lei; Sun, Xude

    2015-01-01

    Excessive microglial activation often contributes to inflammation-mediated neurotoxicity in the ischemic penumbra during the acute stage of ischemic stroke. Toll-like receptor 4 (TLR4) has been reported to induce microglial activation via the NF-?B pathway. Isoflurane preconditioning (IP) can provide neuroprotection and inhibit microglial activation. In this study, we investigated the roles of the TLR4 signalling pathway in IP to exert neuroprotection following ischemic stroke in vivo and in vitro. The results showed that 2% IP alleviated neurological deficits, reduced the infarct volume, attenuated apoptosis and weakened microglial activation in the ischemic penumbra. Furthermore, IP down-regulated the expression of HSP 60, TLR4 and MyD88 and up-regulated inhibitor of I?B-? expression compared with I/R group in vivo. In vitro, 2% IP and a specific inhibitor of TLR4, CLI-095, down-regulated the expression of TLR4, MyD88, IL-1?, TNF-? and Bax, and up-regulated I?B-? and Bcl-2 expression compared with OGD group. Moreover, IP and CLI-095 attenuated microglial activation-induced neuronal apoptosis, and overexpression of the TLR4 gene reversed the neuroprotective effects of IP. In conclusion, IP provided neuroprotection by regulating TLR4 expression directly, alleviating microglial activation and neuroinflammation. Thus, inhibiting the activation of microglial activation via TLR4 may be a new avenue for stroke treatment. PMID:26086415

  7. Rho-kinase inhibition is involved in the activation of PI3-kinase/Akt during ischemic-preconditioning-induced cardiomyocyte apoptosis

    PubMed Central

    Zhang, Juan; Liu, Xiao-Bo; Cheng, Chao; Xu, Dong-Ling; Lu, Qing-Hua; Ji, Xiao-Ping

    2014-01-01

    We and others have reported that Rho-kinase plays an important role in the pathogenesis of heart ischemia/reperfusion (I/R) injury. Studies also have demonstrated that the activation of Rho-kinase was reversed in ischemic preconditioning (IPC). This study aimed to explain the mechanism of Rho-kinase-mediated cardiomyocyte apoptosis increased in I/R and reversed in IPC. Materials and methods: Studies were performed with female Wistar rats. The I/R rats were created by ligating the left anterior descending branch (LAD) for 30 min and releasing the ligature for 180 min. The IPC rats underwent IPC (two cycles of 5 min ligation of the LAD and 5 min reflow) before I/R. Results: Ischemia followed by reperfusion caused a significant increase in Rho-kinase and a decrease in Akt phosphorylation. Administration of fasudil, an inhibitor of Rho-kinase, decreased myocardial infarction size and cardiomyocyte apoptosis and increased Akt activation. IPC also caused the reduced Rho-kinase activity and cardiomyocyte apoptosis and a significant increase in Akt activity (P<0.05 vs I/R). Conclusion: Rho-kinase inhibition by IPC leads to reduced cardiomyocyte apoptosis may be mediated by activation of PI3-kinase/Akt. PMID:25550920

  8. 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

  9. 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. PMID:25783008

  10. 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

  11. Reappraisal of H2S/sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling.

    PubMed

    Whitfield, Nathan L; Kreimier, Edward L; Verdial, Francys C; Skovgaard, Nini; Olson, Kenneth R

    2008-06-01

    Hydrogen sulfide (H(2)S) is rapidly emerging as a biologically significant signaling molecule. Studies published before 2000 report low or undetectable H(2)S (usually as total sulfide) levels in blood or plasma, whereas recent work has reported sulfide concentrations between 10 and 300 microM, suggesting it acts as a circulating signal. In the first series of experiments, we used a recently developed polarographic sensor to measure the baseline level of endogenous H(2)S gas and turnover of exogenous H(2)S gas in real time in blood from numerous animals, including lamprey, trout, mouse, rat, pig, and cow. We found that, contrary to recent reports, H(2)S gas was essentially undetectable (<100 nM total sulfide) in all animals. Furthermore, exogenous sulfide was rapidly removed from blood, plasma, or 5% bovine serum albumin in vitro and from intact trout in vivo. To determine if blood H(2)S could transiently increase, we measured oxygen-dependent H(2)S production by trout hearts in vitro and in vivo. H(2)S has been shown to mediate ischemic preconditioning (IPC) in mammals. IPC is present in trout and, unlike mammals, the trout myocardium obtains its oxygen from relatively hypoxic systemic venous blood. In vitro, myocardial H(2)S production was inversely related to Po(2), whereas we failed to detect H(2)S in ventral aortic blood from either normoxic or hypoxic fish in vivo. These results provide an autocrine or paracrine mechanism for myocardial coupling of hypoxia to H(2)S in IPC, i.e., oxygen sensing, but they fail to provide any evidence that H(2)S signaling is mediated by the circulation. PMID:18417642

  12. 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 transcriptionpolymerase 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

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

    PubMed

    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

    2015-10-01

    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

  14. 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 5min-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 5min-transient ischemia with N; 3) (H+sham)-group was given sham-operation with H; and 4) (H+ischemia)-group was given 5min-transient cerebral ischemia with H. H (390.5C) was induced by subjecting the animals to a heating pad for 30min before and during the operation. In the (N+ischemia)-groups, a significant neuronal death was observed in the polymorphic layer (PL) from 1day 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. PMID:26365286

  15. NMDA receptor antagonism does not inhibit induction of ischemic tolerance in gerbil brain in vivo.

    PubMed

    Duszczyk, M; Gadamski, R; Ziembowicz, A; Danysz, W; Lazarewicz, J W

    2005-01-01

    Effects of high and moderate affinity uncompetitive NMDA receptor antagonists (+)MK-801 and memantine on ischemic tolerance were compared in relation to telemetrically controlled brain temperature. The tolerance to an injurious 3 min test of global forebrain ischemia in Mongolian gerbils was induced 48 h earlier by 2 min preconditioning ischemia. Normothermic preconditioning was virtually harmless, and greatly reduced neurodegeneration evoked by test ischemia. In hyperthermic animals it was injurious and failed to induce tolerance. Memantine (5 mg/kg) and (+)MK-801 (3 mg/kg) injected i.p. 1 h before preconditioning did not inhibit ischemic tolerance in the normothermic gerbils, while in hyperthermic animals treated with (+)MK-801 ischemic tolerance was partially restored. Subchronic 3 day infusion of memantine (30 mg/kg/day) significantly decreased neurodegeneration, and preconditioning in the normothermic gerbils further reduced neuronal damage. Hyperthermia exacerbated preconditioning ischemia and in this way reduced expression of tolerance, while (+)MK-801 partially reversed this effect. Our results do not confirm previous reports on the role of NMDA receptors in the induction of ischemic tolerance in gerbils. PMID:16179265

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

    PubMed Central

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

    2015-01-01

    Background and objective Contrast-induced nephropathy (CIN) is an acute major complication following intravascular administration of iodinated contrast agents; however, the best approach for preventing CIN is not clear. Remote ischemic pre-conditioning (RIPC) is a new, non-pharmacological method that has been considered for the prevention of CIN following coronary angiography. This study assessed the effects of RIPC with four brief episodes of upper limb ischemia and reperfusion in the prevention of contrast-induced nephropathy (CIN) after coronary angiography and/or angioplasty. Methods In this double-blind randomized clinical trial, we enrolled 51 patients with chronic stable angina and non-ST elevation acute coronary syndrome (NSTE.ACS), and they underwent coronary angiography and/or angioplasty. Standard fluid therapy with normal saline was prescribed for all patients before and after the procedure. The patients were divided into two groups, i.e., a study group of patients who had undergone RIPC intervention and a control group of patients who had not undergone RIPC. One hour before the procedure, a sphygmomanometer cuff was placed around one arm and inflated up to 50 mmHg above the systolic pressure for five minutes; then, the cuff was deflated for another five minutes, and this cycle was repeated four times. The patients’ serum creatinine levels were measured at baseline and 48 hours after the procedure, and the incidence of CIN was calculated. Results Twenty-one males and 30 females were studied in two groups, i.e., an RIPC intervention group (n = 25) and a control group (n = 26) that were homogenous considering baseline characteristics. No significant difference was observed in the mean level of serum creatinine between the two groups at a post-intervention time of 48 hours (RICP: 1.74 ± 0.70 mg/dL vs. Control: 1.75 ± 0.87 mg/dL; P = 0.64). However, a lower incidence rate of CIN was observed 48 hours after the administration of the contrast medium in the RIPC group, but it was not statistically significant (RIPC: 23.1% vs. Control: 12.0%; P = 0.30). Conclusion It seems that adequate fluid therapy is still the most effective strategy for preventing CIN and that RIPC might have additional protective effects in very high risk patients, such as those with severe renal insufficiency and heart failure. PMID:26816582

  17. Neuronal Preconditioning by Inhalational Anesthetics

    PubMed Central

    Bantel, Carsten; Maze, Mervyn; Trapp, Stefan

    2010-01-01

    Background Ischemic preconditioning is an important intrinsic mechanism for neuroprotection. Preconditioning can also be achieved by exposure of neurons to K+ channel–opening drugs that act on adenosine triphosphate–sensitive K+ (KATP) channels. However, these agents do not readily cross the blood–brain barrier. Inhalational anesthetics which easily partition into brain have been shown to precondition various tissues. Here, the authors explore the neuronal preconditioning effect of modern inhalational anesthetics and investigate their effects on KATP channels. Methods Neuronal–glial cocultures were exposed to inhalational anesthetics in a preconditioning paradigm, followed by oxygen–glucose deprivation. Increased cell survival due to preconditioning was quantified with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction test. Recombinant plasmalemmal KATP channels of the main neuronal type (Kir6.2/SUR1) were expressed in HEK293 cells, and the effects of anesthetics were evaluated in whole cell patch clamp recordings. Results Both sevoflurane and the noble gas xenon preconditioned neurons at clinically used concentrations. The effect of sevoflurane was independent of KATP channel activation, whereas the effect of xenon required the opening of plasmalemmal KATP channels. Recombinant KATP channels were activated by xenon but inhibited by halogenated volatiles. Modulation of mitochondrial K-ATP channels did not affect the activity of KATP channels, thus ruling out an indirect effect of volatiles via mitochondrial channels. Conclusions The preconditioning properties of halogenated volatiles cannot be explained by their effect on KATP channels, whereas xenon preconditioning clearly involves the activation of these channels. Therefore, xenon might mimic the intrinsic mechanism of ischemic preconditioning most closely. This, together with its good safety profile, might suggest xenon as a viable neuroprotective agent in the clinical setting. PMID:19352153

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-05-13

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

  20. Early stage effect of ischemic preconditioning for patients undergoing on-pump coronary artery bypass grafts surgery: systematic review and meta-analysis

    PubMed Central

    Chai, Qing; Liu, Jin

    2014-01-01

    Background: During the on-pump coronary artery bypass grafts surgery, ischemia/reperfusion injury would happen. Ischemia preconditioning could increase the tolerance against subsequent ischemia and reduce the ischemia/reperfusion injury. However the clinical outcomes of the available trials were different. Methods : We searched the Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 3, 2013), the Medline/PubMed and CNKI in March 2013. RevMan 5.1.6 and GRADEprofiler 3.6 were used for statistical analysis and evidence quality assessment. Heterogeneity was evaluated with significance set at P?0.10. Results: Eighteen randomized controlled trials were included. There were no differences on in-hospital mortality, postoperative myocardial infarction morbidity between ischemia preconditioning and control groups. The heterogeneity of creatine kinase-MB level 24 hours after surgery was obvious. The differences of 72 hours area under the curve of cardiac troponin T (mean differences of -14.50, 95% confidence interval of -21.71 to -7.28) and troponin I (mean differences -181.79, 95% confidence interval of -270.07 to -93.52) after surgery were observed. Conclusion s : All the 18 trails, the positive and the negative results were equal. The meta-analysis results should be interpreted with caution due to limited effective data. Because of high cost-effectiveness, ischemia preconditioning could not be denied completely. Large-scale randomized studies are needed, with the operation procedures and included criteria being more specific. PMID:24948996

  1. Antagonists of group I metabotropic glutamate receptors do not inhibit induction of ischemic tolerance in gerbil hippocampus.

    PubMed

    Duszczyk, Malgorzata; Gadamski, Roman; Ziembowicz, Apolonia; Lazarewicz, Jerzy W

    2006-01-01

    In this study we tested the effect of antagonists of two subtypes of the group I metabotropic glutamate receptors (mGluRs GI) on the induction of ischemic tolerance in relation to brain temperature. These experiments were prompted by indications that glutamate receptors may participate in the mechanisms of ischemic preconditioning. The role of NMDA receptors in the induction of ischemic tolerance has been debated while there is lack of information concerning the involvement of mGluRs GI in this phenomenon. The tolerance to injurious 3 min forebrain ischemia in Mongolian gerbils was induced 48 h earlier by 2 min preconditioning ischemia. Brain temperature was measured using telemetry equipment. EMQMCM and MTEP, antagonists of mGluR1 and mGluR5, respectively, were injected i.p. at a dose of 5 mg/kg. They were administered either before preconditioning ischemia in a single dose or after 2 min ischemia three times every 2 h. Both antagonists did not inhibit the induction of ischemic tolerance. Thus, our data indicate that group I metabotropic glutamate receptors do not play an essential role in the induction of ischemic tolerance. PMID:16524644

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

    PubMed Central

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

    2016-01-01

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

  3. Differential expression of microRNAs in ischemic heart disease.

    PubMed

    Song, Minwoo A; Paradis, Alexandra N; Gay, Maresha S; Shin, John; Zhang, Lubo

    2015-02-01

    Recent studies provide evidence that ischemic preconditioning (IP) and ischemia/reperfusion (IR) injury lead to altered expression of microRNAs (miRNAs) that affect the survival and recovery of cardiomyocytes. These endogenous ?22-nucleotide noncoding RNAs negatively regulate gene expression via degradation and translational inhibition of their target mRNAs. miRNAs are involved in differentiation, proliferation, electrical conduction, angiogenesis and apoptosis. These pathways can lead to physiological and pathological adaptations. This review intends to explore several facets of miRNA expression and the underlying mechanisms involved in IR injury, as well as IP as a cardioprotective strategy. In addition, we will investigate miRNA interaction with the renin-angiotensin system and the potential use of miRNAs in developing sensitive biomarkers for cardiovascular disease. PMID:25461956

  4. Differential expression of microRNAs in ischemic heart disease

    PubMed Central

    Song, Minwoo A.; Paradis, Alexandra N.; Gay, Maresha S.; Shin, John; Zhang, Lubo

    2014-01-01

    Recent studies provide evidence that ischemic preconditioning (IP) and ischemia/reperfusion (IR) injury lead to altered expression of microRNAs (miRNAs) that affect the survival and recovery of cardiomyocytes. These endogenous ~22-nucleotide noncoding RNAs negatively regulate gene expression via degradation and translational inhibition of their target mRNAs. miRNAs are involved in differentiation, proliferation, electrical conduction, angiogenesis and apoptosis. These pathways can lead to physiological and pathological adaptations. This review intends to explore several facets of miRNA expression and the underlying mechanisms involved in IR injury, as well as IP as a cardioprotective strategy. In addition, we will investigate miRNA interaction with the reninangiotensin system and the potential use of miRNAs in developing sensitive biomarkers for cardiovascular disease. PMID:25461956

  5. The Effect of Pre-Condition Cerebella Fastigial Nucleus Electrical Stimulation within and beyond the Time Window of Thrombolytic on Ischemic Stroke in the Rats

    PubMed Central

    Cheng, Pengfei; Bai, Shunjie; Ren, Yifei; Wang, Gong; Chen, Xiuying; Cui, Chun; Zhuang, Yuxiang

    2015-01-01

    Objective To investigate the effect of neurogenic neuroprotection conferred by cerebellar fastigial nucleus stimulation (FNS) and the role of PPAR?- mediated inflammation in a rat model of cerebral ischemia reperfusion. Methods After a continuous 1 hour fastigial nucleus electric stimulation, the male Sprague Dawley (SD) rats were given middle cerebral artery occlusion (MCAO) for 1, 3, 6, 9, 12 and 15 hours undergoing reperfusion with intravenous recombinant tissue plasminogen activator (rt-PA), while the control group received without FNS. After 72h of reperfusion, the neurological deficits, infarct volume and brain edema were evaluated. The brain tissue in ischemic penumbra was determined the myeloperoxidase (MPO) activity by a spectrophotometer and expression of PPAR? was measured by Rt-PCR and Western blotting. Results Our findings showed that FNS group had significantly reduced infarct volume and brain edema, and improved neurological deficits compared with the control group, especially in 6h and 9h reperfusion subgroups(p<0.05). The expression levels of PPAR? increased gradually and the peak may be before and after 9h reperfusion, the 3h, 6h, 9h, 12h and 15h reperfusion subgroups were higher than each control group(p<0.05). The MPO activity of 6h, 12h and 15h reperfusion subgroups were higher than each control group(p<0.05). Conclusions The neuroprotective effects of FNS have been shown to prolong the therapeutic window in cerebral ischemia/reperfusion, which might be related to the PPAR? mediated-inflammation in penumbral region. PMID:26016630

  6. Importance of brain-gut axis in the gastroprotection induced by gastric and remote preconditioning.

    PubMed

    Brzozowski, T; Konturek, P C; Pajdo, R; Kwiecień, S; Sliwowski, Z; Drozdowicz, D; Ptak-Belowska, A; Pawlik, M; Konturek, S J; Pawlik, W W; Hahn, G G

    2004-03-01

    Limitation of the damage to the organs such as heart, liver, intestine, stomach and brain by an earlier brief complete occlusion of their arteries is defined as ischemic preconditioning (IP). No study so for has been undertaken to check whether brain-gut axis is involved in the gastroprotection exhibited by gastric IP or in that induced by repeated brief episodes of ischemia of remote organs such as heart and liver. This study was designed to determine the possible involvement of vagal and sensory afferent nerves, in the mechanism of gastric and remote organ IP on the gastric mucosa in rats exposed to prolonged ischemia-reperfusion with or without functional ablation of sensory nerves by capsaicin or in those with removed vagal innervation by vagotomy. This gastric IP was induced by short ischemia episodes (occlusion of celiac artery 1-5 times for 5 min) applied 30 min before subsequent ischemia followed by 3 h of reperfusion (I/R) and compared with remote IP induced by occlusion of left descending coronary artery or hepatic artery plus portal vein. The area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured by H(2)-gas clearance method and mucosal biopsy samples were taken for the assessment of calcitonin gene-related peptide (CGRP) by RIA. Exposure of gastric mucosa to standard 3 h of I/R produced numerous gastric lesions and significant fall in the GBF and mucosal CGRP content. Two 5 min short ischemic episodes by occlusion of coronary or hepatic arteries, significantly reduced gastric damage induced by I/R with the extent similar to that exhibited by two short (5 min) episodes of gastric ischemia. These protective effects of gastric and remote IPs were accompanied by a restoration of the fall in the CGRP content caused by I/R alone. Protection and hyperemia induced by gastric IP were significantly attenuated in capsaicin-denervated or vagotomized animals and completely removed in those exposed to the combination of vagotomy and capsaicin-denervation. The IP-induced protection and hyperemia were restored by the administration of exogenous CGRP to gastric IP in capsaicin-treated animals. Gastroprotective and hyperemic actions of remote IP were markedly diminished in capsaicin-denervated rats and in those subjected to vagotomy. We conclude that brief ischemia in remote organs such as heart and liver protects gastric mucosa against gastric injury induced by I/R as effectively as gastric IP via mechanism involving both vagal and sensory nerves releasing vasodilatatory mediators such as CGRP. PMID:15082876

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

    PubMed Central

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

    2015-01-01

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

  8. Sensory preconditioning in honeybees.

    PubMed

    Müller, D; Gerber, B; Hellstern, F; Hammer, M; Menzel, R

    2000-04-01

    Sensory preconditioning means that reinforcement of stimulus A after unreinforced exposure to a compound AB also leads to responses to stimulus B. Here, we describe and analyze sensory preconditioning in an insect, the honeybee Apis mellifera. Using two-element odorant compounds in classical conditioning of the proboscis extension reflex, we found (i) that sensory preconditioning is not due to stimulus generalization, (ii) that paired, but not unpaired, presentation of elements supports sensory preconditioning, (iii) that simultaneous, but not sequential, exposure to the elements of the compound supports sensory preconditioning and (iv) that a single presentation of the compound yields maximal sensory preconditioning. The results are discussed with respect to configural and chain-like associative explanations for sensory preconditioning. We suggest an experience-dependent step of compound processing, establishing configural units, as an additional explanation for sensory preconditioning. PMID:10729283

  9. 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

  10. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

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

    2015-03-01

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

  11. Induction of manganese superoxide dismutase in rat cardiac myocytes increases tolerance to hypoxia 24 hours after preconditioning.

    PubMed Central

    Yamashita, N; Nishida, M; Hoshida, S; Kuzuya, T; Hori, M; Taniguchi, N; Kamada, T; Tada, M

    1994-01-01

    Manganese superoxide dismutase (Mn-SOD) is induced in ischemic hearts 24 h after ischemic preconditioning, when tolerance to ischemia is acquired. We examined the relationship between Mn-SOD induction and the protective effect of preconditioning using cultured rat cardiac myocytes. Exposure of cardiac myocytes to brief hypoxia (1 h) decreased creatine kinase release induced by sustained hypoxia (3 h) that follows when the sustained hypoxia was applied 24 h after hypoxic preconditioning (57% of that in cells without preconditioning). The activity and content of Mn-SOD in cardiac myocytes were increased 24 h after hypoxic preconditioning (activity, 170%; content, 139% compared with cells without preconditioning) coincidentally with the acquisition of tolerance to hypoxia. Mn-SOD mRNA was also increased 20-40 min after preconditioning. Antisense oligodeoxyribonucleotides corresponding to the initiation site of Mn-SOD translation inhibited the increases in the Mn-SOD content and activity and abolished the expected decrease in creatine kinase release induced by sustained hypoxia after 24 h of hypoxic preconditioning. Sense oligodeoxyribonucleotides did not abolish either Mn-SOD induction or tolerance to hypoxia. These results suggest that the induction of Mn-SOD in myocytes by preconditioning plays a pivotal role in the acquisition of tolerance to ischemia at a later phase (24 h) of ischemic preconditioning. Images PMID:7989574

  12. 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 ...

  13. Preconditioning Neuroprotection in Global Cerebral Ischemia Involves NMDA Receptor-Mediated ERK-JNK3 Crosstalk

    PubMed Central

    Zhang, Quan-Guang; Wang, Rui-Min; Han, Dong; Yang, Li-Cai; Li, Jie; Brann, Darrell W.

    2009-01-01

    Previous work has demonstrated that ischemic preconditioning neuroprotection is associated with inhibition of JNK pathway activation. The present study was designed to examine the hypothesis that the suppression of JNK3 activation by preconditioning is mediated by NMDA receptors and crosstalk between ERK1/2 and JNK3. Preconditioning (3 min ischemia) 2 days before global cerebral ischemia (8-min) markedly decreased neuronal degeneration in hippocampus CA1, an effect abolished by pretreatment with the NMDA receptor antagonist, MK-801. Furthermore, preconditioning abolished cerebral ischemia-induced JNK3 activation and enhanced ERK1/2 activation, an effect reversed by MK-801. Due to the inverse relationship between ERK1/2 and JNK3 activation following preconditioning, we hypothesized that ERK1/2 may regulate JNK3 activation following preconditioning. In support of this contention, pretreatment with the MEK inhibitor, PD98059 significantly attenuated preconditioning-induced ERK1/2 phosphorylation, and strongly reversed preconditioning down-regulation of JNK3 phosphorylation. This finding suggests that ERK1/2 signaling is responsible for preconditioning-induced down-regulation of JNK3 activation. Western blot analysis and immunohistochemistry further demonstrated that preconditioning, in an NMDA-dependent manner, enhanced activation of the pro-survival factors, p-CREB and Bcl-2, while attenuating activation of putative pro-death factors, p-c-Jun and Fas-L in the hippocampus CA1. As a whole, the study demonstrates that preconditioning attenuation of pro-death JNK3 in the hippocampus CA1 following global cerebral ischemia is mediated by NMDA receptor-Induced crosstalk between ERK1/2 and JNK3. The ERK1/2-mediated reduction of JNK3 activation leads to enhanced prosurvival signaling (P-CREB and Bcl-2 induction) and attenuation of prodeath signaling (p-c-Jun and Fas-L), with subsequent induction of ischemic tolerance. PMID:19373993

  14. Preconditioned Iterative Solver

    Energy Science and Technology Software Center (ESTSC)

    2002-08-01

    AztecOO contains a collection of preconditioned iterative methods for the solution of sparse linear systems of equations. In addition to providing many of the common algebraic preconditioners and basic iterative methods, AztecOO can be easily extended to interact with user-provided preconditioners and matrix operators.

  15. 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-?. Methods and results: Bone marrow-derived rat mesenchymal stem cells were preconditioned with 10 ?M TMZ for 6 h. TMZ preconditioning of MSCs remarkably increased cell viability and the expression of HIF1-? 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-1?. 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-?, thus contributing to neovascularization and improved cardiac function of rats subjected to myocardial I/R injury. PMID:26629255

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

    PubMed Central

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

    2015-01-01

    Abstract 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. PMID:26664354

  17. 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. PMID:26664354

  18. 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 MPTP/MPP{sup +}.

  19. Thrombin Preconditioning in Surgical Brain Injury in Rats.

    PubMed

    Benggon, Michael; Chen, Hank; Applegate, Richard L; Zhang, John

    2016-01-01

    The surgical brain injury model replicates neurosurgical brain parenchymal damage. Postsurgical brain edema correlates with postoperative neurological dysfunction. Intranasal administration is a proven method of delivering therapies to brain tissue. Thrombin preconditioning decreased brain edema and improved neurological outcomes in models of ischemic brain injury. We hypothesized thrombin preconditioning in surgical brain injury may improve postoperative brain edema and neurological outcomes. Adult male Sprague-Dawley rats (n?=?78) weighing 285-355 g were randomly assigned to sham or pre-injury treatment: one-time pretreatment 1 day prior, one-time pretreatment 5 days prior, and daily preconditioning for 5 days prior. Treatment arms were divided into vehicle or thrombin therapies, and subdivided into intranasal (thrombin 5 units/50 ?L 0.9 % saline) or intracerebral ventricular (thrombin 0.1 unit/10 ?L 0.9 % saline) administration. Blinded observers performed neurological testing 24 h after brain injury followed immediately by measurement of brain water content. There was a significant difference in ipsilateral brain water content and neurological outcomes between all treatment groups and the sham group. However, there was no change in brain water content or neurological outcomes between thrombin- and vehicle-treated animals. Thrombin preconditioning did not significantly improve brain edema or neurological function in surgical brain injury in rats. PMID:26463965

  20. 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

  1. Immune mechanisms in cerebral ischemic tolerance

    PubMed Central

    Garcia-Bonilla, Lidia; Benakis, Corinne; Moore, Jamie; Iadecola, Costantino; Anrather, Josef

    2014-01-01

    Stressor-induced tolerance is a central mechanism in the response of bacteria, plants, and animals to potentially harmful environmental challenges. This response is characterized by immediate changes in cellular metabolism and by the delayed transcriptional activation or inhibition of genetic programs that are not generally stressor specific (cross-tolerance). These programs are aimed at countering the deleterious effects of the stressor. While induction of this response (preconditioning) can be established at the cellular level, activation of systemic networks is essential for the protection to occur throughout the organs of the body. This is best signified by the phenomenon of remote ischemic preconditioning, whereby application of ischemic stress to one tissue or organ induces ischemic tolerance (IT) in remote organs through humoral, cellular and neural signaling. The immune system is an essential component in cerebral IT acting simultaneously both as mediator and target. This dichotomy is based on the fact that activation of inflammatory pathways is necessary to establish IT and that IT can be, in part, attributed to a subdued immune activation after index ischemia. Here we describe the components of the immune system required for induction of IT and review the mechanisms by which a reprogrammed immune response contributes to the neuroprotection observed after preconditioning. Learning how local and systemic immune factors participate in endogenous neuroprotection could lead to the development of new stroke therapies. PMID:24624056

  2. PVM and IP multicast

    SciTech Connect

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

    1996-12-01

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

  3. Bradykinin in ischemic conditioning-induced tissue protection: Evidences and possible mechanisms.

    PubMed

    Sharma, Roohani; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh

    2015-12-01

    Ischemic conditioning is an intrinsic protective mechanism in which repeated short episodes of reversible ischemia protects the tissue and increases its tolerance against a subsequent longer period of ischemia (index ischemia). Bradykinin is a physiologically and pharmacologically active peptide of the kallikrein-kinin system. Besides the involvement of bradykinin in a variety of physiological and pathological responses such as pain, inflammation and in cardiovascular system as a potent vasodilator, it also acts as an endogenous cytoprotective mediator in the ischemic tissue. Pretreatment with various pharmacological modulators of bradykinin has confirmed the involvement of bradykinin in ischemic conditioning-induced protection. The protective actions of bradykinin in three major paradigms of ischemic conditioning i.e. ischemic preconditioning, ischemic postconditioning and remote ischemic preconditioning involves activation and regulation of various endogenous signaling cascades to render the heart resistant to infarction. In ischemic preconditioning, bradykinin exerts cardioprotective effect via activation of PI3K/Akt/eNOS signaling pathway and regulation of redox state via NO release. The role of bradykinin and its B2 receptors in ischemic-postconditioning induced neuroprotection has been described mainly due to its increased redox signaling cascade and activation of mitochondrial anti-apoptotic pathway. Furthermore, its cardioprotective role during remote ischemic preconditioning has been associated with activation of B2 receptors mediated neurogenic pathway and internalization of B2 receptors along with the formation of signalosomes that activates intracellular cytoprotective transduction pathways. The present review focuses on the potential role of bradykinin in mediating different forms of ischemic conditioning (pre/post/remote)-induced cardioprotection and neuroprotection along with the possible mechanisms. PMID:26499976

  4. 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

  5. Metformin Mitigates Apoptosis in Ischemic Myocardium

    PubMed Central

    Elmadhun, Nassrene Y.; Sabe, Ashraf A.; Lassaletta, Antonio D.; Chu, Louis. M.; Sellke, Frank W.

    2014-01-01

    BACKGROUND Epidemiologic data has shown that metformin confers a survival advantage in patients with cardiovascular disease. Although the underlying cardioprotective mechanism is unclear, it appears to be independent of metformins insulin-sensitizing effect. The purpose of this study is to evaluate the effect of metformin on the apoptosis pathway in the ischemic and non-ischemic cardiac tissue in a swine model of metabolic syndrome. MATERIALS AND METHODS Ossabaw miniswine were fed either a regular diet (OC, n=8), a high-cholesterol diet (OHC, n=9), or a high-cholesterol diet supplemented with metformin (OHCM n=8). After three weeks, all animals underwent placement of an ameroid constrictor to the left circumflex coronary artery to induce chronic ischemia. Seven weeks after ameroid placement, animals underwent cardiac harvest. RESULTS In the chronically ischemic myocardium, metformin significantly up-regulates pro-survival proteins: ERK, NF?B, pENOS and P38. Metformin also significantly inhibits/down-regulates pro-apoptosis proteins: FOXO3 and caspase3. Metformin decreased the percent apoptotic cells in the ischemic and non-ischemic myocardium. There was no difference in arteriolar density, capillary density, intramyocardial fibrosis or collagen deposition in the ischemic or non-ischemic myocardium. CONCLUSIONS Metformin selectively alters the apoptosis pathway by inhibiting FoxO3 and decreasing the active form of caspase 3, cleaved caspase 3. Metformin also up-regulates mitogen-activated kinase proteins p38 and ERK1/2, which are considered cardioprotective during ischemic preconditioning. Perhaps the altered activation of the apoptosis pathway in ischemic myocardium is one mechanism by which metformin is cardioprotective. PMID:24969550

  6. Short-term hypoxic preconditioning improved survival following cardiac arrest and resuscitation in rats.

    PubMed

    Xu, Kui; Lamanna, Joseph C

    2014-01-01

    Cardiac arrest and resuscitation produces delayed mortality and hippocampal neuronal death in rats. Hypoxic preconditioning has been to shown to protect the brain from ischemic insults. We have previously reported that with chronic hypobaric hypoxia, the accumulation of hypoxic-inducible factor-1 alpha (HIF-1?) and its target genes was increased for the first several days of hypoxic exposure, and returned to baseline level by 3 weeks when angiogenesis is completed. In this study, we investigated the effect of short-term (3 days) and long-term (21 days) hypoxic preconditioning on recovery from cardiac arrest and resuscitation in rats. Our data showed that the overall survival rate was considerably improved in the short-term hypoxic preconditioning group compared to the non-preconditioned controls (86 %, 6/7 vs. 54 %, 7/13); however, the survival rate in the long-term hypoxic preconditioning group was decreased. Our data suggest that hypoxic preconditioning provides protection after cardiac arrest and resuscitation more likely through increased accumulation of HIF-1? and its target genes rather than through successful vascular adaptation as a result of hypoxia-induced angiogenesis. PMID:24729248

  7. Role of Circulating Immune Cells in Stroke and Preconditioning-Induced Protection.

    PubMed

    Gesuete, Raffaella; Stevens, Susan L; Stenzel-Poore, Mary P

    2016-01-01

    Stroke activates an inflammatory response that results in the infiltration of peripheral immune cells into the ischemic area, contributing to exacerbation of tissue damage. However, evidence indicates that inflammatory cell infiltration can also promote neuroprotection through regulatory immune cells that mitigate injury. These immune regulatory cells may also be important mediators of neuroprotection associated with preconditioning, a phenomenon whereby small exposure to a potential harmful stimulus is able to induce protection against a subsequent ischemic event. The elucidation of mechanisms that allow these immune cells to confer neuroprotection is critical to developing new therapeutic strategies against acute stroke. In the present review, we discuss the dual role of peripheral immune cells in stroke-related brain injury and neuroprotection. Furthermore, we report new data from our laboratory that supports the important role of peripheral cells and their interaction with the brain endothelium for the establishment of the protective phenotype in preconditioning. PMID:26463920

  8. Blood as the carrier of ischemic tolerance in rat brain.

    PubMed

    Bonova, Petra; Gottlieb, Miroslav

    2015-08-01

    This study provides clear evidence that the factor inducing tolerance to ischemia is transmitted via the circulating blood. By using the remote ischemia and the cross-circulation model, the tolerance to ischemia was transmitted from donor to recipient. For this study, the following experimental groups were designed: I, sham control group; II, group of tolerant hindlimb tourniquet-treated rats; III, positive control group; IV, control for cross-circulation influence; preconditioned animals: V, tolerant animals subjected to middle cerebral artery occlusion (MCAO); VI, tolerant animals cross-circulated with SHC, followed by MCAO; VII, SHC animals cross-circulated with tolerant animals and subsequently subjected to MCAO; VIII, tolerant animals cross-circulated with ischemic rats, followed by MCAO; IX, SHC animals cross-circulated with ischemic animals and subjected to MCAO; postconditioned animals: X, ischemic animals treated with a remote limb tourniquet; XI, ischemic animals cross-circulated with SHC control rats; and XII, ischemic animals cross-circulated with tolerant rats. Results confirmed that remote ischemia induced reduction of infarct volume in the preconditioned (V, 60%) as well as in the postconditioned group (X, 52%). Significant diminution was also observed in group XII (56.6%). In the preconditioned group, decreased infarct volume was detected in groups VI and VII (about 65%) and in group IX (about 50%). The greatest infarct reduction (84%) was induced by the presence of ischemic blood in a tolerant rat before ischemia induction. In summary, the factor inducing tolerance to ischemia is generated by remote ischemia and by ischemia itself; from the site of origin to the rest of the body, it is transported by the systemic blood circulation and can be transferred from animal to animal. The effect of conditioning with two different ischemic events (brain and hindlimb ischemia) led to a cumulative, stronger tolerance response. PMID:25787695

  9. Orderings for conjugate gradient preconditionings

    NASA Technical Reports Server (NTRS)

    Ortega, James M.

    1991-01-01

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

  10. 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 might be a translationally relevant strategy to increase the tolerance of cord blood MSCs to ischemia and improve their therapeutic efficacy in clinical applications. PMID:26380983

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

    PubMed Central

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

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

    PubMed

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

    2015-12-15

    10-20% of symptomatic epilepsies are post-traumatic. We examined effect of LPS preconditioning on epileptogenesis after controlled cortical impact (CCI). LPS (0.01, 0.1 and 0.5 mg/kg) was injected i.p. to rats 5 days before induction of CCI to parieto-temporal cortex. Kindling started 24h after CCI by i.p. injection of 30 mg/kg of pentylenetetrazole every other day until manifestation of 3 consecutive generalized seizures. CCI injury accelerated the rate of kindled seizures acquisition. LPS (0.1 and 0.5 mg/kg) prevented the acceleration of kindling. LPS preconditioning significantly decreased IL-1β and TNF-α over-expression and the number of damaged neurons in the hippocampus of traumatic rats. PMID:26616884

  13. Application and Progress of Combined Mesenchymal Stem Cell Transplantation in the Treatment of Ischemic Cardiomyopathy

    PubMed Central

    Hua, Ping; Liu, Jian-Yang; Tao, Jun; Yang, Song-Ran

    2015-01-01

    Treatment of ischemic cardiomyopathy caused by myocardial infarction (MI) using mesenchymal stem cell (MSC) transplantation is a widely researched field, with promising clinical application. However, the low survival rate of transplanted cells has a severe impact on treatment outcome. Currently, research is focused on investigating the strategy of combining genetic engineering, tissue engineering materials, and drug/hypoxia preconditioning to improve ischemic cardiomyopathy treatment outcome using MSC transplantation treatment (MSCTT). This review discusses the application and progress of these techniques. PMID:26295041

  14. Bradykinin preconditioning affects the number of degenerated neurons and the level of antioxidant enzymes in spinal cord ischemia in rabbits.

    PubMed

    Mechrov, Eva; Danielisov, Viera; Domorkov, Iveta; Dankov, Marianna; Stebnick, Milan; Mi?kov, Helena; Burda, Jozef

    2014-01-01

    Bradykinin preconditioning has been used for acquisition of tolerance after spinal cord ischemia. Rabbits were preconditioned intraperitoneally with bradykinin 48 h prior to 20 min of abdominal aorta ligation followed by 24 and 48 h of reperfusion. The activities of SOD and catalase were measured and Fluoro Jade B (FJB)-positive degenerated neurons were evaluated. The outcomes of Tarlov scoring system used to assess neurological functions showed significant improvement in bradykinin groups compared to the ischemic group. The number of FJB-positive degenerated neurons was decreased in ventral horns of both bradykinin groups. Significantly decreased activities of total SOD and mitochondrial Mn-SOD were also detected in both bradykinin groups versus ischemic group while CuZn-SOD and catalase activities were significantly decreased only in the bradykinin group after 24h of reperfusion versus ischemic group. These findings suggest that one of the possibilities of the neuroprotective effect of delayed bradykinin preconditioning against spinal cord ischemic injury could be realized by mitochondrial protection and decreased synthesis of Mn-SOD as well as by promotion of neuronal survival. PMID:23981244

  15. Management of Preconditioned Calves and Impacts of Preconditioning.

    PubMed

    Hilton, W Mark

    2015-07-01

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

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

    PubMed

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

    2016-01-01

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

  17. Ischemic Strokes (Clots)

    MedlinePLUS

    ... Month Twitter Chats American Stroke Month Launch Ischemic Strokes (Clots) Updated:Aug 7,2015 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  18. Dynamic clustering of IP3 receptors by IP3.

    PubMed

    Rahman, Taufiq

    2012-04-01

    The versatility of Ca2+ as an intracellular messenger stems largely from the impressive, but complex, spatiotemporal organization of the Ca2+ signals. For example, the latter when initiated by IP3 (inositol 1,4,5-trisphosphate) in many cells manifest hierarchical recruitment of elementary Ca2+ release events ('blips' and then 'puffs') en route to global regenerative Ca2+ waves as the cellular IP3 concentration rises. The spacing of IP3Rs (IP3 receptors) and their regulation by Ca2+ are key determinants of these spatially organized Ca2+ signals, but neither is adequately understood. IP3Rs have been proposed to be pre-assembled into clusters, but their composition, geometry and whether clustering affects IP3R behaviour are unknown. Using patch-clamp recording from the outer nuclear envelope of DT40 cells expressing rat IP3R1 or IP3R3, we have recently shown that low concentrations of IP3 cause IP3Rs to aggregate rapidly and reversibly into small clusters of approximately four IP3Rs. At resting cytosolic Ca2+ concentrations, clustered IP3Rs open independently, but with lower open probability, shorter open duration and lesser IP3-sensitivity than lone IP3Rs. This inhibitory influence of clustering on IP3R is reversed when the [Ca2+]i (cytosolic free Ca2+ concentration) increases. The gating of clustered IP3Rs exposed to increased [Ca2+]i is coupled: they are more likely to open and close together, and their simultaneous openings are prolonged. Dynamic clustering of IP3Rs by IP3 thus exposes them to local Ca2+ rises and increases their propensity for a CICR (Ca2+-induced Ca2+ rise), thereby facilitating hierarchical recruitment of the elementary events that underlie all IP3-evoked Ca2+ signals. PMID:22435806

  19. 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

  20. Activation of inositol 1,4,5-trisphosphate receptors during preconditioning low-frequency stimulation suppresses subsequent induction of long-term potentiation in hippocampal CA1 neurons.

    PubMed

    Yamazaki, Y; Fujii, S; Goto, J-I; Fujiwara, H; Mikoshiba, K

    2015-12-17

    We investigated the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) activated during preconditioning low-frequency stimulation (LFS) in the subsequent high-frequency stimulation (HFS)-induced induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential (EPSP) or the population spike (PS) by delivery of HFS (a tetanus of 100 pulses at 100 Hz) to the Schaffer collateral-commissural pathway to CA1 neuron synapses was suppressed when the CA1 synapses were preconditioned by LFS of 1000 pulses at 1 Hz. This effect was inhibited when the preconditioning LFS was applied in the presence of an N-methyl-D-aspartate receptors (NMDARs) antagonist, a metabotropic glutamate receptor (mGluR) antagonist, IP3R antagonist, a calmodulin-dependent kinase II inhibitor or a calcineurin inhibitor. Furthermore, blockade of group I mGluRs immediately before the delivery of HFS blocked the inhibitory effect of the preconditioning LFS on subsequent induction of LTP by HFS. These results suggest that, in hippocampal CA1 neuron synapses, co-activation of NMDARs and IP3Rs during a preconditioning LFS results in both phosphorylation and dephosphorylation events that lead to prolonged activation of group I mGluRs that is responsible for the failure of LTP induction. PMID:26500182

  1. 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)-? 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 Patients with preeclampsia have significantly higher serum concentrations of CXCL10/IP-10 than both normal pregnant women and mothers who have SGA neonates. These results are likely to reflect an anti-angiogenic state as well as an enhanced systemic inflammatory response in patients with preeclampsia. Alternatively, since preeclampsia and SGA share several mechanisms of disease, it is possible that a higher concentration of this chemokine may contribute to the clinical presentation of preeclampsia in patients with a similar intrauterine insult. PMID:17943641

  2. 40 CFR 80.52 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... accordance with the “General vehicle handling requirements” per 40 CFR 86.132-96, up to and including the completion of the hot start exhaust test. (b) The preconditioning procedure prescribed at 40 CFR...

  3. Fetal brain genomic reprogramming following asphyctic preconditioning

    PubMed Central

    2013-01-01

    Background Fetal asphyctic (FA) preconditioning is effective in attenuating brain damage incurred by a subsequent perinatal asphyctic insult. Unraveling mechanisms of this endogenous neuroprotection, activated by FA preconditioning, is an important step towards new clinical strategies for asphyctic neonates. Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of preconditioning. Therefore we investigated whole genome differential gene expression in the preconditioned rat brain. FA preconditioning was induced on embryonic day 17 by reversibly clamping uterine circulation. Male control and FA offspring were sacrificed 96h after FA preconditioning. Whole genome transcription was investigated with Affymetrix Gene1.0ST chip. Results Data were analyzed with the Bioconductor Limma package, which showed 53 down-regulated and 35 up-regulated transcripts in the FA-group. We validated these findings with RT-qPCR for adh1, edn1, leptin, rdh2, and smad6. Moreover, we investigated differences in gene expression across different brain regions. In addition, we performed Gene Set Enrichment Analysis (GSEA) which revealed 19 significantly down-regulated gene sets, mainly involved in neurotransmission and ion transport. 10 Gene sets were significantly up-regulated, these are mainly involved in nucleosomal structure and transcription, including genes such as mecp2. Conclusions Here we identify for the first time differential gene expression after asphyctic preconditioning in fetal brain tissue, with the majority of differentially expressed transcripts being down-regulated. The observed down-regulation of cellular processes such as neurotransmission and ion transport could represent a restriction in energy turnover which could prevent energy failure and subsequent neuronal damage in an asphyctic event. Up-regulated transcripts seem to exert their function mainly within the cell nucleus, and subsequent Gene Set Enrichment Analysis suggests that epigenetic mechanisms play an important role in preconditioning induced neuroprotection. PMID:23800330

  4. Laser thermal preconditioning enhances dermal wound repair

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

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

  5. Reduced [3H]IP3 binding but unchanged IP3 receptor levels in the rat hippocampus CA1 region following transient global ischemia and tolerance induction.

    PubMed

    Dahl, C; Haug, L S; Spilsberg, B; Johansen, J; Ostvold, A C; Diemer, N H

    2000-04-01

    Changes in inositol (1,4,5)-trisphosphate (IP3) binding properties and the protein level of the IP3 receptor have been reported in different pathological conditions in the brain, e.g. cerebral ischemia, Alzheimer's disease, and Huntingtons disease. We used the 4-vessel occlusion model in rat brain to investigate the effect of transient ischemia insults on the IP3 receptor mRNA level, the IP3 receptor protein level and [3H]IP3 binding. Recirculation periods were limited (1-72 h) to avoid the development of delayed neuronal death. We found that the IP3 receptor mRNA levels were decreased after damage-inducing ischemia (9 min) in the hippocampus CA1 and CA3 regions. The mRNA levels were unaltered after tolerance-inducing ischemia (3 min). However, [3H]IP3 binding was significantly reduced after both damage- and tolerance-inducing ischemia in the hippocampus CA1 region. Furthermore, all investigated brain areas showed a decreased [3H]IP3 binding when tolerance-inducing ischemia was followed by a second ischemic insult (3 + 8.5 min ischemia). The IP3 receptor protein levels remained constant in all investigated brain areas. These results indicate that a reduced [3H]IP3 binding capability in the particularly vulnerable areas occurs as an early consequence of cerebral ischemia, before IP3 receptor protein levels are reduced in these areas. Structural or conformational changes altering IP3 binding may be of necessity on the pathway leading to down-regulation of IP3 receptor protein levels, as observed by others. PMID:10733005

  6. Ischemic optic neuropathy.

    PubMed

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

    2008-10-01

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

  7. Hypoxic preconditioning promotes the translocation of protein kinase C ? binding with caveolin-3 at cell membrane not mitochondrial in rat heart.

    PubMed

    Yu, Hongmei; Yang, Zhaogang; Pan, Su; Yang, Yudan; Tian, Jiayi; Wang, Luowei; Sun, Wei

    2015-11-17

    Protein kinase C has been shown to play a central role in the cardioprotection of ischemic preconditioning. However, the mechanism underlying PKC-mediated cardioprotection is not completely understood. Given that caveolae are critical for PKC signaling, we sought to determine whether hypoxic preconditioning promotes translocation and association of PKC isoforms with caveolin-3. A cellular model of hypoxic preconditioning from adult rat cardiac myocytes (ARCM) or H9c2 cells was employed to examine PKC isoforms by molecular, biochemical and cellular imaging analysis. Hypoxia was induced by incubating the cells in an airtight chamber in which O2 was replaced by N2 with glucose-free Tyrode's solution. Cells were subjected to hypoxic preconditioning with 10 minutes of hypoxia followed by 30 minutes of reoxygenation. Western blot data indicated that the band intensity for PKC?, PKC? or PKC?, but not PKC? and PKC? was enhanced significantly by hypoxic preconditioning from the caveolin-enriched plasma membrane interactions. Immunoprecipitation experiments from the caveolin-enriched membrane fractions of ARCM showed that the level of PKC?, PKC? and PKC? in the anti-caveolin-3 immunoprecipitates was also increased by hypoxic preconditioning. Further, our FRET analysis in H9c2 cells suggested that there is a minimum FRET signal for caveolin-3 and PKC? along cell peripherals, but hypoxic preconditioning enhanced the FRET signal, indicating a potential interaction between caveolin-3 and PKC?. And also treatment of the cells with hypoxic preconditioning led to a smaller amount of translocation of PKC? to the mitochondria than that to the membrane. We demonstrate that hypoxic preconditioning promotes rapid association of PKC?, PKC? and PKC? with the caveolin-enriched plasma membrane microdomain of cardiac myocytes, and PKC? via direct molecular interaction with caveolin-3. This regulatory mechanism may play an important role in cardioprotection. PMID:26313243

  8. CANOPEN Controller IP Core

    NASA Astrophysics Data System (ADS)

    Caramia, M.; Montagna, M.; Furano, G.; Winton, A.

    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.

  9. IP-10 in autoimmune thyroiditis.

    PubMed

    Ruffilli, I; Ferrari, S M; Colaci, M; Ferri, C; Fallahi, P; Antonelli, A

    2014-08-01

    The interferon-γ-inducible protein 10 (IP-10) was initially identified as a chemokine that is induced by interferon (IFN)-γ. IP-10 exerts its function through binding to chemokine (C-X-C motif) receptor 3 (CXCR3). IP-10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, Graves' disease and ophthalmopathy), or systemic (such as systemic lupus erythematosus, mixed cryoglobulinemia, Sjogren syndrome, or systemic sclerosis). The secretion of IP-10 by (CD)4+, CD8+, and natural killer is dependent on IFN-γ. Under the influence of IFN-γ, IP-10 is secreted by thyrocytes. Determination of high level of IP-10 in peripheral fluids is therefore a marker of a T helper 1 orientated immune response. High levels of circulating IP-10, have been shown in patients with autoimmune thyroiditis (AT). Among patients with AT, IP-10 levels were significantly higher in those with a hypoechoic ultrasonographic pattern, which is a sign of a more severe lympho-monocytic infiltration, and in those with hypothyroidism. For these reasons, it has been postulated that IP-10 could be a marker of a stronger and more aggressive inflammatory response in the thyroid, subsequently leading to thyroid destruction and hypothyroidism. Further studies are needed to investigate whether IP-10 is a novel therapeutic target in AT. PMID:24977661

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

    PubMed Central

    Jimenez-Mateos, Eva M.

    2015-01-01

    Insults to the brain that are sub-threshold for damage activate endogenous protective pathways, which can temporarily protect the brain against a subsequent harmful episode. This mechanism has been named as tolerance and its protective effects have been shown in experimental models of ischemia and epilepsy. The preconditioning-stimulus can be a short period of ischemia or mild seizures induced by low doses of convulsant drugs. Gene-array profiling has shown that both ischemic and epileptic tolerance feature large-scale gene down-regulation but the mechanism are unknown. MicroRNAs are a class of small non-coding RNAs of ~2022 nucleotides length which regulate gene expression at a post-transcriptional level via mRNA degradation or inhibition of protein translation. MicroRNAs have been shown to be regulated after non-harmful and harmful stimuli in the brain and to contribute to neuroprotective mechanisms. This review focuses on the role of microRNAs in the development of tolerance following ischemic or epileptic preconditioning. PMID:25954143

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

    PubMed

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

    2015-12-01

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

  12. Platelet-derived microvesicles are involved in cardio-protective effects of remote preconditioning

    PubMed Central

    Ma, Fang; Liu, Hengchao; Shen, Yong; Zhang, Yingjie; Pan, Shaojun

    2015-01-01

    The ischemia-protective mechanism of remote precondition has been a mystery for a long time. Little was known about details of the inter-organ cardio-protective. Microvesicles, also known as microparticles (MPs), are small membrane-vesicles budding from the plasma membrane of cell. Recent studies have indicated MPs to be an important messenger in various biological processes. Our research mainly examined the hypothesis that remote ischemic conditioning can attenuate heart infarction in a rat after they were subjected to 30 min ischemia and 180 min reperfusion (I/R) by MPs. MPs were extracted from three groups of rat: 1) healthy rats, 2) healthy rats that underwent hindlimb ischemia-reperfusion preconditioning (RIPC) immediately, 3) healthy rats that underwent RIPC in 6 hours. Isolated MPs were transfused into rats that had undergone I/R without RIPC. The transfusion of MPs from rats that underwent RIPC immediately resulted in an increase in platelet-derived MPs in blood and reduction in infarction size, confirmed by 2-3-5-triphenyltetrazolium chloride staining. We further observed the contractile function in hearts after they were subjected to different treatments. However, no significant difference was observed in transfusion of MPs from rats that underwent RIPC in 6 hours. RIPC induces an increase in MPs, and platelet-derived MPs may confer at least part of the remote protective effect against cardiac ischemic-reperfusion injury. PMID:26617796

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

    PubMed

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

    2014-09-01

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

  14. Mitochondrial Mechanisms in Cerebral Vascular Control: Shared Signaling Pathways with Preconditioning

    PubMed Central

    Busija, David W.; Katakam, Prasad V.

    2014-01-01

    Mitochondrial initiated events protect the neurovascular unit against lethal stresses via a process called preconditioning which independently promotes changes in cerebrovascular tone through shared signaling pathways. Activation of the adenosine triphosphate (ATP)-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels) is a specific and dependable way to induce protection of neurons, astroglia, and cerebral vascular endothelium. Through the opening of mitoKATP channels, mitochondrial depolarization leads to activation of protein kinases and transient increases in cytosolic calcium (Ca2+) levels that activate terminal mechanisms that protect the neurovascular unit against lethal stress. Release of reactive oxygen species (ROS) from mitochondria have similar protective effects. Signaling elements of the preconditioning pathways also are involved in the regulation of vascular tone. Activation of mitoKATP channels in cerebral arteries causes vasodilation, with cell-specific contributions from endothelium, vascular smooth muscle (VSM), and nerves. Pre-existing chronic conditions, such as insulin resistance (IR) and/or diabetes, prevent preconditioning and impair relaxation to mitochondrial centered responses in cerebral arteries. Surprisingly, mitochondrial activation after anoxic or ischemic stress appears to protect cerebral vascular endothelium and promotes the restoration of blood flow; therefore, mitochondria may represent an important, but underutilized target in attenuating vascular dysfunction and brain injury in stroke patients. PMID:24862206

  15. Ionizing radiation as preconditioning against transient cerebral ischemia in rats.

    PubMed

    Kokoov, Natlia; Danielisov, Viera; Smajda, Be?adik; Burda, Jozef

    2014-01-01

    Induction of ischemic tolerance (IT), the ability of an organism to survive an otherwise lethal ischemia, is the most effective known approach to preventing postischemic damage. IT can be induced by exposing animals to a broad range of stimuli. In this study we tried to induce IT of brain neurons using ionizing radiation (IR). A preconditioning (pre-C) dose of 10, 20, 30 or 50 Gy of gamma rays was used 2 days before an 8 min ischemia in adult male rats. Ischemia alone caused the degeneration of almost one half of neurons in CA1 region of hippocampus. However, a significant decrease of the number of degenerating neurons was observed after higher doses of radiation (30 and 50 Gy). Moreover, ischemia significantly impaired the spatial memory of rats as tested in Morris's water maze. In rats with a 50 Gy pre-C dose, the latency times were reduced to values close to the control level. Our study is the first to reveal that IR applied in sufficient doses can induce IT and thus allow pyramidal CA1 neurons to survive ischemia. In addition, we show that the beneficial effect of IR pre-C is proportional to the radiation dose. PMID:25032511

  16. REMOTE ISCHEMIC CONDITIONING INFLUENCES MITOCHONDRIAL DYNAMICS.

    PubMed

    Cellier, Laura; Tamareille, Sophie; Kalakech, Hussein; Guillou, Sophie; Lenaers, Guy; Prunier, Fabrice; Mirebeau-Prunier, Delphine

    2016-02-01

    Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy to protect the heart against ischemia-reperfusion (I/R) injury. The mechanisms by which remote ischemic conditioning (RIC) is protective are to date unknown, yet a well-accepted theory holds that the mitochondria play a central role. Mitochondria are dynamic organelles that undergo fusion and fission. Interventions that decrease mitochondrial fission or increase mitochondrial fusion have been associated with reduced I/R injury. However, whether RIPC influences mitochondrial dynamics or not has yet to be ascertained.We sought to determine the role played by mitochondrial dynamics in RIPC-induced cardioprotection. Male adult rats exposed in vivo to myocardial I/R were assigned to one of two groups, either undergoing 40?min of myocardial ischemia followed by 120?min of reperfusion (MI group) or four 5-min cycles of limb ischemia interspersed by 5?min of limb reperfusion, immediately prior to myocardial ischemia and 120?min of reperfusion (MI+RIPC group). After reperfusion, infarct size was assessed and myocardial tissue was analyzed by Western blot and electron microscopy. RIPC induced smaller infarct size (-28%), increased mitochondrial fusion protein OPA1, and preserved mitochondrial morphology. These findings suggest that mitochondrial dynamics play a role in the mechanisms of RIPC-induced cardioprotection. PMID:26555744

  17. Possible role of thromboxane A2 in remote hind limb preconditioning-induced cardioprotection.

    PubMed

    Sharma, Roohani; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh

    2016-01-01

    Remote hind limb preconditioning (RIPC) is a protective strategy in which short episodes of ischemia and reperfusion in a remote organ (hind limb) protects the target organ (heart) against sustained ischemic reperfusion injury. The present study was designed to investigate the possible role of thromboxane A2 in RIPC-induced cardioprotection in rats. Remote hind limb preconditioning was performed by four episodes of 5 min of inflation and 5 min of deflation of pressure cuff. Occlusion of the hind limb with blood pressure cuff is most feasible, non-invasive, clinically relevant, and safe method for inducing RIPC. Isolated rat hearts were perfused on Langendorff apparatus and were subjected to global ischemia for 30 min followed by 120-min reperfusion. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in coronary effluent to assess the degree of myocardial injury. The extent of myocardial infarct size along with the functional parameters including left ventricular developed pressure (LVDP), dp/dtmax, and dp/dtmin were also measured. Ozagrel (thromboxane synthase inhibitor) and seratrodast (thromboxane A2 receptor antagonist) were employed as pharmacological modulators of thromboxane A2. Remote hind limb preconditioning significantly attenuated ischemia/reperfusion-induced myocardial injury and produced cardioprotective effects. However, administration of ozagrel and seratrodast completely abolished the cardioprotective effects of RIPC suggesting the key role of thromboxane A2 in RIPC-induced cardioprotection. It may be concluded that brief episodes of preconditioning ischemia and reperfusion activates the thromboxane synthase enzyme that produces thromboxane A2, which may elicit cardioprotection either involving humoral or neurogenic pathway. PMID:26531833

  18. Revealing Preconditions for Trustful Collaboration in CSCL

    ERIC Educational Resources Information Center

    Gerdes, Anne

    2010-01-01

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

  19. Revealing Preconditions for Trustful Collaboration in CSCL

    ERIC Educational Resources Information Center

    Gerdes, Anne

    2010-01-01

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

  20. 40 CFR 1065.518 - Engine preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., such as with a diesel engine that relies on urea-based selective catalytic reduction. Note that § 1065... cycle specified in 40 CFR 1039.505(b)(1), the second half of the cycle consists of modes three through... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Engine preconditioning....

  1. Acceleration of TDP43 and FUS/TLS protein expressions in the preconditioned hippocampus following repeated transient ischemia.

    PubMed

    Sun, Miao; Yamashita, Toru; Shang, Jingwei; Liu, Ning; Deguchi, Kentaro; Liu, Wentao; Ikeda, Yoshio; Feng, Juan; Abe, Koji

    2014-01-01

    The 43-kDa transactivation response DNA binding protein (TDP43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), heat shock protein 70 (HSP70), and β-amyloid (Aβ) are induced and involved in cerebral ischemia, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD), but their relationships in ischemic tolerance have never been examined, although they could be involved in endogenous neuroprotection under ischemic preconditioning. In the present study, Mongolian gerbils were subjected to one or three incidents of basically nonlethal 2-min transient common carotid arteries occlusion (tCCAO). Hippocampal CA1 neurons were lost only in the 2-min three times group at 3 and 7 days, which then gradually recovered from 1 to 6 months. Inductions of TDP43 and FUS/TLS were accelerated from 3 months to 7 days or from 7 days to 1 day, respectively, after 2-min three times ischemia compared with once. The cytoplasmic stainings of TDP43 and FUS/TLS showed a further acceleration of the peaks from 1 months to 3 days or from 1 months to 7 days, respectively, after 2-min three times ischemia compared with once. In contrast, HSP70 was induced only at 7 days after 2-min tCCAO for three times, with no expression for Aβ. These data show that ischemic preconditioning offers a way to induce endogenous neuroprotection and neurogenesis in gerbils, with TDP43, FUS/TLS, and HSP70 involved in this function. PMID:24265138

  2. 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 Hagers 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 Peis 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 Peis matrix, and matrices generated with the finite element method. PMID:25816331

  3. Lubiprostone induced ischemic colitis

    PubMed Central

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

    2013-01-01

    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. PMID:23345954

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

    PubMed

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

    2015-12-01

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

  5. Ozone-Oxidative Preconditioning Prevents Doxorubicin-induced Cardiotoxicity in Sprague-Dawley Rats

    PubMed Central

    Delgado-Roche, Livan; Hernndez-Matos, Yanet; Medina, Emilio A.; Morejn, Dalia .; Gonzlez, Mait R.; Martnez-Snchez, Gregorio

    2014-01-01

    Objectives: Induced dilated cardiomyopathy is the main limitation of the anti-cancer drug doxorubicin, which causes oxidative stress and cardiomyocyte death. As ozone therapy can activate the antioxidant systems, this study aimed to investigate the therapeutic efficacy of ozone-oxidative preconditioning against doxorubicin-induced cardiotoxicity. Methods: The study was carried out from September 2013 to January 2014. Sprague-Dawley rats were randomly distributed in the following treatment groups: Group 1 were treated with 2 mg/kg intraperitoneal (i.p.) of doxorubicin twice a week for 50 days; Group 2 were treated with 0.3 mg of ozone/oxygen mixture at 50 ?g/mL of ozone per 6 mL of oxygen by rectal insufflation and then treated with doxorubicin; Group 3 were treated as Group 2 but only with the oxygen, and Group 4 were treated with oxygen first, and then with sodium chloride i.p. as the control group. Results: The results showed that ozone therapy preserved left ventricle morphology which was accompanied by a reduction of serum pro-brain natriuretic peptide levels. The cardioprotective effects of ozone-oxidative preconditioning were associated with a significant increase (P <0.05) of antioxidant enzymes activities and a reduction of lipid and protein oxidation (P <0.05). Conclusion: Ozone-oxidative preconditioning prevents doxorubicin-induced dilated cardiomyopathy through an increase of antioxidant enzymes and a reduction of oxidised macromolecules. This establishes the background for future studies to determine if ozone therapy can be used as a complementary treatment for attenuating doxorubicin-induced cardiotoxicity in cancer patients. PMID:25097769

  6. Mitochondrial Dihydrolipoamide Dehydrogenase Is Upregulated in Response to Intermittent Hypoxic Preconditioning

    PubMed Central

    Li, Rongrong; Luo, Xiaoting; Wu, Jinzi; Thangthaeng, Nopporn; Jung, Marianna E.; Jing, Siqun; Li, Linya; Ellis, Dorette Z.; Liu, Li; Ding, Zhengnian; Forster, Michael J.; Yan, Liang-Jun

    2015-01-01

    Intermittent hypoxia preconditioning (IHP) has been shown to protect neurons against ischemic stroke injury. Studying how proteins respond to IHP may identify targets that can help fight stroke. The objective of the present study was to investigate whether mitochondrial dihydrolipoamide dehydrogenase (DLDH) would respond to IHP and if so, whether such a response could be linked to neuroprotection in ischemic stroke injury. To do this, we subjected male rats to IHP for 20 days and measured the content and activity of DLDH as well as the three ?-keto acid dehydrogenase complexes that contain DLDH. We also measured mitochondrial electron transport chain enzyme activities. Results show that DLDH content was indeed upregulated by IHP and this upregulation did not alter the activities of the three ?-keto acid dehydrogenase complexes. Results also show that the activities of the five mitochondrial complexes (I-V) were not altered either by IHP. To investigate whether IHP-induced DLDH upregulation is linked to neuroprotection against ischemic stroke injury, we subjected both DLDH deficient mouse and DLDH transgenic mouse to stroke surgery followed by measurement of brain infarction volume. Results indicate that while mouse deficient in DLDH had exacerbated brain injury after stroke, mouse overexpressing human DLDH also showed increased brain injury after stroke. Therefore, the physiological significance of IHP-induced DLDH upregulation remains to be further investigated. PMID:26078703

  7. Imaging in ChIPS

    NASA Astrophysics Data System (ADS)

    Miller, J.; Burke, D.; Evans, I.; Evans, J. D.; McLaughlin, W.

    2011-07-01

    The Chandra Interactive Plotting System (ChIPS) included in CIAO now allows users to incorporate and manipulate images in their plots. ChIPS uses the Visualization Toolkit (VTK) as a back end to provide basic imaging support, which includes displaying images in pseudo color or RGBA true color, adjusting the translucency of images, and several ways to threshold images. Users also have the ability to enhance them with annotations and place curves and contours directly onto the image. ChIPS imaging support provides a mechanism to adjust the image display resolution as necessary to provide high quality publication ready output. Beyond basic imaging, ChIPS includes the ability to recognize and incorporate WCS metadata into plots. ChIPS accurately calculates the intersections of world coordinate grids and plot axes, ensuring that these elements distort correctly with a tangent plane projection. Multiple image overlays are handled by reprojecting the overlaid images onto the reference image's coordinate system. New zooming and panning functions, and existing limits commands, use the WCS information from the image overlays to update the axes to reflect the new field of view being displayed. Although ChIPS already provides a number of user interactive commands, additional interactive capabilities are being considered for future releases. Enhanced interactive interfaces alongside the ability to script ChIPS in Python provide a more capable and user-friendly system.

  8. 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

    2015-12-01

    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-?. 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. PMID:26523514

  9. Preconditioning Stem Cells for In Vivo Delivery

    PubMed Central

    Sart, Sbastien; Ma, Teng

    2014-01-01

    Abstract Stem cells have emerged as promising tools for the treatment of incurable neural and heart diseases and tissue damage. However, the survival of transplanted stem cells is reported to be low, reducing their therapeutic effects. The major causes of poor survival of stem cells in vivo are linked to anoikis, potential immune rejection, and oxidative damage mediating apoptosis. This review investigates novel methods and potential molecular mechanisms for stem cell preconditioning in vitro to increase their retention after transplantation in damaged tissues. Microenvironmental preconditioning (e.g., hypoxia, heat shock, and exposure to oxidative stress), aggregate formation, and hydrogel encapsulation have been revealed as promising strategies to reduce cell apoptosis in vivo while maintaining biological functions of the cells. Moreover, this review seeks to identify methods of optimizing cell dose preparation to enhance stem cell survival and therapeutic function after transplantation. PMID:25126478

  10. 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.

  11. A Hybrid Parallel Preconditioning Algorithm For CFD

    NASA Technical Reports Server (NTRS)

    Barth,Timothy J.; Tang, Wei-Pai; Kwak, Dochan (Technical Monitor)

    1995-01-01

    A new hybrid preconditioning algorithm will be presented which combines the favorable attributes of incomplete lower-upper (ILU) factorization with the favorable attributes of the approximate inverse method recently advocated by numerous researchers. The quality of the preconditioner is adjustable and can be increased at the cost of additional computation while at the same time the storage required is roughly constant and approximately equal to the storage required for the original matrix. In addition, the preconditioning algorithm suggests an efficient and natural parallel implementation with reduced communication. Sample calculations will be presented for the numerical solution of multi-dimensional advection-diffusion equations. The matrix solver has also been embedded into a Newton algorithm for solving the nonlinear Euler and Navier-Stokes equations governing compressible flow. The full paper will show numerous examples in CFD to demonstrate the efficiency and robustness of the method.

  12. 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.

  13. On polynomial preconditioning for indefinite Hermitian matrices

    NASA Technical Reports Server (NTRS)

    Freund, Roland W.

    1989-01-01

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

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

    PubMed

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

    2015-08-01

    Microglia, the innate immune cells of the central nervous system (CNS), react to endotoxins like bacterial lipopolysaccharides (LPS) with a pronounced inflammatory response. To avoid excess damage to the CNS, the microglia inflammatory response needs to be tightly regulated. Here we report that a single LPS challenge results in a prolonged blunted pro-inflammatory response to a subsequent LPS stimulation, both in primary microglia cultures (100 ng/ml) and in vivo after intraperitoneal (0.25 and 1mg/kg) or intracerebroventricular (5 ?g) LPS administration. Chromatin immunoprecipitation (ChIP) experiments with primary microglia and microglia acutely isolated from mice showed that LPS preconditioning was accompanied by a reduction in active histone modifications AcH3 and H3K4me3 in the promoters of the IL-1? and TNF-? genes. Furthermore, LPS preconditioning resulted in an increase in the amount of repressive histone modification H3K9me2 in the IL-1? promoter. ChIP and knock-down experiments showed that NF-?B subunit RelB was bound to the IL-1? promoter in preconditioned microglia and that RelB is required for the attenuated LPS response. In addition to a suppressed pro-inflammatory response, preconditioned primary microglia displayed enhanced phagocytic activity, increased outward potassium currents and nitric oxide production in response to a second LPS challenge. In vivo, a single i.p. LPS injection resulted in reduced performance in a spatial learning task 4 weeks later, indicating that a single inflammatory episode affected memory formation in these mice. Summarizing, we show that LPS-preconditioned microglia acquire an epigenetically regulated, immune-suppressed phenotype, possibly to prevent excessive damage to the central nervous system in case of recurrent (peripheral) inflammation. PMID:25843371

  15. Proof of concept: pharmacological preconditioning with a Toll-like receptor agonist protects against cerebrovascular injury in a primate model of stroke

    PubMed Central

    Bahjat, Frances Rena; Williams-Karnesky, Rebecca L; Kohama, Steven G; West, G Alexander; Doyle, Kristian P; Spector, Maxwell D; Hobbs, Theodore R; Stenzel-Poore, Mary P

    2011-01-01

    Cerebral ischemic injury is a significant portion of the burden of disease in developed countries; rates of mortality are high and the costs associated with morbidity are enormous. Recent therapeutic approaches have aimed at mitigating the extent of damage and/or promoting repair once injury has occurred. Often, patients at high risk of ischemic injury can be identified in advance and targeted for antecedent neuroprotective therapy. Agents that stimulate the innate pattern recognition receptor, Toll-like receptor 9, have been shown to induce tolerance (precondition) to ischemic brain injury in a mouse model of stroke. Here, we demonstrate for the first time that pharmacological preconditioning against cerebrovascular ischemic injury is also possible in a nonhuman primate model of stroke in the rhesus macaque. The model of stroke used is a minimally invasive transient vascular occlusion, resulting in brain damage that is primarily localized to the cortex and as such, represents a model with substantial clinical relevance. Finally, K-type (also referred to as B-type) cytosine-guanine-rich DNA oligonucleotides, the class of agents employed in this study, are currently in use in human clinical trials, underscoring the feasibility of this treatment in patients at risk of cerebral ischemia. PMID:21285967

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

    PubMed Central

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

    2013-01-01

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

  17. 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. PMID:20489953

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

    NASA Technical Reports Server (NTRS)

    Wong, Yau Shu; Jiang, Hong

    1987-01-01

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

  19. 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)

  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. A global hypoxia preconditioning model: neuroprotection against seizure-induced specific gravity changes (edema) and brain damage in rats.

    PubMed

    Emerson, M R; Nelson, S R; Samson, F E; Pazdernik, T L

    1999-12-01

    Hypoxia preconditioning states that a sublethal hypoxia episode will afford neuroprotection against a second challenge in the near future. We describe and discuss a procedure for the development of global hypoxia preconditioning in adult male Wistar rats, using a mildly hypoxic (9% O(2), 91% N(2)) atmospheric exposure of 8 h. The persistence of neuroprotection was analyzed using a kainic acid (KA) model of brain injury. Rats were challenged with KA (14 mg/kg, i.p.) on 1-14 days post-hypoxia. The effects of hypoxia preconditioning on seizure score, weight loss, brain edema and histopathology were assessed. Brain edema, predominantly of vasogenic origin, was measured 24 h after KA administration using a reproducible and quantitative method based on the specific gravities of tissue samples. A density gradient column (1.0250-1.0650 g/cm(3)) comprised of kerosene and bromobenzene was used to assess the presence of edema in regions involved in seizure initiation and propagation that are normally extensively damaged (i.e., piriform cortex and hippocampus). Specific gravities of tissues were calculated through extrapolation with known NaCl standards. We found that hypoxia preconditioning prevented the formation of edema in these brain regions when KA challenge was given 1, 3, and 7, but not 14 days post-hypoxia exposure. Furthermore, neuroprotection was observed in animals that had robust seizures. The described procedure may be used to examine the neuroprotective mechanisms induced by global hypoxia preconditioning against many subsequent challenges reflecting a variety of experimental models of brain injury, and will provide a better understanding of the brain response to hypoxia and stress. PMID:10592346

  2. H(curl) Auxiliary Mesh Preconditioning

    SciTech Connect

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

    2006-08-31

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

  3. Controlled Ionospheric Preconditioning and Stimulated Electromagnetic Radiation

    SciTech Connect

    Cheung, P.Y.; Wong, A.Y.; Pau, J.; Mjo/lhus, E.

    1998-06-01

    New results of stimulated electromagnetic emissions (SEE) from the HIPAS Observatory are reported. A novel hf heating sequence was used to first precondition the ionosphere, and SEE was then excited with low-amplitude test pulses. Through this approach, the nonlinear physics of SEE was studied. The correlation between small-scale field-aligned density striations and SEE generation was demonstrated, and SEE was excited at power density of 24thinspthinspdB less than normally required. The results compare well with theoretical predictions of SEE generation via trapped upper hybrid oscillations decay and cavitation within striations. {copyright} {ital 1998} {ital The American Physical Society}

  4. Effects of morphine and sufentanil preconditioning against myocardial ischemic-reperfusion injury in rabbits

    PubMed Central

    Wang, Xiu-Hong; Zeng, Jian-Feng; Lin, Chao; Chen, Shi-Biao

    2015-01-01

    Objective: This study aims to explore the treatment method of myocardial ischemia-reperfusion injury. Methods: Myocardial Ischemia-reperfusion rabbit model was established in this study. They were divided into four groups: sham operation (S) group, IRI control (I/R) group and IRI with morphine (MF) group and sufentanil (SF). Myocardial infarct size was compared with HE staining method. TUNEL assay was used to detect cell apoptosis. Results: Myocardial infarct size of control group and morphine and sufetanil group was 36.0±3.6, 23.0±1.2 and 27.1±2.3, respectively. There were significant differences between them (P < 0.01). Apoptotic index of I/R, MF and SF groups was 26.9±2.2, 12.5±2.3, 15.8±2.0, with statistical significance (P < 0.05). The concentration of CK-MB in serum: there were no significant differences of CK-MB between each group at baseline. The concentration of CK-MB after reperfusion were higher than that of baseline, except for group S (P < 0.05); Compared with group S, after reperfusion, the CK-MB of other three groups were higher (P < 0.05); The concentration of CK-MB in group MF and SF were lower than group I/R (P < 0.05); In contrast to group MF, the concentration of CK-MB after reperfusion was higher in group SF (P < 0.05). Conclusion: Morphine and sufentanil can specifically protect the myocardial function. PMID:26629064

  5. Encrypted IP video communication system

    NASA Astrophysics Data System (ADS)

    Bogdan, Apetrechioaie; Lumini?a, Mateescu

    2010-11-01

    Digital video transmission is a permanent subject of development, research and improvement. This field of research has an exponentially growing market in civil, surveillance, security and military aplications. A lot of solutions: FPGA, ASIC, DSP have been used for this purpose. The paper presents the implementation of an encrypted, IP based, video communication system having a competitive performance/cost ratio .

  6. 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.

  7. 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.

  8. [Hypoxic preconditioning of stem cells as a new approach to increase the efficacy of cell therapy for myocardial infarction].

    PubMed

    Maslov, L N; Podoksenov, Iu K; Portnichenko, A G; Naumova, A V

    2013-01-01

    During the last decade, stem cell research has developed at an accelerated pace. Various types of stem cells have been tested for myocardial infarction therapy. Despite the preclinical benefits of cell therapy success in clinical trials remains modest. The main obstacles to regeneration of the infarcted heart using stem cells are: 1) not every stem cell type can differentiate into cardiomyocytes; and 2) low survival rates of transplanted cells, due to the harsh environment of the infarcted myocardium. Hypoxic preconditioning (HP) has been shown to improve transplantation efficacy of mesenchymal stem cells and cardiac progenitor cells in animal models of myocardial infarction. It has also been shown that transplantation of preconditioned cells decreases infarct size, prevents postinfarction remodeling of the heart, and positively modulates development of ischemic cardiomyopathy. Hypoxic preconditioning also prevents extensive death of transplanted cells due to necrosis and apoptosis during long-term hypoxia or oxidative stress. The protective effect of HP is based on three main processes: (1) modification of cell phenotypes to help survival during hypoxia (enhancement of HIF-1alpha expression, ERK1/2 and Akt activation, enhancement of erythropoietin receptor expression and erythropoietin production, and an elevation in levels of antiapoptotic proteins Bcl-2 and Bcl-xL); (2) upregulation of various secretable factors including the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and expression of VEGF-2 and HGF-receptors; (3) enhancement in the formation of CXCR4 and CXCR7 receptors, which play an important role in mobilization and homing of stem cells in the ischemic region. PMID:24741938

  9. 40 CFR 1066.407 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  10. 40 CFR 1066.407 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  11. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... than two hours, preconditioning consists of one full Urban Dynamometer Driving Cycle. Manufacturers, at... 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete... begin with the preconditioning drive specified in 86.132-96(c)(1). The test vehicle may not be used...

  12. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... than two hours, preconditioning consists of one full Urban Dynamometer Driving Cycle. Manufacturers, at... 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete... begin with the preconditioning drive specified in 86.132-96(c)(1). The test vehicle may not be used...

  13. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... than two hours, preconditioning consists of one full Urban Dynamometer Driving Cycle. Manufacturers, at... 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete... begin with the preconditioning drive specified in 86.132-96(c)(1). The test vehicle may not be used...

  14. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... than two hours, preconditioning consists of one full Urban Dynamometer Driving Cycle. Manufacturers, at... 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete... begin with the preconditioning drive specified in 86.132-96(c)(1). The test vehicle may not be used...

  15. 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.

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

    PubMed

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

    2015-09-01

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

  17. [Painful ischemic neuropathy].

    PubMed

    Lang, P M

    2015-02-01

    Chronic ischemia in patients with peripheral arterial disease (PAD) represents a common medical problem. Neuropathic changes and pain caused by chronic ischemia are often found in the lower extremities of these patients. Pain in patients with chronic critical limb ischemia fulfill the criteria of neuropathic pain. Diagnostic tools besides medical history and examination are questionnaires, quantitative sensory testing (QST) and measuring intraepidermal nerve fiber density (IENFD) when indicated. A pharmacological approach with non-opioids and opioids as well as antidepressive and anticonvulsive drugs (according to the recommendations for the therapy of neuropathic pain) seems to be indicated for treating painful ischemic neuropathy. Spinal cord stimulation (SCS) provides the best evidence for invasive procedures in treating chronic ischemic pain. PMID:25620734

  18. The relationship between ischemia-reperfusion injury, myocardial stunning and cardiac preconditioning.

    PubMed

    Mitchell, M B; Winter, C B; Banerjee, A; Harken, A H

    1993-07-01

    The high incidence of coronary disease in the current population renders myocardial ischemia a leading cause of morbidity and death. Recent efforts have made rapid restoration of coronary flow a clinical reality. Despite progress in hypothermic arrest and cardioplegia, the widespread performance of open cardiac operation and increasing use of cardiac transplantation obligate myocardial I/R stress. Advances in understanding the pathophysiologic factors of reversible and irreversible I/R injury have been significant, but are incomplete. Myocardial infarction and myocardial "stunning" remain clinically important sequelae of coronary disease. In the long term, the solution to heart disease will likely come through preventative health measures. In the interim, however, measures to limit ischemic duration and prepare the heart for reperfusion are clinically desirable. The presence of intrinsic cellular protective mechanisms intimate the feasibility of the latter measure. Furthermore, recently delineated receptor-mediated mechanisms of ischemic preconditioning may render this phenomenon clinically exploitable. The multifactorial pathophysiologic nature of the I/R process suggests that optimal intervention will likely require a combination of pharmacologic adjuncts intended for the specific type and severity of I/R insult. Continued exploration of I/R pathophysiologic factors is needed to develop practical therapeutic interventions. PMID:8322165

  19. Effect of Bradykinin Postconditioning on Ischemic and Toxic Brain Damage.

    PubMed

    Lalkovi?ov, Mria; Bonov, Petra; Burda, Jozef; Danielisov, Viera

    2015-08-01

    Brain damage caused by ischemia or toxic agents leads in selectively vulnerable regions to apoptosis-like delayed neuronal death and can result in irreversible damage. Selectively vulnerable neurons of the CA1 area of hippocampus are particularly sensitive to ischemic damage. We investigated the effects of bradykinin (BR) postconditioning on cerebral ischemic and toxic injury. Transient forebrain ischemia was induced by four-vessel occlusion for 10 min and toxic injury was induced by trimethyltin (TMT, 8 g/kg i.p.). BR as a postconditioner at a dose of 150 g/kg was applied intraperitoneally 48 h after ischemia or TMT intoxication. Experimental animals were divided into groups according to the length of survival (short-3 and 7 days, and long-28 days survival) and according to the applied ischemic or toxic injury. Glutamate concentration was lowered in both CA1 and dentate gyrus areas of hippocampus after the application of BR postconditioning in both ischemic and toxic brain damage. The number of degenerated neurons in the hippocampal CA1 region was significantly lower in BR-treated ischemic and toxic groups compared to vehicle group. The behavioral test used in our experiments confirms also the memory improvement in conditioned animals. The rats' ability to form spatial maps and learn was preserved, which is visible from our Barnes maze results. By using the methods of delayed postconditioning is possible to stimulate the endogenous protective mechanisms of the organism and induce the neuroprotective effect. In this study we demonstrated that BR postconditioning, if applied before the onset of irreversible neurodegenerative changes, induced neuroprotection against ischemic or toxic injury. PMID:26216051

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

    PubMed

    Zhao, Liang; Nowak, Thaddeus S

    2015-07-01

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

  1. Hypoxic Preconditioning Differentially Affects GABAergic and Glutamatergic Neuronal Cells in the Injured Cerebellum of the Neonatal Rat

    PubMed Central

    Patterson, Sean I.; Muoz, Estela M.; Seltzer, Alicia M.

    2014-01-01

    In this study we examined cerebellar alterations in a neonatal rat model of hypoxic-ischemic brain injury with or without hypoxic preconditioning (Pc). Between postnatal days 7 and 15, the cerebellum is still undergoing intense cellular proliferation, differentiation and migration, dendritogenesis and synaptogenesis. The expression of glutamate decarboxylase 1 (GAD67) and the differentiation factor NeuroD1 were examined as markers of Purkinje and granule cells, respectively. We applied quantitative immunohistochemistry to sagittal cerebellar slices, and Western blot analysis of whole cerebella obtained from control (C) rats and rats submitted to Pc, hypoxia-ischemia (L) and a combination of both treatments (PcL). We found that either hypoxia-ischemia or Pc perturbed the granule cells in the posterior lobes, affecting their migration and final placement in the internal granular layer. These effects were partially attenuated when the Pc was delivered prior to the hypoxia-ischemia. Interestingly, whole nuclear NeuroD1 levels in Pc animals were comparable to those in the C rats. However, a subset of Purkinje cells that were severely affected by the hypoxic-ischemic insultshowing signs of neuronal distress at the levels of the nucleus, cytoplasm and dendritic arborizationwere not protected by Pc. A monoclonal antibody specific for GAD67 revealed a three-band pattern in cytoplasmic extracts from whole P15 cerebella. A ?110 kDa band, interpreted as a potential homodimer of a truncated form of GAD67, was reduced in Pc and L groups while its levels were close to the control animals in PcL rats. Additionally we demonstrated differential glial responses depending on the treatment, including astrogliosis in hypoxiated cerebella and a selective effect of hypoxia-ischemia on the vimentin-immunolabeled intermediate filaments of the Bergmann glia. Thus, while both glutamatergic and GABAergic cerebellar neurons are compromised by the hypoxic-ischemic insult, the former are protected by a preconditioning hypoxia while the latter are not. PMID:25032984

  2. 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 organisms 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

  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. The preconditioning of major sudden stratospheric warmings

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  5. The Spacelab IPS Star Simulator

    NASA Technical Reports Server (NTRS)

    Wessling, Francis C., III

    1993-01-01

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

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

    PubMed Central

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

    2013-01-01

    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. PMID:24961318

  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. 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,

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

    PubMed

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

    2014-06-15

    We examined the hypothesis that repeated exposure to non-convulsive hyperbaric oxygen (HBO) as preconditioning provides protection against central nervous system oxygen toxicity (CNS-OT). Four groups of rats were used in the study. Rats in the control and the negative control (Ctl-) groups were kept in normobaric air. Two groups of rats were preconditioned to non-convulsive HBO at 202 kPa for 1h once every other day for a total of three sessions. Twenty-four hours after preconditioning, one of the preconditioned groups and the control rats were exposed to convulsive HBO at 608 kPa, and latency to CNS-OT was measured. Ctl- rats and the second preconditioned group (PrC-) were not subjected to convulsive HBO exposure. Tissues harvested from the hippocampus and frontal cortex were evaluated for enzymatic activity and nitrotyrosine levels. In the group exposed to convulsive oxygen at 608 kPa, latency to CNS-OT increased from 12.8 to 22.4 min following preconditioning. A significant decrease in the activity of glutathione reductase and glucose-6-phosphate dehydrogenase, and a significant increase in glutathione peroxidase activity, was observed in the hippocampus of preconditioned rats. Nitrotyrosine levels were significantly lower in the preconditioned animals, the highest level being observed in the control rats. In the cortex of the preconditioned rats, a significant increase was observed in glutathione S-transferase and glutathione peroxidase activity. Repeated exposure to non-convulsive HBO provides protection against CNS-OT. The protective mechanism involves alterations in the enzymatic activity of the antioxidant system and lower levels of peroxynitrite, mainly in the hippocampus. PMID:24675062

  10. Hypoxic preconditioning alleviates ethanol neurotoxicity: the involvement of autophagy.

    PubMed

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

    2013-11-01

    Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. A sublethal preconditioning has been proposed as a neuroprotective strategy against several central nervous system neurodegenerative diseases. We have recently demonstrated that autophagy is a protective response to alleviate ethanol toxicity. A modest hypoxic preconditioning (1 % oxygen) did not cause neurotoxicity but induced autophagy (Tzeng et al. Free Radic Biol Med 49: 839-846, 2010). We, therefore, hypothesize that the modest hypoxic preconditioning may offer a protection against ethanol-induced neurotoxicity. We showed here that the modest hypoxic preconditioning (1 % oxygen) for 8 h significantly alleviated ethanol-induced death of SH-SY5Y neuroblastoma cells. Under the normoxia condition, cell viability in ethanol-exposed cultures (316 mg/dl for 48 h) was 49 ± 6 % of untreated controls; however, with hypoxic preconditioning, cell viability in the ethanol-exposed group increased to 78 ± 7 % of the controls (p < 0.05; n = 3). Bafilomycin A1, an inhibitor of autophagosome and lysosome fusion, blocked hypoxic preconditioning-mediated protection. Similarly, inhibition of autophagic initiation by wortmannin also eliminated hypoxic preconditioning-mediated protection. In contrast, activation of autophagy by rapamycin further enhanced neuroprotection caused by hypoxic preconditioning. Taken together, the results confirm that autophagy is a protective response against ethanol neurotoxicity and the modest hypoxic preconditioning can offer neuroprotection by activating autophagic pathways. PMID:23568540

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

    PubMed Central

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

    2016-01-01

    Hypoxic pretreatment of peripheral blood mononuclear cells (PBMNCs) enhances therapeutic angiogenesis in ischemic tissues after cell transplantation. However, newly formed vessels generated using this approach are immature and insufficient for promoting functional recovery from severe ischemia. In this study, we examined whether apelin-13, a regulator of vessel maturation, could be an effective promoter of therapeutic angiogenesis, following severe limb ischemia. Combinatorial treatment of hypoxic preconditioned PBMNCs with apelin-13 resulted in increased blood perfusion and vascular reactivity in ischemic mouse hindlimbs compared with a monotherapy comprising each factor. Apelin-13 upregulated expression of PDGF-BB and TGF-?1 in hypoxic PBMNCs, as well as that of PDGFR-? in vascular smooth muscle cells (VSMCs). Proliferation and migration of VSMCs treated with apelin-13 was accelerated in the presence of PDGF-BB. Interestingly, expression of an apelin receptor, APJ, in PBMNC was increased under hypoxia but not under normoxia. In addition, an in vitro angiogenesis assay using a co-culture model comprising mouse thoracic aorta, hypoxic PBMNCs, and apelin-13 demonstrated that combinatorial treatment recruited mural cells to sprouted vessel outgrowths from the aortic ring, thereby promoting neovessel maturation. Thus, combinatorial injection of hypoxic PBMNCs and apelin-13 could be an effective therapeutic strategy for patients with severe ischemic diseases. PMID:26763337

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

    PubMed

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

    2016-01-01

    Hypoxic pretreatment of peripheral blood mononuclear cells (PBMNCs) enhances therapeutic angiogenesis in ischemic tissues after cell transplantation. However, newly formed vessels generated using this approach are immature and insufficient for promoting functional recovery from severe ischemia. In this study, we examined whether apelin-13, a regulator of vessel maturation, could be an effective promoter of therapeutic angiogenesis, following severe limb ischemia. Combinatorial treatment of hypoxic preconditioned PBMNCs with apelin-13 resulted in increased blood perfusion and vascular reactivity in ischemic mouse hindlimbs compared with a monotherapy comprising each factor. Apelin-13 upregulated expression of PDGF-BB and TGF-?1 in hypoxic PBMNCs, as well as that of PDGFR-? in vascular smooth muscle cells (VSMCs). Proliferation and migration of VSMCs treated with apelin-13 was accelerated in the presence of PDGF-BB. Interestingly, expression of an apelin receptor, APJ, in PBMNC was increased under hypoxia but not under normoxia. In addition, an in vitro angiogenesis assay using a co-culture model comprising mouse thoracic aorta, hypoxic PBMNCs, and apelin-13 demonstrated that combinatorial treatment recruited mural cells to sprouted vessel outgrowths from the aortic ring, thereby promoting neovessel maturation. Thus, combinatorial injection of hypoxic PBMNCs and apelin-13 could be an effective therapeutic strategy for patients with severe ischemic diseases. PMID:26763337

  13. Reactive oxygen species are not a required trigger for exercise-induced late preconditioning in the rat heart.

    PubMed

    Taylor, Ryan P; Starnes, Joseph W

    2012-11-01

    Reactive oxygen species (ROS) have been reported to play a primary role in triggering the cardioprotective adaptations by some preconditioning procedures, but whether they are required for exercise-induced preconditioning is unclear. Thus in this study we used the free radical scavenger N-(2-mercaptopropionyl)glycine (MPG) to test the hypothesis that ROS is the trigger for exercise-induced preconditioning of the heart against ischemia-reperfusion injury. Male F344 rats were assigned to four groups: sedentary (SED, n = 7), SED/MPG (100 mg/kg ip daily for 2 days, n = 12), exercised on a treadmill for 2 days at 20 m/min, 6 grade, for 60 min (RUN, n = 7), and RUN/MPG with 100 mg/kg MPG injected 15 min before exercise (n = 10). Preliminary experiments verified that MPG administration maintained myocardial redox status during the exercise bout. Twenty-four hours postexercise or MPG treatment isolated perfused working hearts were subjected to global ischemia for 22.5 min followed by reperfusion for 30 min. Recovery of myocardial external work (percentage of preischemic systolic pressure times cardiac output) for SED (50.4 4.5) and SED/RUN (54.7 6.6) was similar and improved in both exercise groups (P < 0.05) to 77.9 3.0 in RUN and 76.7 4.5 in RUN/MPG. A 2 2 ANOVA also revealed that exercise decreased lactate dehydrogenase release from the heart during reperfusion (marker of cell damage) without MPG effects or interactions. Expression of the cytoprotective protein inducible heat shock protein 70 increased by similar amounts in the left ventricles of RUN and RUN/MPG compared with sedentary groups (P < 0.05). We conclude that ROS are not a necessary trigger for exercise-induced preconditioning in rats. PMID:22955056

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

    SciTech Connect

    Hong, Kyung-Soo; Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan ; Park, Jun-Ik; Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won; Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan ; Dao, Trong Tuan; Oh, Won Keun; Kang, Chi-Dug; Kim, Sun-Hee; Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan

    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-exposed or hypoxic preconditioned cells. ► SIRT1 deacetylates c-Myc and β-catenin ► HIF-1α is up-regulated by down-regulation of c-Myc and β-catenin expression. ► Polyphenolic SIRT1 activators mimics hypoxic preconditioning.

  15. Enhancement of angiogenic effects by hypoxia-preconditioned human umbilical cord-derived mesenchymal stem cells in a mouse model of hindlimb ischemia.

    PubMed

    Han, Kyu-Hyun; Kim, Ae-Kyeong; Kim, Min-Hee; Kim, Do-Hyung; Go, Ha-Nl; Kim, Dong-Ik

    2016-01-01

    It has been studied that mesenchymal stem cells (MSCs) have the capability to promote angiogenesis. Furthermore, there is strong evidence that hypoxic conditions can enhance angiogenesis and immune modulation mediated by MSCs, a notion that has been applied in many fields of clinical application. In the present study, we compared the efficacy of hypoxia preconditioned human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and normoxia conditioned hUC-MSCs for the treatment of ischemic injury in hindlimbs of an immunodeficient mouse model. Expression of negative markers for MSC such as CD31, CD34, and CD45 or positive markers such as CD44, CD73, CD90, and CD105 was not significantly changed in hypoxia preconditioned hUC-MSCs compared with hUC-MSCs cultured in normoxic condition. Expression of angiogenesis-related genes such as COX-2, VEGF, Tie-2, and TGF-?1 was increased compared with hUC-MSCs cultured in normoxic conditions. In the in vivo model, CD31 expression as a marker of angiogenesis was significantly increased in the ischemic limbs at 1 month after injection with hypoxic hUC-MSCs. Angiogenesis-related genes such as Ang-1, COX-1, PIGF, and MCP-1 were significantly upregulated in the muscle of ischemic hindlimbs treated with hypoxic hUC-MSCs than normoxic hUC-MSCs. Expression of proinflammatory genes such as IL-1, and IL-20 was reduced, whereas TGF-?1, which has an anti-inflammatory effect, was strongly increased. In conclusion, hypoxic culture conditions could induce expression of angiogenesis related genes in hUC-MSCs, and hypoxia preconditioned hUC-MSCs showed enhancing effects by inducing angiogenesis and low inflammatory immune response compared with normoxic hUC-MSCs in the ischemia injured hindlimb of immunodeficient mice. PMID:26222206

  16. 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.

  17. Hypobaric Preconditioning Modifies Group I mGluRs Signaling in Brain Cortex.

    PubMed

    Semenov, Dmitry G; Belyakov, Alexandr V; Glushchenko, Tatjana S; Samoilov, Mikhail O; Salinska, Elzbieta; Lazarewicz, Jerzy W

    2015-11-01

    The study assessed involvement of Ca(2+) signaling mediated by the metabotropic glutamate receptors mGluR1/5 in brain tolerance induced by hypoxic preconditioning. Acute slices of rat piriform cortex were tested 1 day after exposure of adult rats to mild hypobaric hypoxia for 2 h at a pressure of 480 hPa once a day for three consecutive days. We detected 44.1 11.6 % suppression of in vitro anoxia-induced increases of intracellular Ca(2+) levels and a fivefold increase in Ca(2+) transients evoked by selective mGluR1/5 agonist, DHPG. Western blot analysis of cortical homogenates demonstrated a 11 4 % decrease in mGluR1 immunoreactivity (IR), and in the nuclei-enriched fraction a 12 3 % increase in IR of phospholipase C?1 (PLC?1), which is a major mediator of mGluR1/5 signaling. Immunocytochemical analysis of the cortex revealed increase in the mGluR1/5 and PLC?1 IR in perikarya, and a decrease in IR of the neuronal inositol trisphosphate receptors (IP3Rs). We suggest that enhanced expression of mGluR5 and PLC?1 and potentiation of Ca(2+) signaling may represent pro-survival upregulation of Ca(2+)-dependent genomic processes, while decrease in mGluR1 and IP3R IR may be attributed to a feedback mechanism preventing excessive intracellular Ca(2+) release. PMID:26318863

  18. 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.

  19. 40 CFR 1066.816 - Vehicle preconditioning for FTP testing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) AIR POLLUTION CONTROLS VEHICLE-TESTING PROCEDURES Exhaust Emission Test Procedures for Motor Vehicles... measurement as described in 40 CFR 86.132. ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Vehicle preconditioning for...

  20. Preconditioning methods for improved convergence rates in iterative reconstructions

    SciTech Connect

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

    1993-03-01

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

  1. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for... manufacturer has concerns about fuel effects on adaptive memory systems, a manufacturer may precondition a...

  2. 40 CFR 86.1232-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Methanol-Fueled Heavy-Duty Vehicles § 86.1232-96 Vehicle preconditioning. (a) Fuel tank cap(s) of gasoline...), start the diurnal heat build. (x) The fuel shall be heated in such a way that its temperature...

  3. 40 CFR 86.1232-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Methanol-Fueled Heavy-Duty Vehicles § 86.1232-96 Vehicle preconditioning. (a) Fuel tank cap(s) of gasoline...), start the diurnal heat build. (x) The fuel shall be heated in such a way that its temperature...

  4. Remote ischaemic preconditioning for coronary artery bypass grafting

    PubMed Central

    Benstoem, Carina; Stoppe, Christian; Liakopoulos, Oliver J; Meybohm, Patrick; Clayton, Tim C; Yellon, Derek M; Hausenloy, Derek J; Goetzenich, Andreas

    2015-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the benefits and harms of remote ischaemic preconditioning in patients undergoing coronary artery bypass grafting, with or without valve surgery.

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

    PubMed Central

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

    2015-01-01

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

  6. Hypoxia preconditioning protects corneal stromal cells against induced apoptosis

    PubMed Central

    Xing, Dongmei; Sun, Xingcai; Li, Jinhua; Cui, Miao; Tan-Allen, Kah; Bonanno, Joseph A.

    2011-01-01

    The purpose of this study, was to determine whether hypoxia preconditioning can protect corneal stromal cells from UV stress and cytokine mediated apoptosis. Two models were implemented. First, primary cultured bovine corneal fibroblasts were preconditioned with 0.51.5% O2 for 4 hr and stressed with UV-irradiation or stimulation of Fas receptor. Second, bovine eyes were preconditioned with 0.5% O2 for 4 hr and stressed by epithelial scraping to induce anterior keratocyte apoptosis. Cell fate was analyzed at 4 hr after stress using quantitative TUNEL or condensed nuclei assays. Cell apoptotic rates in hypoxia preconditioned groups were significantly lower (5080%) than that of normoxia control groups. Hypoxia prevented the degradation of the transcription factor HIF-1?. CoCl2 (100200 ?M), a chemical inducer of HIF-1?, also produced strong protection against UV and Fas induced apoptosis. Moreover, hypoxia preconditioned media protected cells against UV-induced apoptosis. These findings demonstrate that hypoxia preconditioning has a generalized protective effect against stromal fibroblast and keratocyte apoptosis and suggest that HIF-1? mediated expression and secretion of protective factors is involved. PMID:16364292

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

    SciTech Connect

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

    1988-05-01

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

  8. The Spacelab IPS Star Simulator

    NASA Technical Reports Server (NTRS)

    Wessling, Francis C., III

    1993-01-01

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

  9. HMGB1 in renal ischemic injury

    PubMed Central

    Rabadi, May M.; Ghaly, Tammer; Goligorksy, Michael S.

    2012-01-01

    Factors that initiate cellular damage and trigger the inflammatory response cascade and renal injury are not completely understood after renal ischemia-reperfusion injury (IRI). High-mobility group box-1 protein (HMGB1) is a damage-associated molecular pattern molecule that binds to chromatin, but upon signaling undergoes nuclear-cytoplasmic translocation and release from cells. Immunohistochemical and Western blot analysis identified HMGB1 nuclear-cytoplasmic translocation and release from renal cells (particularly vascular and tubular cells) into the venous circulation after IRI. Time course analysis indicated HMGB1 release into the venous circulation progressively increased parallel to increased renal ischemic duration. Ethyl pyruvate (EP) treatment blocked H2O2 (oxidative stress)-induced HMGB1 release from human umbilical vein endothelial cells in vitro, and in vivo resulted in nuclear retention and significant blunting of HMGB1 release into the circulation after IRI. EP treatment before IRI improved short-term serum creatinine and albuminuria, proinflammatory cyto-/chemokine release, and long-term albuminuria and fibrosis. The renoprotective effect of EP was abolished when exogenous HMGB1 was injected, suggesting EP's therapeutic efficacy is mediated by blocking HMGB1 translocation and release. To determine the independent effects of circulating HMGB1 after injury, exogenous HMGB1 was administered to healthy animals at pathophysiological dose. HMGB1 administration induced a rapid surge in systemic circulating cyto-/chemokines (including TNF-?, eotaxin, G-CSF, IFN-?, IL-10, IL-1?, IL-6, IP-10, and KC) and led to mobilization of bone marrow CD34+Flk1+ cells into the circulation. Our results indicate that increased ischemic duration causes progressively enhanced HMGB1 release into the circulation triggering damage/repair signaling, an effect inhibited by EP because of its ability to block HMGB1 nuclear-cytoplasmic translocation. PMID:22759395

  10. Responsive corneosurfametry following in vivo skin preconditioning.

    PubMed

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

    2003-12-01

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

  11. 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.

  12. Quantification of neurovascular protection following repetitive hypoxic preconditioning and transient middle cerebral artery occlusion in mice.

    PubMed

    Poinsatte, Katherine; Selvaraj, Uma Maheswari; Ortega, Sterling B; Plautz, Erik J; Kong, Xiangmei; Gidday, Jeffrey M; Stowe, Ann M

    2015-01-01

    Experimental animal models of stroke are invaluable tools for understanding stroke pathology and developing more effective treatment strategies. A 2 week protocol for repetitive hypoxic preconditioning (RHP) induces long-term protection against central nervous system (CNS) injury in a mouse model of focal ischemic stroke. RHP consists of 9 stochastic exposures to hypoxia that vary in both duration (2 or 4 hr) and intensity (8% and 11% O2). RHP reduces infarct volumes, blood-brain barrier (BBB) disruption, and the post-stroke inflammatory response for weeks following the last exposure to hypoxia, suggesting a long-term induction of an endogenous CNS-protective phenotype. The methodology for the dual quantification of infarct volume and BBB disruption is effective in assessing neurovascular protection in mice with RHP or other putative neuroprotectants. Adult male Swiss Webster mice were preconditioned by RHP or duration-equivalent exposures to 21% O2 (i.e. room air). A 60 min transient middle cerebral artery occlusion (tMCAo) was induced 2 weeks following the last hypoxic exposure. Both the occlusion and reperfusion were confirmed by transcranial laser Doppler flowmetry. Twenty-two hr after reperfusion, Evans Blue (EB) was intravenously administered through a tail vein injection. 2 hr later, animals were sacrificed by isoflurane overdose and brain sections were stained with 2,3,5- triphenyltetrazolium chloride (TTC). Infarcts volumes were then quantified. Next, EB was extracted from the tissue over 48 hr to determine BBB disruption after tMCAo. In summary, RHP is a simple protocol that can be replicated, with minimal cost, to induce long-term endogenous neurovascular protection from stroke injury in mice, with the translational potential for other CNS-based and systemic pro-inflammatory disease states. PMID:25993394

  13. Preconditioning-mimetics bradykinin and DADLE activate PI3-kinase through divergent pathways.

    PubMed

    Cohen, Michael V; Philipp, Sebastian; Krieg, Thomas; Cui, Lin; Kuno, Atsushi; Solodushko, Viktoriya; Downey, James M

    2007-04-01

    We previously reported that pharmacological preconditioning of rabbit hearts with acetylcholine involves activation of phosphatidylinositol 3-kinase (PI3-K) through transactivation of the epidermal growth factor receptor (EGFR). Transactivation is thought to be initiated by cleavage of membrane-bound pro-heparin-binding EGF-like growth factor (HB-EGF) by a membrane metalloproteinase thus releasing HB-EGF which binds to the EGFR. This pathway leads to redox signaling with the generation of reactive oxygen species (ROS) by mitochondria. We tested whether preconditioning's physiological triggers, bradykinin and opioid, also signal through the EGFR. Both bradykinin and the synthetic delta-opioid agonist DADLE increased ROS production in isolated cardiomyocytes by approximately 50%. DADLE's effect was abrogated by either metalloproteinase inhibitor III (MPI) or the diphtheria toxin mutant CRM-197 which blocks heparin-binding EGF shedding indicating that DADLE signals through EGFR transactivation. MPI also blocked DADLE's infarct-sparing effect in whole hearts. Additionally, blocking Src kinase (a component of the EGFR's signaling complex) with PP2 or PI3-K with wortmannin blocked DADLE's effect on cardiomyocyte ROS production and PP2 blocked DADLE's salvage of ischemic myocardium. Finally, DADLE increased phosphorylation of Akt and extracellular signal-regulated protein kinases (ERK) 1/2 in left ventricular myocardium, and this increase was blocked by the EGFR antagonist AG1478. On the other hand, neither MPI nor CRM-197 prevented bradykinin from increasing ROS production, and MPI did not affect bradykinin's infarct-sparing effect in intact hearts. Conversely, both PP2 and wortmannin blocked bradykinin's effect on ROS generation and also aborted bradykinin's cardioprotective effect in intact hearts. While bradykinin also increased phosphorylation of Akt and ERK in myocardium, that increase was not affected by AG1478. Hence bradykinin, unlike acetylcholine or opioid, does not transactivate EGFR, although all 3 agonists do signal through Src and PI3-K. PMID:17292392

  14. 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. PMID:20127561

  15. Remote Ischemic Conditioning

    PubMed Central

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

    2014-01-01

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

  16. 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.

  17. Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia

    PubMed Central

    2014-01-01

    Background Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of brain preconditioning. Unraveling mechanisms of this endogenous neuroprotection, activated by preconditioning, is an important step towards new clinical strategies for treating asphyctic neonates. Therefore, we investigated whole-genome transcriptional changes in the brain of rats which underwent perinatal asphyxia (PA), and rats where PA was preceded by fetal asphyctic preconditioning (FAPA). Offspring were sacrificed 6h and 96h after birth, and whole-genome transcription was investigated using the Affymetrix Gene1.0ST chip. Microarray data were analyzed with the Bioconductor Limma package. In addition to univariate analysis, we performed Gene Set Enrichment Analysis (GSEA) in order to derive results with maximum biological relevance. Results We observed minimal, 25% or less, overlap of differentially regulated transcripts across different experimental groups which leads us to conclude that the transcriptional phenotype of these groups is largely unique. In both the PA and FAPA group we observe an upregulation of transcripts involved in cellular stress. Contrastingly, transcripts with a function in the cell nucleus were mostly downregulated in PA animals, while we see considerable upregulation in the FAPA group. Furthermore, we observed that histone deacetylases (HDACs) are exclusively regulated in FAPA animals. Conclusions This study is the first to investigate whole-genome transcription in the neonatal brain after PA alone, and after perinatal asphyxia preceded by preconditioning (FAPA). We describe several genes/pathways, such as ubiquitination and proteolysis, which were not previously linked to preconditioning-induced neuroprotection. Furthermore, we observed that the majority of upregulated genes in preconditioned animals have a function in the cell nucleus, including several epigenetic players such as HDACs, which suggests that epigenetic mechanisms are likely to play a role in preconditioning-induced neuroprotection. PMID:24885038

  18. Ischemic ulcers - self-care

    MedlinePLUS

    ... ischemic ulcers include: Dark red, yellow, gray, or black sores. Raised edges around the wound (looks punched ... Diabetes Diseases that cause inflammation, such as lupus High blood pressure Kidney failure Lymphedema, which causes fluid to build ...

  19. 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.

  20. Sevoflurane Preconditioning Reduces Intestinal Ischemia-Reperfusion Injury: Role of Protein Kinase C and Mitochondrial ATP-Sensitive Potassium Channel

    PubMed Central

    Shen, Zhiwen; Miao, Liping; Zhang, Kun; Wang, Fei; Li, Yujuan

    2015-01-01

    Ischemic preconditioning (IPC) has been considered to be a potential therapy to reduce ischemia-reperfusion injury (IRI) since the 1980s. Our previous study indicated that sevoflurane preconditioning (SPC) also reduced intestinal IRI in rats. However, whether the protective effect of SPC is similar to IPC and the mechanisms of SPC are unclear. Thus, we compared the efficacy of SPC and IPC against intestinal IRI and the role of protein kinase C (PKC) and mitochondrial ATP-sensitive potassium channel (mKATP) in SPC. A rat model of intestinal IRI was used in this study. The superior mesenteric artery (SMA) was clamped for 60 min followed by 120 min of reperfusion. Rats with IPC underwent three cycles of SMA occlusion for 5 min and reperfusion for 5 min before intestinal ischemia. Rats with SPC inhaled sevoflurane at 0.5 minimum alveolar concentration (MAC) for 30 min before the intestinal ischemic insult. Additionally, the PKC inhibitor Chelerythrine (CHE) or mKATP inhibitor 5-Hydroxydecanoic (5-HD) was injected intraperitoneally before sevoflurane inhalation. Both SPC and IPC ameliorated intestinal IRI-induced histopathological changes, decreased Chius scores, reduced terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the epithelium, and inhibited the expression of malondialdehyde (MDA) and tumor necrosis factor-? (TNF-?). These protective effects of SPC were similar to those of IPC. Pretreatment with PKC or mKATP inhibitor abolished SPCinduced protective effects by increasing Chius scores, down-regulated the expression of Bcl-2 and activated caspase-3. Our results suggest that pretreatment with 0.5 MAC sevoflurane is as effective as IPC against intestinal IRI. The activation of PKC and mKATP may be involved in the protective mechanisms of SPC. PMID:26505750

  1. 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

  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. Incomplete domain decomposition preconditioning for coarse mesh neutron diffusion problems

    SciTech Connect

    Joo, H.G.; Downar, T.J.

    1995-12-31

    Incomplete domain decomposition preconditioning for parallel implementation of the conjugate gradient-like methods is applied to solve the two-group, three-dimensional, coarse mesh finite differenced neutron diffusion equation on the PARAGON XP/S-10 parallel computer. The linear system resulting from implicit time differencing of the time-dependent neutron diffusion equation is solved by the preconditioned biconjugate gradient squared method without employing the fission source iteration. An efficient domain decomposition preconditioning scheme is constructed by taking advantage of strong diagonal dominance of the coarse mesh finite difference formulation. Simplifications are made in the incomplete LU factorization process to construct a preconditioner for a three dimensional subdomain and the coupling between subdomains is approximated by incorporating only the effect of the non-leakage terms of neighboring subdomains. The method is applied to quarter core and full core fixed source problems which are created from the IAEA three-dimensional benchmark problem. Results show that on a single processor the computation time for the preconditioned biconjugate gradient method is comparable to other conventional iteration methods such as Line-SOR and the cyclic Chebyshev semi-iterative method. The effectiveness of the incomplete domain decomposition preconditioning on a multi-processor is evidenced by the small increase in the number of iterations as the number of subdomains increases. Speedups up to 32.1 are achievable with 64 processing elements for a 34{times}34{times}36 full core three-dimensional problem.

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

    PubMed Central

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

    2011-01-01

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

  5. 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. PMID:16034370

  6. 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.

  7. Differential monocular vs. binocular pupil responses from melanopsin-based photoreception in patients with anterior ischemic optic neuropathy.

    PubMed

    Tsika, Chrysanthi; Crippa, Sylvain V; Kawasaki, Aki

    2015-01-01

    We examined the effect of anterior ischemic optic neuropathy (AION) on the activity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupil as proxy. Eighteen patients with AION (10 unilateral, 8 bilateral) and 29 age-matched control subjects underwent chromatic pupillometry. Red and blue light stimuli increasing in 0.5 log steps were presented to each eye independently under conditions of dark and light adaptation. The recorded pupil contraction was plotted against stimulus intensity to generate scotopic and photopic response curves for assessment of synaptically-mediated ipRGC activity. Bright blue light stimuli presented monocularly and binocularly were used for melanopsin activation. The post-stimulus pupil size (PSPS) at the 6th second following stimulus offset was the marker of intrinsic ipRGC activity. Finally, questionnaires were administered to assess the influence of ipRGCs on sleep. The pupil response and PSPS to all monocularly-presented light stimuli were impaired in AION eyes, indicating ipRGC dysfunction. To binocular light stimulation, the PSPS of AION patients was similar to that of controls. There was no difference in the sleep habits of the two groups. Thus after ischemic injury to one or both optic nerves, the summated intrinsic ipRGC activity is preserved when both eyes receive adequate light exposure. PMID:26074032

  8. Differential monocular vs. binocular pupil responses from melanopsin-based photoreception in patients with anterior ischemic optic neuropathy

    PubMed Central

    Tsika, Chrysanthi; Crippa, Sylvain V.; Kawasaki, Aki

    2015-01-01

    We examined the effect of anterior ischemic optic neuropathy (AION) on the activity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupil as proxy. Eighteen patients with AION (10 unilateral, 8 bilateral) and 29 age-matched control subjects underwent chromatic pupillometry. Red and blue light stimuli increasing in 0.5?log steps were presented to each eye independently under conditions of dark and light adaptation. The recorded pupil contraction was plotted against stimulus intensity to generate scotopic and photopic response curves for assessment of synaptically-mediated ipRGC activity. Bright blue light stimuli presented monocularly and binocularly were used for melanopsin activation. The post-stimulus pupil size (PSPS) at the 6th second following stimulus offset was the marker of intrinsic ipRGC activity. Finally, questionnaires were administered to assess the influence of ipRGCs on sleep. The pupil response and PSPS to all monocularly-presented light stimuli were impaired in AION eyes, indicating ipRGC dysfunction. To binocular light stimulation, the PSPS of AION patients was similar to that of controls. There was no difference in the sleep habits of the two groups. Thus after ischemic injury to one or both optic nerves, the summated intrinsic ipRGC activity is preserved when both eyes receive adequate light exposure. PMID:26074032

  9. 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

  10. 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…

  11. 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

  12. 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.

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

    NASA Technical Reports Server (NTRS)

    Fischer, Bernd; Freund, Roland W.

    1992-01-01

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

  14. 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.

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

    NASA Technical Reports Server (NTRS)

    Wong, G. S.

    1973-01-01

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

  16. The Role of Ionospheric Outflow Preconditioning in Determining Storm Geoeffectiveness

    NASA Astrophysics Data System (ADS)

    Welling, D. T.; Liemohn, M. W.; Ridley, A. J.

    2012-12-01

    It is now well accepted that ionospheric outflow plays an important role in the development of the plasma sheet and ring current during geomagnetic storms. Furthermore, even during quiet times, ionospheric plasma populates the magnetospheric lobes, producing a reservoir of hydrogen and oxygen ions. When the Interplanetary Magnetic Field (IMF) turns southward, this reservoir is connected to the plasma sheet and ring current through magnetospheric convection. Hence, the conditions of the ionosphere and magnetospheric lobes leading up to magnetospheric storm onset have important implications for storm development. Despite this, there has been little research on this preconditioning; most global simulations begin just before storm onset, neglecting preconditioning altogether. This work explores the role of preconditioning in determining the geoeffectiveness of storms using a coupled global model system. A model of ionospheric outflow (the Polar Wind Outflow Model, PWOM) is two-way coupled to a global magnetohydrodynamic model (the Block-Adaptive Tree Solar wind Roe-type Upwind Scheme, BATS-R-US), which in turn drives a ring current model (the Ring current Atmosphere interactions Model, RAM). This unique setup is used to simulate an idealized storm. The model is started at many different times, from 1 hour before storm onset to 12 hours before. The effects of storm preconditioning are examined by investigating the total ionospheric plasma content in the lobes just before onset, the total ionospheric contribution in the ring current just after onset, and the effects on Dst, magnetic elevation angle at geosynchronous, and total ring current energy density. This experiment is repeated for different solar activity levels as set by F10.7 flux. Finally, a synthetic double-dip storm is constructed to see how two closely spaced storms affect each other by changing the preconditioning environment. It is found that preconditioning of the magnetospheric lobes via ionospheric outflow greatly influences the geoeffectiveness of magnetospheric storms.

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

    PubMed Central

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

    2014-01-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Scalable architecture for VoIP privacy

    NASA Astrophysics Data System (ADS)

    Medvinsky, Alexander

    2001-07-01

    An access network for Voice over IP (VoIP) clients (e.g. DOCSIS-based HFC network) often provides a privacy service. However, such a privacy service is limited only to that access network. When VoIP packets are carried over an open IP network or over a network with some connections to the Internet, it is desirable to provide an end-to-end privacy service where each VoIP packet is encrypted at the source and decrypted at the terminating endpoint. Clearly, public key encryption cannot be applied to each voice packet; the performance would be unacceptable regardless of the choice of a public key algorithm. The only alternative is for the two VoIP endpoints to negotiate a shared symmetric key. Since VoIP connections are established only for duration of a phone call, the end-to-end key negotiation needs to occur during each call setup. And it should not noticeably delay the call setup phase. In order to provide end-to-end privacy, it is not sufficient to encrypt all messages between the two endpoints. It is important that the two endpoints authenticate each other - validate each other's identity. Without authentication an adversary might trick two VoIP clients to negotiate keys with her and then sit in the middle of their conversation and record each VoIP packet, before forwarding it to the intended destination. However, direct authentication of the two VoIP endpoints is not always possible in telephony networks - in particular when caller ID blocking services are enabled. To support such anonymity services, it may be sufficient to authenticate not the identity of the caller but the fact that it is a valid subscriber and that all subsequent signaling and voice traffic will be coming from the same source. The PacketCable specifications provide an example of a VoIP architecture with end-to-end privacy that meets the above stated criteria. This paper describes the PacketCable end-to-end privacy approach and suggests additional mechanisms that may be used to further strengthen VoIP privacy under the PacketCable architecture.

  4. 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.

  5. 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.

  6. Ischemic proctosigmoiditis due to retroperitoneal hematoma

    PubMed Central

    Roepstorff, Soeren; Oehlenschläger, Jacob

    2016-01-01

    Gastrointestinal ischemia is caused by ischemic colitis in 50–60% of cases and is associated with high morbidity and mortality among patients. Ischemic proctosigmoiditis is a very rare disorder with only few cases reported. Due to collateral blood supply the rectum is only affected in 2–5% of all cases of ischemic colitis. We report a rare case of ischemic proctosigmoiditis caused by a retroperitoneal hematoma due to a pelvic fracture. PMID:26892890

  7. The mechanistic target of rapamycin (mTOR) pathway and S6 Kinase mediate diazoxide preconditioning in primary rat cortical neurons.

    PubMed

    Dutta, Somhrita; Rutkai, Ibolya; Katakam, Prasad V G; Busija, David W

    2015-09-01

    We examined the role of the mechanistic target of rapamycin (mTOR) pathway in delayed diazoxide (DZ)-induced preconditioning of cultured rat primary cortical neurons. Neurons were treated for 3 days with 500 ?M DZ or feeding medium and then exposed to 3 h of continuous normoxia in Dulbecco's modified eagle medium with glucose or with 3 h of oxygen-glucose deprivation (OGD) followed by normoxia and feeding medium. The OGD decreased viability by 50%, depolarized mitochondria, and reduced mitochondrial respiration, whereas DZ treatment improved viability and mitochondrial respiration, and suppressed reactive oxygen species production, but did not restore mitochondrial membrane potential after OGD. Neuroprotection by DZ was associated with increased phosphorylation of protein kinase B (Akt), mTOR, and the major mTOR downstream substrate, S6 Kinase (S6K). The mTOR inhibitors rapamycin and Torin-1, as well as S6K-targeted siRNA abolished the protective effects of DZ. The effects of DZ on mitochondrial membrane potential and reactive oxygen species production were not affected by rapamycin. Preconditioning with DZ also changed mitochondrial and non-mitochondrial oxygen consumption rates. We conclude that in addition to reducing reactive oxygen species (ROS) production and mitochondrial membrane depolarization, DZ protects against OGD by activation of the Akt-mTOR-S6K pathway and by changes in mitochondrial respiration. Ischemic strokes have limited therapeutic options. Diazoxide (DZ) preconditioning can reduce neuronal damage. Using oxygen-glucose deprivation (OGD), we studied Akt/mTOR/S6K signaling and mitochondrial respiration in neuronal preconditioning. We found DZ protects neurons against OGD via the Akt/mTOR/S6K pathway and alters the mitochondrial and non-mitochondrial oxygen consumption rate. This suggests that the Akt/mTOR/S6k pathway and mitochondria are novel stroke targets. PMID:26016889

  8. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  9. 40 CFR 1066.405 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) AIR POLLUTION CONTROLS VEHICLE-TESTING PROCEDURES Preparing Vehicles and Running an Exhaust Emission Test 1066.405 Vehicle preparation and preconditioning. Prepare the vehicle for testing (including... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Vehicle preparation...

  10. Dexmedetomidine Preconditioning Attenuates Cisplatin-Induced Ototoxicity in Zebrafish

    PubMed Central

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

    2014-01-01

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

  11. 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... the boat. (b) The boat must be loaded with a quantity of weight that, when submerged, is equal to the sum of the following: (1) Two-fifteenths of the persons capacity marked on the boat. (2)...

  12. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Engines of 2 Horsepower or Less General 183.320 Preconditioning for tests. A boat must meet the... the boat. (b) The boat must be loaded with a quantity of weight that, when submerged, is equal to the sum of the following: (1) Two-fifteenths of the persons capacity marked on the boat. (2)...

  13. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Engines of More Than 2 Horsepower General 183.220 Preconditioning for tests. A boat must meet the... boat. (b) The boat must be loaded with a quantity of weight that, when submerged, is equal to the sum... the boat and 121/2 percent of the remainder of the persons capacity. (2) Twenty-five percent of...

  14. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Preconditioning for tests. 183.320 Section 183.320 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Flotation Requirements for Outboard Boats Rated for Engines of 2 Horsepower or Less General ...

  15. 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... boat. (b) The boat must be loaded with a quantity of weight that, when submerged, is equal to the sum... the boat and 121/2 percent of the remainder of the persons capacity. (2) Twenty-five percent of...

  16. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Engines of 2 Horsepower or Less General 183.320 Preconditioning for tests. A boat must meet the... the boat. (b) The boat must be loaded with a quantity of weight that, when submerged, is equal to the sum of the following: (1) Two-fifteenths of the persons capacity marked on the boat. (2)...

  17. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Engines of 2 Horsepower or Less General 183.320 Preconditioning for tests. A boat must meet the... the boat. (b) The boat must be loaded with a quantity of weight that, when submerged, is equal to the sum of the following: (1) Two-fifteenths of the persons capacity marked on the boat. (2)...

  18. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Engines of More Than 2 Horsepower General 183.220 Preconditioning for tests. A boat must meet the... boat. (b) The boat must be loaded with a quantity of weight that, when submerged, is equal to the sum... the boat and 121/2 percent of the remainder of the persons capacity. (2) Twenty-five percent of...

  19. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Preconditioning for tests. 183.220 Section 183.220 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Flotation Requirements for Outboard Boats Rated for Engines of More Than 2 Horsepower General...

  20. 40 CFR 86.532-78 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... dynamometer and operated through one Urban Dynamometer Driving Schedule test procedure (see 86.515 and appendix I). The vehicle need not be cold, and may be used to set dynamometer horsepower. (b) Within five (5) minutes of completion of preconditioning, the vehicle shall be removed from the dynamometer...

  1. 40 CFR 86.532-78 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... dynamometer and operated through one Urban Dynamometer Driving Schedule test procedure (see 86.515 and appendix I). The vehicle need not be cold, and may be used to set dynamometer horsepower. (b) Within five (5) minutes of completion of preconditioning, the vehicle shall be removed from the dynamometer...

  2. 40 CFR 86.232-94 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-Duty Passenger Vehicles; Cold Temperature Test Procedures 86.232-94 Vehicle preconditioning. (a) The... utilized to stabilize the vehicle before the emissions test: (1) Storing at cold temperatures. The vehicle shall be stored for not less than 12 hours nor for more than 36 hours prior to the cold start...

  3. 40 CFR 86.232-94 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-Duty Passenger Vehicles; Cold Temperature Test Procedures 86.232-94 Vehicle preconditioning. (a) The... utilized to stabilize the vehicle before the emissions test: (1) Storing at cold temperatures. The vehicle shall be stored for not less than 12 hours nor for more than 36 hours prior to the cold start...

  4. 40 CFR 86.232-94 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Duty Passenger Vehicles; Cold Temperature Test Procedures 86.232-94 Vehicle preconditioning. (a) The... utilized to stabilize the vehicle before the emissions test: (1) Storing at cold temperatures. The vehicle shall be stored for not less than 12 hours nor for more than 36 hours prior to the cold start...

  5. 40 CFR 86.1774-99 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  6. 40 CFR 1065.516 - Sample system decontamination and preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Sample system decontamination and preconditioning. 1065.516 Section 1065.516 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.516 Sample...

  7. 40 CFR 86.132-96 - 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. 86.132-96 Section 86.132-96 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New...

  8. 40 CFR 86.132-96 - 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. 86.132-96 Section 86.132-96 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New...

  9. Numerical simulation of cavitating flows based on preconditioning technique

    NASA Astrophysics Data System (ADS)

    Goncalvs, E.

    2013-10-01

    A preconditioned numerical method for gas-liquid two-phase flows is applied to solve cavitating flow. The mass transfer between phases is modelled through a void ratio transport equation. Two-dimensional turbulent Venturi flows are computed. Comparisons with a 3-equation model and experimental data are provided and discussed.

  10. Post-ischemic administration of nimodipine following focal cerebral ischemic-reperfusion injury in rats alleviated excitotoxicity, neurobehavioural alterations and partially the bioenergetics.

    PubMed

    Babu, Chidambaram Saravana; Ramanathan, Muthiah

    2011-02-01

    The present study focuses on the temporal calcium significance in middle cerebral artery occluded (2 h ischemia)-reperfused (70 h reperfusion) rats treated with nimodipine (NM) through concurrent measurements of excitotoxicity, bioenergetics and neurobehavioural paradigms. Further, the suitable therapeutic time window of calcium channel antagonism in stroke was also ascertained. NM (5 mg/kg, i.p.) was administered at pre (30 min before the induction of ischemia), during (1 h following occlusion of MCA) and post-ischemic (3 h after begin of reperfusion) states. The magnitude of neuroprotection in terms of excitotoxicity (glutamate, glutamine synthetase, Na(+)K(+)ATPase), bioenergetics (ATP, NAD(+)) and neurobehavioural paradigms (neurological score and open field exploratory behaviour) were measured and compared to ensure the therapeutic time-window of NM in stroke. Middle cerebral artery occlusion-reperfusion (MCAO/R) was found to elevate glutamate, glutamine synthetase levels and deplete Na(+)K(+)ATPase activity in the vehicle treated group (IR group). Significant decrease in bioenergetics such as ATP and NAD(+) levels was also observed. Further, IR group demonstrated grievous oxidative stress (increase in lipid peroxidation, protein carbonyl content, nitrite/nitrate levels and decrease in superoxide dismutase and glutathione levels) along with anxiogenic behaviour, neurological deficits and neuronal damage and decreased nuclear to cytoplasm ratio in CA1 hippocampal region. Post-ischemic NM administration reversed the excitotoxicity, neurobehavioural and histopathological alterations significantly, but it restored bioenergetics level in MCAO/R rats only partially. These findings were further confirmed with the combination treatment (CT) of post-ischemic NM and pre-ischemic memantine (MN) administration, since MN showed protective effect in the pre-ischemic administration (Babu and Ramanathan, 2009). The failure of NM to forefend the neurodegeneration on pre- and during-ischemic administration suggests that the initial phase damages in ischemic-reperfusion (IR) might be mediated through other mechanism(s) such as glutamergic overstimulation or reverse operation of glutamate transporters. From the present study, it is concluded that calcium plays a crucial role in post-ischemic status and the suitable therapeutic time window of calcium antagonism is the post-ischemic state. PMID:20713150

  11. Genetic susceptibility to ischemic stroke

    PubMed Central

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

    2014-01-01

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

  12. Effects of ischemic pre- and postconditioning on HIF-1?, VEGF and TGF-? expression after warm ischemia and reperfusion in the rat liver

    PubMed Central

    2011-01-01

    Background Ischemic pre- and postconditioning protects the liver against ischemia/reperfusion injuries. The aim of the present study was to examine how ischemic pre- and postconditioning affects gene expression of hypoxia inducible factor 1? (HIF-1?), vascular endothelial growth factor A (VEGF-A) and transforming growth factor ? (TGF-?) in liver tissue. Methods 28 rats were randomized into five groups: control; ischemia/reperfusion; ischemic preconditioning (IPC); ischemic postconditioning (IPO); combined IPC and IPO. IPC consisted of 10 min of ischemia and 10 min of reperfusion. IPO consisted of three cycles of 30 sec. reperfusion and 30 sec. of ischemia. Results HIF-1? mRNA expression was significantly increased after liver ischemia compared to controls (p = 0.010). HIF-1? mRNA expression was significantly lower in groups subjected to IPC or combined IPC and IPO when compared to the ischemia/reperfusion group (p = 0.002). VEGF-A mRNA expression increased in the ischemia/reperfusion or combined IPC and IPO groups when compared to the control group (p < 0.05). Conclusion Ischemic conditioning seems to prevent HIF-1? mRNA induction in the rat liver after ischemia and reperfusion. This suggests that the protective effects of ischemic conditioning do not involve the HIF-1 system. On the other hand, the magnitude of the HIF-1? response might be a marker for the degree of I/R injuries after liver ischemia. Further studies are needed to clarify this issue. PMID:21771288

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

    PubMed Central

    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. PMID:26261524

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

    PubMed

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

    2010-01-01

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

  15. Labeling of phosphoinositides in rat brain membranes: an assessment of changes due to post-decapitative ischemic treatment.

    PubMed

    Sun, G Y; Huang, S F

    1987-01-01

    Metabolic changes in brain phosphoinositides with respect to post-decapitative ischemic treatment were examined with rats labeled after i.p. injection of (32)Pi and intracerebral injection of [(3)H]inositol. The ischemic treatment resulted in a large and rapid decrease (40% in 2 min) in labeled polyphosphoinositide (poly-Pl), regardless of the source of the labeling. The rapid disappearance of poly-PI labeling can be similarly detected in the synaptosomes and plasma membrane fractions. On the other hand, the ischemic treatment resulted in an increase (10%) in [(32)P]-labeling of phosphatidylinositol, indicating possible contribution due to the poly-PI phosphomonoesterase pathway. In addition to the decrease in labeling of poly-PI, there was a decrease in radioactivity of phosphatidic acids in brain homogenates and plasma membranes due to the ischemic treatment. The labeling pattern of other phospholipids was not altered by the ischemic treatment. With rats prelabeled with [(3)H]inositol, the amount of labeled inositol monophosphate in brain increased 4-fold after pretreatment with LiCl (8 meq/kg). While no obvious change in labeling of inositol bisphosphate and inositol monophosphate was observed, there was a 40% decrease in labeled inositol trisphosphate after 2 min ischemic treatment. Discussions were made regarding the advantage and disadvantages in labeling brain phosphoinositides with these two types of labeled precursors. PMID:20501107

  16. White Matter Ischemic Changes in Hyperacute Ischemic Stroke

    PubMed Central

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

    2015-01-01

    Background and Purpose The purpose of this study was to evaluate changes in fractional anisotropy (FA), as measured by diffusion tensor imaging, of white matter (WM) infarction and hypoperfusion in patients with acute ischemic stroke using a quantitative voxel-based analysis. Methods In this prospective study, diffusion tensor imaging and dynamic susceptibility contrast perfusion sequences were acquired in 21 patients with acute ischemic stroke who presented within 6 hours of symptom onset. The coregistered FA, apparent diffusion coefficient, and dynamic susceptibility contrast time to maximum (Tmax) maps were used for voxel-based quantification using a region of interest approach in the ipsilateral affected side and in the homologous contralateral WM. The regions of WM infarction versus hypoperfusion were segmented using a threshold method. Data were analyzed by regression and ANOVA. Results There was an overall significant mean difference (P<0.001) for the apparent diffusion coefficient, Tmax, and FA values between the normal, hypoperfused, and infarcted WM. The meanSD of FA was significantly higher (P<0.001) in hypoperfused WM (0.3970.019) and lower (P<0.001) in infarcted WM (0.3130.037) when compared with normal WM (0.3600.020). Regression tree analysis of hypoperfused WM showed the largest mean FA difference at Tmax above versus below 5.4 s with a mean difference of 0.033 (P=0.0096). Conclusions Diffusion tensor imaging-FA was decreased in regions of WM infarction and increased in hypoperfused WM in patients with hyperacute acute ischemic stroke. The significantly increased FA values in the hypoperfused WM with Tmax?5.4 s are suggestive of early ischemic microstructural changes. PMID:25523053

  17. 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

  18. 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 ?=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.

  19. 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.

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

    NASA Astrophysics Data System (ADS)

    Taylor, Colin W.; Swatton, Jane E.

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

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

    PubMed

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

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on those recently reported methodological and mechanistic discoveries in the realm of ischemic conditioning. Due to the varied time differences of ischemic conditioning in different animal models and clinical trials, it is important to define optimal timing to achieve the best conditioning induced neuroprotection. This brings not only an opportunity in the treatment of stroke, but challenges as well, as data is just becoming available and the procedures are not yet optimized. The purpose of this review is to shed light on exploiting these ischemic conditioning modalities to protect the cerebrovascular system against diverse injuries and neurodegenerative disorders. PMID:25900056

  2. 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

  3. 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.

  4. Chromatin immunoprecipitation for ChIP-chip and ChIP-seq.

    PubMed

    Schulz, Sebastian; Häussler, Susanne

    2014-01-01

    Bacterial adaptation to given environmental conditions is largely achieved by complex gene regulatory processes. To address the question how and to what extend single transcriptional regulators modulate gene expression, chromatin immunoprecipitation (ChIP) coupled to DNA microarrays (ChIP-chip) or to next-generation sequencing (ChIP-seq) is one of the preferred methods. Both ChIP-chip and ChIP-seq can generate genome-wide maps of protein-DNA interactions and thus identify primary regulons of transcription factors. In combination with transcriptome analyses, the obtained data can be used to compile complex regulatory networks which in terms will advance our understanding of bacterial adaptation processes to specific environmental conditions. PMID:24818935

  5. Hypothermic Preconditioning of Human Cortical Neurons Requires Proteostatic Priming.

    PubMed

    Rzechorzek, Nina Marie; Connick, Peter; Patani, Rickie; Selvaraj, Bhuvaneish Thangaraj; Chandran, Siddharthan

    2015-06-01

    Hypothermia is potently neuroprotective but poor mechanistic understanding has restricted its clinical use. Rodent studies indicate that hypothermia can elicit preconditioning, wherein a subtoxic cellular stress confers resistance to an otherwise lethal injury. The molecular basis of this preconditioning remains obscure. Here we explore molecular effects of cooling using functional cortical neurons differentiated from human pluripotent stem cells (hCNs). Mild-to-moderate hypothermia (28-32C) induces cold-shock protein expression and mild endoplasmic reticulum (ER) stress in hCNs, with full activation of the unfolded protein response (UPR). Chemical block of a principal UPR pathway mitigates the protective effect of cooling against oxidative stress, whilst pre-cooling neurons abrogates the toxic injury produced by the ER stressor tunicamycin. Cold-stress thus preconditions neurons by upregulating adaptive chaperone-driven pathways of the UPR in a manner that precipitates ER-hormesis. Our findings establish a novel arm of neurocryobiology that could reveal multiple therapeutic targets for acute and chronic neuronal injury. PMID:26287272

  6. Preconditioned alternating projection algorithms for maximum a posteriori ECT reconstruction

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

    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 constraint 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 PAPA. 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.

  7. Preconditioned conjugate gradient methods for the Navier-Stokes equations

    NASA Technical Reports Server (NTRS)

    Ajmani, Kumud; Ng, Wing-Fai; Liou, Meng-Sing

    1994-01-01

    A preconditioned Krylov subspace method (GMRES) is used to solve the linear systems of equations formed at each time-integration step of the unsteady, two-dimensional, compressible Navier-Stokes equations of fluid flow. The Navier-Stokes equations are cast in an implicit, upwind finite-volume, flux-split formulation. Several preconditioning techniques are investigated to enhance the efficiency and convergence rate of the implicit solver based on the GMRES algorithm. The superiority of the new solver is established by comparisons with a conventional implicit solver, namely line Gauss-Seidel relaxation (LGSR). Computational test results for low-speed (incompressible flow over a backward-facing step at Mach 0.1), transonic flow (trailing edge flow in a transonic turbine cascade), and hypersonic flow (shock-on-shock interactions on a cylindrical leading edge at Mach 6.0) are presented. For the Mach 0.1 case, overall speedup factors of up to 17 (in terms of time-steps) and 15 (in terms of CPU time on a CRAY-YMP/8) are found in favor of the preconditioned GMRES solver, when compared with the LGSR solver. The corresponding speedup factors for the transonic flow case are 17 and 23, respectively. The hypersonic flow case shows slightly lower speedup factors of 9 and 13, respectively. The study of preconditioners conducted in this research reveals that a new LUSGS-type preconditioner is much more efficient than a conventional incomplete LU-type preconditioner.

  8. Islet preconditioning via multimodal microfluidic modulation of intermittent hypoxia

    PubMed Central

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

    2012-01-01

    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, 1min/1min 5%21% cycling for 1 hour), translating to improved insulin secretion. Moreover, blocking mitochondrial KATP 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. PMID:22296179

  9. 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.

  10. 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.

  11. 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...--Assessment Questionnaire--IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT). DHS previously...-operators and/or security managers often volunteer to conduct an automated self risk assessment....

  12. 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... managers often volunteer to conduct an automated self risk assessment. The requested questionnaire...: Assessment Questionnaire--IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT). OMB Number:...

  13. De novo ChIP-seq analysis.

    PubMed

    He, Xin; Cicek, A Ercument; Wang, Yuhao; Schulz, Marcel H; Le, Hai-Son; Bar-Joseph, Ziv

    2015-01-01

    Methods for the analysis of chromatin immunoprecipitation sequencing (ChIP-seq) data start by aligning the short reads to a reference genome. While often successful, they are not appropriate for cases where a reference genome is not available. Here we develop methods for de novo analysis of ChIP-seq data. Our methods combine de novo assembly with statistical tests enabling motif discovery without the use of a reference genome. We validate the performance of our method using human and mouse data. Analysis of fly data indicates that our method outperforms alignment based methods that utilize closely related species. PMID:26400819

  14. 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.

  15. Preconditioning Involves Selective Mitophagy Mediated by Parkin and p62/SQSTM1

    PubMed Central

    Ratliff, Eric P.; Hernandez, Genaro; Lee, Pamela; Gottlieb, Roberta A.

    2011-01-01

    Autophagy-dependent mitochondrial turnover in response to cellular stress is necessary for maintaining cellular homeostasis. However, the mechanisms that govern the selective targeting of damaged mitochondria are poorly understood. Parkin, an E3 ubiquitin ligase, has been shown to be essential for the selective clearance of damaged mitochondria. Parkin is expressed in the heart, yet its function has not been investigated in the context of cardioprotection. We previously reported that autophagy is required for cardioprotection by ischemic preconditioning (IPC). In the present study, we used simulated ischemia (sI) in vitro and IPC of hearts to investigate the role of Parkin in mediating cardioprotection ex vivo and in vivo. In HL-1 cells, sI induced Parkin translocation to mitochondria and mitochondrial elimination. IPC induced Parkin translocation to mitochondria in Langendorff-perfused rat hearts and in vivo in mice subjected to regional IPC. Mitochondrial depolarization with an uncoupling agent similarly induced Parkin translocation to mitochondria in cells and Langendorff-perfused rat hearts. Mitochondrial loss was blunted in Atg5-deficient cells, revealing the requirement for autophagy in mitochondrial elimination. Consistent with previous reports indicating a role for p62/SQSTM1 in mitophagy, we found that depletion of p62 attenuated mitophagy and exacerbated cell death in HL-1 cardiomyocytes subjected to sI. While wild type mice showed p62 translocation to mitochondria and an increase in ubiquitination, Parkin knockout mice exhibited attenuated IPC-induced p62 translocation to the mitochondria. Importantly, ablation of Parkin in mice abolished the cardioprotective effects of IPC. These results reveal for the first time the crucial role of Parkin and mitophagy in cardioprotection. PMID:21687634

  16. Hypoxic preconditioning increases triiodothyronine (T3) level in the developing rat brain.

    PubMed

    Minato, Kenji; Tomimatsu, Takuji; Mimura, Kazuya; Jugder, Otgonbaatar; Kakigano, Aiko; Kanayama, Tomoko; Fujita, Satoko; Taniguchi, Yukiko; Kanagawa, Takeshi; Endo, Masayuki; Kimura, Tadashi

    2013-03-21

    Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the major causes of neurodegeneration and mortality in the neonatal period. Although hypoxic preconditioning (HPC) provided strong neuroprotection against HIE in an animal model, the mechanism underlying this effect is not fully understood especially in the immature brain. Here, we investigated whether thyroid hormones (THs), especially triiodothyronine (T3), which are essential during normal brain development, contribute to the neuroprotective mechanisms of HPC by using an established model of HPC in neonatal rats. HPC treatment (8% O2 for 2.5h at 37°C) was performed in immature rats at postnatal day 6 (P6). Subsequently, we investigated the levels of THs, TH receptors (TRs) and type 2 and 3 deiodinase (D2 and D3) mRNA, and glutamate transporter 1 (GLT1) at 24h after HPC treatment, and myelin basic protein (MBP) at 6, 12 and 24h after HPC treatment. The HIE procedure was performed at 24h after HPC, and the neuroprotective effect of HPC was assessed via microtubule-associated protein 2 (MAP2) and MBP immunohistochemical staining at 14 days after HIE (P21). HPC treatment afforded marked neuroprotection at 14 days after HIE. The local level of T3 was upregulated 24h after HPC treatment in the developing rat brain, probably via the upregulation of D2. In addition, the expression of MBP and GLT1, which are the downstream protein of T3, were significantly increased 24h after HPC treatment. The present study indicates that thyroid hormones and their associated molecules may be involved in neuroprotective mechanisms of HPC during the developmental period. PMID:23376195

  17. Barbiturate promotes post-ischemic reaggregation of polyribosomes in gerbil hippocampus.

    PubMed

    Bonnekoh, P; Kuroiwa, T; Oschlies, U; Hossmann, K A

    1992-10-26

    A brief period of cerebral ischemia is followed by severe inhibition of protein synthesis which is slowly reversed in the resistant but not in the selectively vulnerable regions of the brain. Inhibition occurs at the translational level, as evidenced by the disaggregation of ribosomes into monosomes. In order to evaluate the importance of this disturbance for the evolution of ischemic injury, the effect of the neuroprotective drug, pentobarbital, on ribosomal aggregation was studied in gerbils subjected to 5 min bilateral carotid artery occlusion. Pentobarbital (50 mg/kg, i.p.) was applied shortly after the ischemia, and the aggregational state of ribosomes was investigated by electron microscopy after recirculation times ranging from 15 min to 1 day. Pentobarbital treatment did not prevent the initial post-ischemic disaggregation but promoted the subsequent reaggregation in the selectively vulnerable neurons. This suggests that post-ischemic application of barbiturates exerts its beneficial effect by reversing the post-ischemic block of ribosomal reaggregation in vulnerable regions. PMID:1475053

  18. IP validation in remote microelectronics testing

    NASA Astrophysics Data System (ADS)

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

    2004-03-01

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

  19. Operational Space Weather Products at IPS

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

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

  20. 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…

  1. 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…

  2. 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

  3. A native IP satellite communications system

    NASA Astrophysics Data System (ADS)

    Koudelka, O.; Schmidt, M.; Ebert, J.; Schlemmer, H.; Kastner-Puschl, S.; Riedler, W.

    2004-08-01

    ? In the framework of ESA's ARTES-5 program the Institute of Applied Systems Technology (Joanneum Research) in cooperation with the Department of Communications and Wave Propagation has developed a novel meshed satellite communications system which is optimised for Internet traffic and applications (L*IPLocal Network Interconnection via Satellite Systems Using the IP Protocol Suite). Both symmetrical and asymmetrical connections are supported. Bandwidth on demand and guaranteed quality of service are key features of the system. A novel multi-frequency TDMA access scheme utilises efficient methods of IP encapsulation. In contrast to other solutions it avoids legacy transport network techniques. While the DVB-RCS standard is based on ATM or MPEG transport cells, the solution of the L*IP system uses variable-length cells which reduces the overhead significantly. A flexible and programmable platform based on Linux machines was chosen to allow the easy implementation and adaptation to different standards. This offers the possibility to apply the system not only to satellite communications, but provides seamless integration with terrestrial fixed broadcast wireless access systems. The platform is also an ideal test-bed for a variety of interactive broadband communications systems. The paper describes the system architecture and the key features of the system.

  4. 75 FR 13235 - IP-Enabled Services

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-19

    ...The Commission amended part 63 in order to extend to providers of interconnected Voice over Internet Protocol (VoIP) service the discontinuance obligations that apply to domestic non-dominant telecommunications carriers under section 214 of the Communications Act. The amendments to the rules in Sec. 63.60 required Office of Management and Budget approval and the Commission stated previously in......

  5. Call progress time measurement in IP telephony

    NASA Astrophysics Data System (ADS)

    Khasnabish, Bhumip

    1999-11-01

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

  6. 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

  7. Expression of Monocarboxylate Transporter Isoforms in Rat Skeletal Muscle Under Hypoxic Preconditioning and Endurance Training.

    PubMed

    Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju

    2016-03-01

    Saxena, Saurabh, Dhananjay Shukla, and Anju Bansal. Expression of monocarboxylate transporter isoforms in rat skeletal muscle under hypoxic preconditioning and endurance training. High Alt Med Biol 17:32-42, 2016-Previously, we have reported the regulation of monocarboxylate transporters (MCT)1 and MCT4 by physiological stimuli such as hypoxia and exercise. In the present study, we have evaluated the effect of hypoxic preconditioning and training on expression of different MCT isoforms in muscles. We found the increased mRNA expression of MCT1, MCT11, and MCT12 after hypoxic preconditioning with cobalt chloride and training. However, the expression of other MCT isoforms increased marginally or even reduced after hypoxic preconditioning. Only the protein expression of MCT1 increased after hypoxia preconditioning. MCT2 protein expression increased after training only and MCT4 protein expression decreased both in preconditioning and hypoxic training. Furthermore, we found decreased plasma lactate level during hypoxia preconditioning (0.74-fold), exercise (0.78-fold), and hypoxia preconditioning along with exercise (0.67-fold), which indicates increased lactate uptake by skeletal muscle. The protein-protein interactions with hypoxia inducible factor-1 and MCT isoforms were also evaluated, but no interaction was found. In conclusion, we say that almost all MCTs are expressed in red gastrocnemius muscle at the mRNA level and their expression is regulated differently under hypoxia preconditioning and exercise condition. PMID:26716978

  8. Zinc preconditioning protects against neuronal apoptosis through the mitogen-activated protein kinase-mediated induction of heat shock protein 70.

    PubMed

    Lee, Jeong-Min; Lee, Jong-Min; Kim, Ki-Ryeong; Im, Hana; Kim, Yang-Hee

    2015-04-01

    During brain ischemic preconditioning (PC), mild bursts of ischemia render neurons resistant to subsequent strong ischemic injuries. Previously, we reported that zinc plays a key role in PC-induced neuroprotection in vitro and in vivo. Zinc-triggered p75(NTR) induction transiently activates caspase-3, which cleaves poly(ADP-ribose) polymerase-1 (PARP-1). Subsequently, the PARP-1 over-activation-induced depletion of nicotinamide adenine dinucleotide (NAD(+))/adenosine triphosphate (ATP) after exposures to lethal doses of zinc or N-methyl-D-aspartate is significantly attenuated in cortical neuronal cultures. In the present study, zinc-mediated preconditioning (Zn PC) reduced apoptotic neuronal death that was caused by N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), etoposide, or staurosporine in mouse cortical cells. We focused on heat shock protein 70 (HSP70) because NAD(+)/ATP depletion does not directly cause apoptosis, and HSP70 can inhibit the activation of caspase-9 or caspase-3 by preventing apoptosome formation or cytochrome C release. Zn PC-mediated HSP70 induction was required for neuroprotection against neuronal apoptosis, and geldanamycin-induced HSP70 induction sufficiently blocked neuronal apoptotic cell death. Furthermore, Zn PC-mediated HSP70 induction was blocked by chemical inhibitors of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein kinase (MAPK) signaling, but not c-Jun N-terminal protein kinase. Similarly, neuroprotection by Zn PC against TPEN-induced apoptosis was almost completely reversed by the blockade of ERK or p38 MAPK signaling. Our findings suggest that the ERK- or p38 MAPK-mediated induction of HSP70 plays a key role in inhibiting caspase-3 activation during Zn PC. PMID:25712525

  9. Hypoxic preconditioning and cell death from oxygen/glucose deprivation co-opt a subset of the unfolded protein response in hippocampal neurons.

    PubMed

    Bickler, P E; Clark, J P; Gabatto, P; Brosnan, H

    2015-12-01

    The state of protein folding in the endoplasmic reticulum (ER), via the unfolded protein response (UPR), regulates a pro- or anti-apoptotic cell fate. Hypoxic preconditioning (HPC) is a potent anti-apoptotic stimulus, wherein ischemic neural injury is averted by a non-damaging exposure to hypoxia. We tested if UPR modulation contributes to the pro-survival/anti-apoptotic phenotype in neurons preconditioned with hypoxia, using organotypic cultures of rat hippocampus as a model system. Pharmacologic induction of the UPR with tunicamycin increased mRNA of 79 of 84 UPR genes and replicated the pro-survival phenotype of HPC, whereas only small numbers of the same mRNAs were upregulated at 0, 6 and 24h after HPC. During the first 24h after HPC, protein signals in all 3 UPR pathways increased at various times: increased ATF4, phosphorylation of eif2? and IRE1, cleavage of xbb1 mRNA and cleavage of ATF6. Pharmacologic inhibition of ATF6 and IRE1 blocked HPC. Ischemia-like conditions (oxygen/glucose deprivation, OGD) caused extensive neuron cell damage and involved some of the same UPR protein signals as HPC. In distinction to HPC and tunicamycin, OGD caused widespread suppression of UPR genes: 55 of 84 UPR gene mRNAs were numerically downregulated. We conclude that although HPC and ischemic cell death in hippocampal neurons involve protein-based signaling in all 3 UPR pathways, these processes co-opt only a subset of the genomic response elicited by agents known to cause protein misfolding, possibly because of persistent transcription/translation arrest induced by hypoxia and especially OGD. PMID:26404874

  10. Morphine preconditioning confers cardioprotection in doxorubicin-induced failing rat hearts via ERK/GSK-3? pathway independent of PI3K/Akt.

    PubMed

    He, Shu-Fang; Jin, Shi-Yun; Wu, Hao; Wang, Bin; Wu, Yun-Xiang; Zhang, Shu-Jie; Irwin, Michael G; Wong, Tak-Ming; Zhang, Ye

    2015-11-01

    Preconditioning against myocardial ischemia-reperfusion (I/R) injury can be suppressed in some pathological conditions. This study was designed to investigate whether morphine preconditioning (MPC) exerts cardioprotection in doxorubicin (DOX)-induced heart failure in rats and the mechanisms involved. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase (ERK) and glycogen synthase kinase (GSK)-3? pathways were examined. Normal and DOX-induced failing rat hearts were subjected to I/R injury using a Langendorff perfusion system with or without MPC or ischemic preconditioning (IPC). The PI3K inhibitor (wortmannin) or ERK inhibitor (PD98059) was infused before MPC. In normal hearts, both MPC and IPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by I/R injury. Pretreatment with wortmannin or PD98059 abrogated the protective effects of MPC and suppressed the phosphorylation of Akt, ERK and GSK-3?. In failing rat hearts, however, MPC retained its cardioprotection while IPC did not. This protective effect was abolished by PD98059 but not wortmannin. MPC increased the level of p-ERK rather than p-Akt. The phosphorylation of GSK-3? induced by MPC was reversed by PD98059 only. IPC did not elevate the expression of p-ERK, p-Akt and p-GSK-3? in failing rat hearts. We conclude that MPC is cardioprotective in rats with DOX-induced heart failure while IPC is not. The effect of MPC appears to be mediated via the ERK/GSK-3? pathway independent of PI3K/Akt. PMID:26296503

  11. Novel cardioprotective strategy combining three different preconditioning methods to prevent ischemia/reperfusion injury in aged hearts in an improved rabbit model

    PubMed Central

    YE, JIAN-XI; CHEN, DAO-ZHONG

    2015-01-01

    The use of ischemic preconditioning (IPC) to protect the myocardium is usually not effective in elderly patients. The aim of the present study was to design new methods to achieve enhanced myocardial protection, based on the differential role of endogenous adenosine (ADO) and ADO receptors (ARs) in the effects of IPC on young and old animals. An improved New Zealand white rabbit model of ischemia/reperfusion was established based on the Langendorff model. Adult or elderly rabbit hearts, with or without exposure to IPC, were used in order to assess the roles of ADO and ARs in the different effects of IPC. Different protective methods were designed based on a combination of endogenous and exogenous interventions. Cardiac function, as well as biochemical, histopathological and apoptotic indices, were measured in the different intervention groups. The improved Langendorff model was stable, reliable and suitable for the undertaking of the experiments. The ADO levels in the aged rabbit hearts pre- and post-IPC were lower than those in the adult hearts, indicating that ADO levels may be an endogenous factor influencing IPC. A new protection strategy combining ADO-enhanced IPC, A1AR agonist 2-chloro-N(6)-cyclopentyladenosine preconditioning and cold crystalloid cardioplegia had a significant protective effect in aged hearts. The results of the present study suggested that endogenous ADO enhancement, A1AR agonist preconditioning and exogenous treatment yield an additive effect in aged rabbit hearts. The simultaneous application of these three types of intervention provided the most effective myocardial protection in the improved aged rabbit heart model. PMID:26622489

  12. Management of ischemic optic neuropathies

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    Ischemic optic neuropathies (IONs) consist primarily of two types: anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). AION comprises arteritic AION (A-AION: due to giant cell arteritis) and non-arteritic AION (NA-AION: due to other causes). PION consists of arteritic PION (A-PION: due to giant cell arteritis), non-arteritic PION (NA-PION: due to other causes), and surgical PION (a complication of several systemic surgical procedures). These five types of ION are distinct clinical entities etiologically, pathogenetically, clinically and from the management point of view. In the management of AION, the first crucial step with patients aged 50 and over is to identify immediately whether it is arteritic or not because A-AION is an ophthalmic emergency and requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. Patients with NA-AION, when treated with systemic corticosteroid therapy within first 2 weeks of onset, had significantly better visual outcome than untreated ones. Systemic risk factors, particularly nocturnal arterial hypotension, play major roles in the development of NA-AION; management of them is essential in its prevention and management. NA-PION patients, when treated with high-dose systemic steroid therapy during the very early stages of the disease, showed significant improvement in visual acuity and visual fields, compared to untreated eyes. A-PION, like A-AION, requires urgent treatment with high-dose steroid therapy to prevent any further visual loss in one or both eyes. There is no satisfactory treatment for surgical PION, except to take prophylactic measures to prevent its development. PMID:21350282

  13. Glycine preconditioning to ameliorate pulmonary ischemia reperfusion injury in rats†

    PubMed Central

    Sommer, Sebastian-Patrick; Sommer, Stefanie; Sinha, Bhanu; Leyh, Rainer G.

    2012-01-01

    This study examines the impact of glycine (Gly) preconditioning on ischemia reperfusion (IR)-induced pulmonary mitochondrial injury to research the previously, in pig lungs, demonstrated Gly-dependent amelioration of pulmonary IR injury. IR injury was induced in rat lungs by 30 min pulmonary hilum clamping followed by 60 min reperfusion time. Rats were subjected to controls, shams and two study groups (IR30/60, Gly-IR30/60) receiving 37.5 mg Gly i.v. or not before IR induction. The wet/dry-weight ratio, mitochondria viability (MV), membrane integrity (MI), respiratory chain complex (RCC) activities, mitochondrial membrane potential (ΔΨm) and cytochrome C (Cyt C) content were analysed. In IR30/60, RCC and MV were impaired; Cyt C loss and MI combined with matrix metalloproteinase-9 (MMP-9) activation and ΔΨm alteration were observed when compared with controls. In Gly-IR30/60, complex II function and mitochondrial viability were protected during IR, and MMP-9 activation combined with tissue-water content accumulation and ΔΨm alteration were ameliorated. Cyt C loss, mitochondrial membranes damage, tissue GSH oxidation or neutrophil sequestration was not extenuated in Gly-IR30/60. Gly ameliorates IR-associated mitochondrial dysfunction and decay of viability and normalizes ΔΨm but does not protect from Cyt C liberation and mitochondrial membrane damage. Our data suggest that the previously described effect of Gly preconditioning results at least partially from mitochondrial protection. A dose-finding study is necessary to improve results of Gly preconditioning. PMID:22350772

  14. Calcium preconditioning triggers neuroprotection in retinal ganglion cells

    PubMed Central

    Brandt, Sean K.; Weatherly, Monique E.; Ware, Lillian; Linn, David M.; Linn, Cindy L.

    2010-01-01

    In the mammalian retina, excitotoxicity has been shown to be involved in apoptotic retinal ganglion cell (RGC) death and is associated with certain retinal disease states including glaucoma, diabetic retinopathy and retinal ischemia. Previous studies from this lab (Wehrwein et al., 2004) have demonstrated that acetylcholine (ACh) and nicotine protects against glutamate-induced excitotoxicity in isolated adult pig RGCs through nicotinic acetylcholine receptors (nAChRs). Activation of nAChRs in these RGCs triggers cell survival signaling pathways and inhibits apoptotic enzymes (Asomugha et al., 2010). However, the link between binding of nAChRs and activation of neuroprotective pathways is unknown. In this study, we examine the hypothesis that calcium permeation through nAChR channels is required for ACh-induced neuroprotection against glutamate-induced excitotoxicity in isolated pig RGCs. RGCs were isolated from other retinal tissue using a two step panning technique and cultured for 3 days under different conditions. In some studies, calcium imaging experiments were performed using the fluorescent calcium indicator, fluo-4, and demonstrated that calcium permeates the nAChR channels located on pig RGCs. In other studies, the extracellular calcium concentration was altered to determine the effect on nicotine-induced neuroprotection. Results support the hypothesis that calcium is required for nicotine-induced neuroprotection in isolated pig RGCs. Lastly, studies were performed to analyze the effects of preconditioning on glutamate-induced excitotoxicity and neuroprotection. In these studies, a preconditioning dose of calcium was introduced to cells using a variety of mechanisms before a large glutamate insult was applied to cells. Results from these studies support the hypothesis that preconditioning cells with a relatively low level of calcium before an excitotoxic insult leads to neuroprotection. In the future, these results could provide important information concerning therapeutic agents developed to combat various diseases involved with glutamate-induced excitotoxicity. PMID:21044663

  15. Preconditioned Conjugate Gradient methods for low speed flow calculations

    NASA Technical Reports Server (NTRS)

    Ajmani, Kumud; Ng, Wing-Fai; Liou, Meng-Sing

    1993-01-01

    An investigation is conducted into the viability of using a generalized Conjugate Gradient-like method as an iterative solver to obtain steady-state solutions of very low-speed fluid flow problems. Low-speed flow at Mach 0.1 over a backward-facing step is chosen as a representative test problem. The unsteady form of the two dimensional, compressible Navier-Stokes equations are integrated in time using discrete time-steps. The Navier-Stokes equations are cast in an implicit, upwind finite-volume, flux split formulation. The new iterative solver is used to solve a linear system of equations at each step of the time-integration. Preconditioning techniques are used with the new solver to enhance the stability and the convergence rate of the solver and are found to be critical to the overall success of the solver. A study of various preconditioners reveals that a preconditioner based on the lower-upper (L-U)-successive symmetric over-relaxation iterative scheme is more efficient than a preconditioner based on incomplete L-U factorizations of the iteration matrix. The performance of the new preconditioned solver is compared with a conventional line Gauss-Seidel relaxation (LGSR) solver. Overall speed-up factors of 28 (in terms of global time-steps required to converge to a steady-state solution) and 20 (in terms of total CPU time on one processor of a CRAY-YMP) are found in favor of the new preconditioned solver, when compared with the LGSR solver.

  16. 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 brains 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

  17. Optimization of OSPF Routing in IP Networks

    NASA Astrophysics Data System (ADS)

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

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

  18. 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 cavitation on two basic geometries for which experimental data are available, that is, flow over simple foil and a quarter caliber hydrofoil in a tunnel using liquid nitrogen as a fluid. For non-cryogenic conditions, water near boiling conditions is used to predict cavitation on two simple geometries, that is, flow over simple foil in a tunnel and flow over a one caliber ogive. Cavitation predictions in both cryogenic and non-cryogenic cases are shows to agree well with available experimental data.

  19. Preconditioning a product of matrices arising in trust region subproblems

    SciTech Connect

    Hribar, M.E.; Plantenga, T.D.

    1996-03-01

    In solving large scale optimization problems, we find it advantageous to use iterative methods to solve the sparse linear systems that arise. In the ETR software for solving equality constrained optimization problems, we use a conjugate gradient method to approximately solve the trust region subproblems. To speed up the convergence of the conjugate gradient routine, we need to precondition matrices of the form Z{sup T} W Z, which are not explicitly stored. Four preconditioners were implemented and the results for each are given.

  20. 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.

  1. 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. PMID:26385023

  2. Peroxisomal Biogenesis in Ischemic Brain

    PubMed Central

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

    2015-01-01

    Abstract Aims: Peroxisomes are highly adaptable and dynamic organelles, adjusting their size, number, and enzyme composition to changing environmental and metabolic demands. We determined whether peroxisomes respond to ischemia, and whether peroxisomal biogenesis is an adaptive response to cerebral ischemia. Results: Focal cerebral ischemia induced peroxisomal biogenesis in peri-infarct neurons, which was associated with a corresponding increase in peroxisomal antioxidant enzyme catalase. Peroxisomal biogenesis was also observed in primary cultured cortical neurons subjected to ischemic insult induced by oxygen-glucose deprivation (OGD). A catalase inhibitor increased OGD-induced neuronal death. Moreover, preventing peroxisomal proliferation by knocking down dynamin-related protein 1 (Drp1) exacerbated neuronal death induced by OGD, whereas enhancing peroxisomal biogenesis pharmacologically using a peroxisome proliferator-activated receptor-alpha agonist protected against neuronal death induced by OGD. Innovation: This is the first documentation of ischemia-induced peroxisomal biogenesis in mammalian brain using a combined in vivo and in vitro approach, electron microscopy, high-resolution laser-scanning confocal microscopy, and super-resolution structured illumination microscopy. Conclusion: Our findings suggest that neurons respond to ischemic injury by increasing peroxisome biogenesis, which serves a protective function, likely mediated by enhanced antioxidant capacity of neurons. Antioxid. Redox Signal. 22, 109120. PMID:25226217

  3. Technology Transfer Center | Sample IP Management Plans

    Cancer.gov

    This page provides general guidance for preparation of IP Management Plans and lists various sample plans that can be used by extramural funding applicants to prepare intellectual property management plans when required by program announcements that cite this website as a resource. These sample plans are provided to assist applicants in preparing the intellectual property management plans in their partnerships with industry in order to meet certain programmatic objectives and goals of particular funding announcements.

  4. 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.

  5. IP-based storage of image information

    NASA Astrophysics Data System (ADS)

    Fu, Xianglin; Xie, Changsheng; Liu, Zhaobin

    2001-09-01

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

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

    PubMed Central

    2016-01-01

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

  7. Stress Preconditioning of Spreading Depression in the Locust CNS

    PubMed Central

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

    2007-01-01

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

  8. 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...

  9. 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...

  10. 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...

  11. 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

  12. 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…

  13. DETERMINATION OF AN EMPIRICALLY DERIVED IP/TSP RELATIONSHIP

    EPA Science Inventory

    The primary objective of this study was to provide researchers with statistical methodology for comparing data on inhalable particulate (IP) and on the IP/TSP ratios from various sites, predicting IP concentration as a function of total suspended particulate (TSP) concentration, ...

  14. A Conjoint Analysis of Voice Over IP Attributes.

    ERIC Educational Resources Information Center

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

    2002-01-01

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

  15. 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

  16. 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 1015 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 EPOs membrane receptors and signaling components also are expressed in neurons and astrocytes. EPO activates signaling cascades that increase the brains 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 prospects for induction of EPO production within the brain by the intermediary metabolite, pyruvate. PMID:24595981

  17. Impact of genome assembly status on ChIP-Seq and ChIP-PET data mapping

    PubMed Central

    2009-01-01

    Background ChIP-Seq and ChIP-PET can potentially be used with any genome for genome wide profiling of protein-DNA interaction sites. Unfortunately, it is probable that most genome assemblies will never reach the quality of the human genome assembly. Therefore, it remains to be determined whether ChIP-Seq and ChIP-PET are practicable with genome sequences other than a few (e.g. human and mouse). Findings Here, we used in silico simulations to assess the impact of completeness or fragmentation of genome assemblies on ChIP-Seq and ChIP-PET data mapping. Conclusions Most currently published genome assemblies are suitable for mapping the short sequence tags produced by ChIP-Seq or ChIP-PET. PMID:20015379

  18. Contribution of the maritime continent convection during the preconditioning stage of the Madden-Julian Oscillation

    NASA Astrophysics Data System (ADS)

    Kubota, H.; Yoneyama, K.; Nasuno, T.; Hamada, J.

    2013-12-01

    During the international field experiment 'Cooperative Indian Ocean experiment on intraseasonal variability in the Year 2011 (CINDY2011)', the preconditioning process of the MJO was observed. In this study, the contribution of the maritime continent convection was focused on the preconditioning process of the third MJO. During the preconditioning stage of the MJO, westward propagating disturbances were observed from Sumatera Island to the central Indian Ocean and moistened the atmosphere. Convections over the Sumatera Island were activated around December 15th when the moist air mass reached from South China Sea. The origin of the moist air mass was tropical cyclone which was formed in South China Sea in December 10th. The high moisture associated with tropical cyclone activated the convection over Sumatera Island, promoted westward propagating disturbances, and acted a favorable environment for the preconditioning of the MJO. This preconditioning stage of the MJO is simulated by Nonhydrostatic ICosahedral Atmospheric Model (NICAM) and investigated the moistening process.

  19. 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

  20. Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke

    PubMed Central

    Geuskens, Ralph R. E. G.; Borst, Jordi; Lucas, Marit; Boers, A. M. Merel; Berkhemer, Olvert A.; Roos, Yvo B. W. E. M.; van Walderveen, Marianne A. A.; Jenniskens, Sjoerd F. M.; van Zwam, Wim H.; Dippel, Diederik W. J.; Majoie, Charles B. L. M.; Marquering, Henk A.

    2015-01-01

    Background CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up. Materials and Methods This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT?145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests. Results Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.431.79) ml/100g (P<0.01) and 1.38 (IQR:1.151.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly. Conclusion For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly differed between ischemic lesion agreement and misclassified CTP ischemic core, suggesting that CTP analysis may benefit from revisions. PMID:26536226

  1. Preconditioning Stimuli Induce Autophagy via Sphingosine Kinase 2 in Mouse Cortical Neurons*

    PubMed Central

    Sheng, Rui; Zhang, Tong-Tong; Felice, Valeria D.; Qin, Tao; Qin, Zheng-Hong; Smith, Charles D.; Sapp, Ellen; Difiglia, Marian; Waeber, Christian

    2014-01-01

    Sphingosine kinase 2 (SPK2) and autophagy are both involved in brain preconditioning, but whether preconditioning-induced SPK2 up-regulation and autophagy activation are linked mechanistically remains to be elucidated. In this study, we used in vitro and in vivo models to explore the role of SPK2-mediated autophagy in isoflurane and hypoxic preconditioning. In primary mouse cortical neurons, both isoflurane and hypoxic preconditioning induced autophagy. Isoflurane and hypoxic preconditioning protected against subsequent oxygen glucose deprivation or glutamate injury, whereas pretreatment with autophagy inhibitors (3-methyladenine or KU55933) abolished preconditioning-induced tolerance. Pretreatment with SPK2 inhibitors (ABC294640 and SKI-II) or SPK2 knockdown prevented preconditioning-induced autophagy. Isoflurane also induced autophagy in mouse in vivo as shown by Western blots for LC3 and p62, LC3 immunostaining, and electron microscopy. Isoflurane-induced autophagy in mice lacking the SPK1 isoform (SPK1?/?), but not in SPK2?/? mice. Sphingosine 1-phosphate and the sphingosine 1-phosphate receptor agonist FTY720 did not protect against oxygen glucose deprivation in cultured neurons and did not alter the expression of LC3 and p62, suggesting that SPK2-mediated autophagy and protections are not S1P-dependent. Beclin 1 knockdown abolished preconditioning-induced autophagy, and SPK2 inhibitors abolished isoflurane-induced disruption of the Beclin 1/Bcl-2 association. These results strongly indicate that autophagy is involved in isoflurane preconditioning both in vivo and in vitro and that SPK2 contributes to preconditioning-induced autophagy, possibly by disrupting the Beclin 1/Bcl-2 interaction. PMID:24928515

  2. Growth factors in ischemic stroke

    PubMed Central

    Lanfranconi, S; Locatelli, F; Corti, S; Candelise, L; Comi, G P; Baron, P L; Strazzer, S; Bresolin, N; Bersano, A

    2011-01-01

    Abstract Data from pre-clinical and clinical studies provide evidence that colony-stimulating factors (CSFs) and other growth factors (GFs) can improve stroke outcome by reducing stroke damage through their anti-apoptotic and anti-inflammatory effects, and by promoting angiogenesis and neurogenesis. This review provides a critical and up-to-date literature review on CSF use in stroke. We searched for experimental and clinical studies on haemopoietic GFs such as granulocyte CSF, erythropoietin, granulocyte-macrophage colony-stimulating factor, stem cell factor (SCF), vascular endothelial GF, stromal cell-derived factor-1α and SCF in ischemic stroke. We also considered studies on insulin-like growth factor-1 and neurotrophins. Despite promising results from animal models, the lack of data in human beings hampers efficacy assessments of GFs on stroke outcome. We provide a comprehensive and critical view of the present knowledge about GFs and stroke, and an overview of ongoing and future prospects. PMID:20015202

  3. Endovascular Therapy for Ischemic Stroke

    PubMed Central

    Appireddy, Ramana M R; Demchuk, Andrew M; Goyal, Mayank; Menon, Bijoy K; Eesa, Muneer; Choi, Philip

    2015-01-01

    The utility of intravenous tissue plasminogen activator (IV t-PA) in improving the clinical outcomes after acute ischemic stroke has been well demonstrated in past clinical trials. Though multiple initial small series of endovascular stroke therapy had shown good outcomes as compared to IV t-PA, a similar beneficial effect had not been translated in multiple randomized clinical trials of endovascular stroke therapy. Over the same time, there have been parallel advances in imaging technology and better understanding and utility of the imaging in therapy of acute stroke. In this review, we will discuss the evolution of endovascular stroke therapy followed by a discussion of the key factors that have to be considered during endovascular stroke therapy and directions for future endovascular stroke trials. PMID:25628731

  4. In-Hospital Ischemic Stroke

    PubMed Central

    2015-01-01

    Between 2.2% and 17% of all strokes have symptom onset during hospitalization in a patient originally admitted for another diagnosis or procedure. These in-hospital strokes represent a unique population with different risk factors, more mimics, and substantially worsened outcomes compared to community-onset strokes. The fact that these strokes manifest during the acute care hospitalization, in patients with higher rates of thrombolytic contraindications, creates distinct challenges for treatment. However, the best evidence suggests benefit to treating appropriately selected in-hospital ischemic strokes with thrombolysis. Evidence points toward a quality gap for in-hospital stroke with longer in-hospital delays to evaluation and treatment, lower rates of evaluation for etiology, and decreased adherence to consensus quality process measures of care. This quality gap for in-hospital stroke represents a focused opportunity for quality improvement. PMID:26288675

  5. [Pathophysiology of ischemic cardiac pain.].

    PubMed

    Mnzel, T; Bassenge, E

    1988-09-01

    Cardiac pain is a conscious experience that can be explored only indirectly with experimental approaches. The exact machanisms eliciting cardiac pain still remain obscure. The afferent fibres running in the cardiac sympathetic nerves are regarded as the essential pathway for the transmission of cardiac pain. Atria and ventricle are abundantly supplied with sympathetic sensory innervation. In the spinal cord, impulses transmitted by the sympathetic pathway converge with impulses from somatic thoracic structures onto the same ascending spinothalamic neuron which probably explains the mechanism of referred pain (=projection of pain to another organ). Two hypotheses have been put forward to explain the peripheral mechanism for nociception. The intensity mechanism assumes that pain results from an excessive stimulation of receptive structures normally stimulated at lower levels whereas a specific sensation is considered to result from an excitation of a well defined nociceptive apparatus. Ventricular sympathetic afferent fibres whether myelinated or unmyelinated, always possess some mechanosensitivity and respond to normal chemical and mechanical stimuli, thus displaying properties of polymodal receptors. Afferent vagal fibres may contribute to the mechanisms of cardiac nociception by modulating the threshold and characteristics of pain. Experimental studies identified three main mechanisms, which may be responsible for eliciting cardiac pain during ischemic periods in humans: a) nonphysiological motion of the ischemic left ventricular wall (bulging) and an excitation of mechanical receptors by passive stretching. b) The excitation of free sensory nerve endings by chemicals such as bradykinin, PGE(2), adenosin, histamin or potassium. c) A combination of a and b: algogenic chemicals may sensitize mechanical receptors and therefore lower their threshold for nociception. PMID:18415323

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

    PubMed

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

    2014-01-01

    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. PMID:24939562

  7. 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.

  8. Cell Reprogramming, IPS Limitations, and Overcoming Strategies in Dental Bioengineering

    PubMed Central

    Ibarretxe, Gaskon; Alvarez, Antonia; Cañavate, Maria-Luz; Hilario, Enrique; Aurrekoetxea, Maitane; Unda, Fernando

    2012-01-01

    The procurement of induced pluripotent stem cells, or IPS cells, from adult differentiated animal cells has the potential to revolutionize future medicine, where reprogrammed IPS cells may be used to repair disease-affected tissues on demand. The potential of IPS cell technology is tremendous, but it will be essential to improve the methodologies for IPS cell generation and to precisely evaluate each clone and subclone of IPS cells for their safety and efficacy. Additionally, the current state of knowledge on IPS cells advises that research on their regenerative properties is carried out in appropriate tissue and organ systems that permit a safe assessment of the long-term behavior of these reprogrammed cells. In the present paper, we discuss the mechanisms of cell reprogramming, current technical limitations of IPS cells for their use in human tissue engineering, and possibilities to overcome them in the particular case of dental regeneration. PMID:22690226

  9. 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.

  10. Can endurance exercise preconditioning prevention disuse muscle atrophy?

    PubMed Central

    Wiggs, Michael P.

    2015-01-01

    Emerging evidence suggests that exercise training can provide a level of protection against disuse muscle atrophy. Endurance exercise training imposes oxidative, metabolic, and heat stress on skeletal muscle which activates a variety of cellular signaling pathways that ultimately leads to the increased expression of proteins that have been demonstrated to protect muscle from inactivity –induced atrophy. This review will highlight the effect of exercise-induced oxidative stress on endogenous enzymatic antioxidant capacity (i.e., superoxide dismutase, glutathione peroxidase, and catalase), the role of oxidative and metabolic stress on PGC1-α, and finally highlight the effect heat stress and HSP70 induction. Finally, this review will discuss the supporting scientific evidence that these proteins can attenuate muscle atrophy through exercise preconditioning. PMID:25814955

  11. 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.

  12. 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.

  13. 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.

  14. Neuroprotective Mechanisms of Taurine against Ischemic Stroke

    PubMed Central

    Menzie, Janet; Prentice, Howard; Wu, Jang-Yen

    2013-01-01

    Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke. PMID:24961429

  15. Torsades de Pointes due to ischemic stroke.

    PubMed

    Ocak, Tarik; Duran, Arif; Tekelioglu, Umit Yasar; Erdem, Alim; Dagistan, Emine

    2013-08-01

    Cardiac and cerebrovascular illnesses are among the leading causes of mortality and morbidity today. Thromboembolic cases, which are the result of cardiac arrhythmia, are one of the important causes of cerebral stroke. However, various abnormalities, especially ST-T wave changes on electrocardiography can be seen in patients who do not have any heart disease history but had ischemic cerebral stroke. In this study, we have presented an interesting case of Torsades de Pointes due to ischemic cerebral stroke. PMID:23892870

  16. Preconditioning induces tolerance by suppressing glutamate release in neuron culture ischemia models.

    PubMed

    Tauskela, Joseph S; Aylsworth, Amy; Hewitt, Melissa; Brunette, Eric; Mealing, Geoffrey A R

    2012-07-01

    This study determined how preconditioned neurons responded to oxygen-glucose deprivation (OGD) to result in neuroprotection instead of neurotoxicity. Neurons preconditioned using chronically elevated synaptic activity displayed suppressed elevations in extracellular glutamate ([glutamateex ]) and intracellular Ca(2+) (Ca(2+) in ) during OGD. The glutamate uptake inhibitor TBOA induced neurotoxicity, but at a longer OGD duration for preconditioned cultures, suggestive of delayed up-regulation of transporter activity relative to non-preconditioned cultures. This delay was attributed to a critically attenuated release of glutamate, based on tolerance observed against insults mimicking key neurotoxic signaling during OGD (OGD-mimetics). Specifically, in the presence of TBOA, preconditioned neurons displayed potent protection to the OGD-mimetics: ouabain (a Na(+) /K(+) ATPase inhibitor), high 55 mM KCl extracellular buffer (plasma membrane depolarization), veratridine (a Na(+) ionophore), and paraquat (intracellular superoxide producer), which correlated with suppressed [glutamateex ] elevations in the former two insults. Tolerance by preconditioning was reversed by manipulations that increased [glutamateex ], such as by exposure to TBOA or GABAA receptor agonists during OGD, or by exposure to exogenous NMDA or glutamate. Pre-synaptic suppression of neuronal glutamate release by preconditioning, possibly via suppressed exocytic release, represents a key convergence point in neuroprotection during exposure to OGD and OGD-mimetics. PMID:22607164

  17. The Effect of Hypoxic Preconditioning on Induced Schwann Cells under Hypoxic Conditions

    PubMed Central

    Chen, Ou; Wu, Miaomiao; Jiang, Liangfu

    2015-01-01

    Object Our objective was to explore the protective effects of hypoxic preconditioning on induced Schwann cells exposed to an environment with low concentrations of oxygen. It has been observed that hypoxic preconditioning of induced Schwann cells can promote axonal regeneration under low oxygen conditions. Method Rat bone marrow mesenchymal stem cells (MSCs) were differentiated into Schwann cells and divided into a normal oxygen control group, a hypoxia-preconditioning group and a hypoxia group. The ultrastructure of each of these groups of cells was observed by electron microscopy. In addition, flow cytometry was used to measure changes in mitochondrial membrane potential. Annexin V-FITC/PI staining was used to detect apoptosis, and Western blots were used to detect the expression of Bcl-2/Bax. Fluorescence microscopic observations of axonal growth in NG-108 cells under hypoxic conditions were also performed. Results The hypoxia-preconditioning group maintained mitochondrial cell membrane and crista integrity, and these cells exhibited less edema than the hypoxia group. In addition, the cells in the hypoxia-preconditioning group were found to be in early stages of apoptosis, whereas cells from the hypoxia group were in the later stages of apoptosis. The hypoxia-preconditioning group also had higher levels of Bcl-2/Bax expression and longer NG-108 cell axons than were observed in the hypoxia group. Conclusion Hypoxic preconditioning can improve the physiological state of Schwann cells in a severe hypoxia environment and improve the ability to promote neurite outgrowth. PMID:26509259

  18. 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.

  19. 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.

  20. 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.

  1. Angiotensinogen polymorphism and ischemic stroke risk

    PubMed Central

    Bao, Huan; Hao, Jun-Jie; Yang, Yu-Mei; Xu, Xia-Hong; Wang, Yue; Zuo, Lian; Lu, Jing; Zhang, Jing; Zhang, Yue; Xu, Si-Yi; Wang, Xuan; Li, Ying; Li, Gang

    2015-01-01

    The angiotensinogen M235T polymorphism was associated with ischemic stroke risk. However, the results were controversial. Thus, a meta-analysis was conducted. NCBI, Medline, Web of Science and Embase databases were systematically searched. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models. There was a significant association between angiotensinogen M235T polymorphism and ischemic stroke risk (OR = 1.69; 95% CI, 1.35-2.11; P < 0.001). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with ischemic stroke in Asian (OR = 1.85; 95% CI, 1.45-2.35; P < 0.001). In the age subgroup, we found that angiotensinogen M235T polymorphism could increase both early-onset ischemic stroke risk (OR = 1.88; 95% CI, 1.33-2.43; P < 0.001) and late-onset ischemic stroke risk (OR = 1.20; 95% CI, 1.01-1.39; P = 0.04). This meta-analysis suggested that angiotensinogen M235T polymorphism was associated with ischemic stroke. PMID:26550208

  2. 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.

  3. Preconditioned GMRES methods with incomplete Givens orthogonalization method for large sparse least-squares problems

    NASA Astrophysics Data System (ADS)

    Yin, Jun-Feng; Hayami, Ken

    2009-04-01

    We propose to precondition the GMRES method by using the incomplete Givens orthogonalization (IGO) method for the solution of large sparse linear least-squares problems. Theoretical analysis shows that the preconditioner satisfies the sufficient condition that can guarantee that the preconditioned GMRES method will never break down and always give the least-squares solution of the original problem. Numerical experiments further confirm that the new preconditioner is efficient. We also find that the IGO preconditioned BA-GMRES method is superior to the corresponding CGLS method for ill-conditioned and singular least-squares problems.

  4. 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.

  5. Exercise and Cyclic Light Preconditioning Protect Against Light-Induced Retinal Degeneration and Evoke Similar Gene Expression Patterns.

    PubMed

    Chrenek, Micah A; Sellers, Jana T; Lawson, Eric C; Cunha, Priscila P; Johnson, Jessica L; Girardot, Preston E; Kendall, Cristina; Han, Moon K; Hanif, Adam; Ciavatta, Vincent T; Gogniat, Marissa A; Nickerson, John M; Pardue, Machelle T; Boatright, Jeffrey H

    2016-01-01

    To compare patterns of gene expression following preconditioning cyclic light rearing versus preconditioning aerobic exercise. BALB/C mice were preconditioned either by rearing in 800lx 12:12h cyclic light for 8 days or by running on treadmills for 9 days, exposed to toxic levels of light to cause light-induced retinal degeneration (LIRD), then sacrificed and retinal tissue harvested. Subsets of mice were maintained for an additional 2 weeks and for assessment of retinal function by electroretinogram (ERG). Both preconditioning protocols partially but significantly preserved retinal function and morphology and induced similar leukemia inhibitory factor (LIF) gene expression pattern. The data demonstrate that exercise preconditioning and cyclic light preconditioning protect photoreceptors against LIRD and evoke a similar pattern of retinal LIF gene expression. It may be that similar stress response pathways mediate the protection provided by the two preconditioning modalities. PMID:26427444

  6. 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; Bger, 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. PMID:19619135

  7. Preconditioning of Human Skeletal Myoblast with Stromal Cell-derived Factor-1? Promotes Cytoprotective Effects against Oxidative and Anoxic Stress

    PubMed Central

    Elmadbouh, Ibrahim; Haider, Husnain Kh.; Ashraf, Muhammad; Chachques, Juan-Carlos

    2011-01-01

    Background and Objectives: The incidence of human autologous transplanted skeletal myoblast (SkM) cell death in ischemic myocardium was higher in the first few days after cell therapy. We proposed that human SkM treated by human stromal cell-derived factor (SDF-1?) protein or tranfected by SDF-1?, precondition them against oxidative or anoxic injury. Methods and Results: The purification of human SkM (80?90%) culture was assessed for desmin and CXCR4 expression using immunostaining and flow cytometry respectively. Cells were transfected to overexpress SDF-1? or treated with rSDF-1? (10?200 ng/ml, 1?4 h) were either exposed to anoxia or treated with 100?M H2O2 for different time periods (1?6 h anoxia) (1?3 h H2O2). Optimized conditions for transfection of SDF-1? gene into human SkM were achieved, using FuGeneTM6/phSDF-1?(3?2 v/w, 4 h transfection) with 125? M ZnCl2 (p? 0.001), up to 7 days post-transfection as compared with transfected SkM without ZnCl2 and non-transfected control cells. Transfection efficiency was assessed by immunostaining, ELISA, western blots and PCR. LDH analysis showed significant decrease in release of LDH after exposure to 6 h anoxia or 100? M H2O2 for 2 h as compared with the normal un-treated or un-transfected SkM (p? 0.001). In western blots assay, SDF-1? over-expressing human SkM or treated with rSDF-1? induced marked expression of total Akt (1.2-fold) and phospho-Akt (2.7-fold), Bcl2 (1.6-fold) and VEGF (5.8-fold) after exposure to 6 h anoxia as compared with human SkM controls. Conclusions: The preconditioning of donor transplanted human SkM with SDF-1? increased cell survival and promoted cytoprotective effect against oxidative or anoxic injury that may be an innovative approach for clinical application. PMID:24298334

  8. Monophosphoryl lipid A induces pharmacologic 'preconditioning' in rabbit hearts without concomitant expression of 70-kDa heat shock protein.

    PubMed

    Yoshida, K; Maaieh, M M; Shipley, J B; Doloresco, M; Bernardo, N L; Qian, Y Z; Elliott, G T; Kukreja, R C

    1996-03-01

    The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40 % propylene glycol, 10 % ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins. PMID:8709970

  9. Monophosphoryl lipid A induces pharmacologic 'preconditioning' in rabbit hearts without concomitant expression of 70-kDa heat shock protein.

    PubMed

    Yoshida, K; Maaieh, M M; Shipley, J B; Doloresco, M; Bernardo, N L; Qian, Y Z; Elliott, G T; Kukreja, R C

    1996-06-01

    The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40% propylene glycol, 10% ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins. PMID:8813712

  10. Ischemic enteritis with intestinal stenosis

    PubMed Central

    Koshikawa, Yorimitsu; Matsuura, Minoru; Yoshino, Takuya; Honzawa, Yusuke; Minami, Naoki; Yamada, Satoshi; Yasuhara, Yumiko; Fujii, Shigehiko; Kusaka, Toshihiro; Manaka, Dai; Kokuryu, Hiroyuki

    2016-01-01

    A 75-year-old man was admitted to our hospital with sudden onset of vomiting and abdominal distension. The patient was taking medication for arrhythmia. Computed tomography showed stenosis of the ileum and a small bowel dilatation on the oral side from the region of stenosis. A transnasal ileus tube was placed. Enteroclysis using contrast medium revealed an approximately 6-cm afferent tubular stenosis 10 cm from the terminal ileum and thumbprinting in the proximal bowel. Transanal double-balloon enteroscopy showed a circumferential shallow ulcer with a smooth margin and edema of the surrounding mucosa. The stenosis was so extensive that we could not perform endoscopic balloon dilation therapy. During hospitalization, the patient's nutritional status deteriorated. In response, we surgically resected the region of stenosis. Histologic examination revealed disappearance of the mucosal layer and transmural ulceration with marked fibrosis, especially in the submucosal layer. Hemosiderin staining revealed sideroferous cells in the submucosal layers. Based on the pathologic findings, the patient was diagnosed with ischemic enteritis. The patient's postoperative course was uneventful. PMID:26884740

  11. Citalopram Enhances Neurovascular Regeneration and Sensorimotor Functional Recovery after Ischemic Stroke in Mice

    PubMed Central

    Espinera, Alyssa R.; Ogle, Molly E.; Gu, Xiaohuan; Wei, Ling

    2013-01-01

    Recent clinical trials have demonstrated that treatment with selective serotonin reuptake inhibitors (SSRIs) after stroke enhances motor functional recovery; however, the underlying mechanisms remain to be further elucidated. We hypothesized that daily administration of the clinical drug citalopram would produce these functional benefits via enhancing neurovascular repair in the ischemic peri-infarct region. To test this hypothesis, focal ischemic stroke was induced in male C57/B6 mice by permanent ligation of distal branches of the middle cerebral artery to the barrel cortex and 7-min occlusion of the bilateral common carotid arteries. Citalopram (10 mg/kg, i.p.) was injected 24 hrs after stroke and daily thereafter. To label proliferating cells, bromo-deoxyuridine was injected daily beginning 3 days after stroke. Immunohistochemical and functional assays were performed to elucidate citalopram-mediated cellular and sensorimotor changes after stroke. Citalopram treatment had no significant effect on infarct formation or edema 3 days after stroke; however, citalopram-treated mice had better functional recovery than saline-treated controls 3 and 14 days after stroke in the adhesive removal test. Increased expression of brain derived neurotrophic factor was detected in the peri-infarct region 7 days after stroke in citalopram-treated animals. The number of proliferating neural progenitor cells and the distance of neuroblast migration from the sub-ventricular zone towards the ischemic cortex were significantly greater in citalopram-treated mice at 7 days after stroke. Immunohistochemical staining and co-localization analysis showed that citalopram-treated animals generated more new neurons and microvessels in the peri-infarct region 21 and 28 days after stroke. Taken together, these results suggest that citalopram promotes post-stroke sensorimotor recovery likely via enhancing neurogenesis, neural cell migration and the microvessel support in the peri-infarct region of the ischemic brain. PMID:23590907

  12. IPS Empress: a standard of excellence.

    PubMed

    Hornbrook, D S; Roberts, M

    1998-01-01

    For 10 years, clinicians have been able to provide patients with a proven aesthetic and functional restoration that exhibits wear-compatibility, durability, and marginal integrity. This leucite-reinforced, pressed ceramic (IPS Empress, Ivoclar Williams, Amherst, NY) presents to patients and dentists the option of a metal-free alternative which retains the functional advantages of a porcelain-fused-to-metal restoration. This article illustrates the importance of sound laboratory communication in the utilization of this restorative material, focusing upon three aspects: midline and incisal edge inclination, elimination of open gingival embrasures, and incisal edge translucency. Techniques are also presented in order to efficiently communicate details of each case presented to the laboratory. PMID:9543867

  13. An IP Traceback Model for Network Forensics

    NASA Astrophysics Data System (ADS)

    Pilli, Emmanuel S.; Joshi, R. C.; Niyogi, Rajdeep

    Network forensics deals with capture, recording, analysis and investigation of network traffic to traceback the attackers. Its ultimate goal is to provide sufficient evidence to allow the perpetrator to be prosecuted. IP traceback is an important aspect in the investigation process where the real attacker is identified by tracking source address of the attack packets. In this paper we classify the various approaches to network forensics to list the requirements of the traceback. We propose a novel model for traceback based on autonomous systems (AS) and deterministic packet marking (DPM) to enable traceback even with a single packet. The model is analyzed against various evaluation metrics. The traceback solution will be a major step in the direction of attack attribution and investigation.

  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. 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. PMID:10898875

  16. Causal Relationship of Susceptibility Genes to Ischemic Stroke: Comparison to Ischemic Heart Disease and Biochemical Determinants

    PubMed Central

    Bentley, Paul; Peck, George; Smeeth, Liam; Whittaker, John; Sharma, Pankaj

    2010-01-01

    Interrelationships between genetic and biochemical factors underlying ischemic stroke and ischemic heart disease are poorly understood. We: 1) undertook the most comprehensive meta-analysis of genetic polymorphisms in ischemic stroke to date; 2) compared genetic determinants of ischemic stroke with those of ischemic heart disease, and 3) compared effect sizes of gene-stroke associations with those predicted from independent biochemical data using a mendelian randomization strategy. Electronic databases were searched up to January 2009. We identified: 1) 187 ischemic stroke studies (37,481 cases; 95,322 controls) interrogating 43 polymorphisms in 29 genes; 2) 13 meta-analyses testing equivalent polymorphisms in ischemic heart disease; and 3) for the top five gene-stroke associations, 146 studies (65,703 subjects) describing equivalent gene-biochemical relationships, and 28 studies (46,928 subjects) describing biochemical-stroke relationships. Meta-analyses demonstrated positive associations with ischemic stroke for factor V Leiden Gln506, ACE I/D, MTHFR C677T, prothrombin G20210A, PAI-1 5G allele and glycoprotein IIIa Leu33Pro polymorphisms (ORs: 1.11 1.60). Most genetic associations show congruent levels of risk comparing ischemic stroke with ischemic heart disease, but three genesglycoprotein IIIa, PAI-1 and angiotensinogenshow significant dissociations. The magnitudes of stroke risk observed for factor V Leiden, ACE, MTHFR and prothrombin, but not PAI-1, polymorphisms, are consistent with risks associated with equivalent changes in activated protein C resistance, ACE activity, homocysteine, prothrombin, and PAI-1 levels, respectively. Our results demonstrate causal relationships for four of the most robust genes associated with stroke while also showing that PAI-1 4G/5G polymorphism influences cardiovascular risk via a mechanism not simply related to plasma levels of PAI-1 (or tPA) alone. PMID:20161734

  17. 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

  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 shown to meet the criteria for safe and fit for purpose packaging, by meeting the US DOT regulations, and the IAEA Standards for IP-1 and IP-2 including leak tightness. (authors)

  19. Security Research on VoIP with Watermarking

    NASA Astrophysics Data System (ADS)

    Hu, Dong; Lee, Ping

    2008-11-01

    With the wide application of VoIP, many problems have occurred. One of the problems is security. The problems with securing VoIP systems, insufficient standardization and lack of security mechanisms emerged the need for new approaches and solutions. In this paper, we propose a new security architecture for VoIP which is based on digital watermarking which is a new, flexible and powerful technology that is increasingly gaining more and more attentions. Besides known applications e.g. to solve copyright protection problems, we propose to use digital watermarking to secure not only transmitted audio but also signaling protocol that VoIP is based on.

  20. Mapping protein-DNA interactions using ChIP-sequencing.

    PubMed

    Massie, Charles E; Mills, Ian G

    2012-01-01

    Chromatin immunoprecipitation (ChIP) allows enrichment of genomic regions which are associated with specific transcription factors, histone modifications, and indeed any other epitopes which are present on chromatin. The original ChIP methods used site-specific PCR and Southern blotting to confirm which regions of the genome were enriched, on a candidate basis. The combination of ChIP with genomic tiling arrays (ChIP-chip) allowed a more unbiased approach to map ChIP-enriched sites. However, limitations of microarray probe design and probe number have a detrimental impact on the coverage, resolution, sensitivity, and cost of whole-genome tiling microarray sets for higher eukaryotes with large genomes. The combination of ChIP with high-throughput sequencing technology has allowed more comprehensive surveys of genome occupancy, greater resolution, and lower cost for whole genome coverage. Herein, we provide a comparison of high-throughput sequencing platforms and a survey of ChIP-seq analysis tools, discuss experimental design, and describe a detailed ChIP-seq method.Chromatin immunoprecipitation (ChIP) allows enrichment of genomic regions which are associated with specific transcription factors, histone modifications, and indeed any other epitopes which are present on chromatin. The original ChIP methods used site-specific PCR and Southern blotting to confirm which regions of the genome were enriched, on a candidate basis. The combination of ChIP with genomic tiling arrays (ChIP-chip) allowed a more unbiased approach to map ChIP-enriched sites. However, limitations of microarray probe design and probe number have a detrimental impact on the coverage, resolution, sensitivity, and cost of whole-genome tiling microarray sets for higher eukaryotes with large genomes. The combination of ChIP with high-throughput sequencing technology has allowed more comprehensive surveys of genome occupancy, greater resolution, and lower cost for whole genome coverage. Herein, we provide a comparison of high-throughput sequencing platforms and a survey of ChIP-seq analysis tools, discuss experimental design, and describe a detailed ChIP-seq method. PMID:22113275

  1. Exercise-induced cardiac preconditioning: how exercise protects your achy-breaky heart.

    PubMed

    Frasier, Chad R; Moore, Russell L; Brown, David A

    2011-09-01

    The ability of exercise to protect the heart against ischemia-reperfusion (I/R) injury is well known in both human epidemiological studies and experimental animal models. In this review article, we describe what is currently known about the ability of exercise to precondition the heart against infarction. Just 1 day of exercise can protect the heart against ischemia/reperfusion damage, and this protection is upheld with months of exercise, making exercise one of the few sustainable preconditioning stimuli. Exercise preconditioning depends on the model and intensity of exercise, and appears to involve heightened oxidant buffering capacity, upregulated subunits of sarcolemmal ATP-sensitive potassium channels, and adaptations to cardiac mitochondria. We review the putative mechanisms involved in exercise preconditioning and point out many areas where future research is necessary to advance our understanding of how this stimulus confers resistance against I/R damage. PMID:21393468

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

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

    SciTech Connect

    Cai, Yunfeng; Department of Computer Science, University of California, Davis 95616 ; 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. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... plus CO2 must be greater than or equal to six percent. (c) First-chance test. The test timer starts (tt... test time is 200 seconds (tt=200). The first-chance test consists of a preconditioning mode...

  5. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... plus CO2 must be greater than or equal to six percent. (c) First-chance test. The test timer starts (tt... test time is 200 seconds (tt=200). The first-chance test consists of a preconditioning mode...

  6. Time-dependent mechanical behavior of sheep digital tendons, including the effects of preconditioning.

    PubMed

    Sverdlik, A; Lanir, Y

    2002-02-01

    The time-dependent mechanical properties of sheep digital extensor tendons were studied by sequences of stress-relaxation tests. The results exhibited irreversible preconditioning and reversible viscoelasticity. Preconditioning effects were manifested by stress decay during consecutive stretch cycles to the same strain level, accompanied by elongation of the tendon's reference length. They intensified with increased strain level, and were reduced or became negligible as the strain decreased. The significance of intrinsic response mechanisms was studied via a structural model that includes viscoelasticity, preconditioning, and morphology of the tendon's collagen fibers. Model/data comparisons showed good agreement and good predictive power, suggesting that preconditioning can be integrated into comprehensive material characterization of tendons. PMID:11871608

  7. Analysis of a Lipid/Polymer Membrane for Bitterness Sensing with a Preconditioning Process.

    PubMed

    Yatabe, Rui; Noda, Junpei; Tahara, Yusuke; Naito, Yoshinobu; Ikezaki, Hidekazu; Toko, Kiyoshi

    2015-01-01

    It is possible to evaluate the taste of foods or medicines using a taste sensor. The taste sensor converts information on taste into an electrical signal using several lipid/polymer membranes. A lipid/polymer membrane for bitterness sensing can evaluate aftertaste after immersion in monosodium glutamate (MSG), which is called "preconditioning". However, we have not yet analyzed the change in the surface structure of the membrane as a result of preconditioning. Thus, we analyzed the change in the surface by performing contact angle and surface zeta potential measurements, Fourier transform infrared spectroscopy (FTIR), X-ray photon spectroscopy (XPS) and gas cluster ion beam time-of-flight secondary ion mass spectrometry (GCIB-TOF-SIMS). After preconditioning, the concentrations of MSG and tetradodecylammonium bromide (TDAB), contained in the lipid membrane were found to be higher in the surface region than in the bulk region. The effect of preconditioning was revealed by the above analysis methods. PMID:26404301

  8. 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 ?60C because of collagen denaturation, but that tissues will rapidly stiffen and become less susceptible to histotripsy when preheated at ?90C 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 58C. In contrast, preheating to 90C 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 pretreatment strategy to precondition tissue mechanical properties and alter tissue susceptibility to histotripsy. Future work will aim to optimize this thermal pretreatment strategy to determine if this approach is practical for specific clinical applications in vivo without causing unwanted damage to surrounding or overlying tissue. PMID:26318560

  9. Maintaining high-quality IP audio services in lossy IP network environments

    NASA Astrophysics Data System (ADS)

    Barton, Robert J., III; Chodura, Hartmut

    2000-07-01

    In this paper we present our research activities in the area of digital audio processing and transmission. Today's available teleconference audio solutions are lacking in flexibility, robustness and fidelity. There was a need for enhancing the quality of audio for IP-based applications to guarantee optimal services under varying conditions. Multiple tests and user evaluations have shown that a reliable audio communication toolkit is essential for any teleconference application. This paper summarizes our research activities and gives an overview of developed applications. In a first step the parameters, which influence the audio quality, were evaluated. All of these parameters have to be optimized in order to result into the best achievable quality. Therefore it was necessary to enhance existing schemes or develop new methods. Applications were developed for Internet-Telephony, broadcast of live music and spatial audio for Virtual Reality environments. This paper describes these applications and issues of delivering high quality digital audio services over lossy IP networks.

  10. 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

    2015-09-01

    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. PMID:26317794

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

    PubMed Central

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

    2015-01-01

    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. PMID:26317794

  12. Isoflurane preconditioning reduces mouse microglial activation and injury induced by lipopolysaccharide and interferon-γ

    PubMed Central

    Xu^, Xuebing; Kim, Jie Ae; Zuo, Zhiyi

    2008-01-01

    Activation and injury of microglial cells are involved in a broad range of brain diseases including stroke, brain infection and neurodegenerative diseases. However, there is very little information regarding how to reduce microglial reaction and preserve these cells to provide neuroprotection. Here, we showed that the incubation of C8-B4 mouse microglial cells with lipopolysaccharide (LPS) plus interferon-γ (IFNγ) for 24 hr decreased the viability of these cells. Pretreatment of these cells with 1%, 2% or 3% isoflurane, a commonly used volatile anesthetic, for 1 hr at 30 min before the exposure to LPS plus IFNγ attenuated the reduction of cell viability (preconditioning effect). LPS plus IFNγ also activated these microglial cells to express inducible nitric oxide synthase (iNOS) and to induce accumulation of nitrite, a stable oxidation product of nitric oxide, in the incubation medium. Isoflurane preconditioning attenuated these LPS plus IFNγ effects on the iNOS expression and nitrite accumulation. Aminoguanidine, an iNOS inhibitor, attenuated the LPS plus IFNγ-induced glutamate release and decrease of microglial viability. Isoflurane preconditioning also reduced LPS plus IFNγ-induced glutamate release. Exogenous glutamate decreased microglial viability. Finally, the isoflurane preconditioning-induced protection was abolished by chelerythrine, a protein kinase C inhibitor. These results suggest that LPS plus IFNγ activates the iNOS-nitric oxide-glutamate pathway to induce microglial injury and that this activation is attenuated by isoflurane preconditioning. Protein kinase C may be involved in the isoflurane preconditioning effects. PMID:18495358

  13. Telomere Reprogramming and Maintenance in Porcine iPS Cells

    PubMed Central

    Ji, Guangzhen; Ruan, Weimin; Liu, Kai; Wang, Fang; Sakellariou, Despoina; Chen, Jijun; Yang, Yang; Okuka, Maja; Han, Jianyong; Liu, Zhonghua; Lai, Liangxue; Gagos, Sarantis; Xiao, Lei; Deng, Hongkui; Li, Ning; Liu, Lin

    2013-01-01

    Telomere reprogramming and silencing of exogenous genes have been demonstrated in mouse and human induced pluripotent stem cells (iPS cells). Pigs have the potential to provide xenotransplant for humans, and to model and test human diseases. We investigated the telomere length and maintenance in porcine iPS cells generated and cultured under various conditions. Telomere lengths vary among different porcine iPS cell lines, some with telomere elongation and maintenance, and others telomere shortening. Porcine iPS cells with sufficient telomere length maintenance show the ability to differentiate in vivo by teratoma formation test. IPS cells with short or dysfunctional telomeres exhibit reduced ability to form teratomas. Moreover, insufficient telomerase and incomplete telomere reprogramming and/or maintenance link to sustained activation of exogenous genes in porcine iPS cells. In contrast, porcine iPS cells with reduced expression of exogenous genes or partial exogene silencing exhibit insufficient activation of endogenous pluripotent genes and telomerase genes, accompanied by telomere shortening with increasing passages. Moreover, telomere doublets, telomere sister chromatid exchanges and t-circles that presumably are involved in telomere lengthening by recombination also are found in porcine iPS cells. These data suggest that both telomerase-dependent and telomerase-independent mechanisms are involved in telomere reprogramming during induction and passages of porcine iPS cells, but these are insufficient, resulting in increased telomere damage and shortening, and chromosomal instability. Active exogenes might compensate for insufficient activation of endogenous genes and incomplete telomere reprogramming and maintenance of porcine iPS cells. Further understanding of telomere reprogramming and maintenance may help improve the quality of porcine iPS cells. PMID:24098638

  14. Meclizine Preconditioning Protects the Kidney Against Ischemia-Reperfusion Injury.

    PubMed

    Kishi, Seiji; Campanholle, Gabriela; Gohil, Vishal M; Perocchi, Fabiana; Brooks, Craig R; Morizane, Ryuji; Sabbisetti, Venkata; Ichimura, Takaharu; Mootha, Vamsi K; Bonventre, Joseph V

    2015-09-01

    Global or local ischemia contributes to the pathogenesis of acute kidney injury (AKI). Currently there are no specific therapies to prevent AKI. Potentiation of glycolytic metabolism and attenuation of mitochondrial respiration may decrease cell injury and reduce reactive oxygen species generation from the mitochondria. Meclizine, an over-the-counter anti-nausea and -dizziness drug, was identified in a 'nutrient-sensitized' chemical screen. Pretreatment with 100mg/kg of meclizine, 17h prior to ischemia protected mice from IRI. Serum creatinine levels at 24h after IRI were 0.130.06mg/dl (sham, n=3), 1.590.10mg/dl (vehicle, n=8) and 0.890.11mg/dl (meclizine, n=8). Kidney injury was significantly decreased in meclizine treated mice compared with vehicle group (p<0.001). Protection was also seen when meclizine was administered 24h prior to ischemia. Meclizine reduced inflammation, mitochondrial oxygen consumption, oxidative stress, mitochondrial fragmentation, and tubular injury. Meclizine preconditioned kidney tubular epithelial cells, exposed to blockade of glycolytic and oxidative metabolism with 2-deoxyglucose and NaCN, had reduced LDH and cytochrome c release. Meclizine upregulated glycolysis in glucose-containing media and reduced cellular ATP levels in galactose-containing media. Meclizine inhibited the Kennedy pathway and caused rapid accumulation of phosphoethanolamine. Phosphoethanolamine recapitulated meclizine-induced protection both in vitro and in vivo. PMID:26501107

  15. 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.

  16. Abdominal Surgical Incision Induces Remote Preconditioning of Trauma (RPCT) via Activation of Bradykinin Receptors (BK2R) and the Cytochrome P450 Epoxygenase Pathway in Canine Hearts

    PubMed Central

    Gross, Garrett J.; Baker, John E.; Moore, Jeannine; Falck, John R.; Nithipatikom, Kasem

    2012-01-01

    Recently, a novel observation was made in which nonischemic trauma at a site remote from the heart produced by a transverse abdominal incision resulted in a marked reduction of infarct size (IS) in the mouse heart via activation of sensory nerve fibers in the skin and subsequent activation of bradykinin 2 receptors (BK2R). This phenomenon was termed remote preconditioning of trauma (RPCT). Since RPCT may have potential clinical implications we attempted to confirm these findings in a large animal model, the dog. The epoxyeicosatrienoic acids (EETs) have also recently been shown to be antinociceptive and have been shown to mimic ischemic preconditioning (IPC) and postconditioning (POC) in dogs, therefore, we tested the role of the EETs in RPCT. Anesthetized adult mongrel dogs of either sex were subjected to 60 min of left anterior descending (LAD) coronary artery occlusion followed by 3 h of reperfusion. In all groups except the controls (no slit), a transverse slit (9 cm) was applied to the abdominal wall of the dog being careful to only slit the skin. Subsequently, 15 min after the slit the heart was subjected to the ischemia/reperfusion protocol. In the control dogs, the IS as a percent of the area at risk (AAR) was 22.5 2.4%, whereas in the dogs subjected to the slit alone the IS/AAR was reduced to 9.2 1.2% (*P<0.01). The BR2R blocker, HOE 140 (50 ug/kg, iv) given 10 min prior to the slit, completely abolished the protective effects of RCPT as did pretreatment with 14,15-EEZE, a putative EET receptor blocker or pretreatment with the selective EET synthesis inhibitor, MSPPOH. These results suggest that BK and the EETs share cardioprotective properties in a large animal model of RPCT. PMID:21786213

  17. Spectroscopic Monitoring of Kidney Tissue Ischemic Injury

    SciTech Connect

    Demos, S G; Fitzgerald, J T; Michalopoulou, A P; Troppmann, C

    2004-03-11

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  18. Mitral valve repair for ischemic mitral regurgitation

    PubMed Central

    Mohebali, Jahan

    2015-01-01

    Mitral valve repair for ischemic mitral valve regurgitation remains controversial. In moderate mitral regurgitation (MR), controversy exists whether revascularization alone will be adequate to restore native valve geometry or whether intervention on the valve (repair) should be performed concomitantly. When MR is severe, the need for valve intervention is not disputed. Rather, the controversy is whether repair versus replacement should be undertaken. In contrast to degenerative or myxomatous disease that directly affects leaflet integrity and morphology, ischemic FMR results from a distortion and dilation of native ventricular geometry that normally supports normal leaflet coaptation. To address this, the first and most crucial step in successful valve repair is placement of an undersized, complete remodeling annuloplasty ring to restore the annulus to its native geometry. The following article outlines the steps for repair of ischemic mitral regurgitation. PMID:26309832

  19. Resilience in Patients with Ischemic Heart Disease

    PubMed Central

    de Lemos, Conceição Maria Martins; Moraes, David William; Pellanda, Lucia Campos

    2016-01-01

    Background Resilience is a psychosocial factor associated with clinical outcomes in chronic diseases. The relationship between this protective factor and certain diseases, such heart diseases, is still under-explored. Objective The present study sought to investigate the frequency of resilience in individuals with ischemic heart disease. Method This was a cross-sectional study with 133 patients of both genders, aged between 35 and 65 years, treated at Rio Grande do Sul Cardiology Institute - Cardiology University Foundation, with a diagnosis of ischemic heart disease during the study period. Sixty-seven patients had a history of acute myocardial infarction. The individuals were interviewed and evaluated by the Wagnild & Young resilience scale and a sociodemographic questionnaire. Results Eighty-one percent of patients were classified as resilient according to the scale. Conclusion In the sample studied, resilience was identified in high proportion among patients with ischemic heart disease. PMID:26815312

  20. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can rescue salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  1. Colonoscopy-induced ischemic colitis in patients without risk factors

    PubMed Central

    Lee, Sang Ok; Kim, Sae Hee; Jung, Sung Hee; Park, Chan Woong; Lee, Min Ji; Lee, Jin A; Koo, Hyun Cheol; Kim, Anna; Han, Hyun-Young; Kang, Dong-Wook

    2014-01-01

    Ischemic colitis is the most common form of intestinal ischemia. It is a condition that is commonly seen in the elderly and among individuals with risk factors for ischemia. Common predisposing conditions for ischemic colitis are major vascular occlusion, small vessel disorder, shock, some medications, colonic obstructions and hematologic disorders. Ischemic colitis following colonoscopy is rare. Here, we report two cases of ischemic colitis after a routine screening colonoscopy in patients without risk factors for ischemia. PMID:24707156

  2. Flow Augmentation in Acute Ischemic Stroke.

    PubMed

    Yadollahikhales, Golnaz; Borhani-Haghighi, Afshin; Torabi-Nami, Mohammad; Edgell, Randall; Cruz-Flores, Salvador

    2016-01-01

    There is an urgent need for additional therapeutic options for acute ischemic stroke considering the major pitfalls of the options available. Herein, we briefly review the role of cerebral blood flow, collaterals, vasoreactivity, and reperfusion injury in acute ischemic stroke. Then, we reviewed pharmacological and interventional measures such as volume expansion and induced hypertension, intra-aortic balloon counterpulsation, partial aortic occlusion, extracranial-intracranial carotid bypass surgery, sphenopalatine ganglion stimulation, and transcranial laser therapy with regard to their effects on flow augmentation and neuroprotection. PMID:25475112

  3. Protection of the ischaemic heart: investigations into the phenomenon of ischaemic preconditioning.

    PubMed

    Lochner, A; Marais, E; Genade, S; Huisamen, B; du Toit, E F; Moolman, J A

    2009-01-01

    Exposure of the heart to one or more short episodes of ischaemia/reperfusion protects the heart against a subsequent prolonged period of ischaemia, as evidenced by a reduction in infarct size and an improvement in functional recovery during reperfusion. Elucidation of the mechanism of this endogenous protection could lead to the development of pharmacological mimetics to be used in the clinical setting. The aim of our studies was therefore to gain more information regarding the mechanism of ischaemic preconditioning, using the isolated perfused working rat heart as model. A preconditioning protocol of 1 x 5 or 3 x 5 min of ischaemia, interspersed with 5 min of reperfusion was found to protect hearts exposed to 25 min of global ischaemia or 35-45 min of regional ischaemia. These models were used throughout our studies. In view of the release of catecholamines by ischaemic tissue, our first aim was to evaluate the role of the alphaadrenergic receptor in ischaemic preconditioning. However, using a multi-cycle ischaemic preconditioning protocol, we could not find any evidence for alpha-1 adrenergic or PKC activation in the mechanism of preconditioning. Cyclic increases in the tissue cyclic nucleotides, cAMP and cGMP were found, however, to occur during a multi-cycle preconditioning protocol, suggesting roles for the beta-adrenergic signalling pathway and nitric oxide (NO) as triggers of cardioprotection. This was substantiated by the findings that (1) administration of the beta-adrenergic agonist, isoproterenol, or the NO donors SNAP or SNP before sustained ischaemia also elicited cardioprotection similar to ischaemic preconditioning; (2) beta-adrenergic blockade or nitric oxide synthase inhibition during an ischaemic preconditioning protocol abolished protection. Effectors downstream of cAMP, such as p38MAPK and CREB, were also demonstrated to be involved in the triggering process. Our next step was to evaluate intracellular signalling during sustained ischaemia and reperfusion. Our results showed that ischaemic preconditioned-induced cardioprotection was associated with a significant reduction in tissue cAMP, attenuation of p38MAPK activation and increased tissue cGMP levels and HSP27 activation, compared to non-preconditioned hearts. The role of the stress kinase p38MAPK was further investigated by using the inhibitor SB203580. Our results suggested that injury by necrosis and apoptosis share activation of p38MAPK as a common signal transduction pathway and that pharmacological targeting of this kinase offers a tenable option to manipulate both these processes during ischaemia/reperfusion injury. PMID:19287816

  4. 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.

  5. Computational methodology for ChIP-seq analysis

    PubMed Central

    Shin, Hyunjin; Liu, Tao; Duan, Xikun; Zhang, Yong; Liu, X. Shirley

    2015-01-01

    Chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) is a powerful technology to identify the genome-wide locations of DNA binding proteins such as transcription factors or modified histones. As more and more experimental laboratories are adopting ChIP-seq to unravel the transcriptional and epigenetic regulatory mechanisms, computational analyses of ChIP-seq also become increasingly comprehensive and sophisticated. In this article, we review current computational methodology for ChIP-seq analysis, recommend useful algorithms and workflows, and introduce quality control measures at different analytical steps. We also discuss how ChIP-seq could be integrated with other types of genomic assays, such as gene expression profiling and genome-wide association studies, to provide a more comprehensive view of gene regulatory mechanisms in important physiological and pathological processes. PMID:25741452

  6. Defining bacterial regulons using ChIP-seq.

    PubMed

    Myers, Kevin S; Park, Dan M; Beauchene, Nicole A; Kiley, Patricia J

    2015-09-15

    Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is a powerful method that identifies protein-DNA binding sites in vivo. Recent studies have illustrated the value of ChIP-seq in studying transcription factor binding in various bacterial species under a variety of growth conditions. These results show that in addition to identifying binding sites, correlation of ChIP-seq data with expression data can reveal important information about bacterial regulons and regulatory networks. In this chapter, we provide an overview of the current state of knowledge about ChIP-seq methodology in bacteria, from sample preparation to raw data analysis. We also describe visualization and various bioinformatic analyses of processed ChIP-seq data. PMID:26032817

  7. Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis

    PubMed Central

    Leth, Thomas; Wilkens, Rune; Bonderup, Ole K.

    2015-01-01

    Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report sonographic and endoscopic images along with abdominal computed tomography in a case of cocaine-induced ischemic colitis. PMID:26798523

  8. IP switching in a simplified ATM environment

    NASA Astrophysics Data System (ADS)

    Ilvesmaeki, Mika; Luoma, Marko

    1997-10-01

    Key issues in the current development of Internet seem to be its capability to scale and to support new real-time or near real-time applications like video- and audio-conferencing. There are two factors that affect these qualities: one is the ability to distinguish which connections should be switched and the other is the effective control over network resources. ATM is a serious attempt to standardize global multiservice networks. This attempt seems to suit well for the future Internet. ATM was originally meant to be an easy and an efficient protocol but it is now turning to be 'yet another ISDN.' More and more features are implemented to ATM resulting in the overloading of the network with management procedures. Therefore a new approach needs to be taken. In this approach a strong reminder of 'what is necessary' needs to be kept in mind. This paper presents an alternative, simpler approach to the ATM traffic management and introduces some suggestions how to map Internet applications to simplified ATM environment using an advanced IP switching concept.

  9. Probabilistic Route Selection Algorithm for IP Traceback

    NASA Astrophysics Data System (ADS)

    Yim, Hong-Bin; Jung, Jae-Il

    DoS(Denial of Service) or DDoS(Distributed DoS) attack is a major threaten and the most difficult problem to solve among many attacks. Moreover, it is very difficult to find a real origin of attackers because DoS/DDoS attacker uses spoofed IP addresses. To solve this problem, we propose a probabilistic route selection traceback algorithm, namely PRST, to trace the attacker's real origin. This algorithm uses two types of packets such as an agent packet and a reply agent packet. The agent packet is in use to find the attacker's real origin and the reply agent packet is in use to notify to a victim that the agent packet is reached the edge router of the attacker. After attacks occur, the victim generates the agent packet and sends it to a victim's edge router. The attacker's edge router received the agent packet generates the reply agent packet and send it to the victim. The agent packet and the reply agent packet is forwarded refer to probabilistic packet forwarding table (PPFT) by routers. The PRST algorithm runs on the distributed routers and PPFT is stored and managed by routers. We validate PRST algorithm by using mathematical approach based on Poisson distribution.

  10. I.P. Pavlov as a youth.

    PubMed

    Windholz, G

    1991-01-01

    Ivan P. Pavlov's youthful relations with parents and siblings, formal education, and social activities in Riazan' are described. The Pavlovs, a highly achievement-oriented family descending from a lowly serf, improved their social status by serving the Russian Orthodox Church. Pavlov, the son of a priest, studied in the 1860s at the Riazan' Ecclesiastic Seminary for priesthood. The turbulent 1860s' decade was a period of social and political reforms. Western ideas and science were introduced to Russia. The ambitious and idealistic I.P. Pavlov was influenced by popular essays written by the journalist D.I. Pisarev, the works of the German physiologist J. Moleschott, the English writer G.H. Lewes, the German zoologist C. Vogt and the physiologist M.I. Sechenov. Losing his religious faith, Pavlov abandoned the traditional goal of becoming a priest, and, convinced that science was a road to truth and progress, left Riazan' to study natural science at the University of St. Petersburg. PMID:2054299

  11. Fetal asphyctic preconditioning protects against perinatal asphyxia-induced behavioral consequences in adulthood.

    PubMed

    Strackx, Eveline; Van den Hove, Danil L A; Prickaerts, Jos; Zimmermann, Luc; Steinbusch, Harry W M; Blanco, Carlos E; Gavilanes, A W Danilo; Vles, J S Hans

    2010-04-01

    Perinatal asphyxia is one of the major causes of neuronal injury and impaired development in infants. We recently have shown that a brief episode of experimental fetal asphyxia (FA) can provoke an endogenous neuroprotection against subsequent severe perinatal asphyxia (SPA). The long-lasting functional consequences of FA preconditioning are not clear yet. The aim of the study was to determine if FA preconditioning can provide a long-lasting behavioral protection against SPA. FA was induced, as a preconditioning stimulus, by clamping the uterine vasculature for 30 min on E17. At birth, SPA was induced by placing the uterine horns in a water bath for 19 min. At 6 months of age, functional outcome was assessed using different behavioral tests: the open field for locomotor activity, the elevated zero maze for anxiety-related behavior, the forced swim test for depression-related behavior and the object recognition task for cognition. Data showed that FA preconditioning improved postnatal mortality after SPA. At the age of 6 months, the total distance moved in the open field and elevated zero maze was significantly less in the SPA group compared to the control groups. In addition, cognitive performance in the object recognition task was impaired in the SPA offspring compared to the control groups. Most importantly, FA preconditioning was able to preserve both locomotor activity and cognition function. In conclusion, FA preconditioning induces a long-lasting, functional protection against SPA. Therefore, this model seems to offer good opportunities for the identification and characterization of the underlying mechanisms of preconditioning. PMID:19962408

  12. IP3 levels and their modulation FY fusicoccin measured by a novel ( sup 3 H) IP3 binding assay

    SciTech Connect

    Aducci, P.; Marra, M. )

    1990-05-16

    A recently developed sensitive assay based on the binding reaction of IP3 to bovine adrenal preparations has been utilized for determining the level of endogenous inositol-1,4,5 trisphosphate (IP3) in maize roots and coleoptiles. The amount of IP3 found in these tissues ranges from 0.1 to 1.0 nmol g-1 fresh weight. Reproducible results were obtained with extracts of tissues from a same harvest, while they showed a 2-3 fold variation when different batches of plantlets were compared. The fungal phytotoxin fusicoccin (FC) known to affect several physiological processes in higher plants, increases the level of IP3 in coleoptiles. This observation suggests that IP3 might be involved in the transduction of the FC encoded signal from its receptors at the plasmalemma level to the cell machinery.

  13. Meclizine Preconditioning Protects the Kidney Against Ischemia–Reperfusion Injury

    PubMed Central

    Kishi, Seiji; Campanholle, Gabriela; Gohil, Vishal M.; Perocchi, Fabiana; Brooks, Craig R.; Morizane, Ryuji; Sabbisetti, Venkata; Ichimura, Takaharu; Mootha, Vamsi K.; Bonventre, Joseph V.

    2015-01-01

    Global or local ischemia contributes to the pathogenesis of acute kidney injury (AKI). Currently there are no specific therapies to prevent AKI. Potentiation of glycolytic metabolism and attenuation of mitochondrial respiration may decrease cell injury and reduce reactive oxygen species generation from the mitochondria. Meclizine, an over-the-counter anti-nausea and -dizziness drug, was identified in a ‘nutrient-sensitized’ chemical screen. Pretreatment with 100 mg/kg of meclizine, 17 h prior to ischemia protected mice from IRI. Serum creatinine levels at 24 h after IRI were 0.13 ± 0.06 mg/dl (sham, n = 3), 1.59 ± 0.10 mg/dl (vehicle, n = 8) and 0.89 ± 0.11 mg/dl (meclizine, n = 8). Kidney injury was significantly decreased in meclizine treated mice compared with vehicle group (p < 0.001). Protection was also seen when meclizine was administered 24 h prior to ischemia. Meclizine reduced inflammation, mitochondrial oxygen consumption, oxidative stress, mitochondrial fragmentation, and tubular injury. Meclizine preconditioned kidney tubular epithelial cells, exposed to blockade of glycolytic and oxidative metabolism with 2-deoxyglucose and NaCN, had reduced LDH and cytochrome c release. Meclizine upregulated glycolysis in glucose-containing media and reduced cellular ATP levels in galactose-containing media. Meclizine inhibited the Kennedy pathway and caused rapid accumulation of phosphoethanolamine. Phosphoethanolamine recapitulated meclizine-induced protection both in vitro and in vivo. PMID:26501107

  14. Downward-Propagating Temperature Anomalies in the Preconditioned Polar Stratosphere.

    NASA Astrophysics Data System (ADS)

    Zhou, Shuntai; Miller, Alvin J.; Wang, Julian; Angell, James K.

    2002-04-01

    Dynamical links of the Northern Hemisphere stratosphere and troposphere are studied, with an emphasis on whether stratospheric changes have a direct effect on tropospheric weather and climate. In particular, downward propagation of stratospheric anomalies of polar temperature in the winter-spring season is examined based upon 22 years of NCEP-NCAR reanalysis data. It is found that the polar stratosphere is sometimes preconditioned, which allows a warm anomaly to propagate from the upper stratosphere to the troposphere, and sometimes it prohibits downward propagation. The Arctic Oscillation (AO) is more clearly seen in the former case. To understand what dynamical conditions dictate the stratospheric property of downward propagation, the upper-stratospheric warming episodes with very large anomalies (such as stratospheric sudden warming) are selected and divided into two categories according to their downward-propagating features. Eliassen-Palm (E-P) diagnostics and wave propagation theories are used to examine the characteristics of wave-mean flow interactions in the two different categories. It is found that in the propagating case the initial wave forcing is very large and the polar westerly wind is reversed. As a result, dynamically induced anomalies propagate down as the critical line descends. A positive feedback is that the dramatic change in zonal wind alters the refractive index in a way favorable for continuous poleward transport of wave energy. The second pulse of wave flux conducts polar warm anomalies farther down. Consequently, the upper-tropospheric circulations are changed, in particular, the subtropical North Atlantic jet stream shifts to the south by 5 degrees of latitude, and the alignment of the jet stream becomes more zonal, which is similar to the negative phase of the North Atlantic Oscillation (NAO).

  15. Analysis and modeling of neural processes underlying sensory preconditioning.

    PubMed

    Matsumoto, Yukihisa; Hirashima, Daisuke; Mizunami, Makoto

    2013-03-01

    Sensory preconditioning (SPC) is a procedure to demonstrate learning to associate between relatively neutral sensory stimuli in the absence of an external reinforcing stimulus, the underlying neural mechanisms of which have remained obscure. We address basic questions about neural processes underlying SPC, including whether neurons that mediate reward or punishment signals in reinforcement learning participate in association between neutral sensory stimuli. In crickets, we have suggested that octopaminergic (OA-ergic) or dopaminergic (DA-ergic) neurons participate in memory acquisition and retrieval in appetitive or aversive conditioning, respectively. Crickets that had been trained to associate an odor (CS2) with a visual pattern (CS1) (phase 1) and then to associate CS1 with water reward or quinine punishment (phase 2) exhibited a significantly increased or decreased preference for CS2 that had never been paired with the US, demonstrating successful SPC. Injection of an OA or DA receptor antagonist at different phases of the SPC training and testing showed that OA-ergic or DA-ergic neurons do not participate in learning of CS2-CS1 association in phase 1, but that OA-ergic neurons participate in learning in phase 2 and memory retrieval after appetitive SPC training. We also obtained evidence suggesting that association between CS2 and US, which should underlie conditioned response of crickets to CS2, is formed in phase 2, contrary to the standard theory of SPC assuming that it occurs in the final test. We propose models of SPC to account for these findings, by extending our model of classical conditioning. PMID:23380289

  16. Glaciations in response to climate variations preconditioned by evolving topography.

    PubMed

    Pedersen, Vivi Kathrine; Egholm, David Lundbek

    2013-01-10

    Landscapes modified by glacial erosion show a distinct distribution of surface area with elevation (hypsometry). In particular, the height of these regions is influenced by climatic gradients controlling the altitude where glacial and periglacial processes are the most active, and as a result, surface area is focused just below the snowline altitude. Yet the effect of this distinct glacial hypsometric signature on glacial extent and therefore on continued glacial erosion has not previously been examined. Here we show how this topographic configuration influences the climatic sensitivity of Alpine glaciers, and how the development of a glacial hypsometric distribution influences the intensity of glaciations on timescales of more than a few glacial cycles. We find that the relationship between variations in climate and the resulting variation in areal extent of glaciation changes drastically with the degree of glacial modification in the landscape. First, in landscapes with novel glaciations, a nearly linear relationship between climate and glacial area exists. Second, in previously glaciated landscapes with extensive area at a similar elevation, highly nonlinear and rapid glacial expansions occur with minimal climate forcing, once the snowline reaches the hypsometric maximum. Our results also show that erosion associated with glaciations before the mid-Pleistocene transition at around 950,000 years ago probably preconditioned the landscape--producing glacial landforms and hypsometric maxima--such that ongoing cooling led to a significant change in glacial extent and erosion, resulting in more extensive glaciations and valley deepening in the late Pleistocene epoch. We thus provide a mechanism that explains previous observations from exposure dating and low-temperature thermochronology in the European Alps, and suggest that there is a strong topographic control on the most recent Quaternary period glaciations. PMID:23302860

  17. Domain decomposition and preconditioned iterative methods for the Helmholtz equation

    NASA Astrophysics Data System (ADS)

    Larsson, Elisabeth

    New preconditioned iterative solution methods for the Helmholtz equation are constructed. To evaluate the performance of the methods, two-dimensional problems with a waveguide geometry are used as model problems. Second- and fourth-order accurate finite difference discretizations are used. By introducing a domain decomposition framework, problems where the physical domain consists of a number of layers of different materials can be solved. The new algorithms are shown to perform well compared with standard methods. First, a discretization of the Helmholtz equation in a curvilinear waveguide with smoothly varying material properties is studied. Nonlocal radiation boundary conditions are constructed for the artificial in- and outflow boundaries. A preconditioner that can be applied using fast transform methods is constructed. Experiments show that the total arithmetic complexity is much less with the fast transform preconditioner than when using a standard symmetric successive over-relaxation preconditioner. Compared with band Gaussian elimination, the gain is large both in arithmetic complexity and memory requirements. Next, an application with layers of different materials is considered. It is shown that nonlocal radiation boundary conditions can be constructed also in this case. A domain decomposition formulation is employed, where the fast transform preconditioner is used as a subdomain preconditioner. The performance is excellent compared with band Gaussian elimination. The multilayer solver is used for an investigation of the properties of the solutions of a number of underwater acoustics problems. The quality of the solutions obtained by a widely used approximation, the parabolic wave equation, is evaluated. For some problems the agreement is excellent, whereas in other cases the approximation cannot replace the full Helmholtz solution. A parallel version of the solver is implemented, where the algorithms are modified for increased parallel performance. With the parallel code larger problems can be solved in less computational time.

  18. Gene Therapy For Ischemic Heart Disease

    PubMed Central

    Lavu, Madhav; Gundewar, Susheel; Lefer, David J.

    2010-01-01

    Current pharmacologic therapy for ischemic heart disease suffers multiple limitations such as compliance issues and side effects of medications. Revascularization procedures often end with need for repeat procedures. Patients remain symptomatic despite maximal medical therapy. Gene therapy offers an attractive alternative to current pharmacologic therapies and may be beneficial in refractory disease. Gene therapy with isoforms of growth factors such as VEGF, FGF and HGF induces angiogenesis, decreases apoptosis and leads to protection in the ischemic heart. Stem cell therapy augmented with gene therapy used for myogenesis has proven to be beneficial in numerous animal models of myocardial ischemia. Gene therapy coding for antioxidants, eNOS, HSP, mitogen-activated protein kinase and numerous other anti apoptotic proteins have demonstrated significant cardioprotection in animal models. Clinical trials have demonstrated safety in humans apart from symptomatic and objective improvements in cardiac function. Current research efforts are aimed at refining various gene transfection techniques and regulation of gene expression in vivo in the heart and circulation to improve clinical outcomes in patients that suffer from ischemic heart disease. In this review article we will attempt to summarize the current state of both preclinical and clinical studies of gene therapy to combat myocardial ischemic disease. PMID:20600100

  19. Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes

    PubMed Central

    Perna, Robert; Temple, Jessica

    2015-01-01

    Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n = 172) or hemorrhagic stroke (n = 112) within the past six months and were involved in a postacute neurorehabilitation program. Participants completed three months of postacute neurorehabilitation and the Mayo Portland Adaptability Inventory-4 (MPAI-4) at admission and discharge. Admission MPAI-4 scores and level of functioning were comparable. Results. Group ANOVA comparisons show no significant group differences at admission or discharge or difference in change scores. Both groups showed considerably reduced levels of productivity/employment after discharge as compared to preinjury levels. Conclusions. Though the pathophysiology of these types of strokes is different, both ultimately result in ischemic injuries, possibly accounting for lack of findings of differences between groups. In the present study, participants in both groups experienced similar functional levels across all three MPAI-4 domains both at admission and discharge. Limitations of this study include a highly educated sample and few outcome measures. PMID:26246694

  20. Cerebrovascular ischemic events in wind instrument players.

    PubMed

    Evers, S; Altenmller, E; Ringelstein, E B

    2000-09-26

    Two cases of ischemic stroke due to carotid artery dissection occurring during wind instrument playing, probably caused by increased intrathoracic and subsequent intrapharyngeal pressure, are presented. A review of the literature revealed three similar patients with other types of cerebrovascular events, such as paradoxical cerebral embolism due to a patent foramen ovale and spinal epidural hematoma during trumpet playing. PMID:10994010

  1. Carotid Atherosclerosis in Ischemic Cerebrovascular Patients

    PubMed Central

    Zhang, Ai Juan; Zhang, Ai Yuan; Zhong, Chi

    2009-01-01

    Background Cerebral emboli resulting from atherosclerosis at the carotid bifurcation is a major cause of ischemic stroke. A convenient and prompt evaluation is necessary for secondary prevention and treatment. Methods In this study, one hundred and thirty eight patients with cerebral ischemic events were enrolled; 100 patients with nonischemic cerebral diseases were enrolled as controls. Noninvasive ultrasound was used to measure the atherosclerotic plaques and intima-media thickness (IMT) of carotid and femoral artery. Results Our results showed that patients in study group had higher incidence and severity of carotid and femoral plaques, and higher mean intima-media thickness (IMT) at both the carotid and femoral sites compared with that of controls (p < 0.01). Carotid atherosclerosis were highly prone to have instability plaques in study group(p < 0.001). Conclusions This cross-sectional study showed that, the prevalence of carotid atherosclerosis and the unstable plaques were higher in cerebral ischemic patients. Keywords Carotid artery; Atherosclerosis; Intima-media thickness; Cerebral ischemic stroke PMID:22505964

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

    PubMed

    Gmez Escalona, Jos 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 tambin ?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. PMID:24483317

  3. pGlu-serpinin protects the normotensive and hypertensive heart from ischemic injury.

    PubMed

    Pasqua, T; Tota, B; Penna, C; Corti, A; Cerra, M C; Loh, Y P; Angelone, T

    2015-12-01

    Serpinin peptides derive from proteolytic cleavage of Chromogranin-A at C-terminus. Serpinin and the more potent pyroglutaminated-serpinin (pGlu-Serp) are positive cardiac ?-adrenergic-like modulators, acting through ?1-AR/AC/cAMP/PKA pathway. Because in some conditions this pathway and/or other pro-survival pathways, activated by other Chromogranin-A fragments, may cross-talk and may be protective, here we explored whether pGlu-Serp cardioprotects against ischemia/reperfusion injury under normotensive and hypertensive conditions. In the latter condition, cardioprotection is often blunted because of the limitations on pro-survival Reperfusion Injury Salvage Kinases (RISK) pathway activation. The effects of pGlu-Serp were evaluated on infarct size (IS) and cardiac function by using the isolated and Langendorff perfused heart of normotensive (Wistar Kyoto, WKY) and spontaneously hypertensive (SHR) rats exposed to ischemic pre-conditioning (PreC) and post-conditioning (PostC). In both WKY and SHR rat, pGlu-Serp induced mild cardioprotection in both PreC and PostC. pGlu-Serp administered at the reperfusion (Serp-PostC) significantly reduced IS, being more protective in SHR than in WKY. Conversely, left ventricular developed pressure (LVDevP) post-ischemic recovery was greater in WKY than in SHR. pGlu-Serp-PostC reduced contracture in both strains. Co-infusion with specific RISK inhibitors (PI3K/Akt, MitoKATP channels and PKC) blocked the pGlu-Serp-PostC protective effects. To show direct effect on cardiomyocytes, we pre-treated H9c2 cells with pGlu-Serp, which were thus protected against hypoxia/reoxygenation. These results suggest pGlu-Serp as a potential modulatory agent implicated in the protective processes that can limit infarct size and overcome the hypertension-induced failure of PostC. PMID:26400960

  4. Reviewing ChIPS, The Chandra Imaging and Plotting System

    NASA Astrophysics Data System (ADS)

    Miller, J.; Burke, D. J.; Evans, I. N.; Evans, J. D.; McLaughlin, W.

    2015-09-01

    The Chandra Imaging and Plotting System (ChIPS) is a 2D plotting system designed to allow users to easily create, manipulate, and produce publication quality visualizations. ChIPS has a simple but very powerful interactive interface that allows users to dynamically modify the contents and layout of their plots quickly and efficiently, with the results of any changes being immediately visible. ChIPS allows users to construct their plots fully interactively, and then save the final plot commands as a Python script. This bypasses the need to iteratively edit and rerun the script when developing the plot. Features such as undo and redo commands allow users to easily step backwards and forwards through previous commands, while the ability so save ChIPS sessions in a platform-independent state file allows the session to be restored at any time, even on another machine. Because ChIPS offers a Python interface, users can analyze their data using the broad array of modules offered in Python, and visualize the information in ChIPS at the same time. In this paper we explore the design decisions behind the development of ChIPS and some of the lessons learned along the way.

  5. A decentralized software bus based on IP multicas ting

    NASA Technical Reports Server (NTRS)

    Callahan, John R.; Montgomery, Todd

    1995-01-01

    We describe decentralized reconfigurable implementation of a conference management system based on the low-level Internet Protocol (IP) multicasting protocol. IP multicasting allows low-cost, world-wide, two-way transmission of data between large numbers of conferencing participants through the Multicasting Backbone (MBone). Each conference is structured as a software bus -- a messaging system that provides a run-time interconnection model that acts as a separate agent (i.e., the bus) for routing, queuing, and delivering messages between distributed programs. Unlike the client-server interconnection model, the software bus model provides a level of indirection that enhances the flexibility and reconfigurability of a distributed system. Current software bus implementations like POLYLITH, however, rely on a centralized bus process and point-to-point protocols (i.e., TCP/IP) to route, queue, and deliver messages. We implement a software bus called the MULTIBUS that relies on a separate process only for routing and uses a reliable IP multicasting protocol for delivery of messages. The use of multicasting means that interconnections are independent of IP machine addresses. This approach allows reconfiguration of bus participants during system execution without notifying other participants of new IP addresses. The use of IP multicasting also permits an economy of scale in the number of participants. We describe the MULITIBUS protocol elements and show how our implementation performs better than centralized bus implementations.

  6. MACE: model based analysis of ChIP-exo.

    PubMed

    Wang, Liguo; Chen, Junsheng; Wang, Chen; Uuskla-Reimand, Liis; Chen, Kaifu; Medina-Rivera, Alejandra; Young, Edwin J; Zimmermann, Michael T; Yan, Huihuang; Sun, Zhifu; Zhang, Yuji; Wu, Stephen T; Huang, Haojie; Wilson, Michael D; Kocher, Jean-Pierre A; Li, Wei

    2014-11-10

    Understanding the role of a given transcription factor (TF) in regulating gene expression requires precise mapping of its binding sites in the genome. Chromatin immunoprecipitation-exo, an emerging technique using ? 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

  7. 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

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

    PubMed Central

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

    2015-01-01

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

  9. Hypoxic Preconditioning Suppresses Glial Activation and Neuroinflammation in Neonatal Brain Insults

    PubMed Central

    Chen, Chien-Yi; Sun, Wei-Zen; Kang, Kai-Hsiang; Chou, Hung-Chieh; Tsao, Po-Nien; Hsieh, Wu-Shiun; Fu, Wen-Mei

    2015-01-01

    Perinatal insults and subsequent neuroinflammation are the major mechanisms of neonatal brain injury, but there have been only scarce reports on the associations between hypoxic preconditioning and glial activation. Here we use neonatal hypoxia-ischemia brain injury model in 7-day-old rats and in vitro hypoxia model with primary mixed glial culture and the BV-2 microglial cell line to assess the effects of hypoxia and hypoxic preconditioning on glial activation. Hypoxia-ischemia brain insult induced significant brain weight reduction, profound cell loss, and reactive gliosis in the damaged hemisphere. Hypoxic preconditioning significantly attenuated glial activation and resulted in robust neuroprotection. As early as 2 h after the hypoxia-ischemia insult, proinflammatory gene upregulation was suppressed in the hypoxic preconditioning group. In vitro experiments showed that exposure to 0.5% oxygen for 4 h induced a glial inflammatory response. Exposure to brief hypoxia (0.5 h) 24 h before the hypoxic insult significantly ameliorated this response. In conclusion, hypoxic preconditioning confers strong neuroprotection, possibly through suppression of glial activation and subsequent inflammatory responses after hypoxia-ischemia insults in neonatal rats. This might therefore be a promising therapeutic approach for rescuing neonatal brain injury. PMID:26273140

  10. Handbook for Using IP Protocols for Space Missions

    NASA Technical Reports Server (NTRS)

    Hogie, Keith; Criscuolo, Ed; Parise, Ron

    2004-01-01

    This presentation will provide a summary of a handbook developed at GSFC last year that contains concepts and guidelines for using Internet protocols for space missions. It will include topics on: Lessons learned from current Space IP mission. General architectural issues related to use of IP in space. Operational scenarios for common space data transfer applications. Security issues. A general review of protocols applicable for use with IP in space. The presentation will also pose questions on what sort of information would be useful in future versions of the document.

  11. Genomic location analysis by ChIP-Seq

    PubMed Central

    Barski, Artem; Zhao, Keji

    2013-01-01

    The interaction of a multitude of transcription factors and other chromatin proteins with the genome can influence gene expression and subsequently cell differentiation and function. Thus systematic identification of binding targets of transcription factors is key to unraveling gene regulation networks. The recent development of ChIP-Seq has revolutionized mapping of DNA-protein interactions. Now protein binding can be mapped in a truly genome-wide manner with extremely high resolution. This review discusses ChIP-Seq technology, its possible pitfalls, data analysis and several early applications of the ChIP-Seq technology. PMID:19173299

  12. Application of Mobile-ip to Space and Aeronautical Networks

    NASA Technical Reports Server (NTRS)

    Leung, Kent; Shell, Dan; Ivancic, William D.; Stewart, David H.; Bell, Terry L.; Kachmar, Brian A.

    2001-01-01

    The National Aeronautics and Space Administration (NASA) is interested in applying mobile Internet protocol (mobile-ip) technologies to its space and aeronautics programs. In particular, mobile-ip will play a major role in the Advanced Aeronautic Transportation Technology (AAT-F), the Weather Information Communication (WINCOMM), and the Small Aircraft Transportation System (SATS) aeronautics programs. This paper describes mobile-ip and mobile routers--in particular, the features, capabilities, and initial performance of the mobile router are presented. The application of mobile-router technology to NASA's space and aeronautics programs is also discussed.

  13. Architecture of fast IP forwarding engine in gigabit ethernet system

    NASA Astrophysics Data System (ADS)

    Do, Han C.; Lee, Hyeong H.; Cha, Kyoon Hyun

    1999-11-01

    In recent years, Internet traffic has been increased rapidly as a result of the Internet which accommodates multimedia traffic such as IP telephony and video conference. Gigabit routing technology is one possible approach to handle such internet traffic. This paper presents an efficient IP forwarding architecture adequate for Gigabit Ethernet switching system. The presented IP forwarding architecture is based upon distributed and pipelined process, which can effectively facilitate searching, editing, traffic classification, forwarding, and traffic management in parallel. Additionally, it can also process packets at full wire-speed in the ASIC level.

  14. Heliospheric Tomography from IPS Data at 140 MHz

    NASA Astrophysics Data System (ADS)

    Mejia-Ambriz, J. C.; Jackson, B. V.; Gonzalez-Esparza, A.; Buffington, A.

    2014-12-01

    Interplanetary scintillation (IPS) from radio telescopes provides data to study density and velocity evolution of the solar wind and heliospheric disturbances. A tomography program developed at the University of California, San Diego, makes 3D reconstructions and forecasts of the inner heliosphere dynamics from IPS results. For the first time we incorporate 140 MHz IPS results from the MEXican Array Radio Telescope (MEXART) into the tomography program. We show that MEXART data complement observations from other radio-systems located at different longitudes, thus providing more complete heliospheric coverage.

  15. Actuator development for the Instrument Pointing System (IPS)

    NASA Technical Reports Server (NTRS)

    Suttner, K.

    1984-01-01

    The mechanisms of the instrument pointing system (IPS) are described. Particular emphasis is placed on the actuators which are necessary for operating the IPS. The actuators are described as follows: (1) two linear actuators that clamp the gimbals down during ascent and descent; (2) two linear actuators that attach the payload to the IPS during the mission, and release it into the payload clamps; (3) one rotational actuator that opens and closes the payload clamps; and (4) three identical drive units that represent the three orthogonal gimbal axes and are the prime movers for pointing. Design features, manufacturing problems, test performance, and results are presented.

  16. An integrated system CisGenome for analyzing ChIP-chip and ChIP-seq data

    PubMed Central

    Ji, Hongkai; Jiang, Hui; Ma, Wenxiu; Johnson, David S.; Myers, Richard M.; Wong, Wing H.

    2008-01-01

    CisGenome is a software system for analyzing genome-wide chromatin immunoprecipitation (ChIP) data. It is designed to meet all basic needs of ChIP data analyses, including visualization, data normalization, peak detection, false discovery rate (FDR) computation, gene-peak association, and sequence and motif analysis. In addition to implementing previously published ChIP-chip analysis methods, the software contains new statistical methods designed specifically for ChIP-seq data. CisGenome has a modular design so that it supports interactive analyses through a graphic user interface as well as customized batch-mode computation for advanced data mining. A built-in browser allows visualization of array images, signals, gene structure, conservation, and DNA sequence and motif information. We illustrate the use of these tools by a comparative analysis of ChIP-chip and ChIP-seq data for the transcription factor NRSF/REST, a study of ChIP-seq analysis without negative control sample, and an analysis of a novel motif in Nanog- and Sox2-binding regions. PMID:18978777

  17. 78 FR 53684 - Misuse of Internet Protocol (IP) Captioned Telephone Service; Telecommunications Relay Services...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-30

    ... COMMISSION 47 CFR Part 64 Misuse of Internet Protocol (IP) Captioned Telephone Service; Telecommunications... internet protocol captioned telephone relay service (IP CTS). This action is necessary to ensure that... summary of the Commission's Misuse of Internet Protocol (IP) Captioned Telephone...

  18. Research on the Changes to the Lipid/Polymer Membrane Used in the Acidic Bitterness Sensor Caused by Preconditioning.

    PubMed

    Harada, Yuhei; Noda, Junpei; Yatabe, Rui; Ikezaki, Hidekazu; Toko, Kiyoshi

    2016-01-01

    A taste sensor that uses lipid/polymer membranes can evaluate aftertastes felt by humans using Change in membrane Potential caused by Adsorption (CPA) measurements. The sensor membrane for evaluating bitterness, which is caused by acidic bitter substances such as iso-alpha acid contained in beer, needs an immersion process in monosodium glutamate (MSG) solution, called "MSG preconditioning". However, what happens to the lipid/polymer membrane during MSG preconditioning is not clear. Therefore, we carried out three experiments to investigate the changes in the lipid/polymer membrane caused by the MSG preconditioning, i.e., measurements of the taste sensor, measurements of the amount of the bitterness substance adsorbed onto the membrane and measurements of the contact angle of the membrane surface. The CPA values increased as the preconditioning process progressed, and became stable after 3 d of preconditioning. The response potentials to the reference solution showed the same tendency of the CPA value change during the preconditioning period. The contact angle of the lipid/polymer membrane surface decreased after 7 d of MSG preconditioning; in short, the surface of the lipid/polymer membrane became hydrophilic during MSG preconditioning. The amount of adsorbed iso-alpha acid was increased until 5 d preconditioning, and then it decreased. In this study, we revealed that the CPA values increased with the progress of MSG preconditioning in spite of the decrease of the amount of iso-alpha acid adsorbed onto the lipid/polymer membrane, and it was indicated that the CPA values increase because the sensor sensitivity was improved by the MSG preconditioning. PMID:26891299

  19. Major Ozonated Autohemotherapy Preconditioning Ameliorates Kidney Ischemia-Reperfusion Injury.

    PubMed

    Sancak, Eyup Burak; Turkön, Hakan; Çukur, Selma; Erimsah, Sevilay; Akbas, Alpaslan; Gulpinar, Murat Tolga; Toman, Huseyin; Sahin, Hasan; Uzun, Metehan

    2016-02-01

    Medical ozone has therapeutic properties as an antimicrobial, anti-inflammatory, modulator of antioxidant defense system. Major ozonated autohemotherapy (MOA) is a new therapeutic approach that is widely used in the treatment of many diseases. The objective of the present study was to determine whether preischemic application of MOA would attenuate renal ischemia-reperfusion injury (IRI) in rabbits. Twenty-four male New Zealand white rabbits were divided into four groups, each including six animals: (1) Sham-operated group, (2) Ozone group (the MOA group without IRI), (3) IR group (60 min ischemia followed by 24 h reperfusion), and (4) IR + MOA group (MOA group). The effects of MOA were examined by use of hematologic and biochemical parameters consisting of neutrophil to lymphocyte ratio (NLR), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), ischemia-modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). In addition, the histopathological changes including the tubular brush border loss (TBBL), tubular cast (TC), tubular necrosis (TN), intertubular hemorrhage and congestion (IHC), dilatation of bowman space (DBS), and interstitial inflammatory cells infiltration (IECI) were evaluated. In the IR group, compared to the Sham group, biochemical parameters indicating oxidative stress, NLR, IL-6, TNF-α, IMA, TOS, and OSI have increased. MOA reduced inflammation and oxidative stress parameters. Although TAS values have decreased in the IR group and increased in the MOA-pretreated group, no significant changes in TAS values were detected between the IR and MOA groups. The total score was obtained by summing all the scores from morphological kidney damage markers. The total score has increased with IR damage when compared with the Sham group (13.83 ± 4.30 vs 1.51 ± 1.71; p = 0.002). But, the total score has decreased significantly after application of MOA (5.01 ± 1.49; p = 0.002; compared with the IR group). MOA preconditioning is effective in reducing tissue damage induced in kidney ischemia-reperfusion injury. The protective effect of MOA is mediated via reducing inflammatory response and regulating of reactive oxygen species (ROS). Renal histology also showed convincing evidence regarding MOA's protective nature against kidney injury induced renal ischemia-reperfusion. Consequently, MOA might be helpful in protecting the kidneys from IR-induced damage in humans, probably through the anti-inflammatory effect and reducing the total oxidant status. PMID:26282390

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

    PubMed

    Kunst, G; Klein, A A

    2015-04-01

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

  1. Preconditioning for the Navier-Stokes equations with finite-rate chemistry

    NASA Technical Reports Server (NTRS)

    Godfrey, Andrew G.; Walters, Robert W.; Van Leer, Bram

    1993-01-01

    The preconditioning procedure for generalized finite-rate chemistry and the proper preconditioning for the one-dimensional Navier-Stokes equations are presented. Eigenvalue stiffness is resolved and convergence-rate acceleration is demonstrated over the entire Mach-number range from the incompressible to the hypersonic. Specific benefits are realized at low and transonic flow speeds. The extended preconditioning matrix accounts for thermal and chemical non-equilibrium and its implementation is explained for both explicit and implicit time marching. The effect of higher-order spatial accuracy and various flux splittings is investigated. Numerical analysis reveals the possible theoretical improvements from using proconditioning at all Mach numbers. Numerical results confirm the expectations from the numerical analysis. Representative test cases include flows with previously troublesome embedded high-condition-number regions.

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

    PubMed

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

    2015-06-01

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

  3. Wide-field fluorescence molecular tomography with compressive sensing based preconditioning

    PubMed Central

    Yao, Ruoyang; Pian, Qi; Intes, Xavier

    2015-01-01

    Wide-field optical tomography based on structured light illumination and detection strategies enables efficient tomographic imaging of large tissues at very fast acquisition speeds. However, the optical inverse problem based on such instrumental approach is still ill-conditioned. Herein, we investigate the benefit of employing compressive sensing-based preconditioning to wide-field structured illumination and detection approaches. We assess the performances of Fluorescence Molecular Tomography (FMT) when using such preconditioning methods both in silico and with experimental data. Additionally, we demonstrate that such methodology could be used to select the subset of patterns that provides optimal reconstruction performances. Lastly, we compare preconditioning data collected using a normal base that offers good experimental SNR against that directly acquired with optimal designed base. An experimental phantom study is provided to validate the proposed technique. PMID:26713202

  4. Analysis of a Lipid/Polymer Membrane for Bitterness Sensing with a Preconditioning Process

    PubMed Central

    Yatabe, Rui; Noda, Junpei; Tahara, Yusuke; Naito, Yoshinobu; Ikezaki, Hidekazu; Toko, Kiyoshi

    2015-01-01

    It is possible to evaluate the taste of foods or medicines using a taste sensor. The taste sensor converts information on taste into an electrical signal using several lipid/polymer membranes. A lipid/polymer membrane for bitterness sensing can evaluate aftertaste after immersion in monosodium glutamate (MSG), which is called “preconditioning”. However, we have not yet analyzed the change in the surface structure of the membrane as a result of preconditioning. Thus, we analyzed the change in the surface by performing contact angle and surface zeta potential measurements, Fourier transform infrared spectroscopy (FTIR), X-ray photon spectroscopy (XPS) and gas cluster ion beam time-of-flight secondary ion mass spectrometry (GCIB-TOF-SIMS). After preconditioning, the concentrations of MSG and tetradodecylammonium bromide (TDAB), contained in the lipid membrane were found to be higher in the surface region than in the bulk region. The effect of preconditioning was revealed by the above analysis methods. PMID:26404301

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

    PubMed Central

    Kunst, G; Klein, A A

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. Radial velocity solution of the system IP Dra

    NASA Astrophysics Data System (ADS)

    Kjurkchieva, D.; Marchev, D.

    2014-02-01

    High-resolution spectroscopic observations around the H line of the star IP Dra covering the whole orbital period are presented. The first radial velocity solution of the primary corresponded to semiamplitude of =65.7 km/s.

  8. A simulation of the IPS variations from a magnetohydrodynamical simulation

    NASA Technical Reports Server (NTRS)

    Tappin, S. J.; Dryer, M.; Han, S. M.; Wu, S. T.

    1987-01-01

    Calculations of the variations of interplanetary scintillation (IPS) from a disturbance simulated by a 3-D magnetohydrodynamical (MHD) model of the solar wind are presented. The simulated maps are compared with observations and it is found that the MHD model reproduces the qualitative features of observed disturbances. The disturbance produced by the MHD simulation is found to correspond in strength with the weakest disturbance which can be reliably detected by existing single station IPS observations.

  9. 2-(3',5'-Dimethoxybenzylidene) cyclopentanone, a novel synthetic small-molecule compound, provides neuroprotective effects against ischemic stroke.

    PubMed

    Gu, W W; Lu, S Q; Ni, Y; Liu, Z H; Zhou, X Y; Zhu, Y M; Luo, Y; Li, X; Li, L S; Sun, W Z; Zhang, H L; Ao, G Z

    2016-03-01

    2-(3',5'-Dimethoxybenzylidene) cyclopentanone (DMBC) is a novel small-molecule compound synthesized by our group. Here, we found that in rat models of permanent middle cerebral artery occlusion (pMCAO), intraperitoneal injection (ip) of DMBC at 1h after ischemia reduced infarct volume, improved neurological deficits and increased the protein levels of microtubule-associated protein 2 (MAP 2) and glial fibrillary acid protein (GFAP) in the ischemic cortex. Post-treatment of DMBC still produced neuroprotective effects even when administered at 6h after ischemia. In the oxygen-glucose deprivation (OGD)-induced astrocytes or HT22 cell injury, DMBC treatment decreased the OGD-induced lactate dehydrogenase (LDH) leakage and increased the GFAP levels in astrocytes. In addition, Annexin-V-Fluos staining analysis revealed that DMBC treatment attenuated both OGD-induced apoptosis and necrosis in astrocytes. Western blotting analysis showed DMBC treatment inhibited the ischemia or OGD-induced increases in active cathepsin B in the ischemic cortex or in astrocytes or HT22 cells. Immunofluorescence analysis demonstrated that DMBC treatment blocked the ischemia or OGD-induced release of cathepsin B from the lysosomes into the cytoplasm in the ischemic cortex or in astrocytes or HT22 cells. Taken together, our results indicate that DMBC can offer neuroprotective effects against cerebral ischemia with an extended therapeutic window and its mechanism might be associated with inhibition of the cathepsin B activation. PMID:26656221

  10. Gene-delivery systems for iPS cell generation

    PubMed Central

    Shao, Lijian; Wu, Wen-Shu

    2009-01-01

    Importance of the field Induced pluripotent stem (iPS) cells offer extraordinary promise for regenerative medicine applications, and provide new opportunities for use in disease modeling, drug screening and drug toxicology. Areas coved in this review iPS cell technology is still in its infancy. In this review article, we present a comprehensive survey of reprogramming approaches focusing on gene-delivery systems used for generation of iPS cells from somatic cells, categorize gene-delivery vectors, and discuss their advantages and limitations for somatic cell reprogramming. We include pertinent literature published between 2006 and the present. What the reader will gain Although iPS cell technology has been improved via the use of various gene-delivery vectors, it still suffers from either low reprogramming efficiency or too many genomic modification steps. Extensive work is still required to improve current vectors or explore new vectors for effectively reprogramming human somatic cells into iPS cells, with or without minimal genomic modification steps. Take home message A single non-integrating reprogramming vector system with high reprogramming efficiency is probably essential for generation of clinically translatable human iPS cells. PMID:20088717

  11. [Application for Lifestyle disease by iPS cells technologies].

    PubMed

    Takashima, Yasuhiro

    2016-01-01

    Currently it is less advanced to understand the pathology of lifestyle disease by using iPS cells because there is partly less direct connection between life style disease and iPS cells. So much more scientists focus on regenerative medicine such as beta cells therapy using iPS cells technologies. It will be indeed a powerful tool to generate beta cells from iPS cells as even in type2 diabetes patients, hyposecretion of insulin from beta cells in pancreas is one of causes. Another reason is complexity of the pathology of life style disease. There are a lot of reasons to cause lifestyle disease. Lifestyle diseases include cancer, chronic liver disease, Type 2 diabetes, heart disease, metabolic syndrome, chronic renal failure, stroke, and obesity. Since obesity is one of major causes of lifestyle diseases, we want to focus on adipogenesis from iPS cells in this review. We analysed and established the differentiation protocol into adipocytes from mouse ES cells and human iPS cells. The other point in this review is the starting pluripotent cells for differentiation. Quality of pluripotent stem cells are one of most critical factors to succeed in getting well-differentiated cells. Recently, we have developed new naive human pluripotent stem cells(PSC),"Reset cells". Naive PSC have more similar to human epibast cells than conventional human PSC. They will be more ideal cells for differentiation because of their hypomethylated status and earlier stage of development. PMID:26923982

  12. Isoflurane's Effect on Protein Conformation as a Proposed Mechanism for Preconditioning

    PubMed Central

    Baker, Michelle R.; Benton, Sean K.; Theisen, Christopher S.; McClintick, Chad A.; Fibuch, Eugene E.; Seidler, Norbert W.

    2011-01-01

    Persistent alteration of protein conformation due to interaction with isoflurane may be a novel molecular aspect of preconditioning. We preincubated human serum albumin with isoflurane, dialyzed to release agent, and assessed protein conformation. Susceptibility to chemical modification by methylglyoxal and nitrophenylacetate was also examined. Isoflurane had a persistent effect on protein conformation. An increase in the susceptibility of surface residues to chemical modification attended this change in conformation. Modification of isoflurane-treated HSA included intra- and intersubunit cross-linking that may be a consequence of anesthetic-induced changes in multimeric subpopulations. This irreversible effect of isoflurane may represent a mechanism for preconditioning. PMID:21918721

  13. Isoflurane's Effect on Protein Conformation as a Proposed Mechanism for Preconditioning.

    PubMed

    Baker, Michelle R; Benton, Sean K; Theisen, Christopher S; McClintick, Chad A; Fibuch, Eugene E; Seidler, Norbert W

    2011-01-01

    Persistent alteration of protein conformation due to interaction with isoflurane may be a novel molecular aspect of preconditioning. We preincubated human serum albumin with isoflurane, dialyzed to release agent, and assessed protein conformation. Susceptibility to chemical modification by methylglyoxal and nitrophenylacetate was also examined. Isoflurane had a persistent effect on protein conformation. An increase in the susceptibility of surface residues to chemical modification attended this change in conformation. Modification of isoflurane-treated HSA included intra- and intersubunit cross-linking that may be a consequence of anesthetic-induced changes in multimeric subpopulations. This irreversible effect of isoflurane may represent a mechanism for preconditioning. PMID:21918721

  14. Propulsion-related flowfields using the preconditioned Navier-Stokes equations

    NASA Technical Reports Server (NTRS)

    Venkateswaran, S.; Weiss, J. M.; Merkle, C. L.; Choi, Y.-H.

    1992-01-01

    A previous time-derivative preconditioning procedure for solving the Navier-Stokes is extended to the chemical species equations. The scheme is implemented using both the implicit ADI and the explicit Runge-Kutta algorithms. A new definition for time-step is proposed to enable grid-independent convergence. Several examples of both reacting and non-reacting propulsion-related flowfields are considered. In all cases, convergence that is superior to conventional methods is demonstrated. Accuracy is verified using the example of a backward facing step. These results demonstrate that preconditioning can enhance the capability of density-based methods over a wide range of Mach and Reynolds numbers.

  15. Preconditioning for the Navier-Stokes equations with finite-rate chemistry

    NASA Technical Reports Server (NTRS)

    Godfrey, Andrew G.

    1993-01-01

    The extension of Van Leer's preconditioning procedure to generalized finite-rate chemistry is discussed. Application to viscous flow is begun with the proper preconditioning matrix for the one-dimensional Navier-Stokes equations. Eigenvalue stiffness is resolved and convergence-rate acceleration is demonstrated over the entire Mach-number range from nearly stagnant flow to hypersonic. Specific benefits are realized at the low and transonic flow speeds typical of complete propulsion-system simulations. The extended preconditioning matrix necessarily accounts for both thermal and chemical nonequilibrium. Numerical analysis reveals the possible theoretical improvements from using a preconditioner for all Mach number regimes. Numerical results confirm the expectations from the numerical analysis. Representative test cases include flows with previously troublesome embedded high-condition-number areas. Van Leer, Lee, and Roe recently developed an optimal, analytic preconditioning technique to reduce eigenvalue stiffness over the full Mach-number range. By multiplying the flux-balance residual with the preconditioning matrix, the acoustic wave speeds are scaled so that all waves propagate at the same rate, an essential property to eliminate inherent eigenvalue stiffness. This session discusses a synthesis of the thermochemical nonequilibrium flux-splitting developed by Grossman and Cinnella and the characteristic wave preconditioning of Van Leer into a powerful tool for implicitly solving two and three-dimensional flows with generalized finite-rate chemistry. For finite-rate chemistry, the state vector of unknowns is variable in length. Therefore, the preconditioning matrix extended to generalized finite-rate chemistry must accommodate a flexible system of moving waves. Fortunately, no new kind of wave appears in the system. The only existing waves are entropy and vorticity waves, which move with the fluid, and acoustic waves, which propagate in Mach number dependent directions. The nonequilibrium vibrational energies and species densities in the unknown state vector act strictly as convective waves. The essential concept for extending the preconditioning to generalized chemistry models is determining the differential variables which symmetrize the flux Jacobians. The extension is then straight-forward. This algorithm research effort will be released in a future version of the production level computational code coined the General Aerodynamic Simulation Program (GASP), developed by Walters, Slack, and McGrory.

  16. Sensory preconditioning in newborn rabbits: from common to distinct odor memories.

    PubMed

    Coureaud, Grard; Tourat, Audrey; Ferreira, Guillaume

    2013-09-01

    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 with two overlapping pairs of odorants (A+B and B+C) and amnesia of one odorant did not affect memory of the others. Thus, incidental pairing of odorants allows reinforcement of one odorant to implicitly reinforce the others, the bond then vanishes, and the memory of each element becomes independent. PMID:23950192

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  18. Protection of retinal function by sulforaphane following retinal ischemic injury.

    PubMed

    Ambrecht, Lindsay A; Perlman, Jay I; McDonnell, James F; Zhai, Yougang; Qiao, Liang; Bu, Ping

    2015-09-01

    Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. PMID:26142954

  19. Sensory Stimulation as a Precondition for the Learning of a Language Task by Fourth and Sixth Grade Children.

    ERIC Educational Resources Information Center

    March, Lester William

    This study was designed to explore learning behavior of children following four specific preconditioning experiences: sensory deprivation, sensory bombardment, routine worksheet exercises, and a sensory awareness game. The study occurred in three parts: preconditioning of the subjects, teaching of a language skill, and performance of a task

  20. Binding of Inositol 1,4,5-trisphosphate (IP3) and Adenophostin A to the N-Terminal region of the IP3 Receptor: Thermodynamic Analysis Using Fluorescence Polarization with a Novel IP3 Receptor LigandS?

    PubMed Central

    Ding, Zhao; Rossi, Ana M.; Riley, Andrew M.; Rahman, Taufiq; Potter, Barry V. L.

    2010-01-01

    Inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) are intracellular Ca2+ channels. Their op