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1

Resveratrol and ischemic preconditioning in the brain.  

PubMed

Cardiovascular pathologies in the French are not prevalent despite high dietary saturated fat consumption. This is commonly referred to as the "French Paradox" attributing its anti-lipidemic effects to moderate consumption of red wine. Resveratrol, a phytoalexin found in red wine, is currently the focus of intense research both in the cardiovascular system and the brain. Current research suggests resveratrol may enhance prognosis of neurological disorders such as, Parkinson's, Huntington's, Alzheimer's diseases and stroke. The beneficial effects of resveratrol include: antioxidation, free radical scavenger, and modulation of neuronal energy homeostasis and glutamatergic receptors/ion channels. Resveratrol directly increases sirtuin 1 (SIRT1) activity, a NAD(+) (oxidized form of nicotinamide adenine dinucleotide)-dependent histone deacetylase related to increased lifespan in various species similar to calorie restriction. We recently demonstrated that brief resveratrol pretreatment conferred neuroprotection against cerebral ischemia via SIRT1 activation. This neuroprotective effect produced by resveratrol was similar to ischemic preconditioning-induced neuroprotection, which protects against lethal ischemic insults in the brain and other organ systems. Inhibition of SIRT1 abolished ischemic preconditioning-induced neuroprotection in CA1 region of the hippocampus. Since resveratrol and ischemic preconditioning-induced neuroprotection require activation of SIRT1, this common signaling pathway may provide targeted therapeutic treatment modalities as it relates to stroke and other brain pathologies. In this review, we will examine common signaling pathways, cellular targets of resveratrol, and ischemic preconditioning-induced neuroprotection as it relates to the brain. PMID:18537630

Raval, Ami P; Lin, Hung Wen; Dave, Kunjan R; Defazio, R Anthony; Della Morte, David; Kim, Eun Joo; Perez-Pinzon, Miguel A

2008-01-01

2

Cardioprotection acquired through exercise: the role of ischemic preconditioning.  

PubMed

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

Marongiu, Elisabetta; Crisafulli, Antonio

2014-11-01

3

Limb ischemic preconditioning attenuates cerebral ischemic injury in rat model.  

PubMed

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

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

2014-05-01

4

Impact of hypoglycemic agents on myocardial ischemic preconditioning  

PubMed Central

Murry et al in 1986 discovered the intrinsic mechanism of profound protection called ischemic preconditioning. The complex cellular signaling cascades underlying this phenomenon remain controversial and are only partially understood. However, evidence suggests that adenosine, released during the initial ischemic insult, activates a variety of G protein-coupled agonists, such as opioids, bradykinin, and catecholamines, resulting in the activation of protein kinases, especially protein kinase C (PKC). This leads to the translocation of PKC from the cytoplasm to the sarcolemma, where it stimulates the opening of the ATP-sensitive K+ channel, which confers resistance to ischemia. It is known that a range of different hypoglycemic agents that activate the same signaling cascades at various cellular levels can interfere with protection from ischemic preconditioning. This review examines the effects of several hypoglycemic agents on myocardial ischemic preconditioning in animal studies and clinical trials. PMID:24936247

Rahmi Garcia, Rosa Maria; Rezende, Paulo Cury; Hueb, Whady

2014-01-01

5

Impact of hypoglycemic agents on myocardial ischemic preconditioning.  

PubMed

Murry et al in 1986 discovered the intrinsic mechanism of profound protection called ischemic preconditioning. The complex cellular signaling cascades underlying this phenomenon remain controversial and are only partially understood. However, evidence suggests that adenosine, released during the initial ischemic insult, activates a variety of G protein-coupled agonists, such as opioids, bradykinin, and catecholamines, resulting in the activation of protein kinases, especially protein kinase C (PKC). This leads to the translocation of PKC from the cytoplasm to the sarcolemma, where it stimulates the opening of the ATP-sensitive K(+) channel, which confers resistance to ischemia. It is known that a range of different hypoglycemic agents that activate the same signaling cascades at various cellular levels can interfere with protection from ischemic preconditioning. This review examines the effects of several hypoglycemic agents on myocardial ischemic preconditioning in animal studies and clinical trials. PMID:24936247

Rahmi Garcia, Rosa Maria; Rezende, Paulo Cury; Hueb, Whady

2014-06-15

6

Mechanisms of neuroprotection during ischemic preconditioning: lessons from anoxic tolerance.  

PubMed

Different physiological adaptations for anoxia resistance have been described in the animal kingdom. These adaptations are particularly important in organs that are highly susceptible to energy deprivation such as the heart and brain. Among vertebrates, turtles are one of the species that are highly tolerant to anoxia. In mammals however, insults such as anoxia, ischemia and hypoglycemia, all cause major histopathological events to the brain. However, in mammals even ischemic or anoxic tolerance is found when a sublethal ischemic/anoxic insult is induced sometime before a lethal ischemic/anoxic insult is induced. This phenomenon is defined as ischemic preconditioning. Better understanding of the mechanisms inducing both anoxic tolerance in turtles or ischemic preconditioning in mammals may provide novel therapeutic interventions that may aide mammalian brain to resist the ravages of cerebral ischemia. In this review, we will summarize some of the mechanisms implemented in both models of tolerance, emphasizing physiological and biochemical similarities. PMID:17045830

Perez-Pinzon, Miguel A

2007-06-01

7

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

PubMed

Ischemic preconditioning (IP) has been proposed as an endogenous form of protection against ischemia reperfusion injury. IP, however, does not prevent post-ischemic dysfunction in the aging heart but may be partially corrected by exercise training and food restriction. We investigated the role of exercise training combined with food restriction on restoring IP in the aging heart. Effects of IP against ischemia-reperfusion injury in isolated hearts from adult (A, 6 months old), sedentary 'ad libitum' fed (SL), trained ad libitum fed (TL), sedentary food-restricted (SR), trained- and food-restricted senescent rats (TR) (24 months old) were investigated. Norepinephrine release in coronary effluent was determined by high performance liquid cromatography. IP significantly improved final recovery of percent developed pressure in hearts from A (p<0.01) but not in those from SL (p=NS) vs unconditioned controls. Developed pressure recovery was partial in hearts from TL and SR (64.3 and 67.3%, respectively; p<0.05 vs controls) but it was total in those from TR (82.3%, p=NS vs A; p<0.05 vs hearts from TL and SR). Similarly, IP determined a similar increase of norepinephrine release in A (p<0.001) and in TR (p<0.001, p=NS vs adult). IP was abolished by depletion of myocardial norepinephrine stores by reserpine in all groups. Thus, IP reduces post-ischemic dysfunction in A but not in SL. Moreover, IP was preserved partially in TR and SR and totally in TR. Complete IP maybe due to full restoration of norepinephrine release in response to IP stimulus. PMID:15664731

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

2005-01-01

8

Ischemic preconditioning accelerates the fatty acid oxidation of rat hearts  

Microsoft Academic Search

BackgroundIschemic preconditioning (IPC) reduced myocardial ATP depletion during sustained ischemia and has a powerful protective effect on the myocardium. The purpose of the present study was to clarify the effects of IPC on myocardial accumulation of fatty acid (FA) tracer and its intracellular metabolism.

Akira Matsuki; Takashi Nozawa; Akihiko Igawa; Norio Igarashi; Teruo Nakadate; Nozomu Fujii; Hiroshi Inoue

2009-01-01

9

Ischemic preconditioning attenuates of ischemia-induced degradation of spectrin and tau: implications for ischemic tolerance  

Microsoft Academic Search

Global ischemia selectively induces CA1 neuronal death in the hippocampus. Pretreatment with non-lethal ischemia (i.e. ischemic\\u000a preconditioning) prevents CA1 neuronal death induced by lethal ischemia. While ischemic tolerance is a well-known phenomenon,\\u000a the underlying molecular mechanisms are not fully understood. Cytoskeletal proteins including ?-spectrin, tau, and microtubule-associated\\u000a protein 2 (MAP-2) are indispensable for the maintenance of neuronal homeostasis. Here, we

Takayuki Nakajima; Syoichi Ochi; Chika Oda; Maki Ishii; Kazushige Ogawa

2011-01-01

10

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

PubMed Central

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

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

2013-01-01

11

Role of mitochondrial and sarcolemmal K(ATP) channels in ischemic preconditioning of the canine heart.  

PubMed

We tested whether mitochondrial or sarcolemmal ATP-sensitive K(+) (K(ATP)) channels play a key role in ischemic preconditioning (IP) in canine hearts. In open-chest beagle dogs, the left anterior descending artery was occluded four times for 5 min each with 5-min intervals of reperfusion (IP), occluded for 90 min, and reperfused for 6 h. IP as well as cromakalim and nicorandil (nonspecific K(ATP) channel openers) markedly limited infarct size (6.3 +/- 1.2, 8.9 +/- 1.9, and 7.2 +/- 1.6%, respectively) compared with the control group (40.9 +/- 4.1%). A selective mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, partially blunted the limitation of infarct size in the animals subjected to IP and those treated with cromakalim and nicorandil (21.6 +/- 3.8, 25.1 +/- 4.6, and 19.8 +/- 5.2%, respectively). A nonspecific K(ATP) channel blocker, glibenclamide, completely abolished the effect of IP (38.5 +/- 6.2%). Intracoronary or intravenous administration of a mitochondria-selective K(ATP) channel opener, diazoxide, at >100 micromol/l could only partially decrease infarct size (19.5 +/- 4.3 and 20.1 +/- 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal K(ATP) channels independently play an important role in the limitation of infarct size by IP in the canine heart. PMID:11123240

Sanada, S; Kitakaze, M; Asanuma, H; Harada, K; Ogita, H; Node, K; Takashima, S; Sakata, Y; Asakura, M; Shinozaki, Y; Mori, H; Kuzuya, T; Hori, M

2001-01-01

12

Age-related reduction of cerebral ischemic preconditioning: myth or reality?  

PubMed Central

Stroke is one of the leading causes of death in industrialized countries for people older than 65 years of age. The reasons are still unclear. A reduction of endogenous mechanisms against ischemic insults has been proposed to explain this phenomenon. The “cerebral” ischemic preconditioning mechanism is characterized by a brief episode of ischemia that renders the brain more resistant against subsequent longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. This protective mechanism seems to be reduced with aging both in experimental and clinical studies. Alterations of mediators released and/or intracellular pathways may be responsible for age-related ischemic preconditioning reduction. Agents able to mimic the “cerebral” preconditioning effect may represent a new powerful tool for the treatment of acute ischemic stroke in the elderly. In this article, animal and human cerebral ischemic preconditioning, its age-related difference, and its potential therapeutical applications are discussed. PMID:24204128

Della-Morte, David; Cacciatore, Francesco; Salsano, Elisa; Pirozzi, Gilda; Genio, Maria Teresa Del; D’Antonio, Iole; Gargiulo, Gaetano; Palmirotta, Raffaele; Guadagni, Fiorella; Rundek, Tatjana; Abete, Pasquale

2013-01-01

13

Ischemic preconditioning enhances integrity of coronary endothelial tight junctions  

SciTech Connect

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.

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

2012-08-31

14

Ischemic preconditioning of rat livers against cold storage-reperfusion injury: Role of nonparenchymal cells and the phenomenon of heterologous preconditioning  

Microsoft Academic Search

Brief periods of ischemia followed by reperfusion render tissues resistant against subsequent prolonged ischemia, a phenomenon called ischemic preconditioning. The effect of ischemic preconditioning on liver transplantation was investigated in relation to sinusoidal endothelial cell injury and Kupffer-cell activation, which are prominent features of storage and reperfusion injury leading to liver graft failure. Rat livers were preconditioned by 5 or

Masahiro Arai; Ronald G. Thurman; John J. Lemasters

2001-01-01

15

Ischemic preconditioning attenuates lipid peroxidation and apoptosis in the cecal ligation and puncture model of sepsis  

PubMed Central

Sepsis and septic shock are are among the major causes of mortality in intensive care units. The lung and kidney are the organs most affected by sepsis. Evidence exists that lipid peroxidation and apoptosis may be responsible for the high mortality due to sepsis. Ischemic preconditioning (IP) is a method for the protection of tissues and organs against ischemia/reperfusion injury by reducing reactive oxygen species levels, lipid peroxidation and apoptosis. In the present study, the effects of IP were investigated in cecal ligation and puncture (CLP)-induced sepsis in rats. The three groups of animals used in the present controlled study were the sham-operated group (sham, n=7), which only underwent a laparotomy; the sepsis group (sepsis, n=7), which underwent cecal ligation and perforation; and the IP + sepsis group (IP+sepsis, n=7), which underwent CLP immediately prior to the application of three cycles of IP to the hind limb. The study was terminated at 6 h after the induction of CLP. Blood, kidney and lung tissue samples were collected for the determination of serum creatinine, blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL) and lung tissue malondialdehyde (MDA) levels, as well as histological examination. The serum creatinine, plasma NGAL and lung tissue MDA levels in the sepsis group were significantly increased compared with those in the sham and the IP+sepsis groups (P<0.05). Alveolar macrophage counts, histological kidney and lung injury scores, kidney (caspase 3) and lung tissue immuonreactivity (M30) scores in the sepsis group were also significantly increased compared with those in the sham and IP+sepsis groups (P<0.05). The alveolar macrophage count in the IP+sepsis group was increased compared with that in the sham group (P<0.05). In conclusion, IP inhibits lipid peroxidation and attenuates histological injury and apoptosis in the lung and kidney during sepsis. PMID:23837035

OLGUNER, ÇIMEN GÜLBEN; KOCA, U?UR; ALTEKIN, EMEL; ERGÜR, BEKIR U?UR; DURU, SEDEN; GIRGIN, PELIN; TA?DÖ?EN, AYDIN; GÜNDÜZ, KERIM; GÜZELDA?, SEDA; AKKU?, MUHAMMED; MICILI, SERAP CILAKER

2013-01-01

16

Can anaerobic performance be improved by remote ischemic preconditioning?  

PubMed

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

Lalonde, François; Curnier, Daniel Y

2015-01-01

17

Toll-like receptor 9: a new target of ischemic preconditioning in the brain  

Microsoft Academic Search

Preconditioning with lipopolysaccharide (LPS), a toll-like receptor 4 (TLR4) ligand, provides neuroprotection against subsequent cerebral ischemic brain injury, through a tumor necrosis factor (TNF)?-dependent process. Here, we report the first evidence that another TLR, TLR9, can induce neuroprotection. We show that the TLR9 ligand CpG oligodeoxynucleotide (ODN) can serve as a potent preconditioning stimulus and provide protection against ischemic brain

Susan L Stevens; Thomas M P Ciesielski; Brenda J Marsh; Tao Yang; Delfina S Homen; Jo-Lynn Boule; Nikola S Lessov; Roger P Simon; Mary P Stenzel-Poore

2008-01-01

18

Peripheral Vascular Disease as Remote Ischemic Preconditioning for Acute Stroke  

PubMed Central

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

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

2013-01-01

19

Protection of Ischemic Preconditioning on Renal Neural Function in Rats with Acute Renal Failure  

Microsoft Academic Search

We tested whether tolerance induced by ischemic preconditioning (IPC) in kidneys was related to renal nerves. Experimental acute renal failure (ARF) in a rat model was induced for 45 min of left renal arterial occlusion (RAO), followed by 6 or 24 h of reperfusion (ischemic reperfusion (I\\/R) group). The episode of IPC was four cycles of 4 min of RAO

Ming-Shiou Wu; Chiang-Ting Chien; Ming-Chieh Ma; Chau-Fong Chen

20

Remote ischemic preconditioning delays fatigue development during handgrip exercise.  

PubMed

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

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

2014-04-15

21

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

PubMed Central

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

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

2014-01-01

22

Ischemic preconditioning reduces infarct size in swine myocardium.  

PubMed

We evaluated the hypothesis that stunning swine myocardium with brief ischemia reduces oxygen demand in the stunned region and increases tolerance of myocardium to longer periods of ischemia. Wall function was quantified with ultrasonic crystals aligned to measure wall thickening, and stunning was achieved with two cycles of left anterior descending coronary artery (LAD) occlusion (10 minutes) and reperfusion (30 minutes), after which the LAD was occluded for 60 minutes and reperfused for 90 minutes. Infarct size (as a percent of risk region) was then determined by incubating myocardium with para-nitro blue tetrazolium. Regional oxygen demand was measured as myocardial oxygen consumption before the 60-minute LAD occlusion in the stunned region; tracer microspheres were used to determine blood flow, and blood from the anterior interventricular vein and left atrium was used to calculate oxygen saturations. After the second reperfusion period, wall thickening in the stunned region was reduced to 1.4 +/- 2.4% compared with 36.7 +/- 2.5% (mean +/- SEM) before ischemia (p less than 0.001). Regional myocardial oxygen consumption after stunning (3.1 +/- 0.7 ml O2/min/100 g) was no different from regional myocardial oxygen consumption before stunning (3.7 +/- 0.6 ml O2/min/100 g). In the nine pigs "preconditioned" by stunning, infarct size was 10.4 +/- 6.3% of the risk region compared with 48.0 +/- 12.7% in the six control pigs subjected to 60 minutes of ischemia without prior stunning (p less than 0.005). The risk regions were similar (14.4 +/- 1.5% vs. 14.6 +/- 1.9% of the left ventricle, preconditioned vs. control pigs, respectively). We conclude that stunning swine myocardium with two cycles of a 10-minute LAD occlusion followed by reperfusion increases ischemic tolerance but that changes in regional demand in stunned myocardium do not predict the marked reduction in infarct size that follows a subsequent 60-minute period of ischemia. PMID:2317890

Schott, R J; Rohmann, S; Braun, E R; Schaper, W

1990-04-01

23

Myocardial energy metabolism in ischemic preconditioning and cardioplegia: a metabolic control analysis.  

PubMed

For both, cardioplegia (CP) and ischemic preconditioning (IP), increased ischemic tolerance with reduction in infarct size is well documented. These cardioprotective effects are related to a limitation of high energy phosphate (HEP) depletion. As CP and IP have to be assumed to act by different mechanisms, their effects on myocardial HEP metabolism cannot be assumed to be identical. Therefore, a systematic analysis of myocardial HEP metabolism for both procedures and their combination was performed, addressing the question whether there are different effects on myocardial HEP metabolism by IP and CP. In this study, metabolic control analysis was used to analyze the regulation of HEP metabolism. In open chest pigs subjected to 45 min LAD occlusion (index ischemia), CP and IP preserved myocardial ATP (control (C) 0.14 +/- 0.05 micromol/g wwt; CP: 0.95 +/- 0.14, IP: 0.61 +/- 0.12; p<0.05 C vs. CP and IP) and reduced myocardial necrosis (infarct size IA/RA: C: 90.0 +/- 3.0%; CP: 0.0 +/- 0.0% but patchy necroses; IP: 5.05 +/- 2.1%; p<0.05 C vs. CP and IP). The effects on HEP metabolism, however, were different: CP acted predominantly by slowing down the breakdown of phosphocreatine (PCr) during early phases of ischemia (C: DeltaPCr 0-2 min: 5.24 +/- 0.32 micromol/g wwt; CP: DeltaPCr 0-2 min: 3.38 +/- 0.23 micromol/g wwt, p<0.05 vs. C), leaving ATP breakdown during later stages unaffected (C: DeltaATP 5-45 min: 1.77 +/- 0.11 micromol/g wwt CP: DeltaATP 5-45 min: 1.59 +/- 0.28 micromol/g wwt, n.s. vs. C). In contrast to CP, in IP PCr breakdown was even increased (IP: DeltaPCr 0-2 min: 7.06 +/- 0.34 micromol/g wwt, p<0.05 vs. C), but ATP depletion greatly attenuated (IP: DeltaATP 5-45 min: 0.48 +/- 0.10 micromol/g wwt, p<0.05 vs. C and CP). Combining IP and CP yielded an additive effect with slowing down the breakdown of both PCr (IP+CP: DeltaPCr 0-2 min: 5.09+/- 0.35 micromol/g wwt, p<0.05 vs. C and IP) and ATP (IP+CP: DeltaATP 5-45 min: 0.56 +/- 0.48 micromol/g wwt, p<0.05 vs. C and CP), resulting in a higher ATP content at the end of index ischemia (1.86 +/- 0.46 micromol/g wwt, p<0.05 vs. C, CP and IP). Compared to IP, combining IP+CP achieved also a further reduction in infarct size (IA/RA: 0.0 +/- 0.0%, p<0.05 vs IP) and--compared to CP--a disappearance of the patchy necroses. The concept of major differences in myocardial HEP metabolism during CP and IP is further supported at a molecular level by metabolic control analysis. CP but not IP slowed down the CK reaction velocity at high PCr levels. In contrast to CP exerting a continuous decline in vATPase for any given ATP level, in IP myocardium ATPase reaction velocity was even increased at higher ATP contents, whereas a marked decrease in ATPase reaction velocity was found if ATP levels decreased. The equilibrium of the CK-reaction remained unchanged following CP, whereas IP induced a changing CK equilibrium, which was the more shifted towards PCr the more myocardial HEP content decreased. The data demonstrate different effects of CP and IP on myocardial HEP metabolism, i.e. PCr and ATP breakdown as well as the apparent equilibrium of the creatine kinase (CK)-reaction. For these reasons the combination of the two protective interventions has an additive effect. PMID:16180108

Vogt, Achim M; Elsässer, Albrecht; Pott-Beckert, Anja; Ackermann, Cordula; Vetter, Sven Y; Yildiz, Murat; Schoels, Wolfgang; Fell, David A; Katus, Hugo A; Kübler, Wolfgang

2005-10-01

24

Angiotensin II Removes Kidney Resistance Conferred by Ischemic Preconditioning  

PubMed Central

Ischemic preconditioning (IPC) by ischemia/reperfusion (I/R) renders resistance to the kidney. Strong IPC triggers kidney fibrosis, which is involved in angiotensin II (AngII) and its type 1 receptor (AT1R) signaling. Here, we investigated the role of AngII/AT1R signal pathway in the resistance of IPC kidneys to subsequent I/R injury. IPC of kidneys was generated by 30 minutes of bilateral renal ischemia and 8 days of reperfusion. Sham-operation was performed to generate control (non-IPC) mice. To examine the roles of AngII and AT1R in IPC kidneys to subsequent I/R, IPC kidneys were subjected to either 30 minutes of bilateral kidney ischemia or sham-operation following treatment with AngII, losartan (AT1R blocker), or AngII plus losartan. IPC kidneys showed fibrotic changes, decreased AngII, and increased AT1R expression. I/R dramatically increased plasma creatinine concentrations in non-IPC mice, but not in IPC mice. AngII treatment in IPC mice resulted in enhanced morphological damage, oxidative stress, and inflammatory responses, with functional impairment, whereas losartan treatment reversed these effects. However, AngII treatment in non-IPC mice did not change I/R-induced injury. AngII abolished the resistance of IPC kidneys to subsequent I/R via the enhancement of oxidative stress and inflammatory responses, suggesting that the AngII/AT1R signaling pathway is associated with outcome in injury-experienced kidney. PMID:25243156

Kim, Jee In; Park, Jeen-Woo

2014-01-01

25

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

PubMed Central

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

Camara-Lemarroy, Carlos Rodrigo

2014-01-01

26

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

PubMed

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

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

2013-10-22

27

Delayed Energy Protection of Ischemic Preconditioning on Hepatic Ischemia\\/Reperfusion Injury in Rats  

Microsoft Academic Search

Background: Hepatic ischemia\\/reperfusion (IR) injuries associated with hepatic resections are unresolved problems in the clinical practice. The aim of this study is to elucidate the effect of ischemic preconditioning (IPC) on the energy charge (EC) and related mechanisms at the late phase of hepatic IR injury. Methods: 30 Wistar rats were randomly divided into sham, IR and IPC groups. The

E. Ofluoglu; M. Kerem; H. Pasaoglu; N. Turkozkan; I. Seven; A. Bedirli; T. Utku Yilmaz

2006-01-01

28

Mechanisms of the Beneficial Actions of Ischemic Preconditioning on Subcellular Remodeling in Ischemic-Reperfused Heart  

PubMed Central

Cardiac function is compromised by oxidative stress which occurs upon exposing the heart to ischemia reperfusion (I/R) for a prolonged period. The reactive oxygen species (ROS) that are generated during I/R incur extensive damage to the myocardium and result in subcellular organelle remodeling. The cardiac nucleus, glycocalyx, myofilaments, sarcoplasmic reticulum, sarcolemma, and mitochondria are affected by ROS during I/R injury. On the other hand, brief periods of ischemia followed by reperfusion, or ischemic preconditioning (IPC), have been shown to be cardioprotective against oxidative stress by attenuating the cellular damage and alterations of subcellular organelles caused by subsequent I/R injury. Endogenous defense mechanisms, such as antioxidant enzymes and heat shock proteins, are activated by IPC and thus prevent damage caused by oxidative stress. Although these cardioprotective effects of IPC against I/R injury are considered to be a consequence of changes in the redox state of cardiomyocytes, IPC is considered to promote the production of NO which may protect subcellular organelles from the deleterious actions of oxidative stress. The article is intended to focus on the I/R-induced oxidative damage to subcellular organelles and to highlight the cardioprotective effects of IPC. In addition, the actions of various endogenous cardioprotective interventions are discussed to illustrate that changes in the redox state due to IPC are cardioprotective against I/R injury to the heart. PMID:22043201

Müller, By Alison L; Dhalla, Naranjan S

2010-01-01

29

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

PubMed Central

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

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

1994-01-01

30

Epsilon PKC Increases Brain Mitochondrial SIRT1 Protein Levels via Heat Shock Protein 90 following Ischemic Preconditioning in Rats  

PubMed Central

Ischemic preconditioning is a neuroprotective mechanism whereby a sublethal ischemic exposure is protective against a subsequent lethal ischemic attack. We previously demonstrated that SIRT1, a nuclear localized stress-activated deacetylase, is vital for ischemic preconditioning neuroprotection. However, a recent study demonstrated that SIRT1 can also localize to the mitochondria. Mitochondrial localized SIRT1 may allow for a direct protection of mitochondria following ischemic preconditioning. The objective of this study was to determine whether ischemic preconditioning increases brain mitochondrial SIRT1 protein levels and to determine the role of PKC? and HSP90 in targeting SIRT1 to the mitochondria. Here we report that preconditioning rats, with 2 min of global cerebral ischemia, induces a delayed increase in non-synaptic mitochondrial SIRT1 protein levels which was not observed in synaptic mitochondria. This increase in mitochondrial SIRT1 protein was found to occur only in neuronal cells and was mediated by PKC? activation. Inhibition of HSP90, a protein chaperone involved in mitochondrial protein import, prevented preconditioning induced increases in mitochondrial SIRT1 and PKC? protein. Our work provides new insights into a possible direct role of SIRT1 in modulating mitochondrial function under both normal and stress conditions, and to a possible role of mitochondrial SIRT1 in activating preconditioning induced ischemic tolerance. PMID:24058702

Thompson, John W.; Dave, Kunjan R.; Saul, Isabel; Narayanan, Srinivasan V.; Perez-Pinzon, Miguel A.

2013-01-01

31

Influence of ischemic preconditioning on intracellular sodium, pH, and cellular energy status in isolated perfused heart.  

PubMed

The possible relationships between intracellular Na(+) (Na(i)(+)), bioenergetic status and intracellular pH (pH(i)) in the mechanism for ischemic preconditioning were studied using (23)Na and (31)P magnetic resonance spectroscopy in isolated Langendorff perfused rat heart. The ischemic preconditioning (three 5-min ischemic episodes followed by two 5-min and one 10-min period of reperfusion) prior to prolonged ischemia (20 min stop-flow) resulted in a decrease in ischemic acidosis and faster and complete recovery of cardiac function (ventricular developed pressure and heart rate) after 30 min of reperfusion. The response of Na(i) during ischemia in the preconditioned hearts was characterized by an increase in Na(i)(+) at the end of preconditioning and an accelerated decrease during the first few minutes of reperfusion. During post-ischemic reperfusion, bioenergetic parameters (PCr/P(i) and betaATP/P(i) ratios) were partly recovered without any significant difference between control and preconditioned hearts. The reduced acidosis during prolonged ischemia and the accelerated decrease in Na(i)(+) during reperfusion in the preconditioned hearts suggest activation of Na(+)/H(+) exchanger and other ion transport systems during preconditioning, which may protect the heart from intracellular acidosis during prolonged ischemia, and result in better recovery of mechanical function (LVDP and heart rate) during post-ischemic reperfusion. PMID:12094017

Babsky, Andriy; Hekmatyar, Shahryar; Wehrli, Suzanne; Doliba, Nicolai; Osbakken, Mary; Bansal, Navin

2002-07-01

32

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

PubMed Central

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

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

2013-01-01

33

Neuroprotection Induced In Vitro by Ischemic Preconditioning and Postconditioning: Modulation of Apoptosis and PI3K–Akt Pathways  

Microsoft Academic Search

Preconditioning and postconditioning are mild ischemic exposures before or after severe injurious ischemia, respectively,\\u000a that elicit endogenous neuroprotective responses. Molecular mechanisms of neuroprotection through preconditioning and postconditioning\\u000a are not completely understood. Here we optimized the in vitro oxygen and glucose deprivation (OGD) models of preconditioning and postconditioning in primary cortical neuron cultures that\\u000a allow the studies of the corresponding molecular

Shiv S. Prasad; Marsha Russell; Margeryta Nowakowska

2011-01-01

34

Role of adenosine and glycogen in ischemic preconditioning of rat hearts.  

PubMed

We tested whether ischemic preconditioning of the rat heart is mediated by reduced glycogenolysis during ischemia, an event triggered by adenosine A1 receptor activation. Rat hearts (n=40) were studied with [31P] and [13C] nuclear magnetic resonance (NMR) spectroscopy, using the Langendorff perfusion technique (5.5 mM [1-13C]glucose, 10 U/l insulin). In parallel experiments, hearts (n=43) were freeze-clamped at different time-points throughout the protocol. They were subjected to either ischemic preconditioning (PC), PC in the presence of 50 microM adenosine receptor antagonist, 8-(p-sulfophenyl)-theophylline (SPT), or intermittent infusion of 0.25 microM adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA). After 30 min ischemia and reperfusion, recovery of heart ratexpressure product was improved in hearts treated with preconditioning (33+/-13%) or CCPA (58+/-14%) compared with the SPT and ischemic control (IC) groups, which both failed to recover (P<0.05). CCPA administration induced a 58% increase in pre-ischemic [13C]glycogen (P<0.05 vs. all groups). In the PC and SPT groups, [13C]glycogen decreased by 25 and 47%, respectively (P<0.05) due to the short bouts of ischemia, resulting in lower pre-ischemic glycogen compared to ischemic control and CCPA hearts (P<0.05). The rate of [13C]glycogen utilization during the first 15 min of ischemia (in micromol/min g wwt) was not statistically different between IC (0.42+/-0.03), PC (0.30+/-0.04), and CCPA (0.38+/-0.05) hearts, but was reduced in SPT hearts (0.24+/-0.05; P<0.05). Total glycogen depletion during 30-min ischemia was reduced in PC hearts (0.61 mg/g wwt) compared to IC (1.84 mg/g wwt) and CCPA (1.75 mg/g wwt) hearts; SPT did not block reduced glycogenolysis during ischemia in PC hearts (0.77 mg/g wwt vs. IC). This study adds further strong evidence that in rat hearts, adenosine is involved in ischemic preconditioning. However, protection is unrelated to pre-ischemic glycogen levels and glycogenolysis during ischemia. PMID:11230995

de Jonge, R; de Jong, J W; Giacometti, D; Bradamante, S

2001-02-23

35

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

PubMed Central

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

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

2013-01-01

36

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

PubMed

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

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

2013-01-01

37

Exercise-induced ischemic preconditioning detected by sequential exercise stress tests: A meta-analysis.  

PubMed

Exercise-induced ischemic preconditioning (IPC) can be assessed with the second exercise stress test during sequential testing. Exercise-induced IPC is defined as the time to 1?mm ST segment depression (STD), the rate-pressure product (RPP) at 1?mm STD, the maximal ST depression and the rate-pressure product at peak exercise. The purpose of this meta-analysis is to validate the parameters used to assess exercise-induced IPC in the scientific community. A literature search was performed using electronic database. The main key words were limited to human studies, which were (a) ischemic preconditioning, (b) warm-up phenomenon, and (c) exercise. Meta-analyses were performed on the study-specific mean difference between the clinical measures obtained in the two consecutive stress tests (second minus first test score). Random effect models were fitted with inverse variance weighting to provide greater weight to studies with larger sample size and more precise estimates. The search resulted in 309 articles of which 34 were included after revision (1053 patients). Results are: (a) time to 1?mm ST segment depression increased by 91?s (95% confidence interval (CI): 75-108), p?ischemic preconditioning in sequential stress testing. The results of this first meta-analysis on the sequential stress test confirm what is presented in the literature by independent studies on exercise-induced ischemic preconditioning. From now on, the results could be used in further research to set standardized parameters to assess the phenomenon. PMID:23983070

Lalonde, François; Poirier, Paul; Sylvestre, Marie-Pierre; Arvisais, Denis; Curnier, Daniel

2015-01-01

38

Sphingosine kinase 2 mediates cerebral preconditioning and protects mouse brain against ischemic injury  

PubMed Central

Background and purpose Cerebral preconditioning provides insights into endogenous mechanisms that protect the brain from ischemic injury. Hypoxia and the anesthetic isoflurane are powerful preconditioning agents. Recent data show that sphingosine 1-phosphate (S1P) receptor stimulation improves outcome in rodent models of stroke. Endogenous S1P levels are controlled by the expression and activity of sphingosine kinases (SPK). We hypothesize that SPK up-regulation mediates preconditioning induced by isoflurane and hypoxia and reduces ischemic injury. Methods Male wild-type C57BL/J, SPK1?/? and SPK2?/? mice were exposed to isoflurane (IsoPC) or hypoxia preconditioning (HPC) before transient middle cerebral artery occlusion. Infarct volume and neurological outcome were measured 24 hours later. SPK inhibitors (SKI-II and ABC294640) were used to test the involvement of SPK2. Expressions of SPK1, SPK2 and HIF1? were determined. Primary cultures of mouse cortical neurons were exposed to isoflurane before glutamate- or hydrogen peroxide-induced cell death. Results IsoPC and HPC significantly reduced infarct volume and improved neurological outcome in wild-type and SPK1?/? mice, but not in SPK2?/? mice. Pretreatment with SKI-II or ABC294640 abolished the IsoPC-induced tolerance. Western blot showed a rapid and sustained increase in SPK2 level, whereas SPK1 level was similar between preconditioned mice and controls. HIF1? was up-regulated in wild-type IsoPC mice, but not in SPK2?/?. IsoPC protected primary neurons against cell death, which was abolished in ABC294640-treated cells. Conclusions Applying genetic and pharmacological approaches, we demonstrate that neuronal SPK2 isoform plays an important role in cerebral preconditioning. PMID:21980199

Yung, Lai Ming; Wei, Ying; Qin, Tao; Wang, Yumei; Smith, Charles; Waeber, Christian

2011-01-01

39

Ischemic tolerance in an in vivo model of glutamate preconditioning.  

PubMed

Ischemia initiates a complicated biochemical cascade of events that triggers neuronal death. This study focuses on glutamate-mediated neuronal tolerance to ischemia-reperfusion. We employed an animal model of lifelong excess release of glutamate, the glutamate dehydrogenase 1 transgenic (Tg) mouse, as a model of in vivo glutamate preconditioning. Nine- and twenty-two-month-old Tg and wild-type (wt) mice were subjected to 90 min of middle cerebral artery occlusion, followed by 24 hr of reperfusion. The Tg mice suffered significantly reduced infarction and edema volume compared with their wt counterparts. We further analyzed proteasomal activity, level of ubiquitin immunostaining, and microtubule-associated protein-2A (MAP2A) expression to understand the mechanism of neuroprotection observed in the Tg mice. We found that, in the absence of ischemia, the Tg mice exhibited higher activity of the 20S and 26S proteasomes, whereas there was no significant difference in the level of hippocampal ubiquitin immunostaining between wt and Tg mice. A surprising, significant increase was observed in MAP2A expression in neurons of the Tg hippocampus following ischemia-reperfusion compared with that in wt hippocampus. The results suggest that increased proteasome activity and MAP2A synthesis and transport might account for the effectiveness of glutamate preconditioning against ischemia-reperfusion. © 2014 Wiley Periodicals, Inc. PMID:25421886

Badawi, Yomna; Pal, Ranu; Hui, Dongwei; Michaelis, Elias K; Shi, Honglian

2015-04-01

40

Remote ischemic preconditioning for myocardial protection: update on mechanisms and clinical relevance.  

PubMed

Ischemic heart disease is the leading cause of death for both men and women worldwide, accruing 7.4 million deaths in 2012. There has been a continued search for better cardioprotective modalities that would reduce myocardial ischemia-reperfusion injury. Among these attempts, a more convenient model of ischemic preconditioning, known as remote ischemic preconditioning (RIPC) was first introduced in 1993 by Przyklenk and colleagues who reported that brief regional occlusion-reperfusion episodes in one vascular bed of the heart render protection to remote myocardial tissue. Subsequently, major advances in myocardial RIPC came with the use of skeletal muscle as the ischemic stimulus. To date, numerous studies have revealed that RIPC applied to the kidney, liver, mesentery, and skeletal muscle, have all exhibited cardioprotective effects. The main purpose of this review article is to summarize the new advances in understanding the molecular mechanisms of RIPC during the past 5 years, including those related to capsaicin-activated C sensory fibers, hypoxia-inducible factor 1?, connexin 43, extracellular vesicles, microRNA-144, microRNA-1, and nitrite. In addition, we have discussed results from several recent human clinical trials with RIPC. Taken together, the emerging clinical evidence supports the concept that the effectiveness of RIPC paired with its low-cost and non-invasive features makes it an ideal treatment before reperfusion after sustained ischemia. More carefully designed studies are warranted to fully exploit the clinical benefits of RIPC and its potential implications in patients with cardiovascular disease. PMID:25552250

Gill, Rabia; Kuriakose, Robin; Gertz, Zachary M; Salloum, Fadi N; Xi, Lei; Kukreja, Rakesh C

2015-04-01

41

Heme Oxygenase 1 Is Associated with Ischemic Preconditioning-Induced Protection Against Brain Ischemia  

PubMed Central

Ischemic preconditioning (IPC) protects brain against ischemic injury by activating specific mechanisms. Our goal was to determine if the inducible heme oxygenase 1 (HO1) is required for such protection. IPC before transient or permanent ischemia reduced cortical infarct volumes by 57.4% and 33.9%, respectively at 48 h in wildtype adult mice. Interestingly, IPC failed to protect the HO1 gene deleted mice against permanent ischemic brain injury. IPC also resulted in a significant increase in HO1 protein levels in the brain and correlated with reduced neurological deficits after permanent and transient brain ischemia. Our study demonstrates that neuroprotective effects of IPC are at least partially mediated via HO1. Elucidating the physiological/cellular role by which HO1 is protective against brain ischemia may aid the development of selective drugs to treat stroke and its associated neurological disorders. PMID:19465127

Zeynalov, Emil; Shah, Zahoor A.; Li, Rung-chi; Doré, Sylvain

2009-01-01

42

Mechanisms involved in attenuated cardio-protective role of ischemic preconditioning in metabolic disorders.  

PubMed

Myocardial infarction is a pathological state which occurs due to severe abrogation of the blood supply (ischemia) to a part of heart, which can cause myocardial damage. The short intermittent cycles of sub-lethal ischemia and reperfusion has shown to improve the tolerance of the myocardium against subsequent prolonged ischemia/reperfusion (I/R)-induced injury, which is known as ischemic preconditioning (IPC). Although, IPC-induced cardioprotection is well demonstrated in various species, including human beings, accumulated evidence clearly suggests critical abrogation of the beneficial effects of IPC in diabetes mellitus, hyperlipidemia and hyperhomocysteinemia. Various factors are involved in the attenuation of the cardioprotective effect of preconditioning, such as the reduced release of calcitonin gene-related peptide (CGRP), the over-expression of glycogen synthase kinase-3? (GSK-3?) and phosphatase and tensin homolog (PTEN), impairment of mito-KATP channels, the consequent opening of mitochondrial permeability transition pore (MPTP), etc. In this review, we have critically discussed the various signaling pathways involved in abrogated preconditioning in chronic diabetes mellitus, hyperlipidemia and hyperhomocysteinemia. We have also focused on the involvement of PTEN in abrogated preconditioning and the significance of PTEN inhibitors. PMID:24947460

Rana, A; Goyal, N; Ahlawat, A; Jamwal, S; Reddy, Bvk; Sharma, S

2014-06-19

43

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

PubMed Central

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 (25–50 ?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

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

2002-01-01

44

Epigenetics and the Environment: In Search of the “Toleroasome” Vital to Execution of Ischemic Preconditioning  

PubMed Central

Activation and repression of gene expression are key features of ischemic tolerance. Converging lines of inquiry from several groups suggests that epigenetic proteins may transduce sublethal stresses, including bio-energetic or oxidative stress into durable (2–3 days) changes in gene expression that mediate ischemic tolerance. Here we discuss the potential mechanisms by which changes in cell state (e.g., ATP, NAD+, and oxygen) can modify specific targets including polycomb complexes, jumonji domain histone demethylases, and zinc and NAD-dependent histone decetylases and thus trigger an adaptive program. A major unanswered question is whether these proteins work in parallel or convergently as part of a “tolerosome” (tolero is the Latin word for tolerance), a multiprotein complex recruited to promoters or enhancers of specific genes, to mediate preconditioning. Whatever the case may be, epigenetic proteins are fertile targets for the treatment of stroke. PMID:24323190

Brand, David

2014-01-01

45

Pre-conditioned mesenchymal stem cells ameliorate renal ischemic injury in rats by augmented survival and engraftment  

PubMed Central

Background Ischemia is the major cause of acute kidney injury (AKI), associated with high mortality and morbidity. Mesenchymal stem cells (MSCs) have multilineage differentiation potential and can be a potent therapeutic option for the cure of AKI. Methods MSCs were cultured in four groups SNAP (S-nitroso N-acetyl penicillamine), SNAP + Methylene Blue (MB), MB and a control for in vitro analysis. Cultured MSCs were pre-conditioned with either SNAP (100 ?M) or MB (1 ?M) or both for 6 hours. Renal ischemia was induced in four groups (as in in vitro study) of rats by clamping the left renal padicle for 45 minutes and then different pre-conditioned stem cells were transplanted. Results We report that pre-conditioning of MSCs with SNAP enhances their proliferation, survival and engraftment in ischemic kidney. Rat MSCs pre-conditioned with SNAP decreased cell apoptosis and increased proliferation and cytoprotective genes’ expression in vitro. Our in vivo data showed enhanced survival and engraftment, proliferation, reduction in fibrosis, significant improvement in renal function and higher expression of pro-survival and pro-angiogenic factors in ischemic renal tissue in SNAP pre-conditioned group of animals. Cytoprotective effects of SNAP pre-conditioning were abrogated by MB, an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase. Conclusion The results of these studies demonstrate that SNAP pre-conditioning might be useful to enhance therapeutic potential of MSCs in attenuating renal ischemia reperfusion injury. PMID:23217165

2012-01-01

46

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

PubMed Central

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

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

2015-01-01

47

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...

48

Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver  

Microsoft Academic Search

Background\\/Aim: Ischemic preconditioning (IPC) may reduce hepatic ischemia-reperfusion (IR) injury, but efficacy of IPC on mitochondrial proteome is not demonstrated. We investigated how IPC modifies the mitochondrial proteome after IR injury. Methods: Rats were subjected to 25 min of portal triad crossclamping (IR group, n = 8). In the IPC group (n = 8), 10 min of temporal portal triad

R. Oshima; H. Nakano; M. Katayama; J. Sakurai; W. Wu; S. Koizumi; T. Asano; T. Watanabe; T. Asakura; T. Ohta; T. Otsubo

2008-01-01

49

Ischemic Preconditioning and Brain Tolerance Temporal Histological and Functional Outcomes, Protein Synthesis Requirement, and Interleukin1 Receptor Antagonist and Early Gene Expression  

Microsoft Academic Search

Background and Purpose—A short duration of ischemia (ie, ischemic preconditioning (PC)) can provide significant brain protection to subsequent ischemic events (ie, ischemic tolerance (IT)). The present series of studies was conducted to characterize the temporal pattern of a PC paradigm, to systematically evaluate the importance of protein synthesis in PC-induced IT, and to explore candidate gene expression changes associated with

Frank C. Barone; Raymond F. White; Patricia A. Spera; Julie Ellison; R. William Currie; Xinkang Wang; Giora Z. Feuerstein

50

Poly-ICLC preconditioning protects the blood-brain barrier against ischemic injury in vitro through type I interferon signaling  

PubMed Central

Preconditioning with a low dose of harmful stimulus prior to injury induces tolerance to a subsequent ischemic challenge resulting in neuroprotection against stroke. Experimental models of preconditioning primarily focus on neurons as the cellular target of cerebral protection while less attention has been paid to the cerebrovascular compartment whose role in the pathogenesis of ischemic brain injury is crucial. We have shown that preconditioning with polyinosinic polycytidylic acid (poly-ICLC) protects against cerebral ischemic damage. To delineate the mechanism of poly-ICLC protection, we investigated whether poly-ICLC preconditioning preserves the function of the blood-brain-barrier (BBB) in response to ischemic injury. Using an in vitro BBB model, we found that poly-ICLC treatment prior to exposure to oxygen-glucose deprivation maintained the paracellular and transcellular transport across the endothelium and attenuated the drop in transendothelial electric resistance. We found that poly-ICLC treatment induced interferon (IFN) ? mRNA expression in astrocytes and microglia and that type I IFN signaling in brain microvascular endothelial cells was required for protection. Importantly, this implicates a potential mechanism underlying neuroprotection in our in vivo experimental stroke model where type I IFN signaling is required for poly-ICLC-induced neuroprotection against ischemic injury. In conclusion, we are the first to show that preconditioning with poly-ICLC attenuates ischemia-induced BBB dysfunction. This mechanism is likely an important feature of poly-ICLC-mediated neuroprotection and highlights the therapeutic potential of targeting BBB signaling pathways to protect the brain against stroke. PMID:23050645

Gesuete, Raffaella; Packard, Amy E. B.; Vartanian, Keri B.; Conrad, Valerie K.; Stevens, Susan L.; Bahjat, Frances R.; Yang, Tao; Stenzel-Poore, Mary P.

2012-01-01

51

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

PubMed Central

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

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

2014-01-01

52

Cardiac proteomic responses to ischemia-reperfusion injury and ischemic preconditioning.  

PubMed

Cardiac ischemia and ischemia-reperfusion (I/R) injury are major contributors to morbidity and mortality worldwide. Pathological mechanisms of I/R and the physiological mechanisms of ischemic preconditioning (IPC), which is an effective cardiac protective response, have been widely investigated in the last decade to search for means to prevent or treat this disease. Proteomics is a powerful analytical tool that has provided important information to identify target proteins and understand the underlying mechanisms of I/R and IPC. Here, we review the application of proteomics to I/R injury and IPC to discover target proteins. We analyze the functional meaning of the accumulated data on hundreds of proteins using various bioinformatics applications. In addition, we review exercise-induced proteomic alterations in the heart to understand the potential cardioprotective role of exercise against I/R injury. Further developments in the proteomic field that target specialized proteins will yield new insights for optimizing therapeutic targets and developing a wide range of therapeutic agents against ischemic heart disease. PMID:21501017

Kim, Hyoung Kyu; Thu, Vu Thi; Heo, Hye-Jin; Kim, Nari; Han, Jin

2011-04-01

53

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

PubMed Central

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

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

2014-01-01

54

Remote Ischemic Preconditioning Protects against Liver Ischemia-Reperfusion Injury via Heme Oxygenase-1-Induced Autophagy  

PubMed Central

Background Growing evidence has linked autophagy to a protective role of preconditioning in liver ischemia/reperfusion (IR). Heme oxygenase-1 (HO-1) is essential in limiting inflammation and preventing the apoptotic response to IR. We previously demonstrated that HO-1 is up-regulated in liver graft after remote ischemic preconditioning (RIPC). The aim of this study was to confirm that RIPC protects against IR via HO-1-mediated autophagy. Methods RIPC was performed with regional ischemia of limbs before liver ischemia, and HO-1 activity was inhibited pre-operation. Autophagy was assessed by the expression of light chain 3-II (LC3-II). The HO-1/extracellular signal-related kinase (ERK)/p38/mitogen-activated protein kinase (MAPK) pathway was detected in an autophagy model and mineral oil-induced IR in vitro. Results In liver IR, the expression of LC3-II peaked 12–24 h after IR, and the ultrastructure revealed abundant autophagosomes in hepatocytes after IR. Autophagy was inhibited when HO-1 was inactivated, which we believe resulted in the aggravation of liver IR injury (IRI) in vivo. Hemin-induced autophagy also protected rat hepatocytes from IRI in vitro, which was abrogated by HO-1 siRNA. Phosphorylation of p38-MAPK and ERK1/2 was up-regulated in hemin-pretreated liver cells and down-regulated after treatment with HO-1 siRNA. Conclusions RIPC may protect the liver from IRI by induction of HO-1/p38-MAPK-dependent autophagy. PMID:24914543

Xiong, Xuanxuan; Xu, Yonghua; Zhang, Hai; Huang, Changjun; Tian, Yuan; Jiao, Chengyu; Wang, Xuehao; Li, Xiangcheng

2014-01-01

55

Disruption of Caveolae Blocks Ischemic Preconditioning-Mediated S-Nitrosylation of Mitochondrial Proteins  

PubMed Central

Abstract Aims Nitric oxide (NO) and protein S-nitrosylation (SNO) play important roles in ischemic preconditioning (IPC)-induced cardioprotection. Mitochondria are key regulators of preconditioning, and most proteins showing an increase in SNO with IPC are mitochondrial. The aim of this study was to address how IPC transduces NO/SNO signaling to mitochondria in the heart. Results: In this study using Langendorff perfused mouse hearts, we found that IPC-induced cardioprotection was blocked by treatment with either N-nitro-L-arginine methyl ester (L-NAME, a constitutive NO synthase inhibitor), ascorbic acid (a reducing agent to decompose SNO), or methyl-?-cyclodextrin (M?CD, a cholesterol sequestering agent to disrupt caveolae). IPC not only activated AKT/eNOS signaling but also led to translocation of eNOS to mitochondria. M?CD treatment disrupted caveolar structure, leading to dissociation of eNOS from caveolin-3 and blockade of IPC-induced activation of the AKT/eNOS signaling pathway. A significant increase in mitochondrial SNO was found in IPC hearts compared to perfusion control, and the disruption of caveolae by M?CD treatment not only abolished IPC-induced cardioprotection, but also blocked the IPC-induced increase in SNO. Innovation: These results provide mechanistic insight into how caveolae/eNOS/NO/SNO signaling mediates cardioprotection induced by IPC. Conclusion: Altogether these results suggest that caveolae transduce eNOS/NO/SNO cardioprotective signaling in the heart. Antioxid. Redox Signal. 16, 45–56. PMID:21834687

Kohr, Mark J.; Nguyen, Tiffany; Aponte, Angel M.; Connelly, Patricia S.; Esfahani, Shervin G.; Gucek, Marjan; Daniels, Mathew P.; Steenbergen, Charles; Murphy, Elizabeth

2012-01-01

56

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

PubMed

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

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

2015-02-19

57

Mitogen-activated protein kinase p38alpha and retinal ischemic preconditioning.  

PubMed

In previous studies, inhibition of mitogen-activated protein kinase (MAP) p38 significantly improved recovery and attenuated apoptosis after retinal ischemia in rats. Yet, ischemic preconditioning (IPC) attenuated the ischemia-induced increase in p38 expression. We hypothesized that p38 was required for induction of ischemic tolerance by IPC. We examined the mechanisms of involvement of p38 in IPC neuroprotection. IPC or ischemia was induced in rat retina in vivo. Recovery after ischemia performed 24h after IPC was assessed functionally (electroretinography) and histologically at 7d after ischemia in the presence or absence of inhibition of p38. We examined the role of p38alpha in the mimicking of IPC produced by opening mitochondrial KATP channels using diazoxide, or stimulation of p38 activation by anisomycin. The importance of adenosine receptors in p38 activation after IPC was assessed using specific blockers of adenosine A1 and A2a receptors. Interfering RNA (siRNA) or SB203580 was used to block p38alpha. Phosphorylated p38 levels were measured. Phosphorylated p38 protein increased with IPC. Interfering RNA (siRNA) to p38alpha prior to IPC, or inhibiting p38 activation with SB203580, with ischemia following 24h later, significantly attenuated the neuroprotective effect of IPC. Anisomycin administered to increase p38 mimicked IPC, an effect blocked by SB203580. IPC-mimicking with diazoxide, an opener of mitochondrial KATP channels, was diminished with p38alpha siRNA. Adenosine receptor blockade did not decrease the elevated levels of phosphorylated p38 after IPC. Specific inhibition of p38alpha suggests that this MAPK is involved in the protective effects of IPC, and that p38 is downstream of mitochondrial KATP channels, but not adenosine receptors, in this neuroprotection. PMID:19631642

Dreixler, John C; Barone, Frank C; Shaikh, Afzhal R; Du, Eugenie; Roth, Steven

2009-11-01

58

Ischemic Preconditioning Decreases Mitochondrial Proton Leak and Reactive Oxygen Species Production in the Postischemic Heart  

PubMed Central

Background Proton leak (H+ leak) dissipates mitochondrial membrane potential (m??) through the reentry of protons into the mitochondrial matrix independent of ATP synthase. Changes in H+ leak may affect reactive oxygen species (ROS) production. We measured H+ leak and ROS production during ischemia-reperfusion and ischemic preconditioning (IPC) and examined how changing mitochondrial respiration affected m?? and ROS production. Materials/Methods Isolated rat hearts (n=6/group) were subjected to either Control-IR or IPC. Rate pressure product (RPP) was measured. Mitochondria were isolated at end reperfusion. Respiration was measured by polarography and titrated with increasing concentrations of malonate (0.5-2mM). m?? was measured using a tetraphenylphosphonium electrode. H+ leak is the respiratory rate required to maintain membrane potential at -150mV in the presence of oligomycin-A Mitochondrial complex III ROS production was measured by fluorometry using Amplex-Red. Results IPC improved recovery of RPP at end reperfusion (63±4% vs. 21±2% in Control-IR, p<0.05). Ischemia-reperfusion caused increased H+ leak (94±12 vs. 31±1 nanomoles O/mg protein/min in Non-Ischemic Control, p<0.05). IPC attenuates these increases (55±9 nanomoles O/mg protein/min, p< 0.05 vs. Control-IR). IPC reduced mitochondrial ROS production compared to Control-IR (31±2 vs. 40±3 nanomoles/mg protein/min, p<0.05). As mitochondrial respiration decreased, m?? and mitochondrial ROS production also decreased. ROS production remained lower in IPC than in Control-IR for all m?? and respiration rates. Conclusions Increasing H+ leak is not associated with increased ROS production. IPC decreases both the magnitude of H+ leak and ROS production after ischemia-reperfusion. PMID:21035133

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

2010-01-01

59

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

PubMed

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

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

2015-01-01

60

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

PubMed Central

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

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

2014-01-01

61

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

PubMed Central

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

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

2013-01-01

62

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

PubMed Central

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

2012-01-01

63

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

PubMed

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.Journal of Cerebral Blood Flow & Metabolism advance online publication, 12 November 2014; doi:10.1038/jcbfm.2014.193. PMID:25388675

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

2014-11-12

64

Angiotensin II and ischemic preconditioning synergize to improve mitochondrial function while showing additive effects on ventricular postischemic recovery.  

PubMed

Recent studies indicate that the cardioprotective effects of ischemic preconditioning (IPC) against sustained ischemia/reperfusion can be replicated by angiotensin II (Ang II). However, it is not clear whether IPC and Ang II-induced preconditioning (APC) act through similar mechanisms or synergize to enhance cardioprotection. In this study, Langendorff-perfused rat hearts were subjected to IPC, APC, or their combination (IPC/APC) followed by ischemia/reperfusion. IPC, and less potently APC, significantly increased the percent recoveries of the left ventricular developed pressure, the first derivative of developed pressure, and the rate pressure product compared with control. Furthermore, the postischemic recovery of the heart was significantly higher for IPC/APC compared with IPC or APC. The improvements in cardiac function by IPC, APC, and IPC/APC were associated with similar reductions in lactate dehydrogenase release and infarct size. However, a significant improvement in mitochondrial respiration was observed with IPC/APC. The postischemic recovery observed with APC and IPC/APC was inhibited by treatment with losartan, an Ang II type-1 receptor blocker, during the preconditioning phase but not by chelerythrine, a pan-PKC inhibitor. Both drugs, however, abolished the enhanced mitochondrial respiration by IPC/APC. Altogether, these results indicate that APC and IPC interact through mechanisms that enhance cardioprotection by affecting cardiac function and mitochondrial respiration. PMID:24705171

Nuñez, Rebeca E; Castro, Miriam; Javadov, Sabzali; Escobales, Nelson

2014-08-01

65

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...

66

In vivo hypoxic preconditioning protects from warm liver ischemic/reperfusion injury through the adenosine A2B receptor  

PubMed Central

BACKGROUND Liver ischemia(I)/reperfusion(R) injury(I) is a known risk factor for the postoperative outcome of patients undergoing liver surgery/transplantation. Attempts to protect from organ damage require multidisciplinary strategies and are of emerging interest in view of patients with higher age and ASA-status. Ischemic preconditioning has been successfully applied to prevent from IRI during liver resections/transplantation. Since even short periods of ischemia during preconditioning inevitably lead to hypoxia and formation of anti-inflammatory/ cytoprotective acting adenosine, we reasoned that short non-ischemic hypoxia also protects against hepatic IRI. METHODS Mice underwent hypoxic preconditioning(HPC) by breathing 10%-oxygen for 10 minutes, followed by 10 minutes of 21%-oxygen prior to left-liver-lobe-ischemia(45 min) and reperfusion(4 hrs). The interactions of hypoxia->adenosine->adenosine-receptors were tested by pharmacologic antagonism at adenosine receptor(AR) sites in wild type mice and in mice with genetic deletions at the A1-;A2A-;A2B- and A3-ARs. Hepatocellular damage, inflammation and metabolic effects were quantified by enzyme activities, cytokines, liver-myeloperoxidase(MPO), blood adenosine and tissue-adenosinemonophosphate(AMP), respectively. RESULTS Hepatoprotection by HPC was significant in wild type and A1-, A2A-and A3 AR-knock-out mice as quantified by lower ALT serum activities, cytokine levels, histological damage-scores, tissue-myeloperoxidase-concentrations and as well as preserved AMP-concentrations. Protection by HPC was blunted in mice pretreated with the A2B-AR-antagonist MRS1754 or in A2B-AR“knock-outs”. CONCLUSION Because liver protective effects of HPC are negated when the A2B receptor is non-functional, the "hypoxia->adenosine->A2B receptor" pathway plays a critical role in the prevention of warm ischemia reperfusion injury in vivo. Hypoxic activation of this pathway warrants use of selective A2B-AR-agonists or even intermittent hypoxia (e.g. in deceased organ donors) to protect from liver ischemia/reperfusion injury. PMID:23073466

Choukèr, Alexander; Ohta, Akio; Martignoni, André; Lukashev, Dmitriy; Zacharia, Lefteris C; Jackson, Edwin K; Schnermann, Jürgen; Ward, Jerrold M; Kaufmann, Ines; Klaunberg, Brenda; Sitkovsky, Michail V; Thiel, Manfred

2012-01-01

67

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

PubMed Central

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

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

2014-01-01

68

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

PubMed

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

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

2015-01-01

69

Remote ischemic preconditioning has a neutral effect on the incidence of kidney injury after coronary artery bypass graft surgery.  

PubMed

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease (CKD). Remote ischemic preconditioning (RIPC) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI. We undertook a randomized controlled trial of RIPC to prevent AKI in 86 patients with CKD (estimated glomerular filtration rate under 60?ml/min per 1.73?m(2)) undergoing coronary artery bypass graft (CABG) surgery. Forty-three patients each were randomized to receive standard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion. The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3?mg/dl within 48?h of surgery. Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C, neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18), and urinary biomarkers including NGAL, IL-18, and kidney injury molecule-1 measured at 6, 12, and 24?h after CABG, and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury. Clinical and operative characteristics were similar between the preconditioned and control groups. AKI developed in 12 patients in both groups within 48?h of CABG. There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG. Thus, RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD. PMID:25075773

Gallagher, Sean M; Jones, Dan A; Kapur, Akhil; Wragg, Andrew; Harwood, Steve M; Mathur, Rohini; Archbold, R Andrew; Uppal, Rakesh; Yaqoob, Muhammad M

2015-02-01

70

Ischemic preconditioning and diazoxide limit mitochondrial Ca2+ overload during ischemia/reperfusion: Role of reactive oxygen species  

PubMed Central

BACKGROUND: Generation of reactive oxygen species (ROS) is associated with cardioprotection imparted by ischemic preconditioning (IPC) and pharmacological PC (PPC). The authors have previously shown that IPC or PPC, using the mitochondrial ATP-sensitive K+ channel opener diazoxide (DZ), reduce mitochondrial Ca2+ ([Ca2+]m) during ischemia and reperfusion. OBJECTIVES: To test the hypothesis that both IPC and PPC (using DZ) lead to reduced [Ca2+]m and improved functional recovery via a ROS-dependent mechanism. METHODS: Intracellular Ca2+ ([Ca2+]i) and [Ca2+]m were measured in isolated perfused rat hearts loaded with the fluorescent indicator indo-1 acetoxymethyl ester. [Ca2+]m was determined by quenching the cytosolic indo-1 signal using manganese before ischemia (25 min). IPC and DZ (100 ?M) group hearts were studied with and without the ROS scavenger N-2-mercaptopropionyl glycine (400 ?M) (2-MPG). RESULTS: Both IPC and DZ significantly reduced [Ca2+]i and [Ca2+]m on reperfusion compared with the control. Administration of 2-MPG with washout before ischemia significantly attenuated the reduction in [Ca2+]m observed on reperfusion in both the IPC and DZ groups. Additionally, the myocardial functional protection imparted by IPC or DZ was lost with the administration of 2-MPG. CONCLUSIONS: The [Ca2+]m-reducing effect of IPC and DZ was attenuated with the administration of 2-MPG, resulting in decreased myocardial functional performance and increased release of creatine kinase, a marker of cellular injury. It can be concluded that IPC and DZ impart their protective effect via a mechanism involving ROS generation before the ischemic episode. PMID:19641667

Eaton, Matt; Hernandez, Lisa A; Schaefer, Saul

2005-01-01

71

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

PubMed

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 (Wpeak), 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 Wpeak tests (SL and HA) and 4 experimental exercise trials (10 min at 55% altitude-specific Wpeak 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 Wpeak values. IPC did not significantly improve Wpeak at SL or HA. Additionally, IPC failed to improve cardiovascular hemodynamics or SpO2 during submaximal exercise or at Wpeak. In conclusion, IPC performed 45 min prior to exercise does not improve Wpeak 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

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

2015-01-01

72

Influence of diabetic state and that of different sulfonylureas on the size of myocardial infarction with and without ischemic preconditioning in rabbits.  

PubMed

The sensitivity of the myocardium to ischemia and the level of protection achieved by ischemic preconditioning is shaped by the joint influence of several mechanisms in diabetes mellitus. In vivo studies were made in alloxan diabetic and non-diabetic control rabbits to assess if the effects of preconditioning and sulfonylurea pretreatment with either glibenclamide or glimepiride (0.05-0.2-0.6 micromol kg (-1)) influence the extent of the infarcted area caused by one hour ligature of the left coronary artery. For our study, we defined preconditioning as 2 minutes of ischemia followed by 2 minutes of reperfusion, which was repeated 3 times. The interrelationship of the diabetic pathophysiological state, and sulfonylurea treatment during ischemic preconditioning were studied by comparing the infarcted areas and the rate of infarction to risk areas in left ventricular slices using computer planimetry. In healthy control rabbits preconditioning reduced infarcted area (29.6 +/- 3.0% vs. 48.8 +/- 2.8% p < 0.0005), while in diabetic rabbits this protection did not occur (53.3 +/- 7.3% vs. 56.6 +/- 4.4% NS). Glibenclamide in all of applied doses prevented the protective effect in control animals (infarction/ risk area: HP: 0.47 +/- 0.04 vs. HP Glib-0.05 : 0.69+/-0.06 p< 0.004 vs. HP Glib-0.2 : 0.72+/-0.09 p< 0.002 vs. HP Glib-0.6 : 0.75 +/- 0.04 p< 0.001). In contrast, in diabetic rabbits low dose of glibenclamide contributed to the same development of preconditioning. However the highest dose of glibenclamide (infarction/risk area: DP Glib-0.6 : 0.77 +/- 0.17 vs. DP Glib-0.05 : 0.55 < 0.03 p < 0.047) and the consequences of the diabetic state blocked the salutary effect. Glimepiride had no considerable influence on the protective effect, either in control nor in diabetic animals. Glibenclamide and glimepiride, presumably due to their different sulfonylurea receptor affinity in the heart, resulted in different influence on preconditioning in healthy control animals. Glibenclamide treatment seemed to be more harmful when less K (+)ATP channels were activated. The accomplishment of myocardial preconditioning in diabetes mellitus is claimed to be determined by the interaction of both metabolically influenced K (+)ATP channel activity and the dose of sulfonylurea. PMID:12148084

Nieszner, E; Posa, I; Kocsis, E; Pogátsa, G; Préda, I; Koltai, M Z

2002-08-01

73

Junctional protein regulation by sphingosine kinase 2 contributes to blood–brain barrier protection in hypoxic preconditioning-induced cerebral ischemic tolerance  

PubMed Central

Protection of the blood–brain barrier (BBB) is correlated with improved outcome in stroke. Sphingosine kinase (SphK)-directed production of sphingosine-1-phosphate, which we previously documented as being vital to preconditioning-induced stroke protection, mediates peripheral vascular integrity via junctional protein regulation. We used a hypoxic preconditioning (HPC) model in adult wild-type and SphK2-null mice to examine the isoform-specific role of SphK2 signaling for ischemic tolerance to transient middle cerebral artery occlusion and attendant BBB protection. Reductions in infarct volume and BBB permeability in HPC-treated mice were completely lost in SphK2-null mice. Hypoxic preconditioning-induced attenuation of postischemic BBB disruption in wild types, evidenced by reduced extravascular immunoglobulin G intensity, suggests direct protection of BBB integrity. Measurement of BBB junctional protein status in response to HPC revealed SphK2-dependent increases in triton-insoluble claudin-5 and VE-cadherin, which may serve to strengthen the BBB before stroke. Postischemic loss of VE-cadherin, occludin, and zona occludens-1 in SphK2-null mice with prior HPC suggests that SphK2-dependent protection of these adherens and tight junction proteins is compulsory for HPC to establish a vasculoprotective phenotype. Further elucidation of the mediators of this endogenous, HPC-activated lipid signaling pathway, and their role in protecting the ischemic BBB, may provide new therapeutic targets for cerebrovascular protection in stroke patients. PMID:22314269

Wacker, Bradley K; Freie, Angela B; Perfater, Jennifer L; Gidday, Jeffrey M

2012-01-01

74

SirT1 mediates hyperbaric oxygen preconditioning-induced ischemic tolerance in rat brain.  

PubMed

Our previous studies have shown that hyperbaric oxygen preconditioning (HBO-PC) induces tolerance to cerebral ischemia/reperfusion (I/R). This study aimed to investigate whether SirT1, a class III histone deacetylase, is involved in neuroprotection elicited by HBO-PC in animal and cell culture models of ischemia. Rats were subjected to middle cerebral artery occlusion for 120?minutes after HBO-PC (once a day for 5 days). Primary cultured cortical neurons were exposed to 2?hours of HBO-PC after 2?hours of oxygen-glucose deprivation (OGD). We showed that HBO-PC increased SirT1 protein and mRNA expression, promoted neurobehavioral score, reduced infarct volume, and improved morphology at 24?hours and 7 days after cerebral I/R. Neuroprotection of HBO-PC was attenuated by SirT1 inhibitor EX527 and SirT1 knockdown by short interfering RNA (siRNA), whereas it was mimicked by SirT1 activator resveratrol. Furthermore, HBO-PC enhanced SirT1 expression and cell viability and reduced lactate dehydrogenase release 24?hours after OGD/re-oxygenation. The neuroprotective effect of HBO-PC was emulated through upregulating SirT1 and, reversely, attenuated through downregulating SirT1. The modulation of SirT1 was made by adenovirus infection carrying SirT1 or SirT1 siRNA. Besides, SirT1 increased B-cell lymphoma 2 (Bcl-2) expression and decrease cleaved caspase 3. These results indicate that SirT1 mediates HBO-PC-induced tolerance to cerebral I/R through inhibition of apoptosis. PMID:23299244

Yan, Wenjun; Fang, Zongping; Yang, Qianzi; Dong, Hailong; Lu, Yan; Lei, Chong; Xiong, Lize

2013-03-01

75

SirT1 mediates hyperbaric oxygen preconditioning-induced ischemic tolerance in rat brain  

PubMed Central

Our previous studies have shown that hyperbaric oxygen preconditioning (HBO-PC) induces tolerance to cerebral ischemia/reperfusion (I/R). This study aimed to investigate whether SirT1, a class III histone deacetylase, is involved in neuroprotection elicited by HBO-PC in animal and cell culture models of ischemia. Rats were subjected to middle cerebral artery occlusion for 120?minutes after HBO-PC (once a day for 5 days). Primary cultured cortical neurons were exposed to 2?hours of HBO-PC after 2?hours of oxygen–glucose deprivation (OGD). We showed that HBO-PC increased SirT1 protein and mRNA expression, promoted neurobehavioral score, reduced infarct volume, and improved morphology at 24?hours and 7 days after cerebral I/R. Neuroprotection of HBO-PC was attenuated by SirT1 inhibitor EX527 and SirT1 knockdown by short interfering RNA (siRNA), whereas it was mimicked by SirT1 activator resveratrol. Furthermore, HBO-PC enhanced SirT1 expression and cell viability and reduced lactate dehydrogenase release 24?hours after OGD/re-oxygenation. The neuroprotective effect of HBO-PC was emulated through upregulating SirT1 and, reversely, attenuated through downregulating SirT1. The modulation of SirT1 was made by adenovirus infection carrying SirT1 or SirT1 siRNA. Besides, SirT1 increased B-cell lymphoma 2 (Bcl-2) expression and decrease cleaved caspase 3. These results indicate that SirT1 mediates HBO-PC-induced tolerance to cerebral I/R through inhibition of apoptosis. PMID:23299244

Yan, Wenjun; Fang, Zongping; Yang, Qianzi; Dong, Hailong; Lu, Yan; Lei, Chong; Xiong, Lize

2013-01-01

76

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

PubMed Central

Abstract Remote Ischemic Preconditioning (RIPC) is emerging as a new noninvasive intervention that has the potential to protect a number of organs against ischemia–reperfusion (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 dose–response 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

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

2014-01-01

77

Remote Ischemic Preconditioning in Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass: A Single?Center Double?Blinded Randomized Trial  

PubMed Central

Background Remote ischemic preconditioning (RIPC) harnesses an innate defensive mechanism that protects against inflammatory activation and ischemia?reperfusion injury, known sequelae of cardiac surgery with cardiopulmonary bypass. We sought to determine the impact of RIPC on clinical outcomes and physiological markers related to ischemia?reperfusion injury and inflammatory activation after cardiac surgery in children. Methods and Results Overall, 299 children (aged neonate to 17 years) were randomized to receive an RIPC stimulus (inflation of a blood pressure cuff on the left thigh to 15 mm Hg above systolic for four 5?minute intervals) versus a blinded sham stimulus during induction with a standardized anesthesia protocol. Primary outcome was duration of postoperative hospital stay, with serial clinical and laboratory measurements for the first 48 postoperative hours and clinical follow?up to discharge. There were no significant baseline differences between RIPC (n=148) and sham (n=151). There were no in?hospital deaths. No significant difference in length of postoperative hospital stay was noted (sham 5.4 versus RIPC 5.6 days; difference +0.2; adjusted P=0.91), with the 95% confidence interval (?0.7 to +0.9) excluding a prespecified minimal clinically significant differences of 1 or 1.5 days. There were few significant differences in other clinical outcomes or values at time points or trends in physiological markers. Benefit was not observed in specific subgroups when explored through interactions with categories of age, sex, surgery type, Aristotle score, or first versus second half of recruitment. Adverse events were similar (sham 5%, RIPC 6%; P=0.68). Conclusions RIPC is not associated with important improvements in clinical outcomes and physiological markers after cardiac surgery in children. Clinical Trial Registration URL: clinicaltrials.gov. Unique identifier: NCT00650507. PMID:25074698

McCrindle, Brian W.; Clarizia, Nadia A.; Khaikin, Svetlana; Holtby, Helen M.; Manlhiot, Cedric; Schwartz, Steven M.; Caldarone, Christopher A.; Coles, John G.; Van Arsdell, Glen S.; Scherer, Stephen W.; Redington, Andrew N.

2014-01-01

78

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

PubMed Central

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

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

2012-01-01

79

Remote ischemic preconditioning confers late protection against myocardial ischemia-reperfusion injury in mice by upregulating interleukin-10  

PubMed Central

Remote ischemic preconditioning (RIPC) induces a prolonged late phase of multi-organ protection against ischemia-reperfusion (IR) injury. In the present study, we tested the hypothesis that RIPC confers late protection against myocardial IR injury by upregulating expression of interleukin (IL)-10. Mice were exposed to lower limb RIPC or sham ischemia. After 24 h, mice with RIPC demonstrated decreased myocardial infarct size and improved cardiac contractility following 30-min ischemia and 120-min reperfusion (I-30/R-120). These effects of RIPC were completely blocked by anti-IL-10 receptor antibodies. In IL-10 knockout mice, RIPC cardioprotection was lost, but it was mimicked by exogenous IL-10. Administration of IL-10 to isolated perfused hearts increased phosphory-lation of the protein kinase Akt and limited infarct size after I-30/R-120. In wild-type mice, RIPC increased plasma and cardiac IL-10 protein levels and caused activation of Akt and endothelial nitric oxide synthase in the heart at 24 h, which was also blocked by anti-IL-10 receptor antibodies. In the gastrocnemius muscle, RIPC resulted in immediate inactivation of the phosphatase PTEN and activation of Stat3, with increased IL-10 expression 24 h later. Myocyte-specific PTEN inactivation led to increased Stat3 phosphorylation and IL-10 protein expression in the gastrocnemius muscle. Taken together, these results suggest that RIPC induces late protection against myocardial IR injury by increasing expression of IL-10 in the remote muscle, followed by release of IL-10 into the circulation, and activation of protective signaling pathways in the heart. This study provides a scientific basis for the use of RIPC to confer systemic protection against IR injury. PMID:22752341

Parajuli, Nirmal; Zheng, Xiaoxu; Becker, Lewis

2013-01-01

80

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

PubMed

Diabetes mellitus (DM) has been reported to alter the cardiac response to ischemia-reperfusion (IR). In addition, cardioprotection induced by ischemic preconditioning (IPC) is often impaired in diabetes. We have previously shown that the subcellular localisation of the glycolytic enzyme hexokinase (HK) is causally related to IR injury and IPC protective potential. Especially the binding of HK to mitochondria and prevention of HK solubilisation (HK detachment from mitochondria) during ischemia confers cardioprotection. It is unknown whether diabetes affects HK localisation during IR and IPC as compared to non-diabetes. In this study we hypothesize that DM alters cellular trafficking of hexokinase in response to IR and IPC, possibly explaining the altered response to IR and IPC in diabetic heart. Control (CON) and type I diabetic (DM) rat hearts (65 mg/kg streptozotocin, 4 weeks) were isolated and perfused in Langendorff-mode and subjected to 35 min I and 30 min R with or without IPC (3 times 5 min I). Cytosolic and mitochondrial fractions were obtained at (1) baseline, i.e. after IPC but before I, (2) 35 min I, (3) 5 min R and (4) 30 min R. DM improved rate-pressure product recovery (RPP; 71 ± 10 % baseline (DM) versus 9 ± 1 % baseline (CON) and decreased contracture (end-diastolic pressure: 24 ± 8 mmHg (DM) vs 77 ± 4 mmHg (CON)) after IR as compared to control, and was associated with prevention of HK solubilisation at 35 min I. IPC improved cardiac function in CON but not in DM hearts. IPC in CON prevented HK solubilisation at 35 min I and at 5 min R, with a trend for increased mitochondrial HK. In contrast, the non-effective IPC in DM was associated with solubilisation of HK and decreased mitochondrial HK at early reperfusion and a reciprocal behaviour at late reperfusion. We conclude that type I DM significantly altered cellular HK translocation patterns in the heart in response to IR and IPC, possibly explaining altered response to IR and IPC in diabetes. PMID:23652994

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

2013-07-01

81

Limb ischemic preconditioning protects against contrast-induced acute kidney injury in rats via phosphorylation of GSK-3?  

PubMed

Contrast-induced acute kidney injury (CI-AKI) resulting from the use of intravascular iodinated contrast media for diagnostic and interventional cardiovascular procedures is associated with substantial morbidity and mortality. Despite preventative measures intended to mitigate the risk of CI-AKI, there remains a need for a novel and effective therapeutic approach. Limb ischemic preconditioning (LIPC), where short-term ischemia/reperfusion is applied to an arm prior to administration of the contrast agent, has been shown in several trials to preserve renal function in patients at high risk for CI-AKI. However, the underlying mechanism by which this procedure provides renoprotection against contrast media insults is not known. Here, we explored the molecular mechanism(s) of LIPC-induced protection of the kidneys from CI-AKI, particularly the role of phosphorylated glycogen synthase kinase-3? (GSK-3?). We used a novel CI-AKI model consisting of 5/6 nephrectomized (NE) rats at 6 weeks after the ablative surgery. LIPC- or sham-treated rats were administered iohexol (10ml/kg, 3.5gI) via the tail vein. The results showed that LIPC protected the kidneys against iohexol-induced injury. This protective effect was accompanied by the attenuation of renal dysfunction, tubular damage, apoptosis, mitochondrial swelling, oxidative stress, and inflammation. Furthermore, LIPC-induced renoprotection was blocked via treatment with inhibitors of PI3K (wortmannin or LY294002), but not ERK (U0126 or PD98059). LIPC also increased the protein expression levels of phospho-Akt, phospho-GSK-3?, and nuclear Nrf2, and decreased the levels of nuclear NF-?B. A specific GSK-3? inhibitor (SB216763) mimicked this effect of LIPC, by inhibiting the opening of the mitochondrial permeability transition pore and reducing the levels of oxidative stress and inflammation via activation of Nrf2 and suppression of NF-?B. The above results demonstrate that LIPC induces protection against CI-AKI, making this procedure a promising strategy for preventing CI-AKI. In particular, this renoprotective effect involves the phosphorylation of GSK-3?. PMID:25451640

Liu, Tongqiang; Fang, Yi; Liu, Shaopeng; Yu, Xiaofang; Zhang, Hui; Liang, Mingyu; Ding, Xiaoqiang

2014-10-31

82

Role of mitochondrial permeability transition pore and mitochondrial ATP-sensitive potassium channels in the protective effects of ischemic preconditioning in isolated hearts from fed and fasted rats.  

PubMed

The aim of the present study was to assess whether the protective effects of ischemic preconditioning (PC) are associated with activation of the mitochondrial ATP-sensitive potassium channels (mitoKATP) and if there is any relationship between the activity of these channels and the mitochondrial permeability transition pore (MPTP) opening in ischemic-reperfused rat hearts under different nutritional conditions. Langendorff-perfused hearts of fed and 24-h fasted rats were exposed to 25 min of no-flow global ischemia plus 30 min of reperfusion. Fasting accelerated functional recovery and attenuated MPTP opening. The mitoKATP blocker, 5-hydroxydecanoic (HD), did not influence functional recovery and MPTP opening induced by ischemia-reperfusion in the fed hearts but partially reversed the beneficial effects of fasting. PC and the mitoKATP opener, diazoxide (DZ), improved functional recovery, preserved cell viability, and inhibited MPTP opening in both fed and fasted hearts. The protection elicited by PC and DZ on contractile recovery and MPTP opening was reversed by HD, which did not affect cell viability. Altogether, these results argue for a role of mitoKATP and its impact on preservation mitochondrial inner membrane permeability as a relevant factor in the improvement of contractile function in the ischemic-reperfused rat heart. They also suggest that the functional protection elicited by PC may be related to this mechanism. PMID:25034332

Prendes, M G Marina; Hermann, R; Torresin, M E; Vélez, D; Savino, E A; Varela, A

2014-09-01

83

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

PubMed

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

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

2014-09-01

84

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

PubMed Central

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 naïve 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

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

2014-01-01

85

Signaling pathways leading to ischemic mitochondrial neuroprotection.  

PubMed

There is extensive evidence that ischemic/reperfusion mediated mitochondrial dysfunction is a major contributor to ischemic damage. However data also indicates that mild ischemic stress induces mitochondrial dependent activation of ischemic preconditioning. Ischemic preconditioning is a neuroprotective mechanism which is activated upon a brief sub-injurious ischemic exposure and is sufficient to provide protection against a subsequent lethal ischemic insult. Current research demonstrates that mitochondria are not only the inducers of but are also an important target of ischemic preconditioning mediated protection. Numerous proteins and signaling pathways are activated by ischemic preconditioning which protect the mitochondria against ischemic damage. In this review we examine some of the proteins activated by ischemic precondition which counteracts the deleterious effects of ischemia/reperfusion thereby maintaining normal mitochondrial activity and lead to ischemic tolerance. PMID:25262285

Thompson, John W; Narayanan, Srinivasan V; Koronowski, Kevin B; Morris-Blanco, Kahlilia; Dave, Kunjan R; Perez-Pinzon, Miguel A

2015-04-01

86

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

PubMed Central

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.

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

2014-01-01

87

Essential role of nitric oxide in acute ischemic preconditioning: S-Nitros(yl)ation versus sGC/cGMP/PKG signaling?  

PubMed Central

Nitric oxide (NO) plays an important role in acute ischemic preconditioning (IPC). In addition to activating soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathways, NO-mediated protein S-nitros(yl)ation (SNO) has been recently shown to play an essential role in cardioprotection against ischemia–reperfusion (I/R) injury. In our previous studies, we have shown that IPC-induced cardioprotection could be blocked by treatment with either N-nitro-L-arginine methyl ester (L-NAME, a constitutive NO synthase inhibitor) or ascorbate (a reducing agent to decompose SNO). To clarify NO-mediated sGC/cGMP/PKG-dependent or -independent (i.e., SNO) signaling involved in IPC-induced cardioprotection, mouse hearts were Langendorff-perfused in the dark to prevent SNO decomposition by light exposure. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a highly selective inhibitor of sGC) or KT5823 (a potent and selective inhibitor of PKG) did not abolish IPC-induced acute protection, suggesting that the sGC/cGMP/ PKG signaling pathway does not play an important role in NO-mediated cardioprotective signaling during acute IPC. In addition, treatment with ODQ in IPC hearts provided an additional protective effect on functional recovery, in parallel with a higher SNO level in these ODQ+IPC hearts. In conclusion, these results suggest that the protective effect of NO is not related primarily to activation of the sGC/ cGMP/PKG signaling pathway, but rather through SNO signaling in IPC-induced acute cardioprotection. PMID:22989471

Sun, Junhui; Aponte, Angel M.; Kohr, Mark J.; Tong, Guang; Steenbergen, Charles; Murphy, Elizabeth

2012-01-01

88

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

PubMed Central

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

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

2014-01-01

89

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

PubMed Central

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

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

2013-01-01

90

The abbreviations used are: FCCP, carbonyl cyanide 4-trifluoromethoxyphenylhydrazone; H2O2, hydrogen peroxide; IPC, ischemic preconditioning; L-NAME, L-NG-Nitroarginine  

E-print Network

-expression modulates mitochondrial function through an NO-sensitive mechanism. In cardiac mitochondria isolated from function during ischemia. Keywords: H11 Kinase, heart, heat shock protein, mitochondria, nitric oxide target of NO-mediated preconditioning is the mitochondria, where NO reduces O2 consumption and reactive

Boyer, Edmond

91

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

PubMed Central

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

Chai, Qing; Liu, Jin

2014-01-01

92

Transient Ischemic Attack Before Nonlacunar Ischemic Stroke in the Elderly  

PubMed Central

Background: Several studies suggest transient ischemic attack (TIA) may be neuroprotective against ischemic stroke analogous to preinfarction angina's protection against acute myocardial infarction. However, this protective ischemic preconditioning-like effect may not be present in all ages, especially among the elderly. The purpose of this study was to determine the neuroprotective effect of TIAs (clinical equivalent of cerebral ischemic preconditioning) to neurologic damage after cerebral ischemic injury in patients over 65 years of age. Methods: We reviewed the medical charts of patients with ischemic stroke for presence of TIAs within 72 hours before stroke onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale and disability by a modified Rankin scale. Results: We evaluated 203 patients (?65 years) with diagnosis of acute ischemic stroke and categorized them according to the presence (n = 42, 21%) or absence (n = 161, 79%) of TIAs within 72 hours of stroke onset. Patients were monitored until discharged from the hospital (length of hospital stay 14.5 ± 4.8 days). No significant differences in the National Institutes of Health Stroke Scale and modified Rankin scale scores were observed between those patients with TIAs and those without TIAs present before stroke onset at admission or discharge. Conclusion: These results suggest that the neuroprotective mechanism of cerebral ischemic preconditioning may not be present or functional in the elderly. PMID:18755403

Morte, David Della; Abete, Pasquale; Gallucci, Ferdinando; Scaglione, Anna; D'Ambrosio, Daniele; Gargiulo, Gaetano; De Rosa, Giovanna; Dave, Kunjan R.; Lin, Hung Wen; Cacciatore, Francesco; Mazzella, Francesca; Uomo, Generoso; Rundek, Tanja; Perez-Pinzon, Miguel A.; Rengo, Franco

2009-01-01

93

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

PubMed

Although both sevoflurane postconditioning (SPoC) and delayed remote ischemic preconditioning (DRIPC) have been proved effective in various animal and human studies, the combined effect of these 2 strategies remains unclear. Therefore, this study was designed to investigate this effect and elucidate the related signal mechanisms in a Langendorff perfused rat heart model. After 30-minute balanced perfusion, isolated hearts were subjected to 30-minute ischemia followed by 60-minute reperfusion except 90-minute perfusion for control. A synergic cardioprotective effect of SPoC (3% v/v) and DRIPC (4 cycles 5-minute occlusion/5-minute reflow at the unilateral hindlimb once per day for 3 days before heart isolation) was observed with facilitated cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect was more pronounced in the combined group (6.76% ± 2.18%) than in the SPoC group (16.50% ± 4.55%, P < .001) or in the DRIPC group (10.22% ± 2.57%, P = .047). Subsequent analysis revealed that an enhanced heme oxygenase 1 (HO-1) expression, but not protein kinase B/AKt or extracellular signal-regulated kinase 1 and 2 activation, was involved in the synergic cardioprotective effect, which was further confirmed in the messenger RNA level of HO-1. Such trend was also observed in the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, an upstream regulation of HO-1. In addition, correlation analysis showed a significantly positive relationship between HO-1 expression and Nrf2 translocation (r = 0.729, P < .001). Hence, we conclude that DRIPC may produce an additive cardioprotection to SPoC through an enhanced HO-1 expression partly via Nrf2 translocation. PMID:24651515

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

2014-11-01

94

Novel role of NADPH oxidase in ischemic myocardium: a study with Nox2 knockout mice.  

PubMed

Several potential sources of reactive oxygen species (ROS) in cells exist. One source is NADPH oxidase, which is especially important for superoxide radical production. Nox2 is a primary regulatory subunit of NADPH oxidase. In the present study, we examined the role of ROS and NADPH oxidase in ischemic preconditioning (IP)-mediated cardioprotection by using Nox2(-/-) mice. Both wild-type (WT) and Nox2(-/-) mice were subjected to either 30 min of ischemia followed by 2 h of reperfusion (IR) or IP prior to 30 min ischemia and 2 h of reperfusion. Reduction in left ventricular developed pressure (60.1 versus 63 mmHg), dp/dt (max) (893 versus 1,027 mmHg/s), and aortic flow (0.9 versus 1.8 ml/min) was observed in Nox2(-/-)IPIR compared to WTIPIR along with increased infarct size (33% versus 22%) and apoptosis after 120 min of reperfusion. Differentially regulated genes were demonstrated by comparing gene expression in WTIPIR versus Nox2(-/-) IPIR hearts. Selected differentially regulated genes such as ?-catenin, SRPK3, ERDR1, ACIN1, Syntaxin-8, and STC1 were validated by real-time PCR. Taken together, this is the first report identifying important, differentially expressed genes during ischemic preconditioning in Nox2(-/-) mice by using microarray analysis. PMID:22038056

Thirunavukkarasu, Mahesh; Adluri, Ram Sudheer; Juhasz, Bela; Samuel, Samson Mathews; Zhan, Lijun; Kaur, Anupinder; Maulik, Gautam; Sanchez, Juan A; Hager, Janet; Maulik, Nilanjana

2012-08-01

95

Hypoxic preconditioning increases survival and angiogenic potency of peripheral blood mononuclear cells via oxidative stress resistance.  

PubMed

Cell-based angiogenesis is a promising treatment for ischemic diseases; however, the survival of implanted cells is impaired by oxidative stress in the ischemic microenvironment. We tested the hypothesis that hypoxic preconditioning of implanted cells enhances their resistance against oxidative stress, increasing cell survival and angiogenic potency after implantation into ischemic tissue. Mouse peripheral blood mononuclear cells (PBMNCs) were collected and subjected to hypoxic preconditioning by culture for 24 h in 2% O(2) at 33 degrees C. Hypoxic preconditioning of PBMNCs increased the expression of various genes related to antioxidant and survival signals remarkably. Compared with cells cultured under normoxia, the hypoxia-preconditioned PBMNCs showed significantly lower reactive oxygen species (ROS) accumulation and higher cell survival under oxidative stress induced by LY-83583 (a superoxide generator). Three days after intramuscular implantation into the ischemic hindlimbs of mice, survival of the hypoxia-preconditioned PBMNCs was high, whereas that of the normoxia-cultured PBMNCs was relatively low. Furthermore, 28 days after treatment microvessel density and blood flow in the ischemic hindlimbs were significantly better in the mice implanted with hypoxia-preconditioned PBMNCs than in those implanted with normoxia-cultured PBMNCs. Hypoxic preconditioning increased the survival and angiogenic potency of PBMNCs, through oxidative stress resistance mechanisms. PMID:18156196

Kubo, Masayuki; Li, Tao-Sheng; Suzuki, Ryo; Shirasawa, Bungo; Morikage, Noriyasu; Ohshima, Mako; Qin, Shu-Lan; Hamano, Kimikazu

2008-02-01

96

Myocardial ischemic protection in natural mammalian hibernation.  

PubMed

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

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

2015-03-01

97

Hypoxically preconditioned human peripheral blood mononuclear cells improve blood flow in hindlimb ischemia xenograft model.  

PubMed

Transplantation of peripheral blood mononuclear cells (PBMNCs) is a promising therapeutic approach for the treatment of hindlimb ischemia. However, insufficient angiogenesis in ischemic hindlimb after cell transplantation reduces the importance and practicality of this approach. Previously, we demonstrated using mouse models that hypoxic preconditioning augmented the cellular functions of rodent PBMNCs, such as increased cell adhesion capacity and accelerated neovascularization in ischemic hindlimb. To test the clinical application of this therapeutic strategy in this study, we investigated whether the protocol of hypoxic preconditioning, which was established in a condition of 2% O2 for 24 h, can be made available for human PBMNCs (hPBMNCs). In addition, we grafted preconditioned hPBMNCs in a hindlimb ischemia mouse model. Hypoxic preconditioning enhanced cell adhesion capacity and oxidative stress resistance in hPBMNCs. We also observed an up-regulation of platelet endothelial cell adhesion molecule-1 (PECAM-1) in hPBMNCs by hypoxic preconditioning. Furthermore, preconditioned hPBMNCs significantly recovered limb blood flow in ischemic mice after transplantation. These results indicate that our established preconditioning protocol is available for hPBMNCs to effectively reinforce multiple cellular functions. Taken together with our series of study, we believe that this simple but powerful therapeutic strategy will be helpful in curing patients with severe hindlimb ischemia. PMID:25360221

Kudo, Tomoaki; Kubo, Masayuki; Katsura, Shunsaku; Nishimoto, Arata; Ueno, Koji; Samura, Makoto; Fujii, Yasuhiko; Hosoyama, Tohru; Hamano, Kimikazu

2014-01-01

98

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

SciTech Connect

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 +}.

Chiueh, C.C. [School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan (China) and Laboratory of Clinical Science, NIMH, NIH, Bethesda, MD 20892-1264 (United States)]. E-mail: chiueh@tmu.edu.tw; Andoh, Tsugunobu [Department of Applied Pharmacology, Toyama Medical and Pharmaceutical University (Japan); Chock, P. Boon [Laboratory of Biochemistry, NHLBI, NIH, Bethesda, MD 20892-8012 (United States)

2005-09-01

99

Nitric Oxide Synthase (NOS) Does Not Contribute to Simulated Ischaemic Preconditioning in an Isolated Rat Cardiomyocyte Model  

Microsoft Academic Search

It is widely accepted that nitric oxide (NO) is a trigger and mediator of late ischaemic preconditioning (IP), however its\\u000a role in classic (protection observed within 2–4 hours after the IP stimulus) IP is less certain. In addition, the contribution\\u000a of cardiomyocyte nitric oxide synthase (NOS) activation to NO production in ischaemia is unknown. The aim of this study was

Hans Strijdom; Sonia Genade; Amanda Lochner

2004-01-01

100

Pre-ischemic exercise alleviates oxidative damage following ischemic stroke in rats  

PubMed Central

Physical exercise has been proved to be neuroprotective in clinical trials and animal experiments. However, the exact mechanism underlying this neuroprotective effect remains unclear. The aim of the present study was to explore whether pre-ischemic treadmill training could act as a form of ischemic preconditioning in a rat following ischemic stroke by reducing oxidative damage. Fifty-four rats were randomly divided into three groups (n=18 per group): Sham surgery, middle cerebral artery occlusion (MCAO) without exercise and MCAO with exercise. Subsequent to treadmill training, ischemic stroke was induced by occluding the MCA for 1.5 h, followed by reperfusion. Six rats in each group were evaluated for neurological deficits and then sacrificed by decapitation to calculate the infarct volume. The remaining rats in each group were sacrificed to detect the level of superoxide dismutase (SOD) activity (n=6) and malondialdehyde (MDA) concentration (n=6). The results indicated that pre-ischemic exercise training reduced brain infarct volume and neurological deficits, increased SOD activity and decreased the concentration of MDA following ischemic stroke. In conclusion, treadmill exercise training prior to MCAO/reperfusion increased the antioxidant ability and decreased the oxidative damage in the brain subsequent to ischemic stroke. PMID:25187848

FENG, RUI; ZHANG, MIN; WANG, XIAO; LI, WEN-BIN; REN, SHI-QING; ZHANG, FENG

2014-01-01

101

From rapid to delayed and remote postconditioning: the evolving concept of ischemic postconditioning in brain ischemia.  

PubMed

Ischemic postconditioning is a concept originally defined to contrast with that of ischemic preconditioning. While both preconditioning and postconditioning confer a neuroprotective effect on brain ischemia, preconditioning is a sublethal insult performed in advance of brain ischemia, and postconditioning, which conventionally refers to a series of brief occlusions and reperfusions of the blood vessels, is conducted after ischemia/reperfusion. In this article, we first briefly review the history of preconditioning, including the experimentation that initially uncovered its neuroprotective effects and later revealed its underlying mechanisms-of-action. We then discuss how preconditioning research evolved into that of postconditioning--a concept that now represents a broad range of stimuli or triggers, including delayed postconditioning, pharmacological postconditioning, remote postconditioning--and its underlying protective mechanisms involving the Akt, MAPK, PKC and K(ATP) channel cell-signaling pathways. Because the concept of postconditioning is so closely associated with that of preconditioning, and both share some common protective mechanisms, we also discuss whether a combination of preconditioning and postconditioning offers greater protection than preconditioning or postconditioning alone. PMID:22204317

Zhao, Heng; Ren, Chuancheng; Chen, Xingmiao; Shen, Jiangang

2012-02-01

102

Mobile IPMobile IP Mobile IPMobile IP  

E-print Network

Mobile IPMobile IP #12;2 Mobile IPMobile IP · How do we support mobile users whose point of attachment to the network changes dynamically? #12;3 Mobile IPMobile IP · The goal of Mobile IP is to allow connectivity automatically, despite the change. · While Mobile IP can work with wired connections, where you

Yeom, Ikjun

103

SIP Server VoIP UA IP  

E-print Network

SIP Server UA UA IP VoIP UA IP 1 1 Transport Layer Security (TLS) SIP server TLS Client TLS TLS Client VoIP SRTP SIP server TLS Client TLS SRTP .2> Skype (Skype Trunk) skype server skype ( Skype Client ) skype 20 20 VoIP Option

104

The neuroprotective effects of isoflurane preconditioning in a murine transient global cerebral ischemia-reperfusion model: the role of the Notch signaling pathway.  

PubMed

Inhalational anesthetic preconditioning can induce neuroprotective effects, and the notch signaling pathway plays an important role in neural progenitor cell differentiation and the inflammatory response after central nervous system injury. This study evaluated whether the neuroprotective effect of isoflurane preconditioning is mediated by the activation of the notch signaling pathway. Mice were divided into two groups consisting of those that did or did not receive preconditioning with isoflurane. The expression levels of notch-1, notch intracellular domain (NICD), and hairy and enhancer of split (HES-1) were measured in mice subjected to transient global cerebral ischemia-reperfusion injury. The notch signaling inhibitor DAPT and conditional notch-RBP-J knockout mice were used to investigate the mechanisms of isoflurane preconditioning-induced neuroprotection. Immunohistochemical staining, real-time polymerase chain reaction assays, and Western blotting were performed. Isoflurane preconditioning induced neuroprotection against global cerebral ischemia. Preconditioning up-regulated the expression of notch-1, HES-1, and NICD after ischemic-reperfusion. However, these molecules were down-regulated at 72 h after ischemic-reperfusion. The inhibition of notch signaling activity by DAPT significantly attenuated the isoflurane preconditioning-induced neuroprotection, and similar results were obtained using notch knockout mice. Our results demonstrate that the neuroprotective effects of isoflurane preconditioning are mediated by the pre-activation of the notch signaling pathway. PMID:24197755

Zhang, Hao-peng; Sun, Yan-yan; Chen, Xiao-mei; Yuan, Li-bang; Su, Bin-xiao; Ma, Rui; Zhao, Rui-ni; Dong, Hai-long; Xiong, Lize

2014-03-01

105

Preconditioning improves function and recovery of single muscle fibers during severe hypoxia and reoxygenation.  

PubMed

Reperfusion following prolonged ischemia induces cellular damage in whole skeletal muscle models. Ischemic preconditioning attenuates the deleterious effects. We tested whether individual skeletal muscle fibers would be similarly affected by severe hypoxia and reoxygenation (H/R) in the absence of extracellular factors and whether cellular damage could be alleviated by hypoxic preconditioning. Force and free cytosolic Ca2+ ([Ca2+]c) were monitored in Xenopus single muscle fibers (n = 24) contracting tetanically at 0.2 Hz during 5 min of severe hypoxia and 5 min of reoxygenation. Twelve cells were preconditioned by a shorter bout of H/R 1 h before the experimental trial. In preconditioned cells, force relative to initial maximal values (P/P(o)) and relative peak [Ca2+]c fell (P < 0.05) during 5 min of hypoxia and recovered during reoxygenation. In contrast, P/P(o) and relative peak [Ca2+]c fell more during hypoxia (P < 0.05) and recovered less during reoxygenation (P < 0.05) in control cells. The ratio of force to [Ca2+]c was significantly higher in the preconditioned cells during severe hypoxia, suggesting that changes in [Ca2+]c were not solely responsible for the loss in force. We conclude that 1) isolated skeletal muscle fibers contracting in the absence of extracellular factors are susceptible to H/R injury associated with changes in Ca2+ handling; and 2) hypoxic preconditioning improves contractility, Ca2+ handling, and cell recovery during subsequent hypoxic insult. PMID:11401836

Kohin, S; Stary, C M; Howlett, R A; Hogan, M C

2001-07-01

106

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

Microsoft Academic Search

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

K R Francis; L Wei

2010-01-01

107

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

PubMed

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

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

2015-04-01

108

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

PubMed Central

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

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

2014-01-01

109

Effects of diabetes on myocardial infarct size and cardioprotection by preconditioning and postconditioning  

PubMed Central

In spite of the current optimal therapy, the mortality of patients with ischemic heart disease (IHD) remains high, particularly in cases with diabetes mellitus (DM) as a co-morbidity. Myocardial infarct size is a major determinant of prognosis in IHD patients, and development of a novel strategy to limit infarction is of great clinical importance. Ischemic preconditioning (PC), postconditioning (PostC) and their mimetic agents have been shown to reduce infarct size in experiments using healthy animals. However, a variety of pharmacological agents have failed to demonstrate infarct size limitation in clinical trials. One of the possible reasons for the discrepancy between the results of animal experiments and clinical trials is that co-morbidities, including DM, modified myocardial responses to ischemia/reperfusion and to cardioprotective agents. Here we summarize observations of the effects of DM on myocardial infarct size and ischemic PC and PostC and discuss perspectives for protection of DM hearts. PMID:22694800

2012-01-01

110

Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury.  

PubMed

Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (?2-AR) agonist, protects against kidney I/R injury. Sprague-Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 ?g/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 ?g/kg). The effects of Dex postconditiong (Dex 1 or 10 ?g/kg i.v. after reperfusion) as well as the effects of peripheral ?2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre- nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning. PMID:25505591

Lempiäinen, Juha; Finckenberg, Piet; Mervaala, Elina E; Storvik, Markus; Kaivola, Juha; Lindstedt, Ken; Levijoki, Jouko; Mervaala, Eero M

2014-06-01

111

PVM and IP multicast  

SciTech Connect

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.

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

1996-12-01

112

Persimmon leaf flavonoid induces brain ischemic tolerance in mice.  

PubMed

The persimmon leaf has been shown to improve cerebral ischemic outcomes; however, its mechanism of action remains unclear. In this study, mice were subjected to 10 minutes of ischemic preconditioning, and persimmon leaf flavonoid was orally administered for 5 days. Results showed that the persimmon leaf flavonoid significantly improved the content of tissue type plasminogen activator and 6-keto prostaglandin-F1 ? in the cerebral cortex, decreased the content of thromboxane B2, and reduced the content of plasminogen activator inhibitor-1 in mice. Following optical microscopy, persimmon leaf flavonoid was also shown to reduce cell swelling and nuclear hyperchromatism in the cerebral cortex and hippocampus of mice. These results suggested that persimmon leaf flavonoid can effectively inhibit brain thrombosis, improve blood supply to the brain, and relieve ischemia-induced pathological damage, resulting in brain ischemic tolerance. PMID:25206432

Miao, Mingsan; Zhang, Xuexia; Wang, Linan

2013-05-25

113

Persimmon leaf flavonoid induces brain ischemic tolerance in mice?  

PubMed Central

The persimmon leaf has been shown to improve cerebral ischemic outcomes; however, its mechanism of action remains unclear. In this study, mice were subjected to 10 minutes of ischemic preconditioning, and persimmon leaf flavonoid was orally administered for 5 days. Results showed that the persimmon leaf flavonoid significantly improved the content of tissue type plasminogen activator and 6-keto prostaglandin-F1 ? in the cerebral cortex, decreased the content of thromboxane B2, and reduced the content of plasminogen activator inhibitor-1 in mice. Following optical microscopy, persimmon leaf flavonoid was also shown to reduce cell swelling and nuclear hyperchromatism in the cerebral cortex and hippocampus of mice. These results suggested that persimmon leaf flavonoid can effectively inhibit brain thrombosis, improve blood supply to the brain, and relieve ischemia-induced pathological damage, resulting in brain ischemic tolerance. PMID:25206432

Miao, Mingsan; Zhang, Xuexia; Wang, Linan

2013-01-01

114

Preconditioning Results in S-Nitrosylation of Proteins Involved in Regulation of Mitochondrial Energetics and Calcium Transport  

Microsoft Academic Search

Nitric oxide has been shown to be an important signaling messenger in ischemic preconditioning (IPC). Accordingly, we investigated whether protein S-nitrosylation occurs in IPC hearts and whether S-nitrosoglutathione (GSNO) elicits similar effects on S-nitrosylation and cardioprotection. Preceding 20 minutes of no-flow ischemia and reperfusion, hearts from C57BL\\/6J mice were perfused in the Langendorff mode and subjected to the following conditions:

Junhui Sun; Meghan Morgan; Rong-Fong Shen; Charles Steenbergen; Elizabeth Murphy

2009-01-01

115

Strategies to promote donor cell survival: combining preconditioning approach with stem cell transplantation  

PubMed Central

Stem cell transplantation has emerged as a potential modality in cardiovascular therapeutics due to their inherent characteristics of self-renewal, unlimited capacity for proliferation and ability to cross lineage restrictions and adopt different phenotypes. Constrained by extensive death in the unfriendly milieu of ischemic myocardium, the results of heart cell therapy in experimental animal models as well as clinical studies have been less than optimal. Several factors which play a role in early cell death after engraftment in the ischemic myocardium include; absence of survival factors in the transplanted heart, disruption of cell-cell interaction coupled with loss of survival signals from matrix attachments, insufficient vascular supply and elaboration of inflammatory cytokines resulting from ischemia and/or cell death. This article reviews various signaling pathways involved in triggering highly complex forms of cell death and provides critical appreciation of different novel anti-death strategies developed from the knowledge gained from using an ischemic preconditioning approach. The use of pharmacological preconditioning for up-regulation of pro-survival proteins and cardiogenic markers in the transplanted stem cells will be discussed. PMID:18561945

Haider, Husnain Kh; Ashraf, Muhammad

2008-01-01

116

Laser thermal preconditioning enhances dermal wound repair  

Microsoft Academic Search

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 (lambda

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

2008-01-01

117

Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA  

PubMed Central

We have shown that the cellular process of macroautophagy plays a protective role in HL-1 cardiomyocytes subjected to simulated ischemia/reperfusion (sI/R) (Hamacher-Brady et al. in J Biol Chem 281(40):29776–29787). Since the nucleoside adenosine has been shown to mimic both early and late phase ischemic preconditioning, a potent cardioprotective phenomenon, the purpose of this study was to determine the effect of adenosine on autophagosome formation. Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles, and can be monitored by imaging the incorporation of microtubule-associated light chain 3 (LC3) fused to a fluorescent protein (GFP or mCherry) into nascent autophagosomes. We investigated the effect of adenosine receptor agonists on autophagy and cell survival following sI/R in GFP-LC3 infected HL-1 cells and neonatal rat cardiomyocytes. The A1 adenosine receptor agonist 2-chloro-N(6)-cyclopentyl-adenosine (CCPA) (100 nM) caused an increase in the number of autophagosomes within 10 min of treatment; the effect persisted for at least 300 min. A significant inhibition of autophagy and loss of protection against sI/R measured by release of lactate dehydrogenase (LDH), was demonstrated in CCPA-pretreated cells treated with an A1 receptor antagonist, a phospholipase C inhibitor, or an intracellular Ca(+2) chelator. To determine whether autophagy was required for the protective effect of CCPA, autophagy was blocked with a dominant negative inhibitor (Atg5K130R) delivered by transient transfection (in HL-1 cells) or protein transduction (in adult rat cardiomyocytes). CCPA attenuated LDH release after sI/R, but protection was lost when autophagy was blocked. To assess autophagy in vivo, transgenic mice expressing the red fluorescent autophagy marker mCherry-LC3 under the control of the alpha myosin heavy chain promoter were treated with CCPA 1 mg/kg i.p. Fluorescence microscopy of cryosections taken from the left ventricle 30 min after CCPA injection revealed a large increase in the number of mCherry-LC3-labeled structures, indicating the induction of autophagy by CCPA in vivo. Taken together, these results indicate that autophagy plays an important role in mediating the cardioprotective effects conferred by adenosine pretreatment. PMID:19242639

Yitzhaki, Smadar; Huang, Chengqun; Liu, Wayne; Lee, Youngil; Gustafsson, Åsa B.; Mentzer, Robert M.

2013-01-01

118

Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype.  

PubMed

TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily released by microglia, appears to be involved in the induction of apoptosis following focal brain ischemia. Indeed, brain ischemia is associated with progressive enlargement of damaged areas and prominent inflammation. As ischemic preconditioning reduces inflammatory response to brain ischemia and ameliorates brain damage, the purpose of the present study was to evaluate the role of TRAIL and its receptors in stroke and ischemic preconditioning and to propose, by modulating TRAIL pathway, a new therapeutic strategy in stroke. In order to achieve this aim a rat model of harmful focal ischemia, obtained by subjecting animals to 100 min of transient occlusion of middle cerebral artery followed by 24 h of reperfusion and a rat model of ischemic preconditioning in which the harmful ischemia was preceded by 30 mins of tMCAO, which represents the preconditioning protective stimulus, were used. Results show that the neuroprotection elicited by ischemic preconditioning occurs through both upregulation of TRAIL decoy receptors and downregulation of TRAIL itself and of its death receptors. As a counterproof, immunoneutralization of TRAIL in tMCAO animals resulted in significant restraint of tissue damage and in a marked functional recovery. Our data shed new light on the mechanisms that propagate ongoing neuronal damage after ischemia in the adult mammalian brain and provide new molecular targets for therapeutic intervention. Strategies aimed to repress the death-inducing ligands TRAIL, to antagonize the death receptors, or to activate the decoy receptors open new perspectives for the treatment of stroke. PMID:25032854

Cantarella, G; Pignataro, G; Di Benedetto, G; Anzilotti, S; Vinciguerra, A; Cuomo, O; Di Renzo, G F; Parenti, C; Annunziato, L; Bernardini, R

2014-01-01

119

NMDA preconditioning attenuates cortical and hippocampal seizures induced by intracerebroventricular quinolinic acid infusion.  

PubMed

Searching for new therapeutic strategies through modulation of glutamatergic transmission using effective neuroprotective agents is essential. Glutamatergic excitotoxicity is a common factor to neurodegenerative diseases and acute events such as cerebral ischemia, traumatic brain injury, and epilepsy. This study aimed to evaluate behavioral and electroencephalographic (EEG) responses of mice cerebral cortex and hippocampus to subconvulsant and convulsant application of NMDA and quinolinic acid (QA), respectively. Moreover, it aimed to evaluate if EEG responses may be related to the neuroprotective effects of NMDA. Mice were preconditioned with NMDA (75 mg/kg, i.p.) and EEG recordings were performed for 30 min. One day later, QA was injected (36.8 nmol/site) and EEG recordings were performed during 10 min. EEG analysis demonstrated NMDA preconditioning promotes spike-wave discharges (SWDs), but it does not display behavioral manifestation of seizures. Animals that were protected by NMDA preconditioning against QA-induced behavioral seizures, presented higher number of SWD after NMDA administration, in comparison to animals preconditioned with NMDA that did display behavioral seizures after QA infusion. No differences were observed in latency for the first seizure or duration of seizures. EEG recordings after QA infusion demonstrated there were no differences in the number of SWD, latency for the first seizure or duration of seizures in animals pretreated with saline or in animals preconditioned by NMDA that received QA. A negative correlation was identified between the number of NMDA-induced SWD and QA-induced seizures severity. These results suggest a higher activation during NMDA preconditioning diminishes mice probability to display behavioral seizures after QA infusion. PMID:23184648

Vandresen-Filho, Samuel; Hoeller, Alexandre A; Herculano, Bruno A; Duzzioni, Marcelo; Duarte, Filipe S; Piermartiri, Tetsadê C B; Boeck, Carina C; de Lima, Thereza C M; Marino-Neto, José; Tasca, Carla I

2013-07-01

120

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

PubMed

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

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

2014-07-01

121

Hypercholesterolemia Abrogates Late Preconditioning via a Tetrahydrobiopterin-Dependent Mechanism in Conscious Rabbits  

PubMed Central

Background Although the late phase of ischemic preconditioning (PC) is known to confer cardioprotection in healthy animal models, it is unknown whether this phenomenon exists in the presence of hypercholesterolemia. The goal of this study was to determine whether the infarct-sparing effect of late PC is affected by hypercholesterolemia and, if so, whether a tetrahydrobiopterin (BH4)-dependent mechanism is responsible for the loss of late PC. Methods and Results Conscious rabbits fed a normal diet or a 1% cholesterol diet for 6 weeks were subjected to ischemic PC (six 4-minute coronary occlusion/4-minute reperfusion cycles) and, 24 hours later, underwent a 30-minute occlusion followed by 3 days of reperfusion. A total of 125 rabbits were used. In normocholesterolemic rabbits, ischemic PC reduced infarct size, an effect that was abrogated by administration of the BH4 synthesis inhibitor N-acetylserotonin (15 mg/kg IV) before the 30-minute occlusion. In hypercholesterolemic rabbits, however, ischemic PC failed to reduce infarct size. Myocardial BH4 levels in the ischemic zone increased 24 hours after ischemic PC in normocholesterolemic rabbits but not in hypercholesterolemic rabbits. In addition, in normocholesterolemic rabbits, pretreatment with N-acetylserotonin completely abolished the ischemic PC-induced increase in myocardial BH4 levels. Conclusions This study demonstrates that (1) hypercholesterolemia abrogates both the infarct-sparing effect of late PC and the concomitant upregulation of myocardial BH4, and (2) inhibition of myocardial BH4 synthesis in the absence of hypercholesterolemia is sufficient to abolish the infarct-sparing effect of late PC. The results support the concept that hypercholesterolemia abrogates late PC by preventing the upregulation of BH4, an essential cofactor for inducible nitric oxide synthase. PMID:16186416

Tang, Xian-Liang; Takano, Hitoshi; Xuan, Yu-Ting; Sato, Hiroshi; Kodani, Eitaro; Dawn, Buddhadeb; Zhu, Yanqing; Shirk, Gregg; Wu, Wen-Jian; Bolli, Roberto

2013-01-01

122

Preconditioning with hyperbaric oxygen induces tolerance against oxidative injury via increased expression of heme oxygenase-1 in primary cultured spinal cord neurons.  

PubMed

Hyperbaric oxygen (HBO) preconditioning can induce ischemic tolerance in the spinal cord. The effect can be attenuated by the administration of an oxygen free radical scavenger or by inhibition of antioxidant enzymes. However, the mechanism underlying HBO preconditioning of neurons against ischemic injury remains enigmatic. Therefore, in the present study primary cultured spinal cord neurons were treated with HBO and then subjected to a hydrogen peroxide (H(2)O(2)) insult. The results show that H(2)O(2) stimulation of the cultured spinal neurons caused severe DNA damage and decreased cell viability, and that these neurons were well protected against damage after a single exposure to HBO preconditioning (0.35 MPa, 98% O(2), 37 degrees C, 2 h). The protective effect started 4 h after pretreatment and lasted for at least 24 h. The cultured neurons after HBO treatment also exhibited increased heme oxygenase-1 (HO-1) expression at both the protein and mRNA levels, which paralleled the protective effect of HBO. Treatment with tin-mesoporphyrin IX (SnMP), a specific HO-1 inhibitor, before HBO pretreatment abolished the HBO-induced adaptive protection noted in the cultured spinal neurons. In conclusion, HBO preconditioning can protect primary cultured spinal cord neurons against oxidative stress, and the upregulation of HO-1 expression plays an essential role in HBO induced preconditioning effect. PMID:17291539

Li, Qingbo; Li, Jinsheng; Zhang, Lifan; Wang, Bairen; Xiong, Lize

2007-02-27

123

Immunizing Beef Calves: A Preconditioning Immunization Concept  

E-print Network

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

Faries Jr., Floron C.

2000-12-20

124

REGULARIZATION AND PRECONDITIONING OF KKT SYSTEMS ...  

E-print Network

Technical Report MS-07-004, August 31th, 2007. Abstract. .... We provide the spectral analysis of the preconditioned system and show that the condition number ...... More insight into these failures, first we note that the linear algebra phase is.

2007-08-30

125

40 CFR 1065.518 - Engine preconditioning.  

Code of Federal Regulations, 2014 CFR

...Specified Duty Cycles § 1065.518 Engine preconditioning. (a) This section applies for engines where measured emissions are affected by prior operation, such as with a diesel engine that relies on urea-based...

2014-07-01

126

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

PubMed

Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-? (PKC-?), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-? and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-?-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate. PMID:24907601

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

2014-08-22

127

[Molecular mechanisms of ischemic-reperfusion syndrome and its personalized therapy].  

PubMed

Cardiovascular pathologies are the major causes of morbidity and mortality in the world. Cessation of the blood flow in large vessels, supplying tissues with oxygen and substrates, leads to ischemic conditions accompanied by unwanted shifts of oxidative metabolism and rise of the reactive oxygen species (ROS) generation. Small amounts of ROS are essential elements of the cell metabolism, however pathological elevation of ROS jeopardizes the survival of cells, organs and even organisms. Paradoxically, blood flow restoration during prolonged ischemia leads to oxidative stress that is often fatal for a live system. Oxygen paradox appears to be a limiting factor in clinical practice that intuitively seeks for immediate and complete restoration of a damaged blood flow. Mitochondrion is a major ROS source and a key element of pro-apoptotic signaling, however it is clear, that mitochondria are the main target for anti-ischemic treatment. In the present review we consider two ways of such anti-ischemic strategy, bringing ischemic tolerance to the organ through mitochondrial involvement, such as intrinsic, biological, or artificial, pharmacological adaptive systems (preconditioning). The latter is aimed to simulate elements and high efficiency of intrinsic protective system. The role of antioxidants in anti-ischemic therapy and their effects on preconditioning signaling are discussed in the review. PMID:25306686

Grebenchikov, O A; Likhvantsev, V V; Plotnikov, E Iu; Silachev, D N; Pevzner, I B; Zorova, L D; Zorov, D B

2014-01-01

128

Voice over IP Calculator  

NSDL National Science Digital Library

The Voice over IP Calculator Web site actually consists of four free online tools that can be used to estimate bandwidth requirements and voice paths for a planned VoIP system. The four tools are: Lines and IP Bandwidth Calculator, Erlangs and Bandwidth Calculator, Minutes and Lines Calculator, and Erlangs and Lines Calculator. Each utility is very easy to use, but is mainly intended for experienced IT workers.

129

Pharmacological Preconditioning of Mesenchymal Stem Cells with Trimetazidine (1-[2,3,4-Trimethoxybenzyl]piperazine) Protects Hypoxic Cells against Oxidative Stress and Enhances Recovery of Myocardial Function in Infarcted Heart through Bcl-2 Expression  

PubMed Central

Stem cell transplantation is a possible therapeutic option to repair ischemic damage to the heart. However, it is faced with a number of challenges including the survival of the transplanted cells in the ischemic region. The present study was designed to use stem cells preconditioned with trimetazidine (1-[2,3,4-trimethoxybenzyl]piperazine; TMZ), a widely used anti-ischemic drug for treating angina in cardiac patients, to increase the rate of their survival after transplantation. Bone marrow-derived rat mesenchymal stem cells (MSCs) were subjected to a simulated host tissue environment by culturing them under hypoxia (2% O2) and using hydrogen peroxide (H2O2) to induce oxidative stress. MSCs were preconditioned with 10 ?M TMZ for 6 h followed by treatment with 100 ?M H2O2 for 1 h and characterized for their cellular viability and metabolic activity. The preconditioned cells showed a significant protection against H2O2-induced loss of cellular viability, membrane damage, and oxygen metabolism accompanied by a significant increase in HIF-1?, survivin, phosphorylated Akt (pAkt), and Bcl-2 protein levels and Bcl-2 gene expression. The therapeutic efficacy of the TMZ-preconditioned MSCs was evaluated in an in vivo rat model of myocardial infarction induced by permanent ligation of left anterior descending coronary artery. A significant increase in the recovery of myocardial function and up-regulation of pAkt and Bcl-2 levels were observed in hearts transplanted with TMZ-preconditioned cells. This study clearly demonstrated the potential benefits of pharmacological preconditioning of MSCs with TMZ for stem cell therapy for repairing myocardial ischemic damage. PMID:19218529

Wisel, Sheik; Khan, Mahmood; Kuppusamy, M. Lakshmi; Mohan, I. Krishna; Chacko, Simi M.; Rivera, Brian K.; Sun, Benjamin C.; Hideg, Kálmán; Kuppusamy, Periannan

2009-01-01

130

IP puzzles, probabilistic networking,  

E-print Network

Li Antoine Luu Mike Shea Deepa Srinivasan Jonathan Walpole #12;Outline IP puzzles Motivation Research Fraggle SYN flood Nachi Delode SMTP, TCP, ICMP, UDP, FastTrack, SMB, finger, SSL, SQL, etc. #12;uzzles thwarted by UDP flooding DoS-resistant authentication protocols thwarted by IP flooding Until puzzles

131

Lubiprostone induced ischemic colitis  

PubMed Central

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

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

2013-01-01

132

Preconditioning with levosimendan before implantation of left ventricular assist devices.  

PubMed

In this retrospective study, we investigated the impact of preconditioning of the right ventricle with the calcium sensitizer levosimendan immediately before left ventricular assist device (LVAD) implantation on outcome and survival. Nine consecutive LVAD patients (seven suffering from dilative cardiomyopathy and two from ischemic cardiomyopathy) with echocardiographic and invasive evidence of right heart insufficiency received levosimendan with 0.1 ?g/kg body weight/min for 24 h before implantation of the assist device (seven HeartWare and two Jarvik 2000). Administration of levosimendan was safe and had not to be discontinued in any patient. We observed no relevant side effects. Twelve-month survival after implantation of the LVAD was 89% representing a superior outcome compared with the fifth INTERMACS registry data with 75% survival. Two temporary extracorporeal membrane-oxygenation implantations were necessary due to intraoperative right ventricular dysfunction. Only one patient died 5 weeks after LVAD implantation of multiorgan failure, five patients were successfully transplanted, and three patients underwent LVAD implantation for destination therapy. Levosimendan might improve clinical outcome and survival when used as pretreatment in patients with right heart insufficiency prior to LVAD implantation. However, we recommend a larger controlled trial in the future to confirm our preliminary results. PMID:24147881

Theiss, Hans D; Grabmaier, Ulrich; Kreissl, Nicole; Hagl, Christian; Steinbeck, Gerhard; Sodian, Ralf; Franz, Wolfgang-M; Kaczmarek, Ingo

2014-03-01

133

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

PubMed Central

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

2013-01-01

134

Isoflurane preconditioning reduces oxygen-glucose deprivation-induced neuronal injury via B-cell lymphoma 2 protein  

PubMed Central

A brief exposure to isoflurane prior to brain ischemia reduces ischemic brain injury in rodents. Here we showed that exposure of rat cerebral cortical neuronal cultures to 2% isoflurane for 30 min at 24 h before a 2-h oxygen-glucose deprivation (OGD) reduced the OGD-induced cell injury. This effect was abolished by HA14-1, a selective inhibitor of B-cell lymphoma 2 (Bcl-2) protein. Bcl-2 is well-known for its anti-apoptotic property. HA14-1 alone did not change OGD-induced cell injury. OGD reduced the expression of Bcl-2 in these neurons. This reduction was attenuated by isoflurane preconditioning. These results suggest that isoflurane preconditioning-induced neuroprotection is mediated by Bcl-2. PMID:21359097

Gwak, Mi-Sook; Cao, Lin; Li, Liaoliao; Zuo, Zhiyi

2010-01-01

135

Preconditioning the Helmholtz Equation for Rigid Ducts  

NASA Technical Reports Server (NTRS)

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

Baumeister, Kenneth J.; Kreider, Kevin L.

1998-01-01

136

Cisco 7900 Series IP Phone Cisco 7900 Series IP Phone  

E-print Network

Cisco 7900 Series IP Phone #12;Cisco 7900 Series IP Phone #12;Cisco 7900 Series IP Phone Main Menu a party from a Conference 13. Idivert 14. Call Forward All 15. Call Park 16. Cisco Call Manager Web Page 17. Additional Assistance #12;Cisco 7900 Series IP Phone Phone Parts Main Menu #12;Cisco 7900 Series

137

IPS User's Guide  

Microsoft Academic Search

IntroductionIPS[2] is an interactive, trace driven performance measurement system for parallel and distributedprograms. It runs on DECstation, Sun, Vax, Sequent Symmetry, and Cray Y-MP computers(or a heterogeneous combination of these computers). IPS provides a large amount of performancedata about the execution of a parallel program, and this information is organized hierarchicallyso that access to it is easy and intuitive.Performance data

Barton P. Miller; Bruce Irvin; Hi Low; Jeff Hollingsworth

1989-01-01

138

Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion  

PubMed Central

Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP). We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS), and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline) brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests that in vivo measurement of brain temperature could help to identify whether ischemic tissue survives. PMID:23091367

Sun, Zhihua; Zhang, Jing; Chen, Yingmin; Zhang, Yunting; Zhang, Xuejun; Guo, Hong; Yu, Chunshui

2012-01-01

139

Revealing Preconditions for Trustful Collaboration in CSCL  

ERIC Educational Resources Information Center

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,…

Gerdes, Anne

2010-01-01

140

Protein Kinase C Isoform Diversity in Preconditioning  

Microsoft Academic Search

Protein kinase C (PKC) appears to be a common intracellular effector and signal collector during cardiac preconditioning; however, it remains unknown whether agonists that activate different PKC isoforms are also linked to select aspects of myocardial protection. Using agonists that are known to activate unique combinations of PKC isoforms, we interogated the relationship between isoform activation and the different aspects

Daniel R. Meldrum; Joseph C. Cleveland; Xianzhong Meng; Brett C. Sheridan; Fabia Gamboni; Brian S. Cain; Alden H. Harken; Anirban Banerjee

1997-01-01

141

Original article Preconditioning treatment maintains taste characteristic  

E-print Network

fruits immediately after harvest and prior to cold storage at 20 °C for 24­48 h in special chambers aimed fruit during this 40-day cold- storage period. Preconditioned and control fruit were also segregated maintained their sensory characteristics longer than control fruit during this 40-day cold-storage period

Crisosto, Carlos H.

142

Preconditioned Parallel MLFMA Solution of Metamaterial Structures  

E-print Network

Preconditioned Parallel MLFMA Solution of Metamaterial Structures Levent Gürel, �zgür Ergül, Tahir, Bilkent, Ankara, Turkey E-mail: lgurel@bilkent.edu.tr Since metamaterials display unusual electromagnetic issue. The metamaterial structures considered in this study consist of split-ring resonators (SRRs

Gürel, Levent

143

Preconditioning and tolerance against cerebral ischaemia  

PubMed Central

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

Dirnagl, Ulrich; Becker, Kyra; Meisel, Andreas

2009-01-01

144

Ischemic Stroke and Neuroprotection  

PubMed Central

Stroke is a major cause of morbidity and mortality in both developed and developing countries of the world. Greater understanding of the pathophysiology of neuronal damage in ischemic stroke has generated interest in neuroprotection as a management strategy. This paper aims to review the current concept and place of neuroprotection in ischemic stroke. An extensive search of all materials related to the topic was made using library sources including Pubmed and Medline searches. Current research findings were also included. The findings are as presented. Neuroprotection is an increasingly recognized management strategy in ischemic stroke that promises to assist clinicians in reducing stroke mortality rates and improving the quality of life of survivors. PMID:23439855

Onwuekwe, IO; Ezeala-Adikaibe, B

2012-01-01

145

Review of IP multimedia subsystem  

Microsoft Academic Search

The IP Multimedia Subsystem (IMS) defines a network that has an all-IP core. This enables it to provide convergence across multimedia applications. Legacy networks like PSTN, PLMN are being rapidly phased out and an all-IP based flat network is close to realization. Nevertheless, legacy networks stil form an important part of Telecommunication domain. The IP Multimedia Subsystem supports such legacy

M. Sayyad; N. Ansari; S. Burli; H. Shah; A. Khatanhar

2011-01-01

146

Ischemic Colitis Revealing Polyarteritis Nodosa  

PubMed Central

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

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

2013-01-01

147

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

PubMed Central

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

Delgado-Roche, Livan; Hernández-Matos, Yanet; Medina, Emilio A.; Morejón, Dalia Á.; González, Maité R.; Martínez-Sánchez, Gregorio

2014-01-01

148

Microarray Analyses of Genes Regulated by Isoflurane Anesthesia In Vivo: A Novel Approach to Identifying Potential Preconditioning Mechanisms  

PubMed Central

Background While general anesthetics are recognized for their potential to render patients unconscious during surgery, exposure can also lead to long-term outcomes of both cellular damage and protection. As regards the latter, delayed anesthetic preconditioning is an evolutionarily conserved physiological response that has the potential for protecting against ischemic injury in a number of tissues. While it is known that delayed preconditioning requires de novo protein synthesis, knowledge of anesthetic-regulated genes is incomplete. In this study we used the conserved nature of preconditioning to analyze differentially regulated genes in three different rat tissues. We hypothesized that by selecting those genes regulated in multiple tissues, we could develop a focused list of gene candidates potentially involved in delayed anesthetic preconditioning. Methods Young adult male Sprague Dawley rats were anesthetized with a 2% isoflurane/98% air mixture for 90 min. Immediately after anesthetic exposure, animals were killed and liver, kidney and heart were removed and total RNA was isolated. Differential gene expression was determined using rat oligonucleotide gene arrays. Array data were analyzed to select for genes that were significantly regulated in multiple tissues. Results All three tissues showed differentially regulated genes in response to a clinically relevant exposure to isoflurane. Analysis of coordinately regulated genes yielded a focused list of 34 potential gene candidates with a range of ontologies including regulation of inflammation, modulation of apoptosis, regulation of ion gradients and maintenance of energy pathways. Conclusions We conclude that, through using an analysis approach focusing on coordinately regulated genes, we were able to generate a focused list of interesting gene candidates with potential to enable future preconditioning studies. PMID:23400992

Edmands, Scott D; Hall, Adam C.; LaDow, Eva

2012-01-01

149

Hypoxic-Ischemic Neonatal Encephalopathy: Animal Experiments for Neuroprotective Therapies  

PubMed Central

Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+)-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult. PMID:23533962

Ikenoue, Tsuyomu

2013-01-01

150

Ischemic conditioning: the challenge of protecting the diabetic heart  

PubMed Central

The successful clinical translation of novel therapeutic strategies to attenuate lethal myocardial ischemia-reperfusion injury and limit infarct size has been identified as a major unmet need, and is of particular importance in patients with type-2 diabetes. There is a wealth of preclinical evidence that ischemic conditioning (encompassing the three paradigms of preconditioning, postconditioning and remote conditioning) is profoundly cardioprotective and, via up-regulation of endogenous signaling cascades, renders the heart resistant to infarction. However, current phase II trials aimed at exploiting ischemic conditioning for the clinical treatment of myocardial ischemia-reperfusion injury have yielded mixed results, possibly reflecting the emerging concern that the efficacy of conditioning-induced cardioprotection may be compromised in the diabetic heart. Our goal in this review is to provide a summary of our present understanding of the effect of type-2 diabetes on the infarct-sparing effect of ischemic conditioning, and the challenges of limiting ischemia-reperfusion injury in the diabetic heart. PMID:25414825

Wider, Joseph

2014-01-01

151

Ischemic Nerve Block.  

ERIC Educational Resources Information Center

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…

Williams, Ian D.

152

Preconditioning with Endoplasmic Reticulum Stress Ameliorates Endothelial Cell Inflammation  

PubMed Central

Endoplasmic Reticulum (ER) stress, caused by disturbance in ER homeostasis, has been implicated in several pathological conditions such as ischemic injury, neurodegenerative disorders, metabolic diseases and more recently in inflammatory conditions. Our present study aims at understanding the role of ER stress in endothelial cell (EC) inflammation, a critical event in the pathogenesis of acute lung injury (ALI). We found that preconditioning human pulmonary artery endothelial cells (HPAEC) to ER stress either by depleting ER chaperone and signaling regulator BiP using siRNA, or specifically cleaving (inactivating) BiP using subtilase cytotoxin (SubAB), alleviates EC inflammation. The two approaches adopted to abrogate BiP function induced ATF4 protein expression and the phosphorylation of eIF2?, both markers of ER stress, which in turn resulted in blunting the activation of NF-?B, and restoring endothelial barrier integrity. Pretreatment of HPAEC with BiP siRNA inhibited thrombin-induced I?B? degradation and its resulting downstream signaling pathway involving NF-?B nuclear translocation, DNA binding, phosphorylation at serine536, transcriptional activation and subsequent expression of adhesion molecules. However, TNF?-mediated NF-?B signaling was unaffected upon BiP knockdown. In an alternative approach, SubAB-mediated inactivation of NF-?B was independent of I?B? degradation. Mechanistic analysis revealed that pretreatment of EC with SubAB interfered with the binding of the liberated NF-?B to the DNA, thereby resulting in reduced expression of adhesion molecules, cytokines and chemokines. In addition, both knockdown and inactivation of BiP stimulated actin cytoskeletal reorganization resulting in restoration of endothelial permeability. Together our studies indicate that BiP plays a central role in EC inflammation and injury via its action on NF-?B activation and regulation of vascular permeability. PMID:25356743

Leonard, Antony; Paton, Adrienne W.; El-Quadi, Monaliza; Paton, James C.; Fazal, Fabeha

2014-01-01

153

Preserving Symmetry in Preconditioned Krylov Subspace Methods  

NASA Technical Reports Server (NTRS)

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.

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

1996-01-01

154

Preconditioning Stem Cells for In Vivo Delivery  

PubMed Central

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

Sart, Sébastien; Ma, Teng

2014-01-01

155

M-step preconditioned conjugate gradient methods  

NASA Technical Reports Server (NTRS)

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.

Adams, L.

1983-01-01

156

On polynomial preconditioning for indefinite Hermitian matrices  

NASA Technical Reports Server (NTRS)

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.

Freund, Roland W.

1989-01-01

157

Preconditioning, organ preservation, and postconditioning to prevent ischemia-reperfusion injury to the liver.  

PubMed

Ischemia and reperfusion lead to injury of the liver. Ischemia-reperfusion injury is inevitable in liver transplantation and trauma and, to a great extent, in liver resection. This article gives an overview of the mechanisms involved in this type of injury and summarizes protective and treatment strategies in clinical use today. Intervention is possible at different time points: during harvesting, during the period of preservation, and during implantation. Liver preconditioning and postconditioning can be applied in the transplant setting and for liver resection. Graft optimization is merely possible in the period between the harvest and the implantation. Given that there are 3 stages in which a surgeon can intervene against ischemia-reperfusion injury, we have structured the review as follows. The first section reviews the approaches using surgical interventions, such as ischemic preconditioning, as well as pharmacological applications. In the second section, static organ preservation and machine perfusion are addressed. Finally, the possibility of treating the recipient or postconditioning is discussed. PMID:19790166

de Rougemont, Olivier; Lehmann, Kuno; Clavien, Pierre-Alain

2009-10-01

158

CISCO IP 7902 FONCTIONS TLPHONIQUES  

E-print Network

CISCO IP 7902 FONCTIONS T�L�PHONIQUES FONCTIONS DE BASE FAIRE UN APPEL Soulever le combiné et participants. Mettre un terme à une conférence Raccrocher le combiné. . Cisco_IP_7902_FR_CM%207.0_2009324[1].doc 1 de 2 #12;CISCO IP 7902 FONCTIONS T�L�PHONIQUES Cisco_IP_7902_FR_CM%207.0_2009324[1].doc 2 de 2

Charette, André

159

Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: the Involvement of Autophagy  

PubMed Central

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

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

2013-01-01

160

Approximate polynomial preconditioning applied to biharmonic equations on vector supercomputers  

NASA Technical Reports Server (NTRS)

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.

Wong, Yau Shu; Jiang, Hong

1987-01-01

161

Preconditioning and the limit to the incompressible flow equations  

NASA Technical Reports Server (NTRS)

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

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

1993-01-01

162

Protein Redox Modification as a Cellular Defense Mechanism against Tissue Ischemic Injury  

PubMed Central

Protein oxidative or redox modifications induced by reactive oxygen species (ROS) or reactive nitrogen species (RNS) not only can impair protein function, but also can regulate and expand protein function under a variety of stressful conditions. Protein oxidative modifications can generally be classified into two categories: irreversible oxidation and reversible oxidation. While irreversible oxidation usually leads to protein aggregation and degradation, reversible oxidation that usually occurs on protein cysteine residues can often serve as an “on and off” switch that regulates protein function and redox signaling pathways upon stress challenges. In the context of ischemic tolerance, including preconditioning and postconditioning, increasing evidence has indicated that reversible cysteine redox modifications such as S-sulfonation, S-nitrosylation, S-glutathionylation, and disulfide bond formation can serve as a cellular defense mechanism against tissue ischemic injury. In this review, I highlight evidence of cysteine redox modifications as protective measures in ischemic injury, demonstrating that protein redox modifications can serve as a therapeutic target for attenuating tissue ischemic injury. Prospectively, more oxidatively modified proteins will need to be identified that can play protective roles in tissue ischemic injury, in particular, when the oxidative modifications of such identified proteins can be enhanced by pharmacological agents or drugs that are available or to be developed. PMID:24883175

Yan, Liang-Jun

2014-01-01

163

Protection of the ischemic myocardium during the reperfusion: between hope and reality  

PubMed Central

The heart is an organ that requires an important energy input to ensure its contractile function. Myocardial ischemia happens when there is a deficiency of blood flow that is responsible for the passage from an aerobic to anaerobic metabolism. Myocardial ischemia results from an imbalance between inputs and the needs of nutrient and oxygen to the myocardium. The restoration of myocardial perfusion called reperfusion is a way to save the ischemic myocardium. However, although reperfusion is beneficial for the survival of the ischemic myocardium, it also induces a deleterious effect in addition to that of ischemic stress. Three decade ago, while several studies, strived to elucidate the protective effect of preconditioning, a phenomenon performed before ischemia and having a powerful protective effects against ischemia/reperfusion injury, very few have believed in the possibility of protecting the myocardium after ischemia (during reperfusion). Actually, both ischemic and pharmacological postconditioning as well as controlled reperfusion methods to protect the ischemic heart have proved effective in the reduction of damage related to ischemia/reperfusion. The possibility of protecting the myocardium during reperfusion opens a new area in the research against damage caused by ischemia/reperfusion because these methods are easily transferable in a clinic setting. PMID:22937492

Bopassa, Jean Chrisostome

2012-01-01

164

Intramyocardial Infusion of FGF1 Mimics Ischemic Preconditioning in Pig Myocardium  

Microsoft Academic Search

Previous studies on the mRNA and protein level suggested a cardioprotective role of FGF-1. These presumed actions of FGF-1 and FGF-2, as well as the underlying mechanisms, were investigated in this study. Human recombinant FGF-1 (0.5?g\\/ml, 20?l\\/min) and FGF-2 (2?g\\/ml) were applied by means of direct intramyocardial infusion (IM) for 60 min prior to a 60 min LAD-occlusion and 120

Patrik Htun; Wulf D. Ito; Imo E. Hoefer; Jutta Schaper; Wolfgang Schaper

1998-01-01

165

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

PubMed Central

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

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

2014-01-01

166

SUMO and ischemic tolerance.  

PubMed

Hibernating squirrels slow blood flow to a crawl, but sustain no damage to brain or other tissues. This phenomenon provides an excellent model of natural tolerance to ischemia. Small ubiquitin-like modifier (SUMO) is a 100-residue peptide that modifies other proteins by being attached to the epsilon amino group of specific lysine residues. The discovery of massive SUMOylation (by both SUMO-1 and SUMO-2/3) occurring in the brains of 13-lined ground squirrels (Ictidomys tridecemlineatus) during hibernation torpor had opened the door to the studies on SUMO and ischemic tolerance reviewed here. Ischemic stress was shown to increase the levels of SUMO conjugation, especially SUMO-2/3, mostly during reperfusion in animal models and during restoration of oxygen and glucose in cell culture systems. Over-expression or depletion of SUMOs and/or Ubc9 (the SUMO E2 conjugating enzyme) increases or decreases (respectively) the levels of SUMO conjugates. Elevated global SUMO conjugations were shown to cytoprotect from ischemic insults; conversely, depressed SUMOylation sensitized cells. Global protein conjugation not only by SUMOs, but also by other ubiquitin-like modifiers (ULMs) including NEDD8, ISG15, UFM1 and FUB1 was shown to be significantly increased in the brains of hibernating ground squirrels during torpor. These increases in multiple ULM conjugations may orchestrate the cellular events in hibernating ground squirrels that induce a state of natural tolerance through their multipronged effects. Certain miRNAs such as the miR-200 family and the miR-182 family were shown, at least partly, to control the levels of these ULM conjugations. Lowering the levels of these miRNAs leads to an increase in global SUMOylation/ULM conjugation, thereby providing the tolerance to ischemia. This suggests that these miRNAs may be good targets for therapeutic intervention in stroke. PMID:23775726

Lee, Yang-ja; Hallenbeck, John M

2013-12-01

167

Remote preconditioning, perconditioning, and postconditioning: a comparative study of their cardioprotective properties in rat models  

PubMed Central

OBJECTIVE: Ischemia reperfusion injury is partly responsible for the high mortality associated with induced myocardial injury and the reduction in the full benefit of myocardial reperfusion. Remote ischemic preconditioning, perconditioning, and postconditioning have all been shown to be cardioprotective. However, it is still unknown which one is the most beneficial. To examine this issue, we used adult male Wistar rat ischemia reperfusion models to compare the cardioprotective effect of these three approaches applied on double-sided hind limbs. METHODS: The rats were randomly distributed to the following five groups: sham, ischemia reperfusion, remote preconditioning, remote perconditioning, and remote post-conditioning. The ischemia/reperfusion model was established by sternotomy followed by a 30-min ligation of the left coronary artery and a subsequent 3-h reperfusion. Remote conditioning was induced with three 5-min ischemia/5-min reperfusion cycles of the double-sided hind limbs using a tourniquet. RESULTS: A lower early reperfusion arrhythmia score (1.50±0.97) was found in the rats treated with remote perconditioning compared to those in the ischemia reperfusion group (2.33±0.71). Meanwhile, reduced infarct size was also observed (15.27±5.19% in remote perconditioning, 14.53±3.45% in remote preconditioning, and 19.84±5.85% in remote post-conditioning vs. 34.47±7.13% in ischemia reperfusion, p<0.05), as well as higher expression levels of the apoptosis-relevant protein Bcl-2/Bax following global (ischemia/reperfusion) injury in in vivo rat heart models (1.255±0.053 in remote perconditioning, 1.463±0.290 in remote preconditioning, and 1.461±0.541 in remote post-conditioning vs. 1.003±0.159 in ischemia reperfusion, p<0.05). CONCLUSION: Three remote conditioning strategies implemented with episodes of double-sided hind limb ischemia/reperfusion have similar therapeutic potential for cardiac ischemia/reperfusion injury, and remote perconditioning has a greater ability to prevent reperfusion arrhythmia. PMID:23525325

Zhu, Shui-Bo; Liu, Yong; Zhu, Yu; Yin, Gui-Lin; Wang, Rong-Ping; Zhang, Yu; Zhu, Jian; Jiang, Wei

2013-01-01

168

Footprint Analysis: A Shape Analysis that Discovers Preconditions  

E-print Network

Footprint Analysis: A Shape Analysis that Discovers Preconditions Cristiano Calcagno1 , Dino of London Abstract. Existing shape analysis algorithms infer descriptions of data structures at program points, starting from a given precondition. We describe an analysis that does not require any

Yang, Hongseok

169

Nonnegative Mixed-Norm Preconditioning for Microscopy Image Segmentation  

Microsoft Academic Search

Image segmentation in microscopy, especially in interference- based optical microscopy modalities, is notoriously challenging due to inherent optical artifacts. We propose a general algebraic framework for preconditioning microscopy images. It transforms an image that is un- suitable for direct analysis into an image that can be effortlessly seg- mented using global thresholding. We formulate preconditioning as the minimization of nonnegative-constrained

Kang Li; Takeo Kanade

2009-01-01

170

[Ocular ischemic syndrome.  

PubMed

A 76-year-old patient presented with a reduced visual acuity of 0.8. The clinical examination revealed rubeosis iridis and dilated retinal veins. In fluorescein angiography peripheral retinal ischemia could be observed and panretinal laser coagulation was immediately started. A comprehensive internistic counselling on the risk factors particularly for ocular ischemic syndrome was refused by the patient. Over time there was a progression of loss of visual acuity to complete visual loss. Magnetic resonance angiography revealed a profound stenosis of the internal carotid artery with complete closure of the left ophthalmic artery and percutaneous transluminal angioplasty was performed in vascular surgery. PMID:25480566

Abraham, S; Feucht, N; Lohmann, C P; Maier, M

2014-12-01

171

Molecular mechanisms mediating preconditioning following chronic ischemia differ from those in classical second window  

PubMed Central

A major difference between experimental ischemic preconditioning (IPC), induced by brief ischemic episodes, and the clinical situation is that patients generally have repetitive episodes of ischemia. We used a swine model to examine differences in genes regulated by classical second-window IPC (SWOP) [two 10-min episodes of coronary artery occlusion (CAO) followed by 24 h reperfusion] compared with repetitive CAO/reperfusion (RCO), i.e., two 10-min CAO 12 h apart, and to repetitive coronary stenosis (RCS), six episodes of 90 min coronary stenosis 12 h apart (n = 5/group). All three models reduced infarct size by 60–85%, which was mediated by nitric oxide in SWOP but not in the other two models. We employed microarray analyses to discover additional molecular pathways intrinsic to models of repetitive ischemia and different from classical SWOP. There was an 85% homology in gene response between the RCO and RCS models, whereas SWOP was qualitatively different. Both RCO and RCS, but not SWOP, showed downregulation of genes encoding proteins involved in oxidative metabolism and upregulation of genes involved in protein synthesis, unfolded protein response, autophagy, heat shock response, protein secretion, and an activation of the NF-?B signaling pathway. Therefore, the regulated genes mediating IPC with repetitive ischemia differ radically from SWOP both quantitatively and qualitatively, showing that a repetitive pattern of ischemia, rather than the difference between no-flow vs. low-flow ischemia, dictates the genomic response of the heart. These findings illustrate new cardioprotective mechanisms developed by repetitive IPC, which are potentially more relevant to patients with chronic ischemic heart disease, who are subjected to repetitive episodes of ischemia. PMID:20581088

Park, Ji Yeon; Shen, You-Tang; Zhao, Xin; Qiu, Hongyu; Yan, Lin; Tian, Bin; Vatner, Stephen F.; Vatner, Dorothy E.

2010-01-01

172

IP-10 in autoimmune thyroiditis.  

PubMed

The interferon-?-inducible protein 10 (IP-10) was initially identified as a chemokine that is induced by interferon (IFN)-?. 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-?. Under the influence of IFN-?, 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

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

2014-08-01

173

Stroke: transient ischemic attack.  

PubMed

The definitions of transient ischemic attack (TIA) and stroke have evolved with advancements in medical imaging. Approximately one-third of events that last less than 24 hours are associated with new infarctions on modern imaging sequences. These events, previously called apoplexy, are now called strokes. Approximately 10% of patients with TIA will have a stroke within 90 days without urgent evaluation and management; 50% of these events will occur within the first 48 hours. The ABCD(2) and ABCD(3)-I scores are validated measures that can help predict which patients are at greatest risk. With urgent evaluation and management, the rate of stroke after TIA can be reduced by up to 80%. Measures that reduce the rate of recurrence include rapid diagnosis and management of atrial fibrillation, identification and repair of carotid artery stenosis, early antithrombotic management, and use of statins for appropriate patients. Dual antiplatelet management with aspirin and clopidogrel may be useful in the first 30 days after TIA, but these drugs should not be used in combination after that time. Adverse events, including major bleeding and mortality, occur more frequently than with monotherapy with no reduction in ischemic events. Patients also should be encouraged to adopt lifestyle changes, such as regular exercise and weight loss. PMID:24818554

Silver, Brian; Wulf Silver, Rachel

2014-05-01

174

Involvement of SIRT1 in hypoxic down-regulation of c-Myc and ?-catenin and hypoxic preconditioning effect of polyphenols  

SciTech Connect

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 ?-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-1? and down-regulation of c-Myc and ?-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-1? expression but increased c-Myc and ?-catenin expression. SIRT1 was also found to stabilize HIF-1? protein and destabilize c-Myc, ?-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1? and down-regulated c-Myc, PHD2 and ?-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-1? and SIRT1 and down-regulating c-Myc, PHD2, and ?-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-1?, SIRT1, c-Myc, ?-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 ?-catenin ? HIF-1? is up-regulated by down-regulation of c-Myc and ?-catenin expression. ? Polyphenolic SIRT1 activators mimics hypoxic preconditioning.

Hong, Kyung-Soo [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of) [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Park, Jun-Ik [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of)] [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of) [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Dao, Trong Tuan; Oh, Won Keun [BK21 Project Team, College of Pharmacy, Chosun University, Gwangju (Korea, Republic of)] [BK21 Project Team, College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Kang, Chi-Dug, E-mail: kcdshbw@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of)] [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Sun-Hee, E-mail: ksh7738@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of) [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

2012-03-01

175

Maneesh Bakshi The paper discusses the implementation of Voice over IP (VoIP) and IP Multimedia Subsystem services (IMS)  

E-print Network

Maneesh Bakshi The paper discusses the implementation of Voice over IP (VoIP) and IP Multimedia addressed are : Introduction to the working of VoIP and multimedia transmission over wireless.3.2 Interactive TV 2.3.3 PC-TV 2. WiMAX - Quality of Service (QoS)3. VoIP/Multimedia over WiMAX file

Jain, Raj

176

Hyperbaric oxygen preconditioning protects rats against CNS oxygen toxicity.  

PubMed

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

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

2014-06-15

177

The Mitochondria-Targeted Antioxidants and Remote Kidney Preconditioning Ameliorate Brain Damage through Kidney-to-Brain Cross-Talk  

PubMed Central

Background Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. Methodology/Principal Findings We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3? (GSK-3?) in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s) which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3? in brain. Co-cultivation of SkQR1-treated kidney cells with cortical neurons resulted in enchanced phosphorylation of GSK-3? in neuronal cells. Conclusion The results indicate that renal preconditioning and SkQR1-induced brain protection may be mediated through the release of EPO from the kidney. PMID:23272118

Silachev, Denis N.; Isaev, Nikolay K.; Pevzner, Irina B.; Zorova, Ljubava D.; Stelmashook, Elena V.; Novikova, Svetlana V.; Plotnikov, Egor Y.; Skulachev, Vladimir P.; Zorov, Dmitry B.

2012-01-01

178

Integration of multiple memories in sensory preconditioning.  

PubMed

The present study demonstrates that humans' response to a single stimulus (S1) is determined by what follows S1's associates. The experiment used a sensory preconditioning (SPC) design where S1 was associated with both S2 and S3 on separate trials before establishing relationships between these latter stimuli with an outcome or its absence in a second phase. When S2 and S3 were associated with the same consequence, either an outcome or its absence, strong consequence-based responding to S1 was observed in a reaction time test. Participants responded quickly to indicate that the outcome was, or was not, predicted by S1. When S2 predicted the outcome and S3 did not, SPC was weaker although participants were not slower to respond to S1. Implications on the understanding of the mechanisms that allow for the response to S1 to emerge are discussed. PMID:25290440

Craddock, Paul; Renaux, Charlotte; Lefèvre, Françoise; Nelson, James Byron; Molet, Mikael

2014-10-01

179

Ip micro-mobility protocols  

Microsoft Academic Search

Abstract: The IETF Mobile IP Working Group is discussing a number of enhancements to the base protocol to reduce the latency, packet loss... In this article, we discuss a number of "micro-mobility protocols" that extend Mobile IP with fast handoff and paging capabilities. The aim of this article is not to provide an exhaustive survey of these protocols. Rather, we

A. T. Campbell; J. Gomez

2001-01-01

180

Voice Over IP Reference Page  

NSDL National Science Digital Library

This site is a collection of architectural specifications, network and signaling protocols, and technical papers related to virtually every aspect of VoIP. Detailed articles and standards information are regularly updated on the site. There is also a collection of documents containing VoIP references, and in this sections, visitors will find an H.323 tutorial.

181

40 CFR 1065.516 - Sample system decontamination and preconditioning.  

Code of Federal Regulations, 2014 CFR

...PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.516 Sample system decontamination and preconditioning...measure hydrocarbon and PM emissions by sampling purified air or nitrogen. (3) When calculating zero emission levels, apply...

2014-07-01

182

PRECONDITIONING AND PARALLEL IMPLEMENTATION OF IMPLICIT RUNGE-KUTTA METHODS.  

E-print Network

iterative methods, nonlinear equations, ordinary differential equations, parallelism, preconditioning) methods applied to systems of differential equations is to solve the underlying systems of nonlinear equations of IRK methods. A detailed presentation of the new preconditioner i

Jay, Laurent O.

183

Distributed Kalman filtering compared to Fourier domain preconditioned conjugate gradient  

E-print Network

Distributed Kalman filtering compared to Fourier domain preconditioned conjugate gradient for laser of the tomography problem. The second algorithm is the distributed Kalman filter (DKF) developed by Massioni et al

Greer, Julia R.

184

Progress in Parallel Schur Complement Preconditioning for Computational Fluid Dynamics  

NASA Technical Reports Server (NTRS)

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

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

1997-01-01

185

Biological networks in ischemic tolerance - Rethinking the approach to clinical conditioning  

PubMed Central

The adaptive response (conditioning) to environmental stressors evokes evolutionarily conserved programs in uni- and multicellular organisms that result in increased fitness and resistance to stressor induced injury. Although the concept of conditioning has been around for a while, its translation into clinical therapies targeting neurovascular diseases has only recently begun. The slow pace of clinical adoption might be partially explained by our poor understanding of underpinning mechanisms and of the complex responses of the organism to the stressor. At the 2nd Translational Preconditioning Meeting participants engaged in an intense discussion addressing whether the time has come to more aggressively implement clinical conditioning protocols in the treatment of cerebrovascular diseases or whether it would be better to wait until preclinical data would help to minimize clinical empiricism. This review addresses the complex involvement of biological networks in establishing ischemic tolerance at the organism level using two clinically promising conditioning modalities, namely remote ischemic preconditioning, and per- or post-conditioning, as examples. PMID:24223074

Anrather, Josef; Hallenbeck, John M.

2013-01-01

186

Pulsatile reperfusion does not modify global myocardial ischemic injury.  

PubMed

In an attempt to arbitrate the reputed clinical efficacy of pulsatile flow during reperfusion in minimizing ischemic injury, 32 mongrel dogs supported by normothermic cardiopulmonary bypass were subjected to 30 minutes (Groups IC and IP) or 60 minutes (Groups IIC and IIP) of global myocardial ischemia. The effect of pulsatile flow (P) initiated during 30 minutes of reperfusion on the recovery of myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores, coronary blood flow, and myocardial water content (MWC) was compared to the effect of linear reperfusion (C) in another group of animals. ATP stores, which significantly decreased to 43% and 53% of preischemic levels (Groups IC and IP, respectively, p less than 0.01) and 36% and 31% of control values (Groups IIC and IIP, respectively. p less than 0.001), did not increase with either pulsatile or linear reperfusion. CP stores, depleted 97% during ischemia in all groups, returned to preischemic levels regardless of the mode of reperfusion flow. Coronary blood flow measured 30 minutes after aortic unclamping was not significantly different from control flow in any group. MWC significantly decreased during ischemia from 80.5% +/- 0.8% to 76.5% +/- 1.1% in Group IC and from 81.8% +/- 1.2% to 76.8% +/- 0.8% in Groups IP (p less than 0.05) and returned to preischemic levels with reperfusion. However, following 60 minutes of ischemia, pulsatile reperfusion prevented the significant increase in MWC that accrued after linear reperfusion (80.7% +/- 1.5% to 84.0% +/- 0.7%, p less than 0.05). These data indicate that pulsatile reperfusion initiated after an ischemic injury that results in a 50% or greater depletion of myocardial ATP stores does not restore myocardial nucleotide levels or enhance coronary blood flow, although the pathological increase in MWC may be avoided. PMID:6213820

Silverman, N A; Levitsky, S; Kohler, J; Trenkner, M; Feinberg, H

1982-09-01

187

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

PubMed Central

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

2013-01-01

188

Reactive Oxygen Species and Mitochondrial KATP Channels Mediate Helium-Induced Preconditioning Against Myocardial Infarction In Vivo  

PubMed Central

Objectives Helium produces preconditioning by activating prosurvival kinases, but the roles of reactive oxygen species (ROS) or mitochondrial KATP channels in this process are unknown. We tested the hypothesis that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. Design Randomized, prospective study. Setting University research laboratory. Participants Male New Zealand white rabbits. Interventions Rabbits (n=64) were instrumented for measurement of systemic hemodynamics and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion. In separate experimental groups, rabbits (n=7 or 8 per group) were randomly assigned to receive 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before LAD occlusion with or without the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptoproprionyl glycine (2-MPG; 75 mg/kg), or the mitochondrial KATP antagonist 5-hydroxydecanoate (5-HD; 5 mg/kg). Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni's modification of Student's t test. Measurements and Main Results Myocardial infarct size was determined using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium significantly (P<0.05) reduced infarct size (23±4% of the area at risk; mean±SD) compared with control (46±3%). NAC, 2-MPG, and 5-HD did not affect irreversible ischemic injury when administered alone (49±5, 45±6, and 45±3%), but these drugs blocked reductions in infarct size produced by helium (45±4, 45±2, and 44±3%). Conclusions The results suggest that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. PMID:18662630

Pagel, Paul S.; Krolikowski, John G.; Pratt, Phillip F.; Shim, Yon Hee; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

2008-01-01

189

Cardiac Protection by Preconditioning Is Generated via an Iron-Signal Created by Proteasomal Degradation of Iron Proteins  

PubMed Central

Ischemia associated injury of the myocardium is caused by oxidative damage during reperfusion. Myocardial protection by ischemic preconditioning (IPC) was shown to be mediated by a transient ‘iron-signal’ that leads to the accumulation of apoferritin and sequestration of reactive iron released during the ischemia. Here we identified the source of this ‘iron signal’ and evaluated its role in the mechanisms of cardiac protection by hypoxic preconditioning. Rat hearts were retrogradely perfused and the effect of proteasomal and lysosomal protease inhibitors on ferritin levels were measured. The iron-signal was abolished, ferritin levels were not increased and cardiac protection was diminished by inhibition of the proteasome prior to IPC. Similarly, double amounts of ferritin and better recovery after ex vivo ischemia-and-reperfusion (I/R) were found in hearts from in vivo hypoxia pre-conditioned animals. IPC followed by normoxic perfusion for 30 min (‘delay’) prior to I/R caused a reduced ferritin accumulation at the end of the ischemia phase and reduced protection. Full restoration of the IPC-mediated cardiac protection was achieved by employing lysosomal inhibitors during the ‘delay’. In conclusion, proteasomal protein degradation of iron-proteins causes the generation of the ‘iron-signal’ by IPC, ensuing de-novo apoferritin synthesis and thus, sequestering reactive iron. Lysosomal proteases are involved in subsequent ferritin breakdown as revealed by the use of specific pathway inhibitors during the ‘delay’. We suggest that proteasomal iron-protein degradation is a stress response causing an expeditious cytosolic iron release thus, altering iron homeostasis to protect the myocardium during I/R, while lysosomal ferritin degradation is part of housekeeping iron homeostasis. PMID:23155431

Bulvik, Baruch E.; Berenshtein, Eduard; Meyron-Holtz, Esther G.

2012-01-01

190

IP Version 6, Online Version  

NSDL National Science Digital Library

This page offers five videos of lectures from Sam Bowne's IP Version 6 course. Each video varies in length from ten minutes to an hour. These materials would be most useful for individuals with some experience with IP technology; the end goal of the course was for individuals enrolled to gain IPv6 certification and be able to set up IPv6 on a router. Flash is required to view the videos.

Bowne, Sam

191

Architecture of IP Multimedia Subsystem  

Microsoft Academic Search

IP multimedia subsystem (IMS) is standardized network architecture for telecom operators that want to provide mobile and fixed multimedia services. IMS-enabled networks provide access to these services from both IP networks and circuit-switched PSTN\\/PLMNs. This paper describes the IMS architecture and explains its benefits. It concentrates on the main IMS system components and briefly summarizes their key system functions. However,

M. Koukal; R. Bestak

2006-01-01

192

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

SciTech Connect

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.

Yeh, S.H.; Liu, R.S.; Hu, H.H. [National Yang-Ming Medical College (Taiwan, Province of China)] [and others

1994-05-01

193

The ERK1/2 Signaling Pathway Is Involved in Sulfur Dioxide Preconditioning-Induced Protection against Cardiac Dysfunction in Isolated Perfused Rat Heart Subjected to Myocardial Ischemia/Reperfusion  

PubMed Central

Ischemia/reperfusion injury (IRI) occurs frequently during reperfusion of ischemic myocardium, and preconditioning has been regarded as one of the best strategies to prevent myocardial injury during the ischemia/reperfusion process. Our previous studies indicated that a small dose of sulfur dioxide (SO2) used as preconditioning exerts cardioprotection. However, the mechanisms underlying the cardioprotection remain unclear. The present study was designed to examine if the extracellular regulated protein kinases 1/2 (ERK1/2) signaling pathway mediated protection against cardiac dysfunction after SO2 preconditioning in isolated rat hearts subjected to ischemia/reperfusion (I/R). Langendorff heart perfusion was performed in vitro, where 56 male Wistar rats were randomly divided into seven groups: control group, 5 ?mol/L SO2 group (S5), 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) + 5 ?mol/L SO2 (PD98059 + S5) group, PD98059 group, I/R group, 5 ?mol/L SO2 + I/R (S5 + I/R) group and PD98059 + 5 ?mol/L SO2 + I/R (PD98059 + S5 + I/R) group. Cardiac function and myocardial phosphorylated ERK1/2 protein were measured. We found that I/R in isolated rat heart resulted in cardiac dysfunction with a significant increase in phosphorylated ERK1/2 protein. SO2 preconditioning markedly suppressed phosphorylated ERK1/2 protein and improved cardiac function in isolated rat heart with I/R (p < 0.05). However, pre-treatment with PD98059 could prevent the above effects of SO2 preconditioning. In conclusion, SO2 preconditioning protected against cardiac dysfunction in isolated rat heart subjected to I/R via suppression of the over-activation of the ERK1/2 signaling pathway. PMID:24217229

Huang, Pan; Sun, Yan; Yang, Jinyan; Chen, Siyao; Liu, Angie Dong; Holmberg, Lukas; Huang, Xiaomei; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

2013-01-01

194

Inflammation in ischemic stroke subtypes.  

PubMed

Determining the cause of stroke does influence choices for management. categorization of subtypes of ischemic stroke has had considerable study, but definitions are hard to formulate and their application for diagnosis in an individual patient is often problematic. Cerebral ischemia initiates a complex cascade of events at genomic, molecular, and cellular levels, and inflammation is important in this cascade. In 1993 for For the Trial of Org 10172 in Acute Stroke Treatment (TOAST), Adams et al] conducted a placebo-controlled, randomized, blinded study of the low-molecular-weight heparinoid given to patients within 24 hours after stroke and developed a system for diagnosis of subtype of ischemic stroke that uses components of existing diagnostic schemes. The type of acute ischemic stroke was classified according to the TOAST classification: 1) Large Artery AtheroSclerosis (LAAS); 2) CardioEmbolic Infarct (CEI); 3) LACunar infarct (LAC); 4) stroke of Other Determined Etiology (ODE); 5) stroke of UnDetermined Etiology (UDE) (see Fig. (1)). On the basis of pathophysiologic differences of each stroke subtype it's possible to hypothesize a different pattern of immuno-inflammatory activation in relation of ischemic stroke subtype. A nonspecific systemic inflammatory response occurs after both ischemic and hemorrhagic stroke, either as part of the process of brain damage or in response to complications such as deep venous thrombosis. Several studies have reported that higher levels of inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with worse outcome after ischemic stroke. Our group reported that patients with cardioembolic subtype showed significantly higher median plasma levels of TNF-?, IL-6, IL-1? whereas the lacunar subtype showed significantly lower median plasma levels of TNF-?, IL-6 and IL-1?. Our findings underlined the significant association was noted between the severity of neurological deficit at admission, the diagnostic subtype and some inflammatory variables. PMID:22390641

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Arnao, Valentina; Pinto, Antonio; Licata, Giuseppe

2012-01-01

195

IP routing issues in satellite constellation networks  

Microsoft Academic Search

SUMMARY The growth in use of Internet-based applications in recent years has led to telecommunication networks transporting an increasingly large amount of Internet Protocol (IP)-based traffic. Proposed broadband satellite constellation networks, currently under development, will be required to transport IP traffic. A case can be made for implementing IP routing directly within the constellation network, in order to transport IP

L. Wood; A. Clerget; I. Andrikopoulos; G. Pavlou; W. Dabbous

2001-01-01

196

Isoflurane preconditioning protects motor neurons from spinal cord ischemia: its dose-response effects and activation of mitochondrial adenosine triphosphate-dependent potassium channel.  

PubMed

We examined in a rabbit model of transient spinal cord ischemia (SCI) whether isoflurane (Iso) preconditioning induces ischemic tolerance to SCI in a dose-response manner, and whether this effect is dependent on mitochondrial adenosine triphosphate-dependent potassium (K(ATP)) channel. Eighty-six rabbits were randomly assigned to 10 groups: Control group (n=8) received no pretreatment. Ischemic preconditioning (IPC) group (n=8) received 5 min of IPC 30 min before SCI. The Iso 1, Iso 2 and Iso 3 groups (n=10, 9, 8) underwent 30 min of 1.05, 2.1 and 3.15% Iso inhalation commencing 45 min before SCI. The Iso 1HD, Iso 2HD and Iso 3HD groups (n=9, 9, 8) each received a specific mitochondrial K(ATP) channel blocker, 5-hydroxydecanoic acid (5HD, 20mg/kg), 5 min before each respective Iso inhalation. The 5HD group (n=8) received 5HD without Iso inhalation. The sham group (n=9) had no SCI. SCI was produced by infra-renal aortic occlusion via the inflated balloon of a Swan-Ganz catheter for 20 min. The Iso 1, Iso 2 and Iso 3 groups showed a better neurologic outcome and more viable motor nerve cells (VMNCs) in the anterior spinal cord 72 h after reperfusion than the control group (p<0.05). Iso 3 group showed a better neurologic outcome and more VMNCs than Iso 1 group (p<0.05). And, the Iso 1, Iso 2 and Iso 3 groups showed a better neurologic outcome and higher VMNC numbers than the corresponding Iso 1HD, Iso 2HD and Iso 3HD groups (p<0.05). This study demonstrates that Iso preconditioning protects the spinal cord against neuronal damage due to SCI in a dose-response manner via the activation of mitochondrial K(ATP) channels. PMID:16076524

Park, Hee-Pyoung; Jeon, Young-tae; Hwang, Jung-won; Kang, Hoon; Lim, Seung-Woon; Kim, Chong-Sung; Oh, Yong-Seok

2005-10-21

197

Acute ischemic stroke and hyperglycemia.  

PubMed

To increase the comprehension about the profound effects of hyperglycemia within the first 48 hours poststroke on the outcomes of acute ischemic stroke, the authors reviewed multiple studies and literature reviews. Research supports the detrimental effects of hyperglycemia on the morbidity and mortality of patients diagnosed with acute ischemic stroke. The studies that were examined revealed that although further research is necessary, controlling hyperglycemia is overall beneficial to support superior clinical outcomes. The purpose of this article was to discuss the importance of not only glucose control but also the vital role of nurses in controlling glucose levels efficiently and immediately during the first 48 hours poststroke. PMID:24595255

Clark, Margaret E; Payton, Jessica E; Pittiglio, Laura I

2014-01-01

198

Gastrointestinal complications after ischemic stroke.  

PubMed

Ischemic stroke is an important cause of morbidity and mortality, and currently the leading cause of adult disability in developed countries. Stroke is associated with various non-neurological medical complications, including infections and thrombosis. Gastrointestinal complications after stroke are also common, with over half of all stroke patients presenting with dysphagia, constipation, fecal incontinence or gastrointestinal bleeding. These complications are associated with increased hospital length of stay, the development of further complications and even increased mortality. In this article we review the epidemiology, pathophysiology, diagnosis, management and prevention of the most common gastrointestinal complications associated with ischemic stroke. PMID:25214444

Camara-Lemarroy, Carlos R; Ibarra-Yruegas, Beatriz E; Gongora-Rivera, Fernando

2014-11-15

199

Ischemic tolerance in stroke treatment  

PubMed Central

Although outcome after stroke treatment has significantly improved over the last 30 years, there has been no revolutionary breakthrough. Among different combined approaches, systemic thrombolysis in combination with neuroprotection became a favorite research target. Recent studies suggest that transient ischemic attacks may represent a clinical model of such ischemic tolerance; thus, a new focus on this research has emerged. In this review, we show the parallels between ischemia and neuroprotection and discuss the potential therapeutic options that may be opened by this new molecular knowledge. PMID:19814668

Sandu, Nora; Cornelius, Jan; Filis, Andreas; Arasho, Belachew; Perez-Pinzon, Miguel; Schaller, Bernhard

2010-01-01

200

Nanoparticle Pre-Conditioning for Enhanced Thermal Therapies in Cancer  

PubMed Central

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

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

2011-01-01

201

Implementation of Preconditioned Dual-Time Procedures in OVERFLOW  

NASA Technical Reports Server (NTRS)

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.

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

2003-01-01

202

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

PubMed Central

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

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

2014-01-01

203

Clustering of IP3 receptors by IP3 retunes their regulation by IP3 and Ca2+  

PubMed Central

The versatility of Ca2+ signals derives from their spatio-temporal organization1,2. For Ca2+ signals initiated by inositol trisphosphate (IP3) this requires local interactions between IP3 receptors (IP3R)3,4 mediated by their rapid stimulation and slower inhibition4 by cytosolic Ca2+. This allows hierarchical recruitment of Ca2+ release events as the IP3 concentration increases5. Single IP3R respond first, then clustered IP3R open together giving a local Ca2+ puff, and as puffs become more frequent they ignite regenerative Ca2+ waves1,5-9. We demonstrate, using nuclear patch-clamp recording10, that IP3R are initially randomly distributed with an estimated separation of ~1 ?m. Low concentrations of IP3 cause IP3R to aggregate rapidly and reversibly into small clusters of ~4 closely associated IP3R. At resting cytosolic [Ca2+], clustered IP3R open independently, but with lower open probability (Po), shorter open time, and lesser IP3 sensitivity than lone IP3R. Increasing cytosolic [Ca2+] reverses the inhibition caused by clustering, IP3R gating becomes coupled, and the duration of multiple openings is prolonged. Clustering both exposes IP3R to local Ca2+ rises and increases the effects of Ca2+. Dynamic regulation of clustering by IP3 tunes IP3R sensitivity to IP3 and Ca2+, facilitating hierarchical recruitment of the elementary events that underlie all IP3-evoked Ca2+ signals3,5. PMID:19348050

Taufiq-Ur-Rahman; Skupin, Alexander; Falcke, Martin; Taylor, Colin W.

2009-01-01

204

Effect on eNOS/NO Pathway in MIRI rats with preconditioning of GFPC from Dang Gui Si Ni decoction  

PubMed Central

Objective: In order to discover whether the eNOS/NO (endothelial nitric oxide synthase/nitric oxide) pathway is involved in the protective mechanisms of ischemic myocardium of DGSND (Dang Gui Si Ni Decoction) in MIRI (myocardial ischemia-reperfusion injury) SD rats. Materials and Methods: We made I/R (ischemia-reperfusion) model by ligating the left anterior-descending branch of the coronary artery (LAD) for 30 min and releasing the ligature for 120 min. eNOS (nitric oxide synthase) mRNA (message ribonucleic acid) and iNOS (inducible nitric oxide synthase) mRNA were measured by the methods of real-time RT-PCR (Real time Polychainase Chain Reaction), peNOS (phosphorylated eNOS) and iNOS protein were measured by the means of western blot. Results: In PPC group, real-time RT-PCR and western-blot analysis showed that eNOS mRNA and peNOS protein increased markedly (P < 0.05); iNOS mRNA and protein decreased significantly (P < 0.05). Conclusion: These results indicate that ischemic preconditioning (IPC) of GFPC from DGSND plays a protective role in I/R heart through regulating the eNOS/NO signal pathway, which could increase the eNOS gene expression and decrease the expression of iNOS mRNA. PMID:24761117

Qian, Guo-qiang; Peng, Xia; Cai, Chuan; Zhao, Guo-ping

2014-01-01

205

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

PubMed Central

Hyperglycemia dramatically aggravates brain infarct and hemorrhagic transformation (HT) after ischemic stroke. Oxidative stress and matrix metalloproteinases (MMPs) play an important role in the pathophysiology of HT. Hyperbaric oxygen preconditioning (HBO-PC) has been proved to decrease oxidative stress and be neuroprotective in experimental stroke models. The present study determined whether HBO-PC would ameliorate HT by a pre-ischemic increase of reactive oxygen species (ROS) generation, and a suppression of MMP-2 and MMP-9 in hyperglycemic middle cerebral artery occlusion (MCAO) rats. Rats were pretreated with HBO (100% O2, 2.5 atmospheres absolute) 1 h daily for 5 days before MCAO. Acute hyperglycemia was induced by an injection of 50% dextrose. Neurological deficits, infarction volume and hemorrhagic volume were assessed 24 h and 7 days after ischemia. ROS scavenger n-acetyl cysteine (NAC), hypoxia-inducible factor-1? (HIF-1?) inhibitor 2-methoxyestradiol (2ME2) and activator cobalt chloride (CoCl2), and MMPs inhibitor SB-3CT were administrated for mechanism study. The activity of MMP-2 and MMP-9, and the expression HIF-1? were measured. HBO-PC improved neurological deficits, and reduced hemorrhagic volume; the expression of HIF-1? was significantly decreased, and the activity of MMP-2 and MMP-9 was reduced by HBO-PC compared with vehicle group. Our results suggested that HBO-PC attenuated HT via decreasing HIF-1? and its downstream MMP-2 and MMP-9 in hyperglycemic MCAO rats. PMID:23537951

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

2013-01-01

206

Genetic susceptibility to ischemic stroke  

PubMed Central

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

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

2014-01-01

207

On adaptive weighted polynomial preconditioning for Hermitian positive definite matrices  

NASA Technical Reports Server (NTRS)

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.

Fischer, Bernd; Freund, Roland W.

1992-01-01

208

Multigrid Preconditioning for the Overlap Operator in Lattice QCD  

E-print Network

The overlap operator is a lattice discretization of the Dirac operator of quantum chromodynamics, the fundamental physical theory of the strong interaction between the quarks. As opposed to other discretizations it preserves the important physical property of chiral symmetry, at the expense of requiring much more effort when solving systems with this operator. We present a preconditioning technique based on another lattice discretization, the Wilson-Dirac operator. The mathematical analysis precisely describes the effect of this preconditioning in the case that the Wilson-Dirac operator is normal. Although this is not exactly the case in realistic settings, we show that current smearing techniques indeed drive the Wilson-Dirac operator towards normality, thus providing a motivation why our preconditioner works well in computational practice. Results of numerical experiments in physically relevant settings show that our preconditioning yields accelerations of up to one order of magnitude.

James Brannick; Andreas Frommer; Karsten Kahl; Björn Leder; Matthias Rottmann; Artur Strebel

2014-10-27

209

Operator-Based Preconditioning of Stiff Hyperbolic Systems  

SciTech Connect

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.

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

2009-02-09

210

Choice of Variables and Preconditioning for Time Dependent Problems  

NASA Technical Reports Server (NTRS)

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.

Turkel, Eli; Vatsa, Verr N.

2003-01-01

211

Fourier analysis of finite element preconditioned collocation schemes  

NASA Technical Reports Server (NTRS)

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.

Deville, Michel O.; Mund, Ernest H.

1990-01-01

212

Recent Progress in Parallel Schur Complement Preconditioning for Computational Fluid  

NASA Technical Reports Server (NTRS)

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

Barth, Tim; Kwak, Dochan (Technical Monitor)

1997-01-01

213

Time-reversal Waveform Preconditioning for Clutter Rejection T. Varslot,a  

E-print Network

Time-reversal Waveform Preconditioning for Clutter Rejection T. Varslot,a B. Yazici,a C.-E Yarman preconditioning scheme for optimal clutter rejection in radar imaging is presented. Waveform preconditioning for clutter rejection achieves efficient use of power and computational resources by distributing power

Yazici, Birsen

214

White Matter Ischemic Changes in Hyperacute Ischemic Stroke  

PubMed Central

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

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

2015-01-01

215

IP Storage: The Challenge Ahead  

Microsoft Academic Search

Advanced networking technology has led to the genesis of the storage area networkmodel, where host servers can access storage as a service from various devices connectedto the network. While the initial approach to storage area networks has involvedspecialized networking technology, the emergence of Gigabit Ethernet technology hasraised the question of whether we can use commodity IP networks for storage. This

Prasenjit Sarkar; Kaladhar Voruganti

2002-01-01

216

Continuously Connected With Mobile IP  

NASA Technical Reports Server (NTRS)

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.

2002-01-01

217

Minimal preconditioning effects observed for inflation tests of planar tissues.  

PubMed

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

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

2013-11-01

218

Preconditioning Indefinite Systems in Interior Point Methods for Optimization  

Microsoft Academic Search

Every Newton step in an interior-point method for optimization requires a solution of a symmetric indefinite system of linear equations. Most of today's codes apply direct solution methods to perform this task. The use of logarithmic barriers in interior point methods causes unavoidable ill-conditioning of linear systems and, hence, iterative methods fail to provide sufficient accuracy unless appropriately preconditioned. Two

Luca Bergamaschi; Jacek Gondzio; Giovanni Zilli

2004-01-01

219

Preconditioning the Differential Emission Measure (Te) Inverse Problem  

NASA Astrophysics Data System (ADS)

In an inverse problem of any kind, poor conditioning of the inverse operator decreases the numerical stability of any unregularized solution in the presence of data noise. In this paper we show that the numerical stability of the differential emission measure (DEM) inverse problem can be considerably improved by judicious choice of the integral operator. Specifically, we formulate a combinatorial optimization problem where, in a preconditioning step, a subset of spectral lines is selected in such a way as to minimize explicitly the condition number of the discretized integral operator. We tackle this large combinatorial optimization problem using a genetic algorithm. We apply this preconditioning technique to a synthetic data set comprising of solar UV/EUV emission lines in the SOHO SUMER/CDS wavelength range. Following which we test the same hypothesis on lines observed by the Harvard S-055 EUV spectroheliometer. On performing the inversion we see that the temperature distribution in the emitting region of the solar atmosphere is recovered with considerably better stability and smaller error bars when our preconditioning technique is used, in both synthetic and ``real'' cases, even though this involves the analysis of fewer spectral lines than in the ``All-lines'' approach. The preconditioning step leads to regularized inversions that compare favorably to inversions by singular value decomposition, while providing greater flexibility in the incorporation of physically and/or observationally based constraints in the line selection process.

McIntosh, S. W.; Charbonneau, P.; Brown, J. C.

2000-02-01

220

40 CFR 86.232-94 - Vehicle preconditioning.  

Code of Federal Regulations, 2013 CFR

...Medium-Duty Passenger Vehicles; Cold Temperature Test Procedures § 86.232-94 ...fuel fill. The test fuel shall be at a temperature less than or equal to 60 °F. For...certification testing, precondition vehicles at temperatures above 20 °F (?7 °C) and with...

2013-07-01

221

40 CFR 86.232-94 - Vehicle preconditioning.  

Code of Federal Regulations, 2011 CFR

...Medium-Duty Passenger Vehicles; Cold Temperature Test Procedures § 86.232-94 ...fuel fill. The test fuel shall be at a temperature less than or equal to 60 °F. For...certification testing, precondition vehicles at temperatures above 20 °F (?7 °C) and with...

2011-07-01

222

40 CFR 86.232-94 - Vehicle preconditioning.  

Code of Federal Regulations, 2010 CFR

...Medium-Duty Passenger Vehicles; Cold Temperature Test Procedures § 86.232-94 ...fuel fill. The test fuel shall be at a temperature less than or equal to 60 °F. For...certification testing, precondition vehicles at temperatures above 20 °F (?7 °C) and with...

2010-07-01

223

40 CFR 86.232-94 - Vehicle preconditioning.  

Code of Federal Regulations, 2012 CFR

...Medium-Duty Passenger Vehicles; Cold Temperature Test Procedures § 86.232-94 ...fuel fill. The test fuel shall be at a temperature less than or equal to 60 °F. For...certification testing, precondition vehicles at temperatures above 20 °F (?7 °C) and with...

2012-07-01

224

Multilevel Preconditioning for Partition of Unity Methods -Some Analytic Concepts  

E-print Network

basis functions", "web splines", "generalized finite elements" or " smoothed particle hydrodynamics (see e.g. [11]) centering on atomic decompositions related to PUM. While most of the numerical workMultilevel Preconditioning for Partition of Unity Methods - Some Analytic Concepts W. Dahmen, S

225

33 CFR 183.320 - Preconditioning for tests.  

Code of Federal Regulations, 2011 CFR

...Outboard Boats Rated for Engines of 2 Horsepower or Less General § 183.320 Preconditioning...column 6 of Table 4 for the maximum horsepower marked on the boat; less the persons...purpose depends upon the maximum rated horsepower of the boat being tested and is...

2011-07-01

226

33 CFR 183.220 - Preconditioning for tests.  

Code of Federal Regulations, 2012 CFR

...Boats Rated for Engines of More Than 2 Horsepower General § 183.220 Preconditioning...shown in Column 6 of Table 4 for maximum horsepower marked on the boat; less the persons...purpose depends upon the maximum rated horsepower of the boat being tested and is...

2012-07-01

227

33 CFR 183.320 - Preconditioning for tests.  

Code of Federal Regulations, 2010 CFR

...Outboard Boats Rated for Engines of 2 Horsepower or Less General § 183.320 Preconditioning...column 6 of Table 4 for the maximum horsepower marked on the boat; less the persons...purpose depends upon the maximum rated horsepower of the boat being tested and is...

2010-07-01

228

33 CFR 183.220 - Preconditioning for tests.  

Code of Federal Regulations, 2011 CFR

...Boats Rated for Engines of More Than 2 Horsepower General § 183.220 Preconditioning...shown in Column 6 of Table 4 for maximum horsepower marked on the boat; less the persons...purpose depends upon the maximum rated horsepower of the boat being tested and is...

2011-07-01

229

33 CFR 183.320 - Preconditioning for tests.  

Code of Federal Regulations, 2014 CFR

...Outboard Boats Rated for Engines of 2 Horsepower or Less General § 183.320 Preconditioning...column 6 of Table 4 for the maximum horsepower marked on the boat; less the persons...purpose depends upon the maximum rated horsepower of the boat being tested and is...

2014-07-01

230

33 CFR 183.220 - Preconditioning for tests.  

Code of Federal Regulations, 2013 CFR

...Boats Rated for Engines of More Than 2 Horsepower General § 183.220 Preconditioning...shown in Column 6 of Table 4 for maximum horsepower marked on the boat; less the persons...purpose depends upon the maximum rated horsepower of the boat being tested and is...

2013-07-01

231

33 CFR 183.320 - Preconditioning for tests.  

Code of Federal Regulations, 2013 CFR

...Outboard Boats Rated for Engines of 2 Horsepower or Less General § 183.320 Preconditioning...column 6 of Table 4 for the maximum horsepower marked on the boat; less the persons...purpose depends upon the maximum rated horsepower of the boat being tested and is...

2013-07-01

232

33 CFR 183.220 - Preconditioning for tests.  

Code of Federal Regulations, 2014 CFR

...Boats Rated for Engines of More Than 2 Horsepower General § 183.220 Preconditioning...shown in Column 6 of Table 4 for maximum horsepower marked on the boat; less the persons...purpose depends upon the maximum rated horsepower of the boat being tested and is...

2014-07-01

233

33 CFR 183.320 - Preconditioning for tests.  

Code of Federal Regulations, 2012 CFR

...Outboard Boats Rated for Engines of 2 Horsepower or Less General § 183.320 Preconditioning...column 6 of Table 4 for the maximum horsepower marked on the boat; less the persons...purpose depends upon the maximum rated horsepower of the boat being tested and is...

2012-07-01

234

Preconditions of Change in Schools (FISK). Project Number 6051.  

ERIC Educational Resources Information Center

Preliminary results of this study of the preconditions for pedagogical change in Swedish schools indicate that national curricular emphases have changed, but that accompanying changes in teaching methods may conceal wide variation in content and import. The study's objective was to identify the factors conducive or hostile to change in the…

Svingby, Gunilla

1981-01-01

235

Approximate Schur Complement Preconditioning of the Lowest Order Nodal Discretizations  

E-print Network

Approximate Schur Complement Preconditioning of the Lowest Order Nodal Discretizations J. David moments, making the nodal discretization naturally compatible with the various homogenization techniques\\Gamma 1 2 and \\Deltay j = y j+ 1 2 \\Gamma y j \\Gamma 1 2 . 1.1 The Nodal Discretization Common to all

236

Two-level Overlapping Schwarz Preconditioning of Nodal Discontinuous  

E-print Network

Two-level Overlapping Schwarz Preconditioning of Nodal Discontinuous Galerkin Discretizations method for solving unstructured nodal discontinuous Galerkin discretizations of the indefinite Helmholtz in the subdomain solves as the order of the elements increases. In this paper, we detail the discretization

Olson, Luke

237

Renalase Protects against Ischemic AKI  

PubMed Central

Elevated levels of plasma catecholamines accompany ischemic AKI, possibly contributing the inflammatory response. Renalase, an amine oxidase secreted by the proximal tubule, degrades circulating catecholamines and reduces myocardial necrosis, suggesting that it may protect against renal ischemia reperfusion injury. Here, mice subjected to renal ischemia reperfusion injury had significantly lower levels of renalase in the plasma and kidney compared with sham-operated mice. Consistent with this, plasma NE levels increased significantly after renal ischemia reperfusion injury. Furthermore, renal tubular inflammation, necrosis, and apoptosis were more severe and plasma catecholamine levels were higher in renalase-deficient mice subjected to renal ischemia reperfusion compared with wild-type mice. Administration of recombinant human renalase reduced plasma catecholamine levels and ameliorated ischemic AKI in wild-type mice. Taken together, these data suggest that renalase protects against ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation, and that plasma renalase might be a biomarker for AKI. Recombinant renalase therapy may have potential for the prevention and treatment of AKI. PMID:23393318

Kim, Joo Yun; Kim, Mihwa; Wang, Peili; Tang, Lieqi; Baroni, Sara; D’Agati, Vivette D.; Desir, Gary V.

2013-01-01

238

Renalase protects against ischemic AKI.  

PubMed

Elevated levels of plasma catecholamines accompany ischemic AKI, possibly contributing the inflammatory response. Renalase, an amine oxidase secreted by the proximal tubule, degrades circulating catecholamines and reduces myocardial necrosis, suggesting that it may protect against renal ischemia reperfusion injury. Here, mice subjected to renal ischemia reperfusion injury had significantly lower levels of renalase in the plasma and kidney compared with sham-operated mice. Consistent with this, plasma NE levels increased significantly after renal ischemia reperfusion injury. Furthermore, renal tubular inflammation, necrosis, and apoptosis were more severe and plasma catecholamine levels were higher in renalase-deficient mice subjected to renal ischemia reperfusion compared with wild-type mice. Administration of recombinant human renalase reduced plasma catecholamine levels and ameliorated ischemic AKI in wild-type mice. Taken together, these data suggest that renalase protects against ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation, and that plasma renalase might be a biomarker for AKI. Recombinant renalase therapy may have potential for the prevention and treatment of AKI. PMID:23393318

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

2013-02-01

239

CISCO IP 7906/7911 FONCTIONS TLPHONIQUES  

E-print Network

CISCO IP 7906/7911 FONCTIONS T�L�PHONIQUES FONCTIONS DE BASE FAIRE UN APPEL · Soulever le combiné sur la touche Cisco_IP_7906_7911_Fr_CUCM_V7.0_20090320[1].doc 1 de 6 #12;CISCO IP 7906/7911 FONCTIONS T�L�PHONIQUES CONF�RENCE LISTE Lorsque vous êtes en appel

Charette, André

240

CISCO IP 7905-7912 FONCTIONS TLPHONIQUES  

E-print Network

CISCO IP 7905-7912 FONCTIONS T�L�PHONIQUES FONCTIONS DE BASE FAIRE UN APPEL · Soulever le combiné numéros erronés. Cisco_IP_7905_7912_Fr_CUCM_V7.0_20090320[1].doc 1 de 6 #12;CISCO IP 7905-7912 FONCTIONS

Charette, André

241

Cisco IP 7935/7936 FONCTIONS TLPHONIQUES  

E-print Network

Cisco IP 7935/7936 FONCTIONS T�L�PHONIQUES Légende des touches de fonctions 1 Modèle de l surbrillance dans le menu. 6 Touches interactives Permet de sélectionner les touches interactives. #12;Cisco IP la sonnerie et le contraste. #12;Cisco IP 7935/7936 FONCTIONS T�L�PHONIQUES Légende des touches

Charette, André

242

Inactivation of astroglial NF-?B promotes survival of retinal neurons following ischemic injury  

PubMed Central

Reactive astrocytes have been implicated in neuronal loss following ischemic stroke. However, the molecular mechanisms associated with this process are yet to be fully elucidated. In this work, we tested the hypothesis that astroglial NF-?B, a key regulator of inflammatory responses, is a contributor to neuronal death following ischemic injury. We compared neuronal survival in the ganglion cell layer after retinal ischemia-reperfusion in wild type and in GFAP-I?B?-dn transgenic mice, where the NF-?B classical pathway is suppressed specifically in astrocytes. The GFAP-I?B?-dn mice showed significantly increased survival of neurons in the ganglion cell layer following ischemic injury as compared to WT littermates. Neuroprotection was associated with significantly reduced expression of pro-inflammatory genes, encoding Tnf-?, Ccl2 (Mcp1), Cxcl10 (IP10), Icam1, Vcam1, several subunits of NADPH oxidase and NO synthase in the retinas of GFAP-I?B?-dn mice. These data suggest that certain NF-?B-regulated pro-inflammatory and redox-active pathways are central to glial neurotoxicity induced by ischemic injury. The inhibition of these pathways in astrocytes may represent a feasible neuroprotective strategy for retinal ischemia and stroke. PMID:19614983

Dvoriantchikova, Galina; Barakat, David; Brambilla, Roberta; Agudelo, Christian; Hernandez, Eleut; Bethea, John R.; Shestopalov, Valery I.; Ivanov, Dmitry

2009-01-01

243

POPULATION ECOLOGY Population Dynamics of Ips pini and Ips grandicollis in Red Pine  

E-print Network

POPULATION ECOLOGY Population Dynamics of Ips pini and Ips grandicollis in Red Pine Plantations pini (Say) and Ips grandicollis (Eichhoff). The predominant predators obtained were Thanasimus dubius-killingspeciesisthepine engraver, Ips pini (Say). Adult males select weakened trees as hosts and attract females; their brood

Erbilgin, Nadir

244

Echocardiographic assessment of ischemic mitral regurgitation.  

PubMed

Ischemic mitral regurgitation is an important consequence of LV remodeling after myocardial infarction. Echocardiographic diagnosis and assessment of ischemic mitral regurgitation are critical to gauge its adverse effects on prognosis and to attempt to tailor rational treatment strategy. There is no single approach to the echocardiographic assessment of ischemic mitral regurgitation: standard echocardiographic measures of mitral regurgitation severity and of LV dysfunction are complemented by assessments of displacement of the papillary muscles and quantitative indices of mitral valve deformation. Development of novel approaches to understand mitral valve geometry by echocardiography may improve understanding of the mechanism, clinical trajectory, and reparability of ischemic mitral regurgitation. PMID:25416497

Dudzinski, David M; Hung, Judy

2014-01-01

245

Design and Implementation of the lwIP TCP\\/IP Stack  

Microsoft Academic Search

Abstract lwIP is an implementation of the TCP\\/IP protocol stack. The focus of the lwIP stack is to reduce memory usage and code size, making lwIP suitable for use in small clients with very limited resources such as embedded systems. In order to reduce processing and memory demands, lwIP uses a tailor made API that does not require any data

Adam Dunkels

246

Ethernet\\/IP-industrial protocol  

Microsoft Academic Search

DeviceNet and ControlNet are two well known industrial networks based on the CIP protocol (CIP = Control and Information Protocol). Both networks have been developed by Rockwell Automation, but are now owned and maintained by the two manufacturers organizations ODVA (Open DeviceNet Vendors Association) and ControlNet International. ODVA and ControlNet International have introduced the newest member of this family-Ethernet\\/IP (\\

P. Brooks

2001-01-01

247

Lawrence Ip Vazirani Class #2  

E-print Network

Lawrence Ip Vazirani Class #2 Friday September 8 2000 Hilbert Spaces, Tensor Products and Quan­ tum Circuits 1 Inner Products Let V be a vector space. An inner product on V is a map (\\Delta; \\Delta) : V \\Theta V ! C such that: ffl (v; v) â?? 0 ffl v 6= 0 ) (v; v) ? 0 ffl (ffu + fiv; w) = ff(u; w) + fi(v; w

Vazirani, Umesh

248

Mobile-ip Aeronautical Network Simulation Study  

NASA Technical Reports Server (NTRS)

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.

Ivancic, William D.; Tran, Diepchi T.

2001-01-01

249

Repetitive hypoxic preconditioning induces an immunosuppressed B cell phenotype during endogenous protection from stroke  

PubMed Central

Background Repetitive hypoxic preconditioning (RHP) creates an anti-inflammatory phenotype that protects from stroke-induced injury for months after a 2-week treatment. The mechanisms underlying long-term tolerance are unknown, though one exposure to hypoxia significantly increased peripheral B cell representation. For this study, we sought to determine if RHP specifically recruited B cells into the protected ischemic hemisphere, and whether RHP could phenotypically alter B cells prior to stroke onset. Methods Adult, male SW/ND4 mice received RHP (nine exposures over 2 weeks; 8 to 11 % O2; 2 to 4 hours) or identical exposures to 21 % O2 as control. Two weeks following RHP, a 60-minute transient middle cerebral artery occlusion was induced. Standard techniques quantified CXCL13 mRNA and protein expression. Two days after stroke, leukocytes were isolated from brain tissue (70:30 discontinuous Percoll gradient) and profiled on a BD-FACS Aria flow cytometer. In a separate cohort without stroke, sorted splenic CD19+ B cells were isolated 2 weeks after RHP and analyzed on an Illumina MouseWG-6 V2 Bead Chip. Final gene pathways were determined using Ingenuity Pathway Analysis. Student’s t-test or one-way analysis of variance determined significance (P?ischemic hemisphere, RHP increased B cell representation by attenuating the diapedesis of monocyte, macrophage, neutrophil and T cells, to quantities indistinguishable from the uninjured, contralateral hemisphere. Pre-stroke splenic B cells isolated from RHP-treated mice had >1,900 genes differentially expressed by microarray analysis. Genes related to B-T cell interactions, including antigen presentation, B cell differentiation and antibody production, were profoundly downregulated. Maturation and activation were arrested in a cohort of B cells from pre-stroke RHP-treated mice while regulatory B cells, a subset implicated in neurovascular protection from stroke, were upregulated. Conclusions Collectively, our data characterize an endogenous neuroprotective phenotype that utilizes adaptive immune mechanisms pre-stroke to protect the brain from injury post-stroke. Future studies to validate the role of B cells in minimizing injury and promoting central nervous system recovery, and to determine whether B cells mediate an adaptive immunity to systemic hypoxia that protects from subsequent stroke, are needed. PMID:24485041

2014-01-01

250

Management of ischemic optic neuropathies  

PubMed Central

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

Hayreh, Sohan Singh

2011-01-01

251

Ozone oxidative preconditioning inhibits renal fibrosis induced by ischemia and reperfusion injury in rats  

PubMed Central

Ischemia and reperfusion injury (IRI) is a crucial contributor to the development of renal fibrosis. Ozone has been proposed as a novel medical therapy for various conditions, including organ IRI. The aim of this study was to investigate whether ozone oxidative preconditioning (OzoneOP) has a beneficial effect in preventing the development of renal fibrosis following IRI. Sprague Dawley rats were subjected to 45 min of ischemia followed by 8 weeks of reperfusion. Prior to surgery, rats in the OzoneOP group were treated with ozone and those in the IRI and Sham groups were untreated. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. To assess tissue fibrosis, Masson’s trichrome staining was performed. Immunohistochemistry was also performed to determine the localization of ?-smooth muscle actin (?-SMA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to analyze the expression of transforming growth factor (TGF)-?1, ?-SMA and Smad7. The levels of BUN and Cr did not significantly differ between groups. Rats pretreated with ozone showed markedly less interstitial fibrosis than untreated rats following IRI. In addition, immunohistochemistry revealed that ?-SMA expression was attenuated in the OzoneOP group compared with the IRI group. RT-qPCR and western blot analysis showed that OzoneOP inhibited the IRI-induced increases in ?-SMA and TGF-?1 expression levels, and that the IRI-induced reduction in the expression of Smad7 was inhibited in the OzoneOP group. The results indicate that OzoneOP has beneficial effects on ischemic renal fibrosis. OzoneOP may exert its protective effects by a mechanism involving modulation of the TGF-?1/Smad7 pathway. PMID:25371729

WANG, LEI; CHEN, HUI; LIU, XIU-HENG; CHEN, ZHI-YUAN; WENG, XIAO-DONG; QIU, TAO; LIU, LIN; ZHU, HENG-CHENG

2014-01-01

252

Hyperbaric oxygen preconditioning attenuates hyperglycemia enhanced hemorrhagic transformation after transient MCAO in rats  

PubMed Central

Background Hemorrhagic transformation (HT) can be a devastating complication of ischemic stroke. Hyperbaric oxygen preconditioning (HBO-PC) has been shown to improve blood-brain barrier (BBB) permeability in stroke models. The purpose of this study is to examine whether HBO-PC attenuates HT after focal cerebral ischemia, and to investigate whether the mechanism of HBO-PC against HT includes up-regulation of antioxidants in hyperglycemic rats. Methods Male Sprague-Dawley rats (280-320 g) were divided into the following groups: sham, middle cerebral artery occlusion (MCAO) for 2 h, and MCAO treated with HBO-PC. HBO-PC was conducted giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at every 24 h interval for 5 days. At 24 h after the last session of HBO-PC, rats received an injection of 50% glucose (6 ml/kg intraperitoneally) and were subjected to MCAO 15 min later. At 24 h after MCAO, neurological behavior tests, infarct volume, blood-brain barrier permeability, and hemoglobin content were measured to evaluate the effect of HBO-PC. Western blot analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was evaluated at multiple time-points before and after MCAO. Results HBO-PC improved neurological behavior test, and reduced infarction volume, HT and Evans blue extravasation in the ipsilateral hemisphere at 24 h after MCAO. Western blot analysis failed to demonstrate up-regulation of Nrf2 in HBO-PC group before and after MCAO. Paradoxically, HBO-PC decreased HO-1 expression at 24 h after MCAO, as compared with htMCAO group. Conclusions HBO-PC improved neurological deficits, infarction volume, BBB disruption, and HT after focal cerebral ischemia. However, its mechanism against focal cerebral ischemia and HT may not include activation of Nrf2 and subsequent HO-1 expression. PMID:22494892

2012-01-01

253

Role of uncoupling protein 3 in ischemia-reperfusion injury, arrhythmias, and preconditioning  

PubMed Central

Overexpression of mitochondrial uncoupling proteins (UCPs) attenuates ischemia-reperfusion (I/R) injury in cultured cardiomyocytes. However, it is not known whether UCPs play an essential role in cardioprotection in the intact heart. This study evaluated the cardioprotective efficacy of UCPs against I/R injury and characterized the mechanism of UCP-mediated protection in addition to the role of UCPs in ischemic preconditioning (IPC). Cardiac UCP3 knockout (UCP3?/?) and wild-type (WT) mice hearts were subjected to ex vivo and in vivo models of I/R injury and IPC. Isolated UCP3?/? mouse hearts were retrogradely perfused and found to have poorer recovery of left ventricular function compared with WT hearts under I/R conditions. In vivo occlusion of the left coronary artery resulted in twofold larger infarcts in UCP3?/? mice compared with WT mice. Moreover, the incidence of in vivo I/R arrhythmias was higher in UCP3?/? mice. Myocardial energetics were significantly impaired with I/R, as reflected by a decreased ATP content and an increase in the AMP-to-ATP ratio. UCP3?/? hearts generated more reactive oxygen species (ROS) than WT hearts during I/R. Pretreatment of UCP3?/? hearts with the pharmacological uncoupling agent carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone improved postischemic functional recovery. Also the protective efficacy of IPC was abolished in UCP3?/? mice. We conclude that UCP3 plays a critical role in cardioprotection against I/R injury and the IPC phenomenon. There is increased myocardial vulnerability to I/R injury in hearts lacking UCP3. The mechanisms of UCP3-mediated cardioprotection include regulation of myocardial energetics and ROS generation by UCP3 during I/R. PMID:23457013

Ozcan, Cevher; Palmeri, Monica; Horvath, Tamas L.; Russell, Kerry S.

2013-01-01

254

Ozone oxidative preconditioning inhibits renal fibrosis induced by ischemia and reperfusion injury in rats.  

PubMed

Ischemia and reperfusion injury (IRI) is a crucial contributor to the development of renal fibrosis. Ozone has been proposed as a novel medical therapy for various conditions, including organ IRI. The aim of this study was to investigate whether ozone oxidative preconditioning (OzoneOP) has a beneficial effect in preventing the development of renal fibrosis following IRI. Sprague Dawley rats were subjected to 45 min of ischemia followed by 8 weeks of reperfusion. Prior to surgery, rats in the OzoneOP group were treated with ozone and those in the IRI and Sham groups were untreated. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. To assess tissue fibrosis, Masson's trichrome staining was performed. Immunohistochemistry was also performed to determine the localization of ?-smooth muscle actin (?-SMA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to analyze the expression of transforming growth factor (TGF)-?1, ?-SMA and Smad7. The levels of BUN and Cr did not significantly differ between groups. Rats pretreated with ozone showed markedly less interstitial fibrosis than untreated rats following IRI. In addition, immunohistochemistry revealed that ?-SMA expression was attenuated in the OzoneOP group compared with the IRI group. RT-qPCR and western blot analysis showed that OzoneOP inhibited the IRI-induced increases in ?-SMA and TGF-?1 expression levels, and that the IRI-induced reduction in the expression of Smad7 was inhibited in the OzoneOP group. The results indicate that OzoneOP has beneficial effects on ischemic renal fibrosis. OzoneOP may exert its protective effects by a mechanism involving modulation of the TGF-?1/Smad7 pathway. PMID:25371729

Wang, Lei; Chen, Hui; Liu, Xiu-Heng; Chen, Zhi-Yuan; Weng, Xiao-Dong; Qiu, Tao; Liu, Lin; Zhu, Heng-Cheng

2014-12-01

255

Vasoconstrictive neurovascular coupling during focal ischemic depolarizations  

Microsoft Academic Search

Ischemic depolarizing events, such as repetitive spontaneous periinfarct spreading depolarizations (PIDs), expand the infarct size after experimental middle cerebral artery (MCA) occlusion. This worsening may result from increased metabolic demand, exacerbating the mismatch between cerebral blood flow (CBF) and metabolism. Here, we present data showing that anoxic depolarization (AD) and PIDs caused vasoconstriction and abruptly reduced CBF in the ischemic

Hwa Kyoung Shin; Andrew K Dunn; Phillip B Jones; David A Boas; Michael A Moskowitz; Cenk Ayata

2006-01-01

256

Inflammation in the pathogenesis of ischemic stroke.  

PubMed

Ischemic stroke is a common cause of permanent disability in adults worldwide. Inflammation plays a significant role in the pathogenesis of ischemic stroke and its mechanism is complex. Both pro-inflammatory and anti-inflammatory mediators are involved in the pathogenesis of ischemic stroke, an imbalance of which leads to inflammation. Inflammatory cells from both the innate and acquired immune systems are involved in ischemic stroke-related inflammation; processes that are linked by the action of interleukin-17A (IL-17A). Although most inflammatory cells promote inflammation, T regulatory cells (Tregs) may have a protective function at the early stages of an ischemic injury, but a negative role during later stages. However, the precise mechanism of inflammation in ischemic stroke remains elusive; further understanding of it may provide new ideas for the prevention and treatment of ischemic stroke. In this review, we discuss the role of pro-inflammatory and anti-inflammatory mediators and related immune cells in the pathogenesis of ischemic stroke. PMID:25553478

Pei, Jian; You, Xiaoxin; Fu, Qinghui

2015-01-01

257

Parallel Domain Decomposition Preconditioning for Computational Fluid Dynamics  

NASA Technical Reports Server (NTRS)

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.

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

1998-01-01

258

Preconditioning effects of intermittent stream flow on leaf litter decomposition  

Microsoft Academic Search

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

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

259

Preconditioned Alternating Projection Algorithms for Maximum a Posteriori ECT Reconstruction  

PubMed Central

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

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

2012-01-01

260

Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning.  

PubMed

An essential aspect of episodic memory is the formation of associations between neutral sensory cues in the environment. In light of recent evidence that this critical aspect of learning does not require the hippocampus, we tested the involvement of the retrosplenial cortex (RSC) in this process using a chemogenetic approach that allowed us to temporarily silence neurons along the entire rostrocaudal extent of the RSC. A viral vector containing the gene for a synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC. When the receptor was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transiently silenced (confirmed using a patch-clamp procedure). Rats expressing hM4Di and control rats were trained in a sensory preconditioning procedure in which a tone and light were paired on some trials and a white noise stimulus was presented alone on the other trials during the Preconditioning phase. Thus, rats were given the opportunity to form an association between a tone and a light in the absence of reinforcement. Later, the light was paired with food. During the test phase when the auditory cues were presented alone, controls exhibited more conditioned responding during presentation of the tone compared with the white noise reflecting the prior formation of a tone-light association. Silencing RSC neurons during the Preconditioning phase prevented the formation of an association between the tone and light and eliminated the sensory preconditioning effect. These findings indicate that RSC may contribute to episodic memory formation by linking essential sensory stimuli during learning. PMID:25122898

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

2014-08-13

261

Preconditioned alternating projection algorithms for maximum a posteriori ECT reconstruction  

NASA Astrophysics Data System (ADS)

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.

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

2012-11-01

262

Islet preconditioning via multimodal microfluidic modulation of intermittent hypoxia  

PubMed Central

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

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

2012-01-01

263

Achyranthes bidentata Polypeptides Reduces Oxidative Stress and Exerts Protective Effects against Myocardial Ischemic/Reperfusion Injury in Rats  

PubMed Central

Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP) preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to test the possible mechanisms. Rats were treated with ABPP (10 mg/kg/d, i.p.) or saline once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK)/lactate dehydrogenase (LDH) activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide generation, gp91phox expression, malonaldialdehyde formation and enhanced superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart. PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated anti-oxidant effect and cardioprotection. Our study demonstrated for the first time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R injury in rats. Inhibition of PTEN and activation of Akt may contribute to the anti-oxidant capacity and cardioprotection of ABPP. PMID:24084726

Tie, Ru; Ji, Lele; Nan, Ying; Wang, Wenqing; Liang, Xiangyan; Tian, Fei; Xing, Wenjuan; Zhu, Miaozhang; Li, Rong; Zhang, Haifeng

2013-01-01

264

Insulin Preconditioning Elevates p-Akt and Cardiac Contractility after Reperfusion in the Isolated Ischemic Rat Heart  

PubMed Central

Insulin induces cardioprotection partly via an antiapoptotic effect. However, the optimal timing of insulin administration for the best quality cardioprotection remains unclear. We tested the hypothesis that insulin administered prior to ischemia provides better cardioprotection than insulin administration after ischemia. Isolated rat hearts were prepared using Langendorff method and divided into three groups. The Pre-Ins group (Pre-Ins) received 0.5?U/L insulin prior to 15?min no-flow ischemia for 20?min followed by 20?min of reperfusion. The Post-Ins group (Post-Ins) received 0.5?U/L insulin during the reperfusion period only. The control group (Control) was perfused with KH buffer throughout. The maximum of left ventricular derivative of pressure development (dP/dt(max)) was recorded continuously. Measurements of TNF-? and p-Akt in each time point were assayed by ELISA. After reperfusion, dP/dt(max) in Pre-Ins was elevated, compared with Post-Ins at 10 minutes after reperfusion and Control at all-time points. TNF-? levels at 5 minutes after reperfusion in the Pre-Ins were lower than the others. After 5 minutes of reperfusion, p-Akt was elevated in Pre-Ins compared with the other groups. Insulin administration prior to ischemia provides better cardioprotection than insulin administration only at reperfusion. TNF-? suppression is possibly mediated via p-Akt leading to a reduction in contractile myocardial dysfunction. PMID:25197648

Sato, Tamaki; Fukushima, Hisashi; Schricker, Thomas

2014-01-01

265

Activation of K2P channel–TREK1 mediates the neuroprotection induced by sevoflurane preconditioning  

PubMed Central

Background Preconditioning with volatile anaesthetic agents induces tolerance to focal cerebral ischaemia, although the underlying mechanisms have not been clearly defined. The present study analyses whether TREK-1, a two-pore domain K+ channel and target for volatile anaesthetics, plays a role in mediating neuroprotection by sevoflurane. Methods Differentiated SH-SY5Y cells were preconditioning with sevoflurane and challenged by oxygen–glucose deprivation (OGD). Cell viability and expression of caspase-3 and TREK-1 were evaluated. Rats that were preconditioned with sevoflurane were subjected to middle cerebral artery occlusion (MCAO), and the expression of TREK-1 protein and mRNA was analysed. Neurological scores were evaluated and infarction volume was examined. Results Sevoflurane preconditioning reduced cell death in differentiated SH-SY5Y cells challenged by OGD. Sevoflurane preconditioning reduced infarct volume and improved neurological outcome in rats subjected to MCAO. Sevoflurane preconditioning increased levels of TREK-1 mRNA and protein. Knockdown of TREK-1 significantly attenuated sevoflurane preconditioning-induced neuroprotective effects in vitro and in vivo. Conclusions Sevoflurane preconditioning-induced neuroprotective effects against transient cerebral ischaemic injuries involve TREK-1 channels. These results suggest a novel mechanism for sevoflurane preconditioning-induced tolerance to focal cerebral ischaemia. PMID:24154701

Tong, L.; Cai, M.; Huang, Y.; Zhang, H.; Su, B.; Li, Z.; Dong, H.

2014-01-01

266

Increased perception of post-ischemic paresthesias in depressed subjects  

Microsoft Academic Search

A psychophysical assessment of sensory activity linked to unmyelinated and myelinated primary afferents was conducted by estimating the intensity of thermal and tactile post-ischemic paresthesias in 11 nontreated depressed subjects (Zung's index ?50) and 19 controls. Blood flow in the dominant forearm was arrested until ischemic pain tolerance was reached. Ischemic pain and post-ischemic paresthesias were numerically rated. The duration

H Suarez-Roca; L Piñerua-Shuhaibar; M. E Morales; W Maixner

2003-01-01

267

Erythropoietin: powerful protection of ischemic and post-ischemic brain.  

PubMed

Ischemic brain injury inflicted by stroke and cardiac arrest ranks among the leading causes of death and long-term disability in the United States. The brain consumes large amounts of metabolic substrates and oxygen to sustain its energy requirements. Consequently, the brain is exquisitely sensitive to interruptions in its blood supply, and suffers irreversible damage after 10-15 min of severe ischemia. Effective treatments to protect the brain from stroke and cardiac arrest have proven elusive, due to the complexities of the injury cascades ignited by ischemia and reperfusion. Although recombinant tissue plasminogen activator and therapeutic hypothermia have proven efficacious for stroke and cardiac arrest, respectively, these treatments are constrained by narrow therapeutic windows, potentially detrimental side-effects and the limited availability of hypothermia equipment. Mounting evidence demonstrates the cytokine hormone erythropoietin (EPO) to be a powerful neuroprotective agent and a potential adjuvant to established therapies. Classically, EPO originating primarily in the kidneys promotes erythrocyte production by suppressing apoptosis of proerythroid progenitors in bone marrow. However, the brain is capable of producing EPO, and EPO's membrane receptors and signaling components also are expressed in neurons and astrocytes. EPO activates signaling cascades that increase the brain's resistance to ischemia-reperfusion stress by stabilizing mitochondrial membranes, limiting formation of reactive oxygen and nitrogen intermediates, and suppressing pro-inflammatory cytokine production and neutrophil infiltration. Collectively, these mechanisms preserve functional brain tissue and, thus, improve neurocognitive recovery from brain ischemia. This article reviews the mechanisms mediating EPO-induced brain protection, critiques the clinical utility of exogenous EPO to preserve brain threatened by ischemic stroke and cardiac arrest, and discusses the prospects for induction of EPO production within the brain by the intermediary metabolite, pyruvate. PMID:24595981

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

2014-11-01

268

Erythropoietin: Powerful Protection of Ischemic and Post-Ischemic Brain  

PubMed Central

Ischemic brain injury inflicted by stroke and cardiac arrest ranks among the leading causes of death and long-term disability in the United States. The brain consumes large amounts of metabolic substrates and oxygen to sustain its energy requirements. Consequently, the brain is exquisitely sensitive to interruptions in its blood supply, and suffers irreversible damage after 10–15 minutes of severe ischemia. Effective treatments to protect the brain from stroke and cardiac arrest have proven elusive, due to the complexities of the injury cascades ignited by ischemia and reperfusion. Although recombinant tissue plasminogen activator and therapeutic hypothermia have proven efficacious for stroke and cardiac arrest, respectively, these treatments are constrained by narrow therapeutic windows, potentially detrimental side effects and the limited availability of hypothermia equipment. Mounting evidence demonstrates the cytokine hormone erythropoietin (EPO) to be a powerful neuroprotective agent and a potential adjuvant to established therapies. Classically, EPO originating primarily in the kidneys promotes erythrocyte production by suppressing apoptosis of proerythroid progenitors in bone marrow. However, the brain is capable of producing EPO, and EPO’s membrane receptors and signaling components also are expressed in neurons and astrocytes. EPO activates signaling cascades that increase the brain’s resistance to ischemia-reperfusion stress by stabilizing mitochondrial membranes, limiting formation of reactive oxygen and nitrogen intermediates, and suppressing pro-inflammatory cytokine production and neutrophil infiltration. Collectively, these mechanisms preserve functional brain tissue and, thus, improve neurocognitive recovery from brain ischemia. This article reviews the mechanisms mediating EPO-induced brain protection, critiques the clinical utility of exogenous EPO to preserve brain threatened by ischemic stroke and cardiac arrest, and discusses the prospects for induction of EPO production within the brain by the intermediary metabolite, pyruvate. PMID:24595981

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

2015-01-01

269

CISCO IP 7940-7960 FONCTIONS TLPHONIQUES  

E-print Network

CISCO IP 7940-7960 FONCTIONS T�L�PHONIQUES FONCTIONS DE BASE FAIRE UN APPEL · Soulever le combiné navigation; · appuyer sur la touche Joindre (tous les intervenants seront en communication). Cisco_IP_7940_7960_Fr_CUCM_V7.0_20090320[1].doc 1 de 7 #12;CISCO IP 7940-7960 FONCTIONS T�L�PHONIQUES APPEL CONF�RENCE

Charette, André

270

CISCO IP 7941-7961 FONCTIONS TLPHONIQUES  

E-print Network

CISCO IP 7941-7961 FONCTIONS T�L�PHONIQUES FONCTIONS DE BASE BOUTON DE LIGNE (DESCRIPTION DES raccrocher pour effectuer le transfert de l'appel. Cisco_IP_7941_7961_Fr_CUCM_V7.0_20090320[1].doc 1 de 7 #12;CISCO IP 7941-7961 FONCTIONS T�L�PHONIQUES APPEL CONF�RENCE Vous pouvez établir un appel conférence

Charette, André

271

Endovascular Therapy for Ischemic Stroke  

PubMed Central

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.

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

2015-01-01

272

[Ischemic stroke under anticoagulant therapy].  

PubMed

In order to determine predictive factors of stroke recurrence during anticoagulant therapy and to estimate prognosis, we retrospectively examined clinical data of 197 consecutive patients with acute ischemic stroke. The subjects were divided into two groups, within the therapeutic range group and below therapeutic range group, based on Japanese guidelines for the management of stroke 2004. Univariate analysis revealed that cardioembolic stroke patients were less frequent in the therapeutic range group (61% vs 77%; p = 0.03), while more lacunar stroke patients were experienced (17% vs 6%; p = 0.01). In patients with past history of cardioembolic stroke, significant favorable outcomes as of Barthel index (54 vs 33; p = 0.03) and modified Rankin Scale (3 vs 4; p = 0.04) were found within the therapeutic range group. There is a possibility that adequate anticoagulation prevents thrombogenesis or lead to early recanalization, especially in patients with past history of cardioembolic stroke. PMID:20681261

Inoue, Yasuteru; Inatomi, Yuichiro; Yonehara, Toshiro; Hashimoto, Yoichiro; Hirano, Teruyuki; Uchino, Makoto

2010-07-01

273

Preconditioning with Associated Blocking of Ca2+ Inflow Alleviates Hypoxia-Induced Damage to Pancreatic ?-Cells  

PubMed Central

Objective Beta cells of pancreatic islets are susceptible to functional deficits and damage by hypoxia. Here we aimed to characterize such effects and to test for and pharmacological means to alleviate a negative impact of hypoxia. Methods and Design Rat and human pancreatic islets were subjected to 5.5 h of hypoxia after which functional and viability parameters were measured subsequent to the hypoxic period and/or following a 22 h re-oxygenation period. Preconditioning with diazoxide or other agents was usually done during a 22 h period prior to hypoxia. Results Insulin contents decreased by 23% after 5.5 h of hypoxia and by 61% after a re-oxygenation period. Preconditioning with diazoxide time-dependently alleviated these hypoxia effects in rat and human islets. Hypoxia reduced proinsulin biosynthesis (3H-leucine incorporation into proinsulin) by 35%. Preconditioning counteracted this decrease by 91%. Preconditioning reduced hypoxia-induced necrosis by 40%, attenuated lowering of proteins of mitochondrial complexes I–IV and enhanced stimulation of HIF-1-alpha and phosphorylated AMPK proteins. Preconditioning by diazoxide was abolished by co-exposure to tolbutamide or elevated potassium (i.e. conditions which increase Ca2+ inflow). Preconditioning with nifedipine, a calcium channel blocker, partly reproduced effects of diazoxide. Both diazoxide and nifedipine moderately reduced basal glucose oxidation whereas glucose-induced oxygen consumption (tested with diazoxide) was unaffected. Preconditioning with diaxoxide enhanced insulin contents in transplants of rat islets to non-diabetic rats and lowered hyperglycemia vs. non-preconditioned islets in streptozotocin-diabetic rats. Preconditioning of human islet transplants lowered hyperglycemia in streptozotocin-diabetic nude mice. Conclusions 1) Prior blocking of Ca2+ inflow associates with lesser hypoxia-induced damage, 2) preconditioning affects basal mitochondrial metabolism and accelerates activation of hypoxia-reactive and potentially protective factors, 3) results indicate that preconditioning by K+-ATP-channel openers has therapeutic potential for islet transplantations. PMID:23935835

Ma, Zuheng; Moruzzi, Noah; Catrina, Sergiu-Bogdan; Hals, Ingrid; Oberholzer, José

2013-01-01

274

Energy metabolism in preconditioned and control myocardium: effect of total ischemia.  

PubMed

Myocardium which has been preconditioned by one or several brief episodes of ischemia has much slower energy utilization during a subsequent sustained episode of ischemia. Since preconditioned tissue also is 'stunned', the reduced energy utilization of preconditioned tissue may be due to reduced contractile effort. This study was done to assess whether differences in energy utilization persisted or disappeared under conditions of total ischemia, in vitro, when contractile activity was abolished in both control and preconditioned regions by hyperkalemic cardiac arrest. Preconditioned myocardium was produced in open-chest anesthetized dogs by exposing the circumflex bed to four 5-min episodes of ischemia each followed by 5 min of arterial reperfusion. Non-preconditioned anterior descending bed was used as control myocardium. Hearts were arrested with hyperkalemia after the last reperfusion period in order to reduce or eliminate the effects of contractile activity. Metabolite content was measured in sequential biopsies of the tissue. Large differences in the rate of energy metabolism of the two regions were noted during the first 15 minutes of ischemia. During this time, the preconditioned tissue utilized less glycogen, and produced less lactate, glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), and alpha-glycerol phosphate (alpha GP), than did control myocardium. Moreover, there was a much smaller decrease in net tissue ATP in the preconditioned than in the control tissue. Thus, the decrease in the demand of preconditioned tissue for energy, which has been observed in vivo, persisted despite the elimination of differences in contractile effort between control and preconditioned myocardium. Although the cause of this decrease in energy demand in preconditioned myocardium remains unknown, the present results suggest that it is not due to concomitant stunning. PMID:1811060

Jennings, R B; Murry, C E; Reimer, K A

1991-12-01

275

Calcium preconditioning triggers neuroprotection in retinal ganglion cells  

PubMed Central

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

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

2010-01-01

276

Steps to translate preconditioning from basic research to the clinic  

PubMed Central

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

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

2012-01-01

277

Meat consumption and fatal ischemic heart disease.  

PubMed

In 1960 the meat-consumption habits of 25,153 California Seventh-Day Adventists were assessed by questionnaire. Between 1960 and 1980 ischemic heart disease deaths were identified. Meat consumption was positively associated with fatal ischemic heart disease in both men and women. This association was apparently not due to confounding by eggs, dairy products, obesity, marital status, or cigarette smoking. The positive association between meat consumption and fatal ischemic heart disease was stronger in men than in women and, overall, strongest in young men. For 45- to 64-year-old men, there was approximately a threefold difference in risk between men who ate meat daily and those who did not eat meat. This is the first study to clearly show a dose-response relationship between meat consumption and ischemic heart disease risk. PMID:6527990

Snowdon, D A; Phillips, R L; Fraser, G E

1984-09-01

278

Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats  

E-print Network

Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis online 9 March 2012 Keywords: Hypoxic preconditioning Bone marrow mesenchymal stem cell Transplantation for promoting cell survival after transplantation. The present investigation examined the hypothesis

Hayar, Abdallah

279

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

Code of Federal Regulations, 2010 CFR

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

2010-07-01

280

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

Code of Federal Regulations, 2011 CFR

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

2011-01-01

281

Preconditioning methods for ideal and multiphase fluid flows  

NASA Astrophysics Data System (ADS)

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.

Gupta, Ashish

282

Weighted graph based ordering techniques for preconditioned conjugate gradient methods  

NASA Technical Reports Server (NTRS)

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.

Clift, Simon S.; Tang, Wei-Pai

1994-01-01

283

Approaches for Resolving Dynamic IP Addressing.  

ERIC Educational Resources Information Center

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…

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

1997-01-01

284

An Enhanced Hando# Mechanism for Cellular IP  

E-print Network

networks. Mobile users will expect the same level of service quality as wireline users. Even though the access point of mobile user changes, IP connections should be continued transparently. The Mobile­mobility control. Among these micro­mobility protocols, Cellular IP [4], [5], [6], [7] attracts special attention

Kim, Chong-Kwon

285

Filtering Malicious IP Sources Models and Algorithms  

E-print Network

Problem NotationsNotations p/l : IP prefix : weight assigned to IP address i Framework "price/cost" Knapsack Same "capacity" "weights" Correlation of knapsack "items" Knapsack "items" 7 whose leaves are addresses in BL andthe binary tree whose leaves are addresses in BL, and intermediate

Markopoulou, Athina

286

Histopathologic studies of ischemic optic neuropathy.  

PubMed Central

PURPOSE: To define the histopathologic features of eyes in which a pathologic diagnosis of ischemic optic neuropathy had been made in the years 1951 through 1998. METHODS: The following data were documented: age of patient, race, sex, source of tissue, cause of death, clinical history, interval from loss of vision to death, enucleation, exenteration, and biopsy. The histopathologic criteria for diagnosis of ischemic optic neuropathy were the presence of localized ischemic edema, cavernous degeneration, or an area of atrophy located superior or inferior in the optic nerve. Cases with history of abrupt loss of vision were combined with reports from the literature to construct a time table of histopathologic features and associated conditions. RESULTS: Ischemic optic neuropathy was present in 193 eyes. There were 88 females and 65 males. The average age was 71.6 years. Ischemic edema without (early) and with (later) gitter macrophages was present in 26 (13.5%). Cavernous degeneration was present in 69 nerves (36%). Mucopolysaccharide (MPS) was present in 37 cavernous lesions 1 month or longer after loss of vision. Cavernous lesions were seen in 3 eyes in which peripapillary retinal nerve fiber layer hemorrhage had been observed prior to death. Atrophic lesions, the most common pattern, were observed in 133 optic nerves (66.8%). More than 1 ischemic lesion was seen in 38 optic nerves (19.7%). Bilateral ischemic lesions were seen in 50 (35.2%) of 142 paired eyes. CONCLUSIONS: Ischemic optic nerve lesions are initially acellular and later show macrophage infiltration. Cavernous lesions with MPS are present 4 weeks or longer after vision loss. The location of MPS posteriorly and along the internal margin suggests that MPS is produced at the edges of lesions. Progressive vision loss in ischemic optic neuropathy may be secondary to compression of intact nerve from ischemic edema and cavernous swelling, or a second ischemic lesion. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 FIGURE 20 FIGURE 21 FIGURE 22 FIGURE 23 FIGURE 24 A FIGURE 24 B FIGURE 24 C FIGURE 24 D FIGURE 24 E FIGURE 24 F FIGURE 25 A FIGURE 25 B FIGURE 25 C FIGURE 25 D FIGURE 25 E FIGURE 25 F FIGURE 26 FIGURE 27 FIGURE 28 FIGURE 29 FIGURE 30 FIGURE 31 PMID:11190024

Knox, D L; Kerrison, J B; Green, W R

2000-01-01

287

Docosahexaenoic Acid Therapy of Experimental Ischemic Stroke  

Microsoft Academic Search

We examined the neuroprotective efficacy of docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member, in\\u000a acute ischemic stroke; studied the therapeutic window; and investigated whether DHA administration after an ischemic stroke\\u000a is able to salvage the penumbra. In each series described below, SD rats underwent 2 h of middle cerebral artery occlusion\\u000a (MCAo). In series 1, DHA or saline

Ludmila Belayev; Larissa Khoutorova; Kristal D. Atkins; Tiffany N. Eady; Song Hong; Yan Lu; Andre Obenaus; Nicolas G. Bazan

2011-01-01

288

Achieving quality of service in IP networks  

NASA Astrophysics Data System (ADS)

The Internet Protocol (IP) has served global networks well, providing a standardized method to transmit data among many disparate systems. But IP is designed for simplicity, and only enables a `best effort' service that can be subject to delays and loss of data. For data networks, this is an acceptable trade-off. In the emerging world of convergence, driven by new applications such as video streaming and IP telephony, minimizing latency and packet loss as well as jitter can be critical. Simply increasing the size of the IP network `pipe' to meet those demands is not always sufficient. In this environment, vendors and standards bodies are endeavoring to create technologies and techniques to enable IP to improve the quality of service it can provide, while retaining the characteristics that has enabled it to become the dominant networking protocol.

Hays, Tim

2001-07-01

289

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

ERIC Educational Resources Information Center

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…

Coureaud, Gerard; Tourat, Audrey; Ferreira, Guillaume

2013-01-01

290

Effect of Heat Preconditioning on the Uptake and Permeability of R123 in Brain Microvessel  

E-print Network

Effect of Heat Preconditioning on the Uptake and Permeability of R123 in Brain Microvessel Endothelial Cells during Mild Heat Treatment KA-YUN NG,1 CHEONG-WEON CHO,1 THOMAS K. HENTHORN,2 ROBERT L of this study was to assess the effect of mild heat and heat preconditioning on the uptake and permeability

Tullos, Desiree

291

Algorithm PREQN: Fortran 77 Subroutines for Preconditioning the Conjugate Gradient Method  

E-print Network

Algorithm PREQN: Fortran 77 Subroutines for Preconditioning the Conjugate Gradient Method Jos'e Luis Morales \\Lambda Jorge Nocedal y March 30, 1999 Abstract PREQN is a package of Fortran 7725047­A004. 1 #12; 1 Introduction In this paper we describe Fortran 77 subroutines for preconditioning

Nocedal, Jorge

292

Algorithm PREQN: Fortran 77 Subroutines for Preconditioning the Conjugate Gradient Method  

E-print Network

Algorithm PREQN: Fortran 77 Subroutines for Preconditioning the Conjugate Gradient Method Jose Luis Morales Jorge Nocedaly March 14, 2000 Abstract PREQN is a package of Fortran 77 subroutines-A004. 1 #12;1 Introduction In this paper we describe Fortran 77 subroutines for preconditioning

Nocedal, Jorge

293

WAVEFORM PRECONDITIONING FOR CLUTTER REJECTION IN MULTIPATH FOR SPARSE DISTRIBUTED APERTURES  

E-print Network

WAVEFORM PRECONDITIONING FOR CLUTTER REJECTION IN MULTIPATH FOR SPARSE DISTRIBUTED APERTURES T,The idea of preconditioning transmit waveforms e.g. ultrasound imaging, sonar imaging and microwave clutter the elements Ourapproachis motivatedby communicationtheory: the being atd Wavefor*sprondit for clutter radar

Yazici, Birsen

294

Stress preconditioning of spreading depression in the locust CNS.  

PubMed

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 degrees 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

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

2007-01-01

295

Preconditioning stimuli induce autophagy via sphingosine kinase 2 in mouse cortical neurons.  

PubMed

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

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

2014-07-25

296

Candesartan and glycyrrhizin ameliorate ischemic brain damage through downregulation of the TLR signaling cascade.  

PubMed

Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA). The current study was designed to investigate the protective effects of candesartan (0.15 mg/kg, orally) and glycyrrhizin (30 mg/kg, orally) experimentally-induced ischemic brain damage in C57BL/6 mice (middle cerebral artery occlusion, MCAO) in comparison to the effects of a standard neuroprotective drug (cerebrolysin, 7.5 mg/kg, IP). All drugs were administered 30 min before and 24h after MCAO. Both candesartan and glycyrrhizin ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in behaviour tests, reduction in brain infarction, neuronal degeneration, and leukocyte infiltration. In addition, MCAO induced a significant upregulation in the different elements of the TLR pathway including TLR-2 and TLR-4, Myd88, TRIF and IRF-3 and the downstream effectors TNF-?, IL-1?, IL-6 and NF-kB. All these changes were significantly ameliorated by treatment with candesartan and glycyrrhizin. The results of the current study represent a new indication for both candesartan and glycyrrhizin in the management of ischemic stroke with effects comparable to those of the standard neuroprotective drug cerebrolysin. PMID:24378346

Barakat, Waleed; Safwet, Nancy; El-Maraghy, Nabila N; Zakaria, Mohamed N M

2014-02-01

297

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

PubMed Central

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

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

2013-01-01

298

IPS guidestar selection for stellar mode (ASTRO)  

NASA Technical Reports Server (NTRS)

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.

Mullins, Larry; Wooten, Lewis

1988-01-01

299

Scalable architecture for VoIP privacy  

NASA Astrophysics Data System (ADS)

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.

Medvinsky, Alexander

2001-07-01

300

Importance of timing of magnesium administration in the isolated ischemic-reperfused rat heart: role of K(ATP) channels.  

PubMed

There is a growing interest for the beneficial effect of magnesium (Mg) in cardiovascular disorders. A number of cardiovascular disorders including myocardial infarction, arrhythmias and congestive heart failure have been associated with low extra- cellular or intracellular concentrations of Mg. The efficiency of the preconditioning effect of Mg on cardiac function and infarct size in the globally ischemic-reperfused isolated rat heart was studied together with the role of ATP-sensitive potassium (K(ATP)) channels in protection induced by Mg. Rat hearts were Langendorff perfused, subjected to 30 min of global ischemia and 90 min of reperfusion, including treatment groups which focused on different times of Mg (8 mmol/l) use. Infarct size was measured by triphenyltetrazolium chloride (TTC) method. The left ventricular function was assessed by left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow (CF). The administration of Mg before ischemia had an anti-infarct effect in rat hearts and improved cardiac function. The protective effects of magnesium was abolished by the blocking of K(ATP) channels and suggests that K-ATP channel has an important role in the heart protection effect of Mg as a preconditioning agent. PMID:18052684

Bazargan, M; Faghihi, M; Chitsaz, M

2008-01-01

301

Early events in ischemic renal failure in the rat: effects of antioxidant therapy.  

PubMed

Renal ischemia followed by two hours of reperfusion produces a complex form of acute renal failure characterized by a reduction in nephron filtration rate (SNGFR) and moderate proximal tubular damage. We have examined glomerular hemodynamics, SNGFR and histologic changes after renal ischemia and two hours of reperfusion in untreated (I) rats and rats pretreated with the antioxidant, probucol (IP). SNGFR decreased significantly by 47% in I rats. Reduction in SNGFR was primarily the result of a major decrease in the glomerular capillary hydrostatic pressure gradient, delta P, and a decrease in nephron plasma flow (SNPF). The glomerular ultrafiltration coefficient remained equal to control valves. In IP rats SNGFR was improved to values 89% of control rats due to higher values of delta P and SNPF. Histologic evidence of modest damage to cells of the proximal tubule was equal in both untreated and probucol treated ischemic animals. These studies demonstrate that: (a) primary reductions in nephron filtration rate at the glomerulus result from decreases in delta P and nephron plasma flow; b) pretreatment with the antioxidant, probucol, increases nephron plasma flow and SNGFR, and maintains more normal values for delta P; and c) tubular damage was equivalent in I and IP rats in spite of differences in SNGFR. PMID:2770108

Bird, J E; Evan, A P; Peterson, O W; Blantz, R C

1989-06-01

302

Ocular ischemic syndrome - a systematic review.  

PubMed

Ocular ischemic syndrome is a rare condition, which is caused by ocular hypoperfusion due to stenosis or occlusion of the common or internal carotid arteries. Atherosclerosis is the major cause of changes in the carotid arteries. Ocular ischemic syndrome is manifested as visual loss, orbital pain and, frequently, changes of the visual field, and various anterior and posterior segment signs. Anterior segment signs include iris neovascularization and secondary neovascular glaucoma, iridocyclitis, asymmetric cataract, iris atrophy and sluggish reaction to light. Posterior eye segment changes are the most characteristic, such as narrowed retinal arteries, perifoveal telangiectasias, dilated retinal veins, mid-peripheral retinal hemorrhages, microaneurysms, neovascularization at the optic disk and in the retina, a cherry-red spot, cotton-wool spots, vitreous hemorrhage and normal-tension glaucoma. Differential diagnosis of ocular ischemic syndrome includes diabetic retinopathy and moderate central retinal vein occlusion. Carotid artery imaging and fundus fluorescein angiography help to establish the diagnosis of ocular ischemic syndrome. The treatment can be local, for example, ocular (conservative, laser and surgical) or systemic (conservative and surgical treatment of the carotid artery). Since the condition does not affect the eyes alone, patients with ocular ischemic syndrome should be referred for consultation to the neurologist, vascular surgeon and cardiologist. PMID:22847215

Terelak-Borys, Barbara; Skonieczna, Katarzyna; Grabska-Liberek, Iwona

2012-08-01

303

Hypothermia for hypoxic–ischemic encephalopathy  

PubMed Central

Moderate to severe hypoxic–ischemic injury in newborn infants, manifested as encephalopathy immediately or within hours after birth, is associated with a high risk of either death or a lifetime with disability. In recent multicenter clinical trials, hypothermia initiated within the first 6 postnatal hours has emerged as a therapy that reduces the risk of death or impairment among infants with hypoxic–ischemic encephalopathy. Prior to hypothermia, no therapies directly targeting neonatal encephalopathy secondary to hypoxic–ischemic injury had convincing evidence of efficacy. Hypothermia therapy is now becoming increasingly available at tertiary centers. Despite the deserved enthusiasm for hypothermia, obstetric and neonatology caregivers, as well as society at large, must be reminded that in the clinical trials more than 40% of cooled infants died or survived with impairment. Although hypothermia is an evidence-based therapy, additional discoveries are needed to further improve outcome after HIE. In this article, we briefly present the epidemiology of neonatal encephalopathy due to hypoxic–ischemic injury, describe the rationale for the use of hypothermia therapy for hypoxic–ischemic encephalopathy, and present results of the clinical trials that have demonstrated the efficacy of hypothermia. We also present findings noted during and after these trials that will guide care and direct research for this devastating problem. PMID:20625441

Cotten, C Michael; Shankaran, Seetha

2010-01-01

304

Blood pressure augmentation in acute ischemic stroke.  

PubMed

Although control of hypertension is established as an important factor in the primary and secondary prevention of stroke, management of blood pressure in the setting of acute ischemic stroke remains controversial. Given limited data, the general consensus is that there is no proven benefit to lowering blood pressure in the first hours to days after acute ischemic stroke. Instead, there is concern that relative hypotension may lead to worsening of cerebral ischemia. For many years, the use of blood pressure augmentation ("induced hypertension") has been studied in animal models and in humans as a means of maintaining or improving perfusion to ischemic brain tissue. This approach is now widely used in neurocritical care units to treat delayed neurological deficits after subarachnoid hemorrhage, but its use in ischemic stroke patients remains anecdotal. This article reviews the cerebral physiology, animal models and human studies of induced hypertension as a treatment for acute ischemic stroke. Although there has not been a large, randomized clinical trial of this treatment, the available clinical data suggests that induced hypertension can result in at least short-term neurological improvement, with an acceptable degree of safety. PMID:17582440

Wityk, Robert J

2007-10-15

305

Ocular ischemic syndrome – a systematic review  

PubMed Central

Summary Ocular ischemic syndrome is a rare condition, which is caused by ocular hypoperfusion due to stenosis or occlusion of the common or internal carotid arteries. Atherosclerosis is the major cause of changes in the carotid arteries. Ocular ischemic syndrome is manifested as visual loss, orbital pain and, frequently, changes of the visual field, and various anterior and posterior segment signs. Anterior segment signs include iris neovascularization and secondary neovascular glaucoma, iridocyclitis, asymmetric cataract, iris atrophy and sluggish reaction to light. Posterior eye segment changes are the most characteristic, such as narrowed retinal arteries, perifoveal telangiectasias, dilated retinal veins, mid-peripheral retinal hemorrhages, microaneurysms, neovascularization at the optic disk and in the retina, a cherry-red spot, cotton-wool spots, vitreous hemorrhage and normal-tension glaucoma. Differential diagnosis of ocular ischemic syndrome includes diabetic retinopathy and moderate central retinal vein occlusion. Carotid artery imaging and fundus fluorescein angiography help to establish the diagnosis of ocular ischemic syndrome. The treatment can be local, for example, ocular (conservative, laser and surgical) or systemic (conservative and surgical treatment of the carotid artery). Since the condition does not affect the eyes alone, patients with ocular ischemic syndrome should be referred for consultation to the neurologist, vascular surgeon and cardiologist. PMID:22847215

Terelak-Borys, Barbara; Skonieczna, Katarzyna; Grabska-Liberek, Iwona

2012-01-01

306

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats  

PubMed Central

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage. PMID:23969972

Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

2013-01-01

307

Effect of preconditioning on the viscoelastic response of primate patellar tendon.  

PubMed

Current techniques for anterior cruciate ligament reconstruction with patellar tendon (PT) allow a measurable tension to be applied to the graft at the time of fixation. The viscoelastic nature of the PT, however, ensures that relaxation will cause the graft tension to decrease over time. To better understand this process, a primate model was used to evaluate acute viscoelastic relaxation in the PT. Thirty-five patella-patellar tendon-tibia (P-PT-T) complexes were harvested from normal primate knees (Cynomolgus monkeys), and were divided into five groups for mechanical comparison. Specimens were subjected to two 10-min relaxation tests separated by a 1-30-min unloaded interval. The first test provided baseline relaxation data as well as serving as preconditioning for the second test. Results indicate that preconditioning significantly reduces the tension lost in a graft due to viscoelastic relaxation. The effect of preconditioning is reduced with increasing recovery time (the time between preconditioning and the second relaxation test), but the effect is still significant after 30 min of unloading. No differences were observed in the relaxation behavior of specimens that were cyclicly or isometrically preconditioned, nor were differences observed between irradiated and nonirradiated specimens. These results suggest that preconditioning can reduce acute tension loss in a graft due to viscoelastic relaxation and that simple isometric preconditioning is just as effective as cyclic stretching. PMID:8166908

Graf, B K; Vanderby, R; Ulm, M J; Rogalski, R P; Thielke, R J

1994-02-01

308

On the development of Voice over IP  

E-print Network

Internet Protocol (VoIP) security and proposed an Internet draft on secure retargeting and response identity. The draft provides a simple and comprehensive solution to the response identity, call recipient identity and intermediate server retargeting...

Yang, Xu

2009-05-15

309

Mahalingam Ramkumar TCP/IP Example  

E-print Network

Header #12;IPv6 Header Optional Headers ­ 1) Hop-by-Hop options 2) Routing Header 3) Fragment Header 4 and authentication (MAC code) of IP packets. · Guards against replay attacks. #12;End-to-End vs End

Ramkumar, Mahalingam

310

On the merit of IP\\/MPLS protection\\/restoration in IP over WDM networks  

Microsoft Academic Search

The purpose of this work is to show the benefits gained by dynamically provisioning low-rate traffic streams at the IP\\/MPLS layer in future IP-centric WDM-based optical networks. First, several low-rate data flows are statistically multiplexed (groomed) onto one wavelength at the IP\\/MPLS router. Then, conventional dynamic lightpath provisioning schemes at the physical WDM layer, where the bandwidth of a connection

Chadi Assi; Yinghua Ye; Abdallah Shami; Sudhir Dixit; I. Habib; M. A. Ali

2001-01-01

311

Development of TCP\\/IP processing hardware  

Microsoft Academic Search

TCP\\/IP\\/Ethernet is a widely used data transfer technology in data acquisition systems. This technology is essential to construct back-end systems. On the other hand, it has not been sufficiently adopted in front-end systems because front-end devices have constraints that are difficult to satisfy. To overcome these constraints, we have developed TCP\\/IP processing hardware with the following features: high-speed data transfer,

Tomohisa Uchida; Manobu Tanaka

2006-01-01

312

Preconditioned Mixed Spectral Element Methods for Elasticity and Stokes Problems  

NASA Technical Reports Server (NTRS)

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.

Pavarino, Luca F.

1996-01-01

313

A frequency dependent preconditioned wavelet method for atmospheric tomography  

NASA Astrophysics Data System (ADS)

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.

Yudytskiy, Mykhaylo; Helin, Tapio; Ramlau, Ronny

2013-12-01

314

Is There A Place For Cerebral Preconditioning In The Clinic?  

PubMed Central

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

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

2010-01-01

315

Spectroscopic Monitoring of Kidney Tissue Ischemic Injury  

SciTech Connect

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.

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

2004-03-11

316

A block inverse-free preconditioned Krylov subspace method for symmetric generalized eigenvalue problems  

NASA Astrophysics Data System (ADS)

The inverse-free preconditioned Krylov subspace method of Golub and Ye [G.H. Golub, Q. Ye, An inverse free preconditioned Krylov subspace method for symmetric generalized eigenvalue problems, SIAM J. Sci. Comp. 24 (2002) 312-334] is an efficient algorithm for computing a few extreme eigenvalues of the symmetric generalized eigenvalue problem. In this paper, we first present an analysis of the preconditioning strategy based on incomplete factorizations. We then extend the method by developing a block generalization for computing multiple or severely clustered eigenvalues and develop a robust black-box implementation. Numerical examples are given to illustrate the analysis and the efficiency of the block algorithm.

Quillen, Patrick; Ye, Qiang

2010-01-01

317

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

NASA Technical Reports Server (NTRS)

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.

Darmofal, David L.

1998-01-01

318

Solving large mixed linear models using preconditioned conjugate gradient iteration.  

PubMed

Continuous evaluation of dairy cattle with a random regression test-day model requires a fast solving method and algorithm. A new computing technique feasible in Jacobi and conjugate gradient based iterative methods using iteration on data is presented. In the new computing technique, the calculations in multiplication of a vector by a matrix were recorded to three steps instead of the commonly used two steps. The three-step method was implemented in a general mixed linear model program that used preconditioned conjugate gradient iteration. Performance of this program in comparison to other general solving programs was assessed via estimation of breeding values using univariate, multivariate, and random regression test-day models. Central processing unit time per iteration with the new three-step technique was, at best, one-third that needed with the old technique. Performance was best with the test-day model, which was the largest and most complex model used. The new program did well in comparison to other general software. Programs keeping the mixed model equations in random access memory required at least 20 and 435% more time to solve the univariate and multivariate animal models, respectively. Computations of the second best iteration on data took approximately three and five times longer for the animal and test-day models, respectively, than did the new program. Good performance was due to fast computing time per iteration and quick convergence to the final solutions. Use of preconditioned conjugate gradient based methods in solving large breeding value problems is supported by our findings. PMID:10629826

Strandén, I; Lidauer, M

1999-12-01

319

Iterated preconditioned LSQR method for inverse problems on unstructured grids  

NASA Astrophysics Data System (ADS)

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

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

2014-06-01

320

Anatomical Preconditions for Operative-Technical Errors in Right Trisectionectomy  

PubMed Central

Objective: Certain anatomical variations may represent preconditions for technical operation errors in right trisectionectomy. These variations include: the confluence of the common bile duct, the length of the left hepatic duct, the localization of the bile duct confluence for segments 2 and 3 of the umbilical portion of the left portal vein and the peculiarities of the afferent and efferent blood supply of these two segments. The aim of the present study is to identify and discuss such preconditions. Materials and Methods: The anatomical variations of the common bile duct confluence were analyzed by intraoperative cholangiography in 112 patients undergoing liver resections and in 32 preparations after left hepatectomy. The variations of the afferent and efferent blood supply were morphologically examined in 43 liver resections. Results: Seven types of anatomical variations of the common bile duct confluence were detected through intraoperative cholangiography, and three were extracted from the available literature. Three anatomical types (central, peripheral, and combined) of bile drainage from segment 4 were established. The mean distance between the bile duct confluence for segments 2 and 3 and the main hepatic duct confluence, i. e., the length of the left hepatic duct, was 3.68 cm. The anatomical peculiarities of the afferent and efferent arterial and venous supply of segments 2 and 3 were presented and discussed with respect to their roles in a safe right trisectionectomy. Conclusion: Surgeons’ sound knowledge of anatomical variations of the biliary tract and hepatic blood vessels coupled with increased experience and technique refinements could contribute to better outcomes in right trisectionectomy.

Kostov, Daniel V.; Kobakov, Georgi L.

2012-01-01

321

Drug Delivery to the Ischemic Brain  

PubMed Central

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

Thompson, Brandon J.; Ronaldson, Patrick T.

2014-01-01

322

Risk Factors and Biomarkers of Ischemic Stroke in Cancer Patients  

PubMed Central

Background and Purpose Stroke is common among cancer patients. However, risk factors and biomarkers of stroke in cancer patients are not well established. This study aimed to investigate risk factors and biomarkers as well as etiology of ischemic stroke in cancer patients. Methods A retrospective review was conducted in cancer patients with ischemic stroke who were admitted to a general hospital in Busan, Korea, between January 2003 and December 2012. The risk factors and biomarkers for stroke and stroke subtypes in cancer patients were compared with age- and sex-matched noncancer patients with ischemic stroke who were admitted to the same hospital during the same period. Results One hundred fifty-six cancer patients with ischemic stroke were identified. Cancer patients with ischemic stroke were found to have a significantly lower proportion of hypertension, atrial fibrillation, hyperlipidemia, and ischemic heart disease than noncancer patients with ischemic stroke. However, stroke biomarkers, such as erythrocyte sedimentation rate and high-sensitivity C-reactive protein, fibrinogen, pro-brain natriuretic peptide, and D-dimer levels, were significantly increased in cancer patients with ischemic stroke than in noncancer patients. Large-artery atherosclerosis and stroke of undetermined cause were more common in cancer patients with ischemic stroke than in noncancer patients with ischemic stroke. Conclusions Cancer patients with ischemic stroke showed different risk factors, stroke biomarkers, and stroke etiology compared with noncancer patients with ischemic stroke. PMID:24949315

Lee, Ji-Hun

2014-01-01

323

Clearspan User Guide CSUF VoIP Soft Phone  

E-print Network

Clearspan User Guide CSUF VoIP Soft Phone Last Revised: 05/07/12 #12;UG-CSUF VoIP Soft Phone FINAL Last Revised: 05/07/12 Page ii REVISION CONTROL Document Title: CSUF VoIP Soft Phone User Guide Author: IT Training & Support File Reference: UG-CSUF_VoIP_Soft_Phone.docx Revision History Revision Date Revised

de Lijser, Peter

324

Mobility support in IP: a survey of related protocols  

Microsoft Academic Search

This article presents an overview of a set of IP-based mobility protocols — Mobile IP, HAWAII, Cellular IP, Hierarchical MIP, TeleMIP, Dynamic Mobility Agent, and Terminal Independent MIP — that will play an important role in the forthcoming convergence of IP and legacy wireless networks. A comparative analysis with respect to system parameters such as location update, handoff latency and

Debanjan Saha; Amitava Mukherjee; Iti Saha Misra; Mohuya Chakraborty; N. Subhash

2004-01-01

325

MAP decoder architecture: soft IP for SOC applications  

Microsoft Academic Search

A soft IP for MAP decoder is presented. The Soft IP supports different design objectives, such as high performance and area efficiency. System parameters and required performance configure the IP yielding the architecture. The IP is realized using VHDL and scripts that accept design specification from the designer and automatically generate a synthesizable HDL. FPGA platform is used for rapidly

Mahmoud El-Assal; Magdy Bayoumi

2002-01-01

326

Loss of Potassium Homeostasis Underlies Hyperthermic Conduction Failure in Control and Preconditioned Locusts  

E-print Network

Loss of Potassium Homeostasis Underlies Hyperthermic Conduction Failure in Control homeostasis underlies hyperthermic conduction failure in control and preconditioned locusts. J Neurophysiol, neurons cease to function appropriately. Prior exposure to a heat stress (heat shock [HS]) can extend

Robertson, Meldrum

327

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

NASA Technical Reports Server (NTRS)

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.

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

1997-01-01

328

Impact of Severe Extracranial ICA Stenosis on MRI Perfusion and Diffusion Parameters in Acute Ischemic Stroke  

PubMed Central

Purpose: The aim of this study was to investigate the impact of a coexisting internal carotid artery (ICA) stenosis on lesion volumes as well as diffusion and perfusion parameters in acute ischemic stroke resulting from middle cerebral artery (MCA) occlusion. Material and methods: Magnetic resonance imaging data of 32 patients with MCA occlusion with or without additional ICA stenosis imaged within 4.5?h of symptom onset were analyzed. Both groups consisted of 16 patients. Acute diffusion lesions were semi-automatically segmented in apparent diffusion coefficient (ADC) MRI datasets. Perfusion maps of cerebral blood volume (CBV), cerebral blood flow, mean transit time and Tmax were calculated using perfusion-weighted MRI datasets. Tissue-at-risk (TAR) volumes were generated by subtracting the ADC lesion from the hypoperfusion lesion defined by Tmax >6?s. Median ADC and perfusion parameter values were extracted separately for the diffusion lesion and TAR and used for statistical analysis. Results: No significant differences were found between the groups regarding the diffusion lesion and TAR volumes. Statistical analysis of diffusion and perfusion parameters revealed CBV as the only parameter with a significant difference (p?=?0.009) contributing a small effect (?2?=?0.11) to the group comparison with higher CBV values for the patient group with a coexisting ICA stenosis, while no significant effects were found for the other diffusion and perfusion parameters analyzed. Conclusion: The results of this study suggest that a coexisting ICA stenosis does not have a strong effect on tissue status or perfusion parameters in acute stroke patients except for a moderate elevation of CBV. This may reflect improved collateral circulation or ischemic preconditioning in patients with a pre-existing proximal stenosis balancing impaired perfusion from the stenosis.

Kaesemann, Philipp; Thomalla, Götz; Cheng, Bastian; Treszl, Andras; Fiehler, Jens; Forkert, Nils Daniel

2014-01-01

329

Teleoperation over IP Network: Virtual PUMA Robot IEEEICIT'03 Teleoperation over IP Network  

E-print Network

Teleoperation over IP Network: Virtual PUMA Robot IEEEICIT'03 Teleoperation over IP Network : Virtual PUMA Robot P. Fraisse, C. Agniel, D. Andreu LIRMM - UMR 5506 Université Montpellier II / CNRS 161, we developed a real time Virtual Puma Robot based on RTLinux Operating System. This Virtual Robot

Boyer, Edmond

330

Ischemic Burden and Clinical Outcome: Is One ‘Culprit’ Ischemic Segment by Dobutamine Stress Magnetic Resonance Predictive?  

PubMed Central

Aims We sought to evaluate the impact of ischemic burden for the prediction of hard cardiac events (cardiac death or nonfatal myocardial infarction) in patients with known or suspected CAD who undergo dobutamine stress cardiac magnetic resonance imaging (DCMR) Methods We included 3166 patients (pts.), mean age 63±12 years, 27% female, who underwent DCMR in 3 tertiary cardiac centres (University Hospital Heildelberg, German Heart Institute and Kings College London). Pts. were separated in groups based on the number of ischemic segments by wall motion abnormalities (WMA) as follows: 1. no ischemic segment, 2. one ischemic segment, 3. two ischemic segments and 4. ?three ischemic segments. Cardiac death and nonfatal myocardial infarction were registered as hard cardiac events. Pts. with an “early” revascularization procedure (in the first three months after DCMR) were not included in the final survival analysis. Results Pts. were followed for a median of 3.1 years (iqr 2–4.5 years). 187 (5.9%) pts. experienced hard cardiac events. 2349 (74.2%) had no inducible ischemia, 189 (6%) had ischemia in 1 segment, 292 (9.2%) in 2 segments and 336 (10.6%) ?3 segments. Patients with only 1 ischemic segment showed a high rate of hard cardiac events of ?6% annually, which was 10-fold higher compared to those without ischemia (0.6% annually, p<0.001) but similar to those with 2 and ?3ischemic segments (?5.5% and ?7%, p?=?NS). Conclusions The presence of inducible ischemia even in a single ‘culprit’ myocardial segment during DCMR is enough to predict hard cardiac events in patients with known or suspected CAD. PMID:25517506

Nagel, Eike; Buss, Sebastian Johannes; Puntmann, Valentina; Wellnhofer, Ernst; Fleck, Eckart; Katus, Hugo Albert; Korosoglou, Grigorios

2014-01-01

331

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

NSDL National Science Digital Library

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

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

2005-07-05

332

Inflammatory mechanisms in ischemic stroke: therapeutic approaches  

Microsoft Academic Search

Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA) for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its

Shaheen E Lakhan; Annette Kirchgessner; Magdalena Hofer

2009-01-01

333

Vasoconstrictive neurovascular coupling during focal ischemic depolarizations.  

PubMed

Ischemic depolarizing events, such as repetitive spontaneous periinfarct spreading depolarizations (PIDs), expand the infarct size after experimental middle cerebral artery (MCA) occlusion. This worsening may result from increased metabolic demand, exacerbating the mismatch between cerebral blood flow (CBF) and metabolism. Here, we present data showing that anoxic depolarization (AD) and PIDs caused vasoconstriction and abruptly reduced CBF in the ischemic cortex in a distal MCA occlusion model in mice. This reduction in CBF during AD increased the area of cortex with 20% or less residual CBF by 140%. With each subsequent PID, this area expanded by an additional 19%. Drugs that are known to inhibit cortical spreading depression (CSD), such as N-methyl-D-aspartate receptor antagonists MK-801 and 7-chlorokynurenic acid, and sigma-1 receptor agonists dextromethorphan and carbetapentane, did not reduce the frequency of PIDs, but did diminish the severity of episodic hypoperfusions, and prevented the expansion of severely hypoperfused cortex, thus improving CBF during 90 mins of acute focal ischemia. In contrast, AMPA receptor antagonist NBQX, which does not inhibit CSD, did not impact the deterioration in CBF. When measured 24 h after distal MCA occlusion, infarct size was reduced by MK-801, but not by NBQX. Our results suggest that AD and PIDs expand the CBF deficit, and by so doing negatively impact lesion development in ischemic mouse brain. Mitigating the vasoconstrictive neurovascular coupling during intense ischemic depolarizations may provide a novel hemodynamic mechanism of neuroprotection by inhibitors of CSD. PMID:16340958

Shin, Hwa Kyoung; Dunn, Andrew K; Jones, Phillip B; Boas, David A; Moskowitz, Michael A; Ayata, Cenk

2006-08-01

334

Endovascular therapies in acute ischemic stroke.  

PubMed

Intraarterial therapy for acute ischemic stroke (AIS) was originally described five decades ago. Since then, the endovascular management of AIS endovascular therapy has advanced swiftly, and a promising body of evidence informing patient selection and interventional techniques has accrued. The authors discuss the evolution of endovascular therapy for AIS, including a review of recently published landmark clinical trials. PMID:24504606

Haussen, Diogo C; Yavagal, Dileep R

2013-11-01

335

Systemic corticosteroids in nonarteritic ischemic optic neuropathy  

PubMed Central

Nonarteritic ischemic optic neuropathy (NAION) is one of the most prevalent optic nerve disorders seen in ophthalmic practice. The role of corticosteroid therapy in NAION remains a highly controversial area of debate in ophthalmology. This brief review will provide an overview of the current clinical evidence on this topic as well as some comment on the medical debate. PMID:25449939

Al-Zubidi, Nagham; Zhang, Jason; Spitze, Arielle; Lee, Andrew G

2014-01-01

336

Cell Based Therapies for Ischemic Tissue Repair  

Cancer.gov

As the population ages and the acute mortality from cardiovascular disease decreases, a large population of patients is emerging who have symptomatic chronic ischemic cardiac and vascular disease, many of whom remain severely symptomatic despite exhausting conventional medical therapy and mechanical revascularization. Mounting evidence suggests that microvascular insufficiency plays a significant role in the pathophysiology of ischemia.

337

The cell biology of ischemic renal injury  

Microsoft Academic Search

Work during the past several years has produced new insights into many aspects of the cell biology of ischemic injury to the tubulointerstitium. The major processes are conveniently considered in terms of early events, the prelethal and lethal cell injuries that occur during the period of ischemia and in the first hours of reperfusion, and late events, the proliferation and

Joel M Weinberg

1991-01-01

338

[Thrombolytic therapy in ischemic cerebrovascular accidents].  

PubMed

Thrombolysis together with neuroprotective agents the two most important recent advances in the treatment of acute ischemic stroke. This update summarizes the recent randomized clinical trials and emphasizes the question of risk versus benefit of this potentially useful but dangerous treatment. PMID:7481300

Hommel, M; Kumral, E; Bogousslavsky, J

1995-09-19

339

Modulation of cardiac Na+,K+-ATPase cell surface abundance by simulated ischemia-reperfusion and ouabain preconditioning  

PubMed Central

Na+,K+-ATPase and cell survival were investigated in a cellular model of ischemia-reperfusion (I/R)-induced injury and protection by ouabain-induced preconditioning (OPC). Rat neonatal cardiac myocytes were subjected to 30 min of substrate and coverslip-induced ischemia followed by 30 min of simulated reperfusion. This significantly compromised cell viability as documented by lactate dehydrogenase release and Annexin V/propidium iodide staining. Total Na+,K+-ATPase ?1- and ?3-polypeptide expression remained unchanged, but cell surface biotinylation and immunostaining studies revealed that ?1-cell surface abundance was significantly decreased. Na+,K+-ATPase-activity in crude homogenates and 86Rb+ transport in live cells were both significantly decreased by about 30% after I/R. OPC, induced by a 4-min exposure to 10 ?M ouabain that ended 8 min before the beginning of ischemia, increased cell viability in a PKC?-dependent manner. This was comparable with the protective effect of OPC previously reported in intact heart preparations. OPC prevented I/R-induced decrease of Na+,K+-ATPase activity and surface expression. This model also revealed that Na+,K+-ATPase-mediated 86Rb+ uptake was not restored to control levels in the OPC group, suggesting that the increased viability was not conferred by an increased Na+,K+-ATPase-mediated ion transport capacity at the cell membrane. Consistent with this observation, transient expression of an internalization-resistant mutant form of Na+,K+-ATPase ?1 known to have increased surface abundance without increased ion transport activity successfully reduced I/R-induced cell death. These results suggest that maintenance of Na+,K+-ATPase cell surface abundance is critical to myocyte survival after an ischemic attack and plays a role in OPC-induced protection. They further suggest that the protection conferred by increased surface expression of Na+,K+-ATPase may be independent of ion transport. PMID:23086991

Belliard, Aude; Sottejeau, Yoann; Duan, Qiming; Karabin, Jessa L.

2013-01-01

340

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

NASA Technical Reports Server (NTRS)

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

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

1996-01-01

341

Preconditioning as a potential strategy for the prevention of Parkinson's disease.  

PubMed

Parkinson's disease (PD) is a chronic neurodegenerative movement disorder characterized by the progressive and massive loss of dopaminergic neurons by neuronal apoptosis in the substantia nigra pars compacta and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. A numerous of cellular processes including oxidative stress, mitochondrial dysfunction, and accumulation of ?-synuclein aggregates are considered to contribute to the pathogenesis of Parkinson's disease. A further understanding of the cellular and molecular mechanisms involved in the pathophysiology of PD is crucial for developing effective diagnostic, preventative, and therapeutic strategies to cure this devastating disorder. Preconditioning (PC) is assumed as a natural adaptive process whereby a subthreshold stimulus can promote protection against a subsequent lethal stimulus in the brain as well as in other tissues that affords robust brain tolerance facing neurodegenerative insults. Multiple lines of evidence have demonstrated that preconditioning as a possible neuroprotective technique may reduce the neural deficits associated with neurodegenerative diseases such as PD. Throughout the last few decades, a lot of efforts have been made to discover the molecular determinants involved in preconditioning-induced protective responses; although, the accurate mechanisms underlying this "tolerance" phenomenon are not fully understood in PD. In this review, we will summarize pathophysiology and current therapeutic approaches in PD and discuss about preconditioning in PD as a potential neuroprotective strategy. Also the role of gene reprogramming and mitochondrial biogenesis involved in the preconditioning-mediated neuroprotective events will be highlighted. Preconditioning may represent a promising therapeutic weapon to combat neurodegeneration. PMID:24696268

Golpich, Mojtaba; Rahmani, Behrouz; Mohamed Ibrahim, Norlinah; Dargahi, Leila; Mohamed, Zahurin; Raymond, Azman Ali; Ahmadiani, Abolhassan

2015-02-01

342

Nucleon-nucleus potentials by IP inversion  

NASA Astrophysics Data System (ADS)

The iterative-perturbative (IP) inversion algorithm makes it possible to determine, essentially uniquely, the complex potential, including spin-orbit component, for spin half particles given the elastic scattering S-matrix S ij. The same algorithm can be applied to fixed energy and, in certain cases, fixed partial wave inversion. Moreover, it can be applied to the intermediate "mixed case". We briefly define the classes of cases which can be studied, outline the IP method itself, and then review a wide range of applications of the method which have led to the extraction of information concerning nucleon-nucleus potentials. We then briefly list heavy ion applications. Reference is given to the code IMAGO which embodies the IP algorithm, and which can be applied to a very wide range of inversion situations for nucleons as well as spinless heavy ions, including identical bosons.

Mackintosh, R. S.; Cooper, S. G.

343

A survey of IP over ATM architectures  

SciTech Connect

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.

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

1997-07-01

344

Space-Based Voice over IP Networks  

NASA Technical Reports Server (NTRS)

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.

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

2007-01-01

345

Oat1/3 Restoration Protects against Renal Damage after Ischemic AKI.  

PubMed

Expression of proximal tubular organic anion transporters Oat1 and Oat3 is reduced by prostaglandin E2 (PGE2) after renal ischemia and reperfusion (I/R) injury. We hypothesized that impaired expression of Oat1/3 is decisively involved in deterioration of renal function after I/R injury. Therefore, we administered probenecid, which blocks proximal tubular indomethacin uptake, to abolish indomethacin mediated restoration of Oat1/3 regulation and its effect on renal functional and morphological outcome. Ischemic AKI was induced in rats by bilateral clamping of renal arteries for 45 min with 24h follow up. Low-dose indomethacin (1mg/kg) was given i.p. at the end of ischemia. Probenecid (50mg/kg) was administered i.p. 20 min later. Indomethacin restored Oat1/3 expression, PAH net secretion and PGE2 clearance and improved kidney function as measured by GFR, renal perfusion as determined by corrected PAH clearance and morphology, whereas it reduced renal cortical apoptosis and nitric oxide production. Notably, indomethacin did not affect inflammation parameters in the kidneys (e.g. MCP-1, ED1+-cells). On the other hand, probenecid blocked indomethacin induced restoration of Oat1/3 and moreover abrogated all beneficial effects. Our study indicates that the beneficial effect of low-dose indomethacin in iAKI is not due to its anti-inflammatory potency, but to its restoration of Oat1/3 expression and/or general renal function. Inhibition of proximal tubular indomethacin uptake abrogates the beneficial effect of indomethacin by resetting the PGE2 mediated Oat1/3 impairment, thus re-establishing renal damage. This provides evidence for a mechanistic effect of Oat1/3 in a new model of the induction of renal damage following ischemic AKI. PMID:25391897

Schneider, Reinhard; Meusel, Marcus; Betz, Boris; Held, Christopher; Möller-Ehrlich, Kerstin; Büttner-Herold, Maike; Wanner, Christoph; Gekle, Michael; Sauvant, Christoph

2014-11-12

346

ChIP-Enrich: gene set enrichment testing for ChIP-seq data.  

PubMed

Gene set enrichment testing can enhance the biological interpretation of ChIP-seq data. Here, we develop a method, ChIP-Enrich, for this analysis which empirically adjusts for gene locus length (the length of the gene body and its surrounding non-coding sequence). Adjustment for gene locus length is necessary because it is often positively associated with the presence of one or more peaks and because many biologically defined gene sets have an excess of genes with longer or shorter gene locus lengths. Unlike alternative methods, ChIP-Enrich can account for the wide range of gene locus length-to-peak presence relationships (observed in ENCODE ChIP-seq data sets). We show that ChIP-Enrich has a well-calibrated type I error rate using permuted ENCODE ChIP-seq data sets; in contrast, two commonly used gene set enrichment methods, Fisher's exact test and the binomial test implemented in Genomic Regions Enrichment of Annotations Tool (GREAT), can have highly inflated type I error rates and biases in ranking. We identify DNA-binding proteins, including CTCF, JunD and glucocorticoid receptor ? (GR?), that show different enrichment patterns for peaks closer to versus further from transcription start sites. We also identify known and potential new biological functions of GR?. ChIP-Enrich is available as a web interface (http://chip-enrich.med.umich.edu) and Bioconductor package. PMID:24878920

Welch, Ryan P; Lee, Chee; Imbriano, Paul M; Patil, Snehal; Weymouth, Terry E; Smith, R Alex; Scott, Laura J; Sartor, Maureen A

2014-07-01

347

Effects of hypoxic preconditioning on synaptic ultrastructure in mice.  

PubMed

Hypoxic preconditioning (HPC) elicits resistance to more drastic subsequent insults, which potentially provide neuroprotective therapeutic strategy, but the underlying mechanisms remain to be fully elucidated. Here, we examined the effects of HPC on synaptic ultrastructure in olfactory bulb of mice. Mice underwent up to five cycles of repeated HPC treatments, and hypoxic tolerance was assessed with a standard gasp reflex assay. As expected, HPC induced an increase in tolerance time. To assess synaptic responses, Western blots were used to quantify protein levels of representative markers for glia, neuron, and synapse, and transmission electron microscopy was used to examine synaptic ultrastructure and mitochondrial density. HPC did not significantly alter the protein levels of astroglial marker (GFAP), neuron-specific markers (GAP43, Tuj-1, and OMP), synaptic number markers (synaptophysin and SNAP25) or the percentage of excitatory synapses versus inhibitory synapses. However, HPC significantly affected synaptic curvature and the percentage of synapses with presynaptic mitochondria, which showed concomitant change pattern. These findings demonstrate that HPC is associated with changes in synaptic ultrastructure. Synapse 69:7-14, 2015. © 2014 Wiley Periodicals, Inc. PMID:25155519

Liu, Yi; Sun, Zhishan; Sun, Shufeng; Duan, Yunxia; Shi, Jingfei; Qi, Zhifeng; Meng, Ran; Sun, Yongxin; Zeng, Xianwei; Chui, Dehua; Ji, Xunming

2015-01-01

348

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

PubMed

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

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

2015-02-01

349

ABS Rules for Integrated Power Systems (IPS)  

Microsoft Academic Search

This paper will provide an overview of the american bureau of shipping (ABS) rules and for integrated power systems (IPS). The paper will include a review and comparison of the key requirements from the ABS steel vessel rules (for commercial ships) and the ABS naval vessel rules (for military ships) for integrated electric propulsion systems. The paper will explain how

M. Roa

2009-01-01

350

DNS Extensions to Support IP Version 6  

Microsoft Academic Search

This document defines the changes that need to be made to the Domain Name System (DNS) to support hosts running IP version 6 (IPv6). The changes include a resource record type to store an IPv6 address, a domain to support lookups based on an IPv6 address, and updated definitions of existing query types that return Internet addresses as part of

S. Thomson; C. Huitema; V. Ksinant

1995-01-01

351

Is VoIP Worth It?  

ERIC Educational Resources Information Center

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

Schaffhauser, Dian

2008-01-01

352

IP Cambodge Paris | 14 octobre 2014  

E-print Network

IP Cambodge Paris | 14 octobre 2014 Le papillomavirus humain associé à une maladie auto- immune Le réaction à une infection par le papillomavirus humain (de type HPV-16), ce qui indiquerait un lien entre la muqueuses impliquait des lymphocytes spécifiques de la réponse contre le papillomavirus humain (HPV). Cela

van Tiggelen, Bart

353

A native IP satellite communications system  

NASA Astrophysics Data System (ADS)

? 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*IP—Local 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.

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

2004-08-01

354

An analysis of IP Multimedia Subsystems (IMS)  

Microsoft Academic Search

This paper analyzes the complexity of IP multimedia subsystems (IMS) proposed by 3GPP\\/3GPP2. Using two different mobility models, the paper provides a methodology to determine the number of accesses to the IMS servers. The analysis considers mobility of users across registration areas, which generates IMS registration requests as well as signaling to IMS servers due to service requests initiated by

Lava N. Saleem; Seshadri Mohan

2007-01-01

355

Renewable energy in IP over WDM networks  

Microsoft Academic Search

Recent studies have shown that the Information and Communication Technology (ICT) industry is responsible for about 2% of the global emission of CO2 and this percentage is expected to increase as the Internet expands in bandwidth and reach. In this paper, we propose the use of renewable energy in IP over WDM networks to minimize CO2 emissions. A Linear Programming

Xiaowen Dong; Taisir El-Gorashi; Jaafar M. H. Elmirghani

2010-01-01

356

Operational Space Weather Products at IPS  

NASA Astrophysics Data System (ADS)

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.

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

2008-12-01

357

Advanced DSRC system for supporting mobile IP  

Microsoft Academic Search

ITS (Intelligent Transportation System) will provide traffic efficiency and mobile safety without construction of new roads. To provide ITS services, DSRC (Dedicated Short-Range Communication) has been developed to provide high-speed radio link between RSE (Road Side Equipment) and OBE (On Board Equipment). In this paper, we present the requirements and structure of advanced DSRC system for supporting Mobile IP service

Hyun Mee Choi; Choon Sik Yim; Deock Gil Oh

2001-01-01

358

Integrating IP traffic into fieldbus networks  

Microsoft Academic Search

Fieldbus networks are traditionally used in order to interconnect devices at the field level e.g. sensors and actuators, so that real time or critical time requirements are met concerning data transfer. In addition to traditional fieldbus traffic, novel applications, such as industrial multimedia applications, require the integration of IP traffic into fieldbus networks as well. This integration should be done

Efstratios Nikoloutsos; Aggeliki Prayati; Athanasios P. Kalogeras; Vassilis Kapsalis; Stavros Koubias; George Papadopoulos

2002-01-01

359

Customer choice test is running well for IP  

SciTech Connect

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

NONE

1996-06-01

360

A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice  

PubMed Central

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells. PMID:25617900

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann

2015-01-01

361

Ventricular tachycardia in ischemic heart disease substrates  

PubMed Central

Advances in the treatment of myocardial infarction (MI) have improved survival after ischemic cardiac injury. Post-infarct structural and functional remodeling results in electrophysiologic substrates at risk for monomorphic ventricular tachycardia (MMVT). Characterization of this substrate using a variety of clinical and investigative tools has improved our understanding of MMVT circuits, and has accelerated the development of device and catheter-based therapies aimed at identification and elimination of this arrhythmia. This review will discuss the central role of the ischemic heart disease substrate in the development MMVT. Electrophysiologic characterization of the post-infarct myocardium using bipolar electrogram amplitudes to delineate scar border zones will be reviewed. Functional electrogram determinants of reentrant circuits such as isolated late potentials will be discussed. Strategies for catheter ablation of reentrant ventricular tachycardia, including structural and functional targets will also be examined, as will the role of the epicardial mapping and ablation in the management of recurrent MMVT. PMID:24568826

Ajijola, Olujimi A.; Tung, Roderick; Shivkumar, Kalyanam

2014-01-01

362

Linking Notch signaling to ischemic stroke  

PubMed Central

Vascular smooth muscle cells (SMCs) have been implicated in the pathophysiology of stroke, the third most common cause of death and the leading cause of long-term neurological disability in the world. However, there is little insight into the underlying cellular pathways that link SMC function to brain ischemia susceptibility. Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype. PMID:18347334

Arboleda-Velasquez, Joseph F.; Zhou, Zhipeng; Shin, Hwa Kyoung; Louvi, Angeliki; Kim, Hyung-Hwan; Savitz, Sean I.; Liao, James K.; Salomone, Salvatore; Ayata, Cenk; Moskowitz, Michael A.; Artavanis-Tsakonas, Spyros

2008-01-01

363

Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments  

PubMed Central

Hypoxic ischemic encephalopathy (HIE) is a serious birth complication affecting full term infants: 40–60% of affected infants die by 2 years of age or have severe disabilities. The majority of the underlying pathologic events of HIE are a result of impaired cerebral blood flow and oxygen delivery to the brain with resulting primary and secondary energy failure. In the past, treatment options were limited to supportive medical therapy. Currently, several experimental treatments are being explored in neonates and animal models to ameliorate the effects of secondary energy failure. This review discusses the underlying pathophysiologic effects of a hypoxic-ischemic event and experimental treatment modalities being explored to manage infants with HIE. Further research is needed to better understand if the long-term impact of the experimental treatments and whether the combinations of experimental treatments can improve outcomes in infants with HIE. PMID:21927583

Allen, Kimberly A.; Brandon, Debra H.

2011-01-01

364

Systemic Reperfusion Therapy in Acute Ischemic Stroke  

Microsoft Academic Search

Introduction: Experimental and clinical studies indicate that early reperfusion of occluded brain-supplying arteries reduces the size of injury and improves outcome. Recombinant tissue plasminogen activator (t-PA) is the only drug approved for systemic reperfusion in acute ischemic stroke. However, the use of intravenous t-PA is currently limited by its narrow therapeutic window. Methods: We reviewed the approaches to extending systemic

P. Martínez-Sánchez; E. Díez-Tejedor; B. Fuentes; W. Hacke

2007-01-01

365

Hypoxic Ischemic Encephalopathy in the Term Infant  

PubMed Central

Synopsis Hypoxia-ischemia in the perinatal period is an important cause of cerebral palsy and associated disabilities in children. There has been significant research progress in hypoxic-ischemic encephalopathy over the last two decades and many new molecular mechanisms have been identified. Despite all these advances, therapeutic interventions are still limited. In this review paper, we discuss a number of molecular pathways involved in hypoxia-ischemia, and potential therapeutic targets. PMID:19944838

Fatemi, Ali; Wilson, Mary Ann; Johnston, Michael V.

2010-01-01

366

Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy  

PubMed Central

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common clinical presentation of acute ischemic damage to the optic nerve. Most treatments proposed for NAION are empirical and include a wide range of agents presumed to act on thrombosis, on the blood vessels, or on the disc edema itself. Others are presumed to have a neuroprotective effect. Although there have been multiple therapies attempted, most have not been adequately studied, and animal models of NAION have only recently emerged. The Ischemic Optic Neuropathy Decompression Trial (IONDT), the only class I large multicenter prospective treatment trial for NAION, found no benefit from surgical intervention. One recent large, nonrandomized controlled study suggested that oral steroids might be helpful for acute NAION. Others recently proposed interventions are intravitreal injections of steroids or anti-vascular endothelial growth factor (anti-VEGF) agents. There are no class I studies showing benefit from either medical or surgical treatments. Most of the literature on the treatment of NAION consists of retrospective or prospective case series and anecdotal case reports. Similarly, therapies aimed at secondary prevention of fellow eye involvement in NAION remain of unproven benefit. PMID:20006051

Atkins, Edward J.; Bruce, Beau B.; Newman, Nancy J.; Biousse, Valérie

2013-01-01

367

Transglutaminase 2 protects against ischemic stroke  

PubMed Central

Transglutaminase 2 (TG2) is a multifunctional protein that modulates cell survival and death pathways. It is upregulated in numerous ischemic models, and protects primary neurons from oxygen and glucose deprivation. TG2 binds to the hypoxia inducible factor (HIF) 1? and decreases the upregulation of hypoxic-induced proapoptotic genes. To investigate the role of TG2 in ischemic stroke in vivo, we used the murine, permanent middle cerebral artery (MCA) ligation model. TG2 mRNA levels are increased after MCA ligations, and transgenic mice that express human TG2 in neurons had significantly smaller infarct volumes than wild type littermates. Further, TG2 translocates into the nucleus within 2 hours post ligation. Nuclear-localized TG2 is also apparent in human stroke cases. TG2 suppressed the up regulation of the HIF-induced, proapoptotic gene, Noxa. The findings of this study indicate that TG2 plays a role in attenuating ischemic-induced cell death possibly by modulating hypoxic-induced transcriptional processes. PMID:20451610

Filiano, AJ; Tucholski, J; Dolan, PJ; Colak, G; Johnson, GVW

2010-01-01

368

The Long Wavelength Array (LWA) and Interplanetary Scintillation (IPS)  

E-print Network

The Long Wavelength Array (LWA) and Interplanetary Scintillation (IPS) Patrick C. Crane 12 January scintillation (IPS) is the random fluctuation in the intensity and phase of electromagnetic waves passing

Ellingson, Steven W.

369

Service Invocation Issues within the IP Multimedia Subsystem  

Microsoft Academic Search

IP Multimedia Subsystem (IMS) is a standardized service control overlay meant to offer rich IP multimedia services to the users in different networks. However, IMS service invocation as specified by 3 GPP encounters multiple issues and ambiguities including \\

Anahita Gouya; Noël Crespi; Emmanuel Bertin

2007-01-01

370

Bestellung und Umbuchungsantrag Cisco 6945 VoIP Telefon -Wei  

E-print Network

20120208 Bestellung und Umbuchungsantrag Cisco 6945 VoIP Telefon - Wei� Verbindliche Bestellung eines VoIP Telefons des Typs Cisco 6945 (Farbe Wei�) aus dem Portfolio des HRZ der Universität Bielefeld

Moeller, Ralf

371

Bestellung und Umbuchungsantrag Cisco 6901 VoIP Telefon -Wei  

E-print Network

20120208 Bestellung und Umbuchungsantrag Cisco 6901 VoIP Telefon - Wei� Verbindliche Bestellung eines VoIP Telefons des Typs Cisco 6901 (Farbe Wei�) aus dem Portfolio des HRZ der Universität Bielefeld

Moeller, Ralf

372

Gauss-Newton inspired preconditioned optimization in large deformation diffeomorphic metric mapping.  

PubMed

In this work, we propose a novel preconditioned optimization method in the paradigm of Large Deformation Diffeomorphic Metric Mapping (LDDMM). The preconditioned update scheme is formulated for the non-stationary and the stationary parameterizations of diffeomorphisms, yielding three different LDDMM methods. The preconditioning matrices are inspired in the Hessian approximation used in Gauss-Newton method. The derivatives are computed using Frechet differentials. Thus, optimization is performed in a Sobolev space, in contrast to optimization in L(2) commonly used in non-rigid registration literature. The proposed LDDMM methods have been evaluated and compared with their respective implementations of gradient descent optimization. Evaluation has been performed using real and simulated images from the Non-rigid Image Registration Evaluation Project (NIREP). The experiments conducted in this work reported that our preconditioned LDDMM methods achieved a performance similar or superior to well-established-in-literature gradient descent non-stationary LDDMM in the great majority of cases. Moreover, preconditioned optimization showed a substantial reduction in the execution time with an affordable increase of the memory usage per iteration. Additional experiments reported that optimization using Frechet differentials should be preferable to optimization using L(2) differentials. PMID:25254606

Hernandez, Monica

2014-10-21

373

Gauss–Newton inspired preconditioned optimization in large deformation diffeomorphic metric mapping  

NASA Astrophysics Data System (ADS)

In this work, we propose a novel preconditioned optimization method in the paradigm of Large Deformation Diffeomorphic Metric Mapping (LDDMM). The preconditioned update scheme is formulated for the non-stationary and the stationary parameterizations of diffeomorphisms, yielding three different LDDMM methods. The preconditioning matrices are inspired in the Hessian approximation used in Gauss–Newton method. The derivatives are computed using Frechet differentials. Thus, optimization is performed in a Sobolev space, in contrast to optimization in L2 commonly used in non-rigid registration literature. The proposed LDDMM methods have been evaluated and compared with their respective implementations of gradient descent optimization. Evaluation has been performed using real and simulated images from the Non-rigid Image Registration Evaluation Project (NIREP). The experiments conducted in this work reported that our preconditioned LDDMM methods achieved a performance similar or superior to well-established-in-literature gradient descent non-stationary LDDMM in the great majority of cases. Moreover, preconditioned optimization showed a substantial reduction in the execution time with an affordable increase of the memory usage per iteration. Additional experiments reported that optimization using Frechet differentials should be preferable to optimization using L2 differentials.

Hernandez, Monica

2014-10-01

374

Preconditioning of Microglia by ?-Synuclein Strongly Affects the Response Induced by Toll-like Receptor (TLR) Stimulation  

PubMed Central

In recent years, it has become accepted that ?-synuclein (?Syn) has a key role in the microglia-mediated neuroinflammation, which accompanies the development of Parkinson’s disease and other related disorders, such as Dementia with Lewy Bodies and Alzheimer’s disease. Nevertheless, the cellular and molecular mechanisms underlying its pathological actions, especially in the sporadic forms of the diseases, are not completely understood. Intriguingly, several epidemiological and animal model studies have revealed a link between certain microbial infections and the onset or progression of sporadic forms of these neurodegenerative disorders. In this work, we have characterized the effect of toll-like receptor (TLR) stimulation on primary murine microglial cultures and analysed the impact of priming cells with extracellular wild-type (Wt) ?Syn on the subsequent TLR stimulation of cells with a set of TLR ligands. By assaying key interleukins and chemokines we report that specific stimuli, in particular Pam3Csk4 (Pam3) and single-stranded RNA40 (ssRNA), can differentially affect the TLR2/1- and TLR7-mediated responses of microglia when pre-conditioned with ?Syn by augmenting IL-6, MCP-1/CCL2 or IP-10/CXCL10 secretion levels. Furthermore, we report a skewing of ?Syn-primed microglia stimulated with ssRNA (TLR7) or Pam3 (TLR2/1) towards intermediate but at the same time differential, M1/M2 phenotypes. Finally, we show that the levels and intracellular location of activated caspase-3 protein change significantly in ?Syn-primed microglia after stimulation with these particular TLR agonists. Overall, we report a remarkable impact of non-aggregated ?Syn pre-sensitization of microglia on TLR-mediated immunity, a phenomenon that could contribute to triggering the onset of sporadic ?-synuclein-related neuropathologies. PMID:24236103

Gonzalez-Rey, Elena; Lachaud, Christian C.; Guilliams, Tim; Fernandez-Montesinos, Rafael; Benitez-Rondan, Alicia; Robledo, Gema; Hmadcha, Abdelkrim; Delgado, Mario; Dobson, Christopher M.; Pozo, David

2013-01-01

375

Extracting transcription factor targets from ChIP-Seq data  

Microsoft Academic Search

ChIP-Seq technology, which combines chromatin immunoprecipitation (ChIP) with massively parallel sequencing, is rapidly replacing ChIP-on-chip for the genome-wide identification of transcription factor binding events. Identifying bound regions from the large number of sequence tags produced by ChIP-Seq is a challenging task. Here, we present GLITR (GLobal Identifier of Target Regions), which accurately identifies enriched regions in target data by calculating

Geetu Tuteja; Peter White; Jonathan Schug; Klaus H. Kaestner

2009-01-01

376

QoS architecture in IP multimedia subsystem of UMTS  

Microsoft Academic Search

IMS is the evolution of the UMTS toward an all-IP network supporting IP-based multimedia services, like VoIP, conferencing, push-to-talk or mobile gaming. As new services require high restrictions in network parameters, the support for QoS in necessary. The aim of this paper is to present the policy based architecture in IP multimedia subsystem of UMTS, its components and their interactions.

S. Zoric; J. Barakovic; H. Hodzic

2008-01-01

377

Lysine deacetylation in ischaemic preconditioning: the role of SIRT1  

PubMed Central

Aims Acute ischaemic preconditioning (IPC) induces protection against cardiac ischaemia–reperfusion (IR) via post-translational modification of key proteins. Lysine (Lys) acetylation is an important regulator of protein function, but this type of modification has not been studied in the context of IPC. We investigated Lys acetylation in IPC and its upstream regulation by SIRT1. Methods and results Hearts from C57BL/6 mice were Langendorff-perfused and subjected to IPC and IR injury. Mice were exposed to IPC by in vivo coronary artery occlusion. An isolated cardiomyocyte model of IPC was also developed. Lys acetylation was measured by western blotting, and pharmacological modulators of Lys acetylation were tested. More Lys deacetylation was observed in IPC, in the Langendorff, in vivo, and cellular IPC models; this was concurrent with an increase in SIRT1 activity measured by p53 Lys379 deacetylation. IPC was not accompanied by changes in SIRT1 protein level, but evidence was obtained for SIRT1 modification by Small Ubiquitin-like Modifier (SUMOylation) in IPC. Furthermore, the specific SIRT1 inhibitor splitomicin reversed both IPC-mediated Lys deacetylation and IPC-induced cardioprotection. Inhibition of nicotinamide phosphoribosyltransferase (Nampt, an important enzyme which regulates SIRT1 activity by maintaining availability of the substrate NAD+) also blocked both IPC-induced deacetylation and cardioprotection. Conclusion Lys deacetylation occurs during IPC and an elevation in SIRT1 activity plays a role in this phenomenon. Inhibition of SIRT1, either directly or by restricting the availability of its substrate NAD+, inhibits IPC. Together these data suggest a role for SIRT1-mediated Lys deacetylation in the mechanism of acute IPC. PMID:20823277

Nadtochiy, Sergiy M.; Redman, Emily; Rahman, Irfan; Brookes, Paul S.

2011-01-01

378

Human Amniotic Fluid Stem Cell Preconditioning Improves Their Regenerative Potential  

PubMed Central

Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell–derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line–derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning. PMID:22066606

Rota, Cinzia; Imberti, Barbara; Pozzobon, Michela; Piccoli, Martina; De Coppi, Paolo; Atala, Anthony; Gagliardini, Elena; Xinaris, Christodoulos; Benedetti, Valentina; Fabricio, Aline S.C.; Squarcina, Elisa; Abbate, Mauro; Benigni, Ariela; Remuzzi, Giuseppe

2012-01-01

379

Preconditioning mediated by sublethal oxygen–glucose deprivation-induced cyclooxygenase-2 expression via the signal transducers and activators of transcription 3 phosphorylation  

PubMed Central

The signal transducers and activators of transcription (STATs) were found to be essential for cardioprotection. However, their role in preconditioning (PC) neuroprotection remains undefined. Previously, our studies showed that PC mediated a signaling cascade that involves activation of epsilon protein kinase C (?PKC), extracellular signal-regulated kinase (ERK1/2), and cyclooxygenase-2 (COX-2) pathways. However, the intermediate pathway by which ERK1/2 activates COX-2 was not defined. In this study, we investigated whether the PC-induced signaling pathway requires phosphorylation of STAT isoforms for COX-2 expression. To mimic PC or lethal ischemia, mixed cortical neuron/astrocyte cell cultures were subjected to 1 and/or 4 h of oxygen–glucose deprivation (OGD), respectively. The results indicated serine phosphorylation of STAT3 after PC or ?PKC activation. Inhibition of either ?PKC or ERK1/2 activation abolished PC-induced serine phosphorylation of STAT3. Additionally, inhibition of STAT3 prevented PC-induced COX-2 expression and neuroprotection against OGD. Therefore, our findings suggest that PC signaling cascade involves STAT3 activation after ?PKC and ERK1/2 activation. Finally, we show that STAT3 activation mediates COX-2 expression and ischemic tolerance. PMID:18398416

Kim, Eun J; Raval, Ami P; Perez-Pinzon, Miguel A

2008-01-01

380

Endothelial NOS activity and myocardial oxygen metabolism define the salvageable ischemic time window for ischemic postconditioning  

PubMed Central

Ischemic postconditioning (IPOC) could be ineffective or even detrimental if the index ischemic duration is either too short or too long. The present study is to demonstrate that oxygen supply and metabolism defines a salvageable ischemic time window of IPOC in mice. C57BL/6 mice underwent coronary artery occlusion followed by reperfusion (I/R), with or without IPOC by three cycles of 10 s/10 s R/I. In vivo myocardial tissue oxygenation was monitored with electron paramagnetic resonance oximetry. Regional blood flow (RBF) was measured with a laser Doppler monitor. At the end of 60 min reperfusion, tissue from the risk area was collected, and mitochondrial enzyme activities were assayed. Tissue oximetry demonstrated that I/R induced a reperfusion hyperoxygenation state in the 30- and 45-min but not 15- and 60-min ischemia groups. IPOC attenuated the hyperoxygenation with 45 but not 30 min ischemia. RBF, eNOS phosphorylation, and mitochondrial enzyme activities were suppressed after I/R with different ischemic time, and IPOC afforded protection with 30 and 45 but not 60 min ischemia. Infarct size measurement indicated that IPOC reduced infarction with 30 and 45 min but not 60 min ischemia. Clearly, IPOC protected mouse heart with a defined ischemic time window between 30 and 45 min. This salvageable time window was accompanied by the improvement of RBF due to increased phosphorylated eNOS and the preservation of mitochondrial oxygen consumption due to conserved mitochondrial enzyme activities. Interestingly, this salvageable ischemic time window was mirrored by tissue hyperoxygenation status in the postischemic heart. PMID:21217066

Cai, Ming; Li, Yuanjing; Xu, Yi; Swartz, Harold M.; Chen, Chwen-Lih; Chen, Yeong-Renn

2011-01-01

381

Role of ipsdienol, ipsenol, and cis-verbenol in chemical ecology of Ips avulsus, Ips calligraphus, and Ips grandicollis (Coleoptera: Curculionidae: Scolytinae).  

PubMed

Stressed or damaged pine (Pinus sp.) trees in the southeastern United States are often colonized simultaneously by three southern Ips species (Coleoptera: Curculionidae: Scolytinae): small southern pine engraver, Ips avulsus (Eichhoff); sixspined ips, Ips calligraphus (Germar); and eastern fivespined ips, Ips grandicollis (Eichhoff). All three species mediate colonization of host material with volatile pheromones. All of the southern Ips produce cis-verbenol, and either ipsdienol or ipsenol, and electrophysiological studies have demonstrated that all three southern Ips are able to detect all three compounds. This study examined the role of ipsdienol, ipsenol, and cis-verbenol in the chemical ecology of the southern Ips in Georgia and Louisiana. The most attractive blends of pheromones, with the fewest number of components, were ipsdienol plus ipsenol for I. avulsus, cis-verbenol plus ipsdienol for I. calligraphus, and either cis-verbenol plus ipsenol or ipsdienol plus ipsenol for I. grandicollis. Cross-attraction of I. grandicollis to the pheromone blend most attractive to I. avulsus was observed. Although the presence of heterospecific pheromone reduced the catches of all three species (i.e., the tertiary blend captured fewer beetles than the most attractive binary blends) in both states (significantly in two cases), high numbers of all three species were still captured in traps baited with all three compounds. These results suggest that the pheromones cis-verbenol, ipsdienol, and ipsenol can be combined for monitoring all three species of the southern Ips simultaneously. PMID:22812131

Allison, Jeremy D; McKenney, Jessica L; Miller, Daniel R; Gimmel, Matthew L

2012-06-01

382

Toward a More Practical Marking Scheme for IP Traceback  

Microsoft Academic Search

Probabilistic packet marking (PPM) has been studied as a promising approach to realize IP traceback. In this pa- per, we propose a new PPM approach that improves the current state of the art in two practical directions: (1) it improves the efciency and accuracy of IP traceback and (2) it provides incentives for ISPs to deploy IP traceback in their

Chao Gong; Kamil Saraç

2006-01-01

383

Voice over IP: Risks, Threats and Vulnerabilities Angelos D. Keromytis  

E-print Network

Europe Sophia-Antipolis, France Abstract-- Voice over IP (VoIP) and Internet Multimedia Subsystem (IMS Multimedia Subsystem (IMS), refers to a class of products that enable advanced communication services overVoice over IP: Risks, Threats and Vulnerabilities Angelos D. Keromytis Symantec Research Labs

Yang, Junfeng

384

Convergent IPTV Services over IP Multimedia Alia Bellabas  

E-print Network

Convergent IPTV Services over IP Multimedia Subsystem Alia Bellabas IRISA, INSA Rennes alia.najah@orange-ftgroup.com Abstract--IP multimedia Subsystem (IMS) is one the most promising architectures for IP Television (IPTV Telecommunication concepts and Internet service technologies. This gives another dimension to the multimedia

Boyer, Edmond

385

CISCO IP 7905/7906 / 7912 FONCTIONS TLPHONIQUES  

E-print Network

CISCO IP 7905/7906 / 7912 FONCTIONS T�L�PHONIQUES FONCTIONS DE BASE Documentation Cisco_IP_7905'initiateur peut se retirer sans interrompre l'appel mais aucun autre participant ne pourra s'y ajouter. #12;CISCO à plusieurs personnes de se joindre à un appel conférence en cours. Documentation Cisco_IP_7905

Skorobogatiy, Maksim

386

IP ROUTING ISSUES IN SATELLITE CONSTELLATION NETWORKS A. CLERGET,2  

E-print Network

1 IP ROUTING ISSUES IN SATELLITE CONSTELLATION NETWORKS L. WOOD,*1 A. CLERGET,2 I. ANDRIKOPOULOS,1 broadband satellite constellation networks, currently under development, will be required to transport IP traffic. A case can be made for implementing IP routing directly within the constellation network

Wood, Lloyd

387

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

Federal Register 2010, 2011, 2012, 2013, 2014

...IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT) AGENCY...to conduct an automated self risk assessment. The requested questionnaire...electronic execution of SOPD's risk assessment to focus protection...

2012-06-05

388

Preconditioning for the Navier-Stokes equations with finite-rate chemistry  

NASA Technical Reports Server (NTRS)

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.

Godfrey, Andrew G.; Walters, Robert W.; Van Leer, Bram

1993-01-01

389

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

NASA Technical Reports Server (NTRS)

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

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

1999-01-01

390

I want my voice to be heard: IP over Voice-over-IP for unobservable censorship circumvention  

E-print Network

unobservability against traffic analysis and standard censorship techniques. Keywords-Internet Censorship the Internet. Censorship devices leverage various techniques [2], [3] ranging from simple IP address blockingI want my voice to be heard: IP over Voice-over-IP for unobservable censorship circumvention Amir

Borisov, Nikita

391

Mechanical preconditioning enables electrophysiologic coupling of skeletal myoblast cells to myocardium  

PubMed Central

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

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

2015-01-01

392

IP3 Receptor-Operated Calcium Entry  

NSDL National Science Digital Library

This Perspective by Mikoshiba and Hattori is the third in a series on cellular calcium release mechanisms. The authors describe the regulated release of calcium from intracellular stores by the inositol 1,4,5 trisphosphate receptor (IP3R) and the relationship of this release mechanism to calcium influx from the extracellular milieu through store-operated calcium channels. They discuss a model proposing that intracellular and plasma membrane calcium channels are functionally and physically coupled.

Katsuhiko Mikoshiba (Japan; University of Tokyo and the Laboratory for Developmental Neurobiology REV)

2000-09-26

393

Optimizing resources utilization in IP Multimedia Subsystem  

Microsoft Academic Search

IP Multimedia Subsystem (IMS), an architectural framework for delivering multimedia services standardized by Third Generation Partnership (3GPP\\/3GPP2), is deployed as part of 3G and beyond wireless networks. It facilitates wireless carriers to offer rich multimedia services such as Chat, Presence, and Video Conference with a high degree of flexibility. These services vary in terms of their delay sensitivity and cost.

Lava Al-Doski; Ayman Abbosh; Radu F. Babiceanu; Seshadri Mohan

2012-01-01

394

Interworking Architectures for IP Multimedia Subsystems  

Microsoft Academic Search

The future fourth generation wireless heterogeneous networks aim to integrate various wireless access technologies and to\\u000a support the IMS (IP multimedia subsystem) sessions. In this paper, we propose the Loosely Coupled Satellite-Cellular-WiMAX-WLAN\\u000a (LCSCW2) and the Tightly Coupled Satellite- Cellular-WiMAX-WLAN (TCSCW2) interworking architectures. The LCSCW2 and TCSCW2\\u000a architectures use the loosely coupling and tightly coupling approach, respectively. Both of them integrate

Arslan Munir; Vincent W. S. Wong

2007-01-01

395

Policy control framework for IP Multimedia Subsystem  

Microsoft Academic Search

In this paper, we propose a subscription-based policy control framework that implements a subscription-centered approach for policy control for IP Multimedia Subsystem (IMS), defined by 3rd Generation Partnership Project (3GPP), Release 7. The framework also enables flexible policy definitions based on the subscriber's profile at the application level. In addition, the framework provides functionalities of organizing the subscription data, identifying

Nidal Nasser; Ming Shang

2009-01-01

396

A Distributed IP Multimedia Subsystem (IMS)  

Microsoft Academic Search

This document presents the architecture of a distributed IP Multimedia Subsystem (IMS). The architecture distributes network functional elements in Distributed Hash Tables (DHT) overlay network. This work focuses on distributing the SIP proxies, such as the Serving-Call\\/Session Control Function (S-CSCF) and the Interrogating-Call\\/Session Control Function, as well as the Home Subscriber server (HSS), and up to some degree, presence servers.

Marcin Matuszewski; Miguel A. Garcia-martin

2007-01-01

397

Research study on IPS digital controller design  

NASA Technical Reports Server (NTRS)

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.

Kuo, B. C.; Folkerts, C.

1976-01-01

398

Propulsion-related flowfields using the preconditioned Navier-Stokes equations  

NASA Astrophysics Data System (ADS)

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.

Venkateswaran, S.; Weiss, J. M.; Merkle, C. L.; Choi, Y.-H.

1992-07-01

399

Preconditioning for the Navier-Stokes equations with finite-rate chemistry  

NASA Technical Reports Server (NTRS)

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.

Godfrey, Andrew G.

1993-01-01

400

Preconditioning electromyographic data for an upper extremity model using neural networks  

NASA Technical Reports Server (NTRS)

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.

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

1994-01-01

401

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

PubMed Central

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

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

2014-01-01

402

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

SciTech Connect

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.

Nayar, R. Daniel

2005-08-01

403

Structural genomic variation in ischemic stroke  

PubMed Central

Technological advances in molecular genetics allow rapid and sensitive identification of genomic copy number variants (CNVs). This, in turn, has sparked interest in the function such variation may play in disease. While a role for copy number mutations as a cause of Mendelian disorders is well established, it is unclear whether CNVs may affect risk for common complex disorders. We sought to investigate whether CNVs may modulate risk for ischemic stroke (IS) and to provide a catalog of CNVs in patients with this disorder by analyzing copy number metrics produced as a part of our previous genome-wide single-nucleotide polymorphism (SNP)-based association study of ischemic stroke in a North American white population. We examined CNVs in 263 patients with ischemic stroke (IS). Each identified CNV was compared with changes identified in 275 neurologically normal controls. Our analysis identified 247 CNVs, corresponding to 187 insertions (76%; 135 heterozygous; 25 homozygous duplications or triplications; 2 heterosomic) and 60 deletions (24%; 40 heterozygous deletions;3 homozygous deletions; 14 heterosomic deletions). Most alterations (81%) were the same as, or overlapped with, previously reported CNVs. We report here the first genome-wide analysis of CNVs in IS patients. In summary, our study did not detect any common genomic structural variation unequivocally linked to IS, although we cannot exclude that smaller CNVs or CNVs in genomic regions poorly covered by this methodology may confer risk for IS. The application of genome-wide SNP arrays now facilitates the evaluation of structural changes through the entire genome as part of a genome-wide genetic association study. PMID:18288507

Matarin, Mar; Simon-Sanchez, Javier; Fung, Hon-Chung; Scholz, Sonja; Gibbs, J. Raphael; Hernandez, Dena G.; Crews, Cynthia; Britton, Angela; Wavrant De Vrieze, Fabienne; Brott, Thomas G.; Brown, Robert D.; Worrall, Bradford B.; Silliman, Scott; Case, L. Douglas; Hardy, John A.; Rich, Stephen S.; Meschia, James F.; Singleton, Andrew B.

2008-01-01

404

Antithrombotic and Thrombolytic Therapy for Ischemic Stroke  

PubMed Central

Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID:22315273

Lansberg, Maarten G.; O’Donnell, Martin J.; Khatri, Pooja; Lang, Eddy S.; Nguyen-Huynh, Mai N.; Schwartz, Neil E.; Sonnenberg, Frank A.; Schulman, Sam; Vandvik, Per Olav; Spencer, Frederick A.; Alonso-Coello, Pablo; Guyatt, Gordon H.

2012-01-01

405

Cellular pathophysiology of ischemic acute kidney injury  

PubMed Central

Ischemic kidney injury often occurs in the context of multiple organ failure and sepsis. Here, we review the major components of this dynamic process, which involves hemodynamic alterations, inflammation, and endothelial and epithelial cell injury, followed by repair that can be adaptive and restore epithelial integrity or maladaptive, leading to chronic kidney disease. Better understanding of the cellular pathophysiological processes underlying kidney injury and repair will hopefully result in the design of more targeted therapies to prevent the injury, hasten repair, and minimize chronic progressive kidney disease. PMID:22045571

Bonventre, Joseph V.; Yang, Li

2011-01-01

406

Ischemic colitis in chronic intermittent peritoneal dialysis.  

PubMed

A 6-year and 8-month-old boy on chronic intermittent peritoneal dialysis for end stage kidney disease presented with severe diarrhea, abdominal distension, cramps, tenesmus and vomiting. Barium enema showed rigidity and irregularity of the mucosa of the sigmoid and distal descending colon, with 'thumb print like' appearance, findings compatible with ischemic colitis. The institution of hemodialysis and discontinuation of the peritoneal dialysis resulted in a marked clinical and radiological improvement. Kidney transplantation performed a month later was associated with a complete cure of his intestinal disease. PMID:6709119

Koren, G; Aladjem, M; Militiano, J; Seegal, B; Jonash, A; Boichis, H

1984-01-01

407

Ischemic Neuropathy Associated with Livedoid Vasculitis  

PubMed Central

Background Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy. Case Report We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which was confirmed by electrophysiological and pathological studies. Conclusions Our report supports the possible vaso-occlusive etiology of livedoid vasculitis in multifocal ischemic neuropathy. PMID:22259622

Kim, Jee-Eun; Park, Su-Yeon; Sinn, Dong In; Kim, Sung-Min; Hong, Yoon-Ho; Park, Kyung Seok; Lee, Kwang-Woo

2011-01-01

408

Computer analyzed histology of ischemic injury to the gut  

Microsoft Academic Search

Histopathologic alterations in the intestinal mucosa after ischemic injury have been extensively described in the literature, but these descriptions have primarily been qualitative in nature. The purpose of this study was twofold: (1) to establish parameters obtained by computerized digital image analysis that would be useful in identifying ischemic injury, and (2) to use these parameters to identify the critical

Roberto N Puglisi; Thomas V Whalen; Edward J Doolin

1995-01-01

409

Study on frequency and predictors of dementia after ischemic stroke  

Microsoft Academic Search

Objective: We studied a large hospitalized cohort of patients aged 55 years and over with acute ischemic stroke to identify the frequency and predictors of poststroke dementia. Methods: A total of 434 consecutive patients with ischemic stroke were enrolled in this study. During admission, the demographic data, vascular risk factors, stroke features, and neurological status information were collected. All subjects

David H. D. Zhou; John Y. J. Wang; Jingcheng Li; Juan Deng; Changyue Gao; Man’e Chen

2004-01-01

410

Hyperglycemia, acute ischemic stroke, and thrombolytic therapy.  

PubMed

Ischemic stroke is a leading cause of disability and is considered now the fourth leading cause of death. Many clinical trials have shown that stroke patients with acute elevation in blood glucose at onset of stroke suffer worse functional outcomes, longer in-hospital stay, and higher mortality rates. The only therapeutic hope for these patients is the rapid restoration of blood flow to the ischemic tissue through intravenous administration of the only currently proven effective therapy, tissue plasminogen activator (tPA). However, even this option is associated with the increased risk of intracerebral hemorrhage. Nonetheless, the underlying mechanisms through which hyperglycemia (HG) and tPA worsen the neurovascular injury after stroke are not fully understood. Accordingly, this review summarizes the latest updates and recommendations about the management of HG and coadministration of tPA in a clinical setting while focusing more on the various experimental models studying (1) the effect of HG on stroke outcomes, (2) the potential mechanisms involved in worsening the neurovascular injury, (3) the different therapeutic strategies employed to ameliorate the injury, and finally, (4) the interaction between HG and tPA. Developing therapeutic strategies to reduce the hemorrhage risk with tPA in hyperglycemic setting is of great clinical importance. This can best be achieved by conducting robust preclinical studies evaluating the interaction between tPA and other therapeutics in order to develop potential therapeutic strategies with high translational impact. PMID:24619488

Hafez, Sherif; Coucha, Maha; Bruno, Askiel; Fagan, Susan C; Ergul, Adviye

2014-08-01

411

Metabolic Prosthesis for Oxygenation of Ischemic Tissue  

SciTech Connect

This communication discloses new ideas and preliminary results on the development of a "metabolic prosthesis" for local oxygenation of ischemic tissue under physiological neutral conditions. We report for the first time the selective electrolysis of physiological saline by repetitively pulsed charge-limited electrolysis for the production of oxygen and suppression of free chlorine. For example, using 800 A amplitude current pulses and <200 sec pulse durations, we demonstrated prompt oxygen production and delayed chlorine production at the surface of a shiny 0.85 mm diameter spherical platinum electrode. The data, interpreted in terms of the ionic structure of the electric double layer, suggest a strategy for in situ production of metabolic oxygen via a new class of "smart" prosthetic implants for dealing with ischemic disease such as diabetic retinopathy. We also present data indicating that drift of the local pH of the oxygenated environment can be held constant using a feedback-controlled three electrode electrolysis system that chooses anode and cathode pair based on pH data provided by local microsensors. The work is discussed in the context of diabetic retinopathy since surgical techniques for multielectrode prosthetic implants aimed at retinal degenerative diseases have been developed.

Greenbaum, Elias [ORNL

2009-01-01

412

Remote ischemic conditioning: the cardiologist's perspective.  

PubMed

Early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome. However, revascularization per se may induce further myocardial damage by myocardial ischemia-reperfusion injury and worsen clinical outcome. Therefore, new therapeutic strategies are required to protect the myocardium against ischemia-reperfusion injury in patients with coronary artery disease. Remote ischemic conditioning (RIC) by brief nonlethal episodes of ischemia and reperfusion to an organ or tissue remote from the heart activates innate cardioprotective mechanisms. The discovery that RIC can be performed noninvasively using a blood pressure cuff on the upper arm to induce brief episodes of limb ischemia and reperfusion has facilitated the translation of RIC into the clinical arena. Whereas some trials have shown contradictory results, recently published proof-of-concept clinical studies have reported encouraging results with RIC. Large-scale multicenter clinical trials are needed to establish the role of RIC in the current clinical practice. At present, the use of RIC in acute coronary syndromes seems particularly attractive due to its potential in-ambulance application and apparent dramatic reduction in infarct size in the patients with the largest infarcts. Cardiac arrest and stroke represent ischemia-reperfusion disorders where RIC has further potential to improve outcome beyond rapid revascularization alone. PMID:23114270

Schmidt, Michael R; Sloth, Astrid D; Johnsen, Jacob; Bøtker, Hans E

2012-11-01

413

White matter injury: Ischemic and nonischemic.  

PubMed

Ischemic pathologies of white matter (WM) include a large proportion of stroke and developmental lesions while multiple sclerosis (MS) is the archetype nonischemic pathology. Growing evidence suggests other important diseases including neurodegenerative and psychiatric disorders also involve a significant WM component. Axonal, oligodendroglial, and astroglial damage proceed via distinct mechanisms in ischemic WM and these mechanisms evolve dramatically with maturation. Axons may pass through four developmental stages where the pattern of membrane protein expression influences how the structure responds to ischemia; WM astrocytes pass through at least two and differ significantly in their ischemia tolerance from grey matter astrocytes; oligodendroglia pass through at least three, with the highly ischemia intolerant pre-oligodendrocyte (pre-Oli) stage linking the less sensitive precursor and mature phenotypes. Neurotransmitters play a central role in WM pathology at all ages. Glutamate excitotoxicity in WM has both necrotic and apoptotic components; the latter mediated by intracellular pathways which differ between receptor types. ATP excitotoxicity may be largely mediated by the P2X7 receptor and also has both necrotic and apoptotic components. Interplay between microglia and other cell types is a critical element in the injury process. A growing appreciation of the significance of WM injury for nonischemic neurological disorders is currently stimulating research into mechanisms; with curious similarities being found with those operating during ischemia. A good example is traumatic brain injury, where axonal pathology can proceed via almost identical pathways to those described during acute ischemia. PMID:25043122

Fern, Robert F; Matute, Carlos; Stys, Peter K

2014-11-01

414

PRECONDITIONING FOR THE p-VERSION BOUNDARY ELEMENT METHOD IN THREE DIMENSIONS WITH  

E-print Network

approximation of the three dimensional integral equation with hypersingular operators. The preconditioner, hypersingular integral equation, iterative methods, preconditioning. The first author was supported in part preconditioners in the case of the p-version approximation of boundary integral equations with hypersingular

Guo, Benqi

415

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

E-print Network

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

Nau, Dana S.

416

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

E-print Network

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

Hiptmair, Ralf

417

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

ERIC Educational Resources Information Center

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

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

2014-01-01

418