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1

Ischemic preconditioning prevents in vivo hyperoxygenation in postischemic myocardium with preservation of mitochondrial oxygen consumption.  

PubMed

Ischemic preconditioning (IPC) strongly protects against ischemia-reperfusion injury; however, its effect on subsequent myocardial oxygenation is unknown. Therefore, we determine in an in vivo mouse model of regional ischemia and reperfusion (I/R) if IPC attenuates postischemic myocardial hyperoxygenation and decreases formation of reactive oxygen/nitrogen species (ROS/RNS), with preservation of mitochondrial function. The following five groups of mice were studied: sham, control (I/R), ischemic preconditioning (IPC + I/R, 3 cycles of 5 min coronary occlusion/5 min reperfusion) and IPC + I/R N(G)-nitro-L-arginine methyl ester treated, and IPC + I/R eNOS knockout mice. I/R and IPC + I/R mice were subjected to 30 min regional ischemia followed by 60 min reperfusion. Myocardial Po(2) and redox state were monitored by electron paramagnetic resonance spectroscopy. In the IPC + I/R, but not the I/R group, regional blood flow was increased after reperfusion. Po(2) upon reperfusion increased significantly above preischemic values in I/R but not in IPC + I/R mice. Tissue redox state was measured from the reduction rate of a spin probe, and this rate was 60% higher in IPC than in non-IPC hearts. Activities of NADH dehydrogenase (NADH-DH) and cytochrome c oxidase (CcO) were reduced in I/R mice after 60 min reperfusion but conserved in IPC + I/R mice compared with sham. There were no differences in NADH-DH and CcO expression in I/R and IPC + I/R groups compared with sham. After 60 min reperfusion, strong nitrotyrosine formation was observed in I/R mice, but only weak staining was observed in IPC + I/R mice. Thus IPC markedly attenuates postischemic myocardial hyperoxygenation with less ROS/RNS generation and preservation of mitochondrial O(2) metabolism because of conserved NADH-DH and CcO activities. PMID:17513495

Zhu, Xuehai; Liu, Bin; Zhou, Shaotang; Chen, Yeong-Renn; Deng, Yuanmu; Zweier, Jay L; He, Guanglong

2007-09-01

2

Preconditioning with soluble guanylate cyclase activation prevents postischemic inflammation and reduces nitrate tolerance in heme oxygenase-1 knockout mice.  

PubMed

Previously we have shown that, unlike wild-type mice (WT), heme oxygenase-1 knockout (HO-1-/-) mice developed nitrate tolerance and were not protected from inflammation caused by ischemia-reperfusion (I/R) when preconditioned with a H2S donor. We hypothesized that stimulation (with BAY 41-2272) or activation (with BAY 60-2770) of soluble guanylate cyclase (sGC) would precondition HO-1-/- mice against an inflammatory effect of I/R and increase arterial nitrate responses. Intravital fluorescence microscopy was used to visualize leukocyte rolling and adhesion to postcapillary venules of the small intestine in anesthetized mice. Relaxation to ACh and BAY compounds was measured on superior mesenteric arteries isolated after I/R protocols. Preconditioning with either BAY compound 10 min (early phase) or 24 h (late phase) before I/R reduced postischemic leukocyte rolling and adhesion to sham control levels and increased superior mesenteric artery responses to ACh, sodium nitroprusside, and BAY 41-2272 in WT and HO-1-/- mice. Late-phase preconditioning with BAY 60-2770 was maintained in HO-1-/- and endothelial nitric oxide synthase knockout mice pretreated with an inhibitor (dl-propargylglycine) of enzymatically produced H2S. Pretreatment with BAY compounds also prevented the I/R increase in small intestinal TNF-?. We speculate that increasing sGC activity and related PKG acts downstream to H2S and disrupts signaling processes triggered by I/R in part by maintaining low cellular Ca²?. In addition, BAY preconditioning did not increase sGC levels, yet increased the response to agents that act on reduced heme-containing sGC. Collectively these actions would contribute to increased nitrate sensitivity and vascular function. PMID:23771693

Wang, Walter Z; Jones, Allan W; Wang, Meifang; Durante, William; Korthuis, Ronald J

2013-08-15

3

Isoform-selective 5?-AMP-activated protein kinase-dependent preconditioning mechanisms to prevent postischemic leukocyte-endothelial cell adhesive interactions  

PubMed Central

We previously demonstrated that preconditioning induced by ethanol consumption at low levels [ethanol preconditioning (EPC)] or with 5-aminoimidazole-4-carboxamide 1-?-d-ribofuranoside (AICAR-PC) 24 h before ischemia-reperfusion prevents postischemic leukocyte-endothelial cell adhesive interactions (LEI) by a mechanism that is initiated by nitric oxide formed by endothelial nitric oxide synthase. Recent work indicates that 1) ethanol increases the activity of AMP-activated protein kinase (AMPK) and 2) AMPK phosphorylates endothelial nitric oxide synthase at the same activation site seen following EPC (Ser1177). In light of these observations, we postulated that the heterotrimeric serine/threonine kinase, AMPK, may play a role in triggering the development of the anti-inflammatory phenotype induced by EPC. Ethanol was administered to C57BL/6J mice by gavage in the presence or absence of AMPK inhibition. Twenty-four hours later, the numbers of rolling and adherent leukocytes in postcapillary venules of the small intestine were recorded using an intravital microscopic approach. Following 45 min of ischemia, LEI were recorded after 30 and 60 min of reperfusion or at equivalent time points in control animals. Ischemia-reperfusion induced a marked increase in LEI relative to sham-operated control mice. The increase in LEI was prevented by EPC, an effect that was lost with AMPK inhibition during the period of ethanol exposure. Studies conducted in AMPK ?1- and ?2-knockout mice suggest that the anti-inflammatory effects of AICAR are not dependent on which isoform of the catalytic ?-subunit is present because a deficiency of either isoform results in a loss of protection. In sharp contrast, EPC appears to be triggered by an AMPK ?2-isoform-dependent mechanism.

Spencer Gaskin, F.; Kamada, Kazuhiro; Zuidema, Mozow (Yusof); Jones, Allan W.; Rubin, Leona J.

2011-01-01

4

Free radical ablation for the prevention of post-ischemic renal failure following renal transplantation  

Microsoft Academic Search

Summary The toxic metabolites of oxygen, including those which are free radicals, have been found to constitute a fundamental common pathway of tissue injury in a wide variety of disease processes, including injury in many organs resulting from post-ischemic reperfusion. Research efforts designed to prevent or ameliorate tissue injury have therefore centered on the pharmacologic inhibition of free radical-mediated mechanisms.

H. J. Schiller; K. A. Andreoni; G. B. Bulkley

1991-01-01

5

Plasmin Inhibitors Prevent Leukocyte Accumulation and Remodeling Events in the Postischemic Microvasculature  

PubMed Central

Clinical trials revealed beneficial effects of the broad-spectrum serine protease inhibitor aprotinin on the prevention of ischemia-reperfusion (I/R) injury. The underlying mechanisms remained largely unclear. Using in vivo microscopy on the cremaster muscle of male C57BL/6 mice, aprotinin as well as inhibitors of the serine protease plasmin including tranexamic acid and ?-aminocaproic acid were found to significantly diminish I/R-elicited intravascular firm adherence and (subsequent) transmigration of neutrophils. Remodeling of collagen IV within the postischemic perivenular basement membrane was almost completely abrogated in animals treated with plasmin inhibitors or aprotinin. In separate experiments, incubation with plasmin did not directly activate neutrophils. Extravascular, but not intravascular administration of plasmin caused a dose-dependent increase in numbers of firmly adherent and transmigrated neutrophils. Blockade of mast cell activation as well as inhibition of leukotriene synthesis or antagonism of the platelet-activating-factor receptor significantly reduced plasmin-dependent neutrophil responses. In conclusion, our data suggest that extravasated plasmin(ogen) mediates neutrophil recruitment in vivo via activation of perivascular mast cells and secondary generation of lipid mediators. Aprotinin as well as the plasmin inhibitors tranexamic acid and ?-aminocaproic acid interfere with this inflammatory cascade and effectively prevent postischemic neutrophil responses as well as remodeling events within the vessel wall.

Reichel, Christoph A.; Lerchenberger, Max; Uhl, Bernd; Rehberg, Markus; Berberich, Nina; Zahler, Stefan; Wymann, Matthias P.; Krombach, Fritz

2011-01-01

6

Prevention of post-ischemic brain lipid conjugated diene production and neurological injury by hydroxyethyl starch-conjugated deferoxamine.  

PubMed

Hydroxyethyl starch conjugated deferoxamine (DFO) was administered to rats following resuscitation from 6.5 min cardiac arrest (CA) in an attempt to prevent the iron-catalyzed production of oxygen free radicals which may lead to neurologic injury and ultimately death following restoration of spontaneous circulation (ROSC). Brain conjugated dienes were analyzed spectrophotometrically 4 and 24 hr following ROSC, and were found to be significantly elevated when compared to non-ischemic controls. Hydroxyethyl starch-DFO treated rats demonstrated no increased conjugated diene production at either period. Neurologic injury was significantly less in drug treated rats surviving 24 or 72 hours when compared to controls. While mortality was similar in drug treated or control rats for the first 24 hours following ROSC, delayed mortality (days 1-10) was significantly less in drug treated animals, presumably as a result of neurologic protection afforded by post-ischemic drug administration. Administration of DFO conjugated to hydroxyethyl starch appears to modulate the neurologic injury which occurs during brain ischemia and reperfusion. PMID:1371490

Rosenthal, R E; Chanderbhan, R; Marshall, G; Fiskum, G

1992-01-01

7

Post-ischemic treatment with cannabidiol prevents electroencephalographic flattening, hyperlocomotion and neuronal injury in gerbils  

Microsoft Academic Search

The potential activity of cannabidiol, a non-psychoactive constituent of marijuana, in preventing damage caused by cerebral ischemia was studied. Cannabidiol (1.25–20 mg\\/kg) was given 5 min after 10 min bilateral carotid occlusion in freely-moving awake gerbils. Seven days after ischemia, it antagonized the electroencephalographic flattening of total spectral power, with a dose-dependent bell-shaped curve; the neuroprotective effect was greatest with

Daniela Braida; Simona Pegorini; Maria Vittoria Arcidiacono; Gian Giacomo Consalez; Laura Croci; Mariaelvina Sala

2003-01-01

8

Morinda citrifolia fruit juice prevents ischemic neuronal damage through suppression of the development of post-ischemic glucose intolerance  

Microsoft Academic Search

Fruit juice of Morinda citrifolia (Noni juice) is a well-known health drink and has various pharmacological properties including antioxidant and anti-inflammatory\\u000a effects. We have hitherto found the protective effect of Noni juice on brain damage caused by ischemic stress in mice. In\\u000a addition, we also recently reported that regulation of post-ischemic glucose intolerance might be important for good prognosis.\\u000a Here,

Shinichi Harada; Wakako Fujita-Hamabe; Kohei Kamiya; Yoshiyuki Mizushina; Toshiko Satake; Shogo Tokuyama

2010-01-01

9

Dystrophin proteolysis: a potential target for MMP-2 and its prevention by ischemic preconditioning.  

PubMed

Dystrophin is responsible for the mechanical stabilization of the sarcolemma, and it has been shown that it is one of the most sensitive proteins to ischemic injury. However, the enzyme responsible for this proteolysis is still unknown. Isolated rabbit hearts were subjected to 30 min of global ischemia with and without reperfusion (180 min) to determine whether dystrophin is cleaved by matrix metalloproteinase (MMP)-2 during acute ischemia and whether ischemic preconditioning (PC) prevents dystrophin breakdown through MMP-2 inhibition. The activity of MMP-2 was evaluated by zymography and using doxycycline as an inhibitor. Also, to stimulate MMP-2 activity without ischemia, SIN-1 was administered in the absence and presence of doxycycline. Finally, we considered the PC effect on MMP-2 activity and dystrophin expression. The dystrophin level decreased during ischemia, reaching 21% of control values (P < 0.05), but the spectrin level remained unchanged. MMP-2 activity increased 71% during ischemia compared with control values (P < 0.05). Doxycycline administration before ischemia prevented dystrophin breakdown. In normoxic hearts, SIN-1 increased thiobarbituric acid-reactive substances by 33% (P < 0.05) and MMP-2 activity by 36% (P < 0.05) and significantly reduced the dystrophin level to 23% of control values (P < 0.05). PC significantly prevented dystrophin breakdown by inhibiting MMP-2 activity, and the dystrophin level reached 89% of control values (P < 0.05). In conclusion, MMP-2 could be responsible for the proteolysis of dystrophin. Thus, dystrophin emerges as a possible novel substrate for MMP-2 in the context of ischemic injury. Furthermore, our results demonstrate that ischemic PC prevents dystrophin breakdown most likely by inhibiting MMP-2 activity. PMID:24791785

Buchholz, Bruno; Perez, Virginia; Siachoque, Nadezda; Miksztowicz, Verónica; Berg, Gabriela; Rodríguez, Manuel; Donato, Martín; Gelpi, Ricardo J

2014-07-01

10

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.

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

2013-01-01

11

In vivo hyperoxic preconditioning prevents myocardial infarction by expressing bcl-2.  

PubMed

Preconditioning with oxidative stress has been demonstrated in vitro to stimulate the cellular adaptation to subsequent severe oxidative stress. However, it is uncertain whether this preconditioning works in vivo. In the present study, we examined in vivo the beneficial effect of oxidative preconditioning. After rats were pretreated with whole-body hyperoxygenation (100% O(2) at 3 atmosphere for 20 mins, four cycles with 20-min intermission), isolated hearts were subjected to 45-min ischemia followed by 90-min reperfusion. This hyperoxic preconditioning significantly reduced infarct size, cytochrome-c release, DNA fragmentation, and terminal deoxynucleotidyl transferase-mediated dUTD nick-end labeling-positive cell frequency in the left ventricle, biphasically with an early (30-min) and a delayed (48-hr) effect after the hyperoxygenation. Mechanistically, the NF-kappaB activity and Bcl-2 expression were enhanced in the hearts, and a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, abolished the Bcl-2 induction as well as the infarct-limiting effect. An antioxidant, N-acetylcysteine, and protein kinase C (PKC) inhibitors chelerythrine and Gö 6983 also blocked the preconditioning effects. These results indicate that hyperoxia induces myocardial tolerance against ischemia-reperfusion injury in association with Bcl-2 induction by NF-kappaB activation through reactive oxygen species and PKC-dependent signaling pathway. PMID:16565442

Choi, Hong; Kim, Sang-Hyun; Chun, Yang-Sook; Cho, Young-Suk; Park, Jong-Wan; Kim, Myung-Suk

2006-04-01

12

Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of heme oxygenase-1  

PubMed Central

We recently demonstrated that preconditioning with an exogenous hydrogen sulfide donor (NaHS-PC) 24 h before ischemia and reperfusion (I/R) causes postcapillary venules to shift to an anti-inflammatory phenotype in C57BL/6J wild-type (WT) mice such that these vessels fail to support increases in postischemic leukocyte rolling (LR) and leukocyte adhesion (LA). The objective of the present study was to determine whether heme oxygenase-1 (HO-1) is a mediator of these anti-inflammatory effects noted during I/R in mice preconditioned with NaHS. Intravital fluorescence microscopy was used to visualize LR and LA in single postcapillary venules of the murine small intestine. I/R induced marked increases in LR and LA, effects that were prevented by NaHS-PC. Treatment with the HO inhibitor tin protoporphyrin IX, but not the inactive protoporphyrin CuPPIX, just before reperfusion prevented the anti-inflammatory effects of antecedent NaHS. The anti-inflammatory effects of NaHS-PC were mimicked by preconditioning with hemin, an agent that induces HO-1 expression. We then evaluated the effect of NaHS as a preconditioning stimulus in mice that were genetically deficient in HO-1 (HO-1?/? on an H129 background with appropriate WT strain controls). NaHS-PC was ineffective in HO-1?/? mice. Our work indicates that HO-1 serves as an effector of the anti-inflammatory effects of NaHS-PC during I/R 24 h later.

Zuidema, Mozow Y.; Peyton, Kelly J.; Fay, William P.; Durante, William

2011-01-01

13

Mechanistic role of calpains in postischemic neurodegeneration  

Microsoft Academic Search

The calpain family of proteases is causally linked to postischemic neurodegeneration. However, the precise mechanisms by which calpains contribute to postischemic neuronal death have not been fully elucidated. This review outlines the key features of the calpain system, and the evidence for its causal role in postischemic neuronal pathology. Furthermore, the consequences of specific calpain substrate cleavage at various subcellular

Matthew B Bevers; Robert W Neumar

2008-01-01

14

The GRONORUN 2 study: effectiveness of a preconditioning program on preventing running related injuries in novice runners. The design of a randomized controlled trial  

PubMed Central

Background Distance running is a popular recreational exercise. It is a beneficial activity for health and well being. However, running may also cause injuries, especially of the lower extremities. In literature there is no agreement what intrinsic and extrinsic factors cause running related injuries (RRIs). In theory, most RRIs are elicited by training errors, this too much, too soon. In a preconditioning program runners can adapt more gradually to the high mechanical loads of running and will be less susceptible to RRIs. In this study the effectiveness of a 4-week preconditioning program on the incidence of RRIs in novice runners prior to a training program will be studied. Methods/Design The GRONORUN 2 (Groningen Novice Running) study is a two arm randomized controlled trial studying the effect of a 4-week preconditioning (PRECON) program in a group of novice runners. All participants wanted to train for the recreational Groningen 4-Mile running event. The PRECON group started a 4-week preconditioning program with walking and hopping exercises 4 weeks before the start of the training program. The control (CON) and PRECON group started a frequently used 9-week training program in preparation for the Groningen 4-Mile running event. During the follow up period participants registered their running exposure, other sporting activities and running related injuries in an Internet based running log. The primary outcome measure was the number of RRIs. RRI was defined as a musculoskeletal ailment or complaint of the lower extremities or back causing a restriction on running for at least three training sessions. Discussion The GRONORUN 2 study will add important information to the existing running science. The concept of preconditioning is easy to implement in existing training programs and will hopefully prevent RRIs especially in novice runners. Trial registration The Netherlands National Trial Register NTR1906. The NTR is part of the WHO Primary Registries.

2010-01-01

15

Ischemic preconditioning-induced hyperperfusion correlates with hepatoprotection after liver resection  

PubMed Central

AIM: To characterize the impact of the Pringle maneuver (PM) and ischemic preconditioning (IP) on total blood supply to the liver following hepatectomies. METHODS: Sixty one consecutive patients who underwent hepatic resection under inflow occlusion were randomized either to receive PM alone (n = 31) or IP (10 min of ischemia followed by 10 min of reperfusion) prior to PM (n = 30). Quantification of liver perfusion was measured by Doppler probes at the hepatic artery and portal vein at various time points after reperfusion of remnant livers. RESULTS: Occlusion times of 33 ± 12 min (mean ± SD) and 34 ± 14 min and the extent of resected liver tissue (2.7 segments) were similar in both groups. In controls (PM), on reperfusion of liver remnants for 15 min, portal perfusion markedly decreased by 29% while there was a slight increase of 8% in the arterial blood flow. In contrast, following IP + PM the portal vein flow remained unchanged during reperfusion and a significantly increased arterial blood flow (+56% vs baseline) was observed. In accordance with a better postischemic blood supply of the liver, hepatocellular injury, as measured by alanine aminotransferase (ALT) levels on day 1 was considerably lower in group B compared to group A (247 ± 210 U/I vs 550 ± 650 U/I, P < 0.05). Additionally, ALT levels were significantly correlated to the hepatic artery inflow. CONCLUSION: IP prevents postischemic flow reduction of the portal vein and simultaneously increases arterial perfusion, suggesting that improved hepatic macrocirculation is a protective mechanism following hepatectomy.

Heizmann, Oleg; Meimarakis, Georgios; Volk, Andreas; Matz, Daniel; Oertli, Daniel; Schauer, Rolf J

2010-01-01

16

Honokiol suppresses the development of post-ischemic glucose intolerance and neuronal damage in mice.  

PubMed

Honokiol, a constituent of Magnolia obovata, has various pharmacological effects, including protection against cerebral ischemia. However, few studies have been conducted to evaluate the possible neuroprotective effects of honokiol against cerebral ischemia. We recently reported that cerebral ischemic neuronal damage could be triggered by glucose intolerance that develops after the onset of ischemic stress (i.e., post-ischemic glucose intolerance). In addition, suppression of post-ischemic glucose intolerance significantly ameliorated ischemic neuronal damage. Here, we investigated the effects of honokiol on the development of post-ischemic glucose intolerance and neuronal damage. Mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. The development of post-ischemic glucose intolerance on day 1 and neuronal damage on day 3 after MCAO were significantly reduced by intraperitoneal administration of honokiol (10 mg/kg) compared with the vehicle-treated group. Honokiol did not affect serum insulin or adiponectin levels. However, honokiol significantly decreased the expression of phosphoenolpyruvate carboxykinase and increased the expression of 5'-AMP-activated protein kinase (AMPK) on day 1 after MCAO, compared with the vehicle-treated MCAO group. The results of this study suggest that honokiol could prevent post-ischemic glucose intolerance in an AMPK-dependent manner, which may be involved in the neuroprotective effects of honokiol against cerebral ischemia. PMID:22261858

Harada, Shinichi; Kishimoto, Maya; Kobayashi, Mana; Nakamoto, Kazuo; Fujita-Hamabe, Wakako; Chen, Hwei-Hsien; Chan, Ming-Huan; Tokuyama, Shogo

2012-10-01

17

Stunning, preconditioning, and functional recovery after global myocardial ischemia.  

PubMed

Stunning (reversible myocardial ischemia without necrosis) occurs with induced global ischemia during cardiac operations and depresses the ability of the heart to utilize oxygen efficiently because less contractile work is developed per unit of oxygen utilized. Interestingly, regional studies have demonstrated dramatic infarct size reduction with stunning episodes before prolonged ischemia, a phenomenon known as myocardial preconditioning. It is postulated that the postischemic contractile dysfunction noted after stunning causes reduced energy demands, which "preconditions" myocardium to withstand a subsequent longer ischemic episode. Some evidence from regional studies suggests that preconditioning may improve functional recovery after ischemia. This study examined the complex relationship between stunning and preconditioning to functional recovery in a surgical setting of global ischemia. To study the effect of stunning, myocardial oxygen consumption, oxygen extraction, and functional indices of contractility were measured before and after isolated rabbit hearts were subjected to 10, 20, or 45 minutes of normothermic 37 degrees C global ischemic stun intervals. This demonstrated that while oxygen consumption and extraction quickly recover to prestun levels, contractility remains depressed well beyond the stun interval. To study the effect of preconditioning using stunning, isolated hearts were then subjected to 120 minutes of 34 degrees C cardioplegic-induced ischemia after preconditioning. Hearts received either modified St. Thomas cardioplegic solution as a control or cardioplegia administered after preconditioning with 37 degrees C ischemic stunning for 5, 10, 15, 20, or 45 minutes or multiple 5- or 10-minute stuns, with reperfusion before cardioplegic-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7944710

Bolling, S F; Olszanski, D A; Childs, K F; Gallagher, K P; Ning, X H

1994-09-01

18

Targeted deletion of the A3 adenosine receptor confers resistance to myocardial ischemic injury and does not prevent early preconditioning.  

PubMed

We used mice with genetic disruption of the A3 adenosine receptor (AR) gene (A3AR(-/-)mice) to assess the in vivo role of the A3AR in modulating myocardial ischemia/reperfusion injury and preconditioning (PC). Surprisingly, infarct size induced by 30 min of coronary artery occlusion and 24 h of reperfusion was 35% smaller in A3AR(-/-)compared to wild-type mice (A3AR(+/+)). The reduction in infarct size was not the result of differences in heart rate, body temperature or increased cardiac expression of A1ARs. However, neutrophil infiltration within infarcted regions was less in A3AR(-/-)mice. Furthermore, ischemic PC induced by either a single episode (one 5 min occlusion) or multiple episodes (six 4 min occlusions) of ischemia produced equivalent reductions in infarct size in A3AR(-/-)and A3AR(+/+)mice. These results indicate that, in the mouse, (i) A3ARs play an injurious role during acute myocardial ischemia/reperfusion injury, possibly by exacerbating the inflammatory response, and (ii) A3ARs are not necessary for the development of the early phase of ischemic PC. PMID:11273734

Guo, Y; Bolli, R; Bao, W; Wu, W J; Black, R G; Murphree, S S; Salvatore, C A; Jacobson, M A; Auchampach, J A

2001-04-01

19

Targeted Deletion of the A3 Adenosine Receptor Confers Resistance to Myocardial Ischemic Injury and does not Prevent Early Preconditioning  

PubMed Central

We used mice with genetic disruption of the A3 adenosine receptor (AR) gene (A3AR?/? mice) to assess the in vivo role of the A3AR in modulating myocardial ischemia/reperfusion injury and preconditioning (PC). Surprisingly, infarct size induced by 30 min of coronary artery occlusion and 24 h of reperfusion was 35% smaller in A3AR?/? compared to wild-type mice (A3AR+/+). The reduction in infarct size was not the result of differences in heart rate, body temperature or increased cardiac expression of A1ARs. However, neutrophil infiltration within infarcted regions was less in A3AR?/? mice. Furthermore, ischemic PC induced by either a single episode (one 5 min occlusion) or multiple episodes (six 4 min occlusions) of ischemia produced equivalent reductions in infarct size in A3AR?/? and A3AR+/+ mice. These results indicate that, in the mouse, (i) A3ARs play an injurious role during acute myocardial ischemia/reperfusion injury, possibly by exacerbating the inflammatory response, and (ii) A3ARs are not necessary for the development of the early phase of ischemic PC.

Guo, Yiru; Bolli, Roberto; Bao, Weike; Wu, Wen-Jian; Black, Richard G.; Murphree, Sidney S.; Salvatore, Christopher A.; Jacobson, Marlene A.; Auchampach, John A.

2013-01-01

20

A Top Pilot Tunnel Preconditioning Method for the Prevention of Extremely Intense Rockbursts in Deep Tunnels Excavated by TBMs  

NASA Astrophysics Data System (ADS)

The headrace tunnels at the Jinping II Hydropower Station cross the Jinping Mountain with a maximum overburden depth of 2,525 m, where 80% of the strata along the tunnels consist of marble. A number of extremely intense rockbursts occurred during the excavation of the auxiliary tunnels and the drainage tunnel. In particular, a tunnel boring machine (TBM) was destroyed by an extremely intense rockburst in a 7.2-m-diameter drainage tunnel. Two of the four subsequent 12.4-m-diameter headrace tunnels will be excavated with larger size TBMs, where a high risk of extremely intense rockbursts exists. Herein, a top pilot tunnel preconditioning method is proposed to minimize this risk, in which a drilling and blasting method is first recommended for the top pilot tunnel excavation and support, and then the TBM excavation of the main tunnel is conducted. In order to evaluate the mechanical effectiveness of this method, numerical simulation analyses using the failure approaching index, energy release rate, and excess shear stress indices are carried out. Its construction feasibility is discussed as well. Moreover, a microseismic monitoring technique is used in the experimental tunnel section for the real-time monitoring of the microseismic activities of the rock mass in TBM excavation and for assessing the effect of the top pilot tunnel excavation in reducing the risk of rockbursts. This method is applied to two tunnel sections prone to extremely intense rockbursts and leads to a reduction in the risk of rockbursts in TBM excavation.

Zhang, Chuanqing; Feng, Xiating; Zhou, Hui; Qiu, Shili; Wu, Wenping

2012-05-01

21

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

22

[Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].  

PubMed

Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug. PMID:24791334

Makarova, L M; Prikhod'ko, M A; Pogorely?, V E; Skachilova, S Ia; Mirzoian, R S

2014-01-01

23

Hyperbaric oxygen pretreatment and preconditioning.  

PubMed

Exposure to hyperbaric oxygen (HBO2) before a crucial event, with the plan to create a preventing therapeutic situation, has been defined "preconditioning" and is emerging as a useful adjunct both in diving medicine as well before ischemic or inflammatory events. Oxygen pre-breathing before diving has been extensively documented in recreational, technical, commercial and military diving for tissue denitrogenation, resulting in reduced post-diving bubble loads, reduced decompression requirements and more rapid return to normal platelet function after a decompression. Preoxygenation at high atmospheric pressure has also been used in patients before exposure to clinical situations with beneficial effects, but the mechanisms of action have not yet been ascertained. During the reperfusion of ischemic tissue, oxygenated blood increases numbers and activities of oxidants generated in tissues. Previous reports showed that HBO2 preconditioning caused the activation of antioxidative enzymes and related genes in the central nervous system, including catalase (CAT), superoxide dismutase and heme oxygenase-1. Despite the increasing number of basic science publications on this issue, studies describing HBO2 preconditioning in the clinical practice remain scarce. To date, only a few studies have investigated the preconditioning effects of HBO2 in relation to the human brain and myocardium with robust and promising results. PMID:24984322

Camporesi, Enrico M; Bosco, Gerardo

2014-01-01

24

Supplemental l-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury  

Microsoft Academic Search

Unenhanced hypothermic cardioplegia does not prevent postischemic endothelial and contractile dysfunction in hearts subjected to antecedent regional or global ischemia. This study tested the hypothesis that supplementing blood cardioplegic solution and reperfusion with the nitric oxide precursor l-arginine would preserve endothelial function, reduce infarct size, and reverse postcardioplegia regional contractile dysfunction by the L-arginine-nitric oxide pathway. In 23 anesthetized dogs,

Hiroki Sato; Zhi-Qing Zhao; D. Scott McGee; Mark W. Williams; John W. Hammon; J. Vinten-Johansen

1995-01-01

25

Dichloroacetate improves postischemic function of hypertrophied rat hearts  

Microsoft Academic Search

OBJECTIVESWe sought to determine whether improving coupling between glucose oxidation and glycolysis by stimulating glucose oxidation during reperfusion enhances postischemic recovery of hypertrophied hearts.BACKGROUNDLow rates of glucose oxidation and high glycolytic rates are associated with greater postischemic dysfunction of hypertrophied as compared with nonhypertrophied hearts.METHODSHeart function, glycolysis and glucose oxidation were measured in isolated working control and hypertrophied rat hearts

Richard B Wambolt; Gary D Lopaschuk; Roger W Brownsey; Michael F Allard

2000-01-01

26

Equilibrative nucleoside transporter 1 (ENT1) regulates postischemic blood flow during acute kidney injury in mice  

PubMed Central

A complex biologic network regulates kidney perfusion under physiologic conditions. This system is profoundly perturbed following renal ischemia, a leading cause of acute kidney injury (AKI) — a life-threatening condition that frequently complicates the care of hospitalized patients. Therapeutic approaches to prevent and treat AKI are extremely limited. Better understanding of the molecular pathways promoting postischemic reflow could provide new candidate targets for AKI therapeutics. Due to its role in adapting tissues to hypoxia, we hypothesized that extracellular adenosine has a regulatory function in the postischemic control of renal perfusion. Consistent with the notion that equilibrative nucleoside transporters (ENTs) terminate adenosine signaling, we observed that pharmacologic ENT inhibition in mice elevated renal adenosine levels and dampened AKI. Deletion of the ENTs resulted in selective protection in Ent1–/– mice. Comprehensive examination of adenosine receptor–knockout mice exposed to AKI demonstrated that renal protection by ENT inhibitors involves the A2B adenosine receptor. Indeed, crosstalk between renal Ent1 and Adora2b expressed on vascular endothelia effectively prevented a postischemic no-reflow phenomenon. These studies identify ENT1 and adenosine receptors as key to the process of reestablishing renal perfusion following ischemic AKI. If translatable from mice to humans, these data have important therapeutic implications.

Grenz, Almut; Bauerle, Jessica D.; Dalton, Julee H.; Ridyard, Douglas; Badulak, Alexander; Tak, Eunyoung; McNamee, Eoin N.; Clambey, Eric; Moldovan, Radu; Reyes, German; Klawitter, Jost; Ambler, Kelly; Magee, Kristann; Christians, Uwe; Brodsky, Kelley S.; Ravid, Katya; Choi, Doo-Sup; Wen, Jiaming; Lukashev, Dmitriy; Blackburn, Michael R.; Osswald, Hartmut; Coe, Imogen R.; Nurnberg, Bernd; Haase, Volker H.; Xia, Yang; Sitkovsky, Michail; Eltzschig, Holger K.

2012-01-01

27

Fetal brain genomic reprogramming following asphyctic preconditioning  

PubMed Central

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

2013-01-01

28

Heat stress preconditioning and delayed myocardial protection: what is new?  

Microsoft Academic Search

As other preconditioning phenomena, heat stress is able to induce a delayed myocardial protection against ischaemia-reperfusion injury by preserving ventricular function, preventing arrhythmia occurrence and reducing cellular necrosis. The development of heat stress response has been extensively studied in order to characterize the different steps of this form of preconditioning. It appears that chemical signals (such as nitric oxide, reactive

Marie Joyeux-Faure; Claire Arnaud; Diane Godin-Ribuot; Christophe Ribuot

2003-01-01

29

Correction of consequences of postischemic reperfusion brain damages with cytoflavin  

Microsoft Academic Search

Cytoflavin normalized energy metabolism, decreased the intensity of lipid peroxidation, and restored activity of the antioxidant\\u000a system in rat brain during postischemic reperfusion. Cerebroprotective effect of cytoflavin was similar to that of piracetam.

V. V. Bul'on; L. K. Khnychenko; N. S. Sapronov; A. L. Kovalenko; L. E. Alekseeva

2000-01-01

30

Nicotine aggravates the brain postischemic inflammatory response  

PubMed Central

A substantial body of evidence suggests that nicotine adversely affects cerebral blood flow and the blood-brain barrier and is a risk factor for stroke. The present study investigated the effect of nicotine on cerebrovascular endothelium under basal and ischemia/reperfusion injury under in vivo condition. Nicotine (2 mg/kg sc) was administered to mice over 14 days, which resulted in plasma nicotine levels of ?100 ng/ml, reflecting plasma concentrations in average to heavy smokers. An analysis of the phenotype of isolated brain microvessels after nicotine exposure indicated higher expression of inflammatory mediators, cytokines (IL-1?, TNF-?, and IL-18), chemokines (CCL2 and CX3CL1), and adhesion molecules (ICAM-1, VCAM-1, and P-selectins), and this was accompanied by enhanced leukocyte infiltration into brain during ischemia/reperfusion (P < 0.01). Nicotine had a profound effect on ischemia/reperfusion injury; i.e., increased brain infarct size (P < 0.01), worse neurological deficits, and a higher mortality rate. These experiments illuminate, for the first time, how nicotine regulates brain endothelial cell phenotype and postischemic inflammatory response at the brain-vascular interface.

Bradford, Shayna T.; Stamatovic, Svetlana M.; Dondeti, Raj S.; Keep, Richard F.

2011-01-01

31

Preconditioning during warm blood cardioplegia  

Microsoft Academic Search

Objective: Preconditioning describes the cardioprotective effects of multiple brief episodes of warm ischemia. The purpose of the study was to determine whether warm ischemia, during the intermittent delivery of warm blood cardioplegia, would induce preconditioning during cardioplegia arrest. Methods: Dogs, 15, were randomized to a preconditioning protocol or to serve as controls. The control group received 60 min of continuous

Roderick Landymore; John You; Thomas Murphy; John Fris

1997-01-01

32

Preconditioning during warm blood cardioplegia  

Microsoft Academic Search

Objective: Preconditioning describes the cardioprotective effects of multiple brief episodes of warm ischemia. The purpose of the study was to determine whether warm ischemia, during the intermittent delivery of warm blood cardioplegia, would induce preconditioning during cardioplegia arrest. Methods: Dogs, 15, were randomized to a preconditioning protocol or to serve as controls. The control group received 60 min of continuous

Roderick Landymore; John You; Thomas Murphy; John Fris

33

Hyperbaric oxygen preconditioning attenuates postoperative cognitive impairment in aged rats.  

PubMed

Cognitive decline after surgery in the elderly population is a major clinical problem with high morbidity. Hyperbaric oxygen (HBO) preconditioning can induce significant neuroprotection against acute neurological injury. We hypothesized that HBO preconditioning would prevent the development of postoperative cognitive impairment. Elderly male rats (20 months old) underwent stabilized tibial fracture operation under general anesthesia after HBO preconditioning (once a day for 5 days). Separate cohorts of animals were tested for cognitive function with fear conditioning and Y-maze tests, or euthanized at different times to assess the blood-brain barrier integrity, systemic and hippocampal proinflammatory cytokines, and caspase-3 activity. Animals exhibited significant cognitive impairment evidenced by a decreased percentage of freezing time and an increased number of learning trials on days 1, 3, and 7 after surgery, which were significantly prevented by HBO preconditioning. Furthermore, HBO preconditioning significantly ameliorated the increase in serum and hippocampal proinflammatory cytokines tumor necrosis factor-?, interleukin-1 ? (IL-1?), IL-6, and high-mobility group protein 1 in surgery-challenged animals. Moreover, HBO preconditioning markedly improved blood-brain barrier integrity and caspase-3 activity in the hippocampus of surgery-challenged animals. These findings suggest that HBO preconditioning could significantly mitigate surgery-induced cognitive impairment, which is strongly associated with the reduction of systemic and hippocampal proinflammatory cytokines and caspase-3 activity. PMID:24870985

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

2014-06-18

34

Orchiectomy attenuates post-ischemic oxidative stress and ischemia/reperfusion injury in mice. A role for manganese superoxide dismutase.  

PubMed

Males are much more susceptible to ischemia/reperfusion (I/R)-induced kidney injury when compared with females. Recently we reported that the presence of testosterone, rather than the absence of estrogen, plays a critical role in gender differences in kidney susceptibility to I/R injury in mice. Although reactive oxygen species and antioxidant defenses have been implicated in I/R injury, their roles remain to be defined. Here we report that the orchiectomized animal had significantly less lipid peroxidation and lower hydrogen peroxide levels in the kidney 4 and 24 h after 30 min of bilateral renal ischemia when compared with intact or dihydrotestosterone-treated orchiectomized males. The post-ischemic kidney expression and activity of manganese superoxide dismutase (MnSOD) in orchiectomized mice was much greater than in intact or dihydrotestosterone-administered orchiectomized mice. Four hours after 30 min of bilateral ischemia, superoxide formation was significantly lower in orchiectomized mice than in intact mice. In Madin-Darby canine kidney cells, a kidney epithelial cell line, 1 mm H(2)O(2) decreased MnSOD activity, an effect that was potentiated by pretreatment with dihydrotestosterone. Orchiectomy prevented the post-ischemic decrease of catalase activity. Treatment of male mice with manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a SOD mimetic, reduced the post-ischemic increase of plasma creatinine, lipid peroxidation, and tissue hydrogen peroxide. These results suggest that orchiectomy accelerates the post-ischemic activation of MnSOD and reduces reactive oxygen species and lipid peroxidation, resulting in reduced kidney susceptibility to I/R injury. PMID:16682413

Kim, Jinu; Kil, In Sup; Seok, Young Mi; Yang, Eun Sun; Kim, Dae Kyong; Lim, Dong Gun; Park, Jeen-Woo; Bonventre, Joseph V; Park, Kwon Moo

2006-07-21

35

miR-15b Suppression of Bcl-2 Contributes to Cerebral Ischemic Injury and is Reversed by Sevoflurane Preconditioning  

PubMed Central

Ischemic neuroprotection afforded by sevoflurane preconditioning has been previously demonstrated, yet the underlying mechanism is poorly understood and likely affects a wide range of cellular activities. Several individual microRNAs have been implicated in both the pathogenesis of cerebral ischemia and cellular survival, and are capable of affecting a range of target mRNA. Conceivably, sevoflurane preconditioning may lead to alterations in ischemia-induced microRNA expression that may subsequently exert neuroprotective effects. We first examined the microRNA expression profile following transient cerebral ischemia in rats and the impact of sevoflurane preconditioning. Microarray analysis revealed that 3 microRNAs were up-regulated (>2.0 fold) and 9 were down-regulated (< 0.5 fold) following middle cerebral artery occlusion (MCAO) compared to sham controls. In particular, miR-15b was expressed at significantly high levels after MCAO. Preconditioning with sevoflurane significantly attenuated the upregulation of miR-15b at 72h after reperfusion. Bcl-2, an anti-apoptotic gene involved in the pathogenesis of cerebral ischemia, has been identified as a direct target of miR-15b. Consistent with the observed downregulation of miR-15b in sevoflurane-preconditioned brain, post-ischemic Bcl-2 expression was significantly increased by sevoflurane preconditioning. We identified the 3’-UTR of Bcl-2 as the target for miR-15b. Molecular inhibition of miR-15b was capable of mimicking the neuroprotective effect of sevoflurane preconditioning, suggesting that the suppression of miR-15b due to sevoflurane contributes to its ischemic neuroprotection. Thus, sevoflurane preconditioning may exert its anti-apoptotic effects by reducing the elevated expression of miR-15b following ischemic injury, allowing its target proteins, including Bcl-2, to be translated and expressed at the protein level.

Shi, Hong; Sun, Bao-liang; Zhang, Jia; Lu, Shiduo; Zhang, Pengyue; Wang, Hailian; Yu, Qiong; Stetler, R Anne; Vosler, Peter S.; Chen, Jun; Gao, Yanqin

2014-01-01

36

Neuronal Preconditioning by Inhalational Anesthetics  

PubMed Central

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

Bantel, Carsten; Maze, Mervyn; Trapp, Stefan

2010-01-01

37

Mitochondrial ROS production and subsequent ERK phosphorylation are necessary for temperature preconditioning of isolated ventricular myocytes  

PubMed Central

Hypothermia and hypothermic preconditioning are known to be profoundly cardioprotective, but the molecular mechanisms of this protection have not been fully explained. In this study, temperature preconditioning (16?°C) was found to be cardioprotective in isolated adult rat ventricular myocytes, enhancing contractile recovery and preventing calcium dysregulation after oxidative stress. Hypothermic preconditioning preserved mitochondrial function by delaying the pathological opening of the mitochondrial permeability transition pore (mPTP), whereas transient mPTP flickering remained unaltered. For the first time, reactive oxygen species (ROS) from the mitochondria are shown to be released exclusively during the hypothermic episodes of the temperature-preconditioning protocol. Using a mitochondrially targeted ROS biosensor, ROS release was shown during the brief bursts to 16?°C of temperature preconditioning. The ROS scavenger N-(2-mercaptopropionyl) glycine attenuated ROS accumulation during temperature preconditioning, abolishing the protective delay in mPTP opening. Temperature preconditioning induces ROS-dependant phosphorylation of the prosurvival kinase extracellular signal-regulated kinase (ERK)1/2. ERK1/2 activation was shown to be downstream of ROS release, as the presence of a ROS scavenger during temperature preconditioning completely blocked ERK1/2 activation. The cardioprotective effects of temperature preconditioning on mPTP opening were completely lost by inhibiting ERK1/2 activation. Thus, mitochondrial ROS release and ERK1/2 activation are both necessary to signal the cardioprotective effects of temperature preconditioning in cardiac myocytes.

Bhagatte, Y; Lodwick, D; Storey, N

2012-01-01

38

Sex Differences in Postischemic Neuronal Necrosis in Gerbils  

Microsoft Academic Search

Summary: Twenty-four hour postischemic neuronal necrosis was compared in male vs. female Mongolian gerbils subjected to a 3-h period of severe incomplete hemispheric ischemia produced by unilateral carotid occlusion. The incidence of stroke-prone males was 42.9% versus 26.7% for the females. Among the stroke-prone animals, the males displayed significantly greater neuronal necrosis at 24 h after ischemia compared to the

Edward D. Hall; Kay E. Pazara; Kelley L. Linseman

1991-01-01

39

Sepiapterin reduces postischemic injury in the rat heart  

Microsoft Academic Search

A reduced availability of tetrahydrobiopterin (BH4), an essential cofactor for NO-synthesis, is causally involved in the development of endothelial dysfunction associated with ischemia\\/reperfusion. We, therefore, investigated the effect of sepiapterin, a substrate for BH4 synthesis, on postischemic injury in myocardial infarction and myocardial stunning. In rats, myocardial stunning was induced by repetitive ischemia (5×10-min ligature of the left coronary artery,

Christiane P. Tiefenbacher; Ching-Hua Lee; Jolanthe Kapitza; Volker Dietz; Feraydoon Niroomand

2003-01-01

40

Disulfiram is protective against postischemic cell death in the liver.  

PubMed

The effect of the scavenger compound disulfiram (Antabus) on postischemic cell injury was investigated. Rats were subjected to 90 min of liver ischemia and 3 h of reperfusion. The extent of cell injury was evaluated morphologically by a dye exclusion test and a histochemical stain for calcium. It was found that pretreatment with disulfiram significantly reduced the number of injured cells compared to untreated controls. PMID:6516872

Jennische, E; Hansson, H A

1984-10-01

41

Sustained postischemic cardiodepression following magnesium-diltiazem cardioplegia  

SciTech Connect

Magnesium-diltiazem cardioplegia was evaluated in the intact, perfused rat heart to determine whether the joint administration of these agents would adversely affect myocardial contractile and high-energy phosphate recovery following intermittent, normothermic global ischemic arrest. Sequential metabolic and functional analyses were performed on isolated perfused rat hearts during each phase of the experimental protocol: control, normoxic cardioplegia, intermittent global ischemic arrest, and normoxic postischemic control reperfusion. Four different cardioplegic solutions were evaluated: 30 mM KCl, 30 mM KCl with 2 mg diltiazem/liter, 20 mM MgCl/sub 2/, and 20 mM MgCl/sub 2/ with 2 mg diltiazem/liter. Myocardial phosphatic metabolite levels and intracellular pH were analyzed nondestructively in the intact hearts by phosphorus-31 NMR spectroscopy. Corresponding measurements of peak left intraventricular pressure, rate of peak pressure development (dP/dt), and contraction frequency were performed at the midpoint during each 5-min interval of /sup 31/P NMR signal averaging. Magnesium plus diltiazem-treated hearts were distinguished from all other groups by a marked delay in postischemic functional recovery consisting of a prolonged depression in contractility (34% of control, P < 0.01) that persisted throughout the first 50 min of postischemic reperfusion. The apparent adverse interactive effects of excess magnesium and diltiazem suggest that elective ischemic arrest with magnesium cardioplegia in combination with diltiazem may be contraindicated clinically.

Wallis, D.E.; Gierke, L.W.; Scanlon, P.J.; Wolfson, P.M.; Kopp, S.J.

1986-07-01

42

Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional recovery.  

PubMed

Although pre-clinical evidence has suggested that partial inhibition of myocardial fatty acid oxidation (FAO) and subsequent switch to greater glucose oxidation for ATP production can prevent ischemia/reperfusion injury, controversy about this approach persists. For example, mice with germline deletion of the FA transporter CD36, exhibited either impaired or unchanged post-ischemic functional recovery despite a 40-60% reduction in FAO rates. Because there are limitations to cardiac studies utilizing whole body CD36 knockout (totalCD36KO) mice, we have now generated an inducible and cardiomyocyte-specific CD36 KO (icCD36KO) mouse to better address the role of cardiomyocyte CD36 and its regulation of FAO and post-ischemic functional recovery. Four to six weeks following CD36 ablation, hearts from icCD36KO mice had significantly decreased FA uptake compared to controls, which was paralleled by significant reductions in intramyocardial triacylglycerol content. Analysis of cardiac energy metabolism using ex vivo working heart perfusions showed that reduced FAO rates were compensated by enhanced glucose oxidation in the hearts from icCD36KO mice. In contrast to the totalCD36KO mice, hearts from icCD36KO mice exhibited significantly improved functional recovery following ischemia/reperfusion (18min of global no-flow ischemia followed by 40min of aerobic reperfusion). This improved recovery was associated with lower calculated proton production prior to and following ischemia compared to controls. Moreover, the amount of ATP generated relative to cardiac work was significantly lower in the hearts from icCD36KO mice compared to controls, indicating significantly increased cardiac efficiency in the hearts from icCD36KO mice. These data provide genetic evidence that reduced FAO as a result of diminished CD36-mediated FA uptake improves post-ischemic cardiac efficiency and functional recovery. As such, targeting cardiomyocyte FA uptake and FAO via inhibition of CD36 in the adult myocardium may provide therapeutic benefit during ischemia-reperfusion. PMID:23948483

Nagendran, Jeevan; Pulinilkunnil, Thomas; Kienesberger, Petra C; Sung, Miranda M; Fung, David; Febbraio, Maria; Dyck, Jason R B

2013-10-01

43

Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine A 1 receptor agonist  

Microsoft Academic Search

Agonists of adenosine A1 receptors have been frequently proposed as candidates for clinical development in treatment of cerebral ischemia and stroke. Numerous experimental studies have shown that pre- and postischemic administration of these drugs results in a very significant reduction of postischemic brain damage. However, only a few studies determined the impact of cerebral ischemia and drug treatment on postischemic

Mark Beenhakker; Rick C.-S. Lin; Margaret F. Carter; Ian A. Paul; Norbert Bischofberger; Kenneth A. Jacobson

1996-01-01

44

Delayed Postischemic Hypothermia: A Six Month Survival Study Using Behavioral and Histological A ssessments of Neuroprotection  

Microsoft Academic Search

In the gerbil, brief global forebrain ischemia induces pro- found habituation and working memory impairments that stem from delayed hippocampal CA1 death. Short duration postischemic hypothermia has been shown to reduce CA1 loss, but such reports are controversial, as it is thought that protection may be transient. The purpose of this study was to investigate whether prolonged postischemic hypo- thermia

Frederick Colbourne; Dale Corbett

45

Translation Arrest and Ribonomics In Post-ischemic Brain: Layers and Layers of Players  

PubMed Central

A persistent translation arrest (TA) correlates precisely with the selective vulnerability of post-ischemic neurons. Mechanisms of post-ischemic TA that have been assessed include ribosome biochemistry, the link between TA and stress responses, and the inactivation of translational components via sequestration in subcellular structures. Each of these approaches provides a perspective on post-ischemic TA. Here we develop the notion that mRNA regulation via RNA binding proteins, or ribonomics, also contributes to post-ischemic TA. We describe the ribonomic network, or structures involved in mRNA regulation, including nuclear foci, polysomes, stress granules, ELAV/Hu granules, processing bodies, exosomes and RNA granules. Transcriptional, ribonomic and ribosomal regulation together provide multiple layers mediating cell reprogramming. Stress gene induction via the heat shock response, immediate early genes, and endoplasmic reticulum stress represents significant reprogramming of post-ischemic neurons. We present a model of post-ischemic TA in ischemia-resistant neurons that incorporates ribonomic considerations. In this model, selective translation of stress-induced mRNAs contributes to translation recovery. This model provides a basis to study dysfunctional stress responses in vulnerable neurons, with a key focus on the inability of vulnerable neurons to selectively translate stress-induced mRNAs. We suggest a ribonomic approach will shed new light on the roles of mRNA regulation in persistent TA in vulnerable post-ischemic neurons.

DeGracia, Donald J.; Jamison, Jill T.; Szymanski, Jeffrey R.; Marshall, Monique K.

2008-01-01

46

Effects of Daflon 500mg on postischemic macromolecular leak syndrome in striated skin muscle of the hamster.  

PubMed

We have recently shown that the purified micronized flavonoid fraction (90% diosmin and 10% hesperidin) Daflon 500 mg attenuates reperfusion injury in the striated skin muscle of the hamster. Herein, we report on the action of Daflon 500 mg on postischemic macromolecular leakage of FITC-dextran 150 kD provoked by tourniquet ischemia. Intravital fluorescence microscopy was used for analysis of macromolecular leakage in the microcirculation model of the hamster. A tourniquet ischemia of 4 h duration was induced followed by reperfusion. Animals were treated by gavage of Daflon 500 mg (n = 6) for 8 days at a daily dose of 30 mg kg(-1) body weight. Control animals received equivalent volumes of the vehicle (5% Arabic gum solution, n = 6). Measurements of the microcirculatory parameters were made before induction of ischemia and at 0.5, 2 and 24 h of reperfusion. After induction of ischemia, macromolecular leakage from postcapillary venules was significantly enhanced in vehicle-treated animals. Treatment with Daflon 500 mg significantly attenuated macromolecular leakage of FITC-dextran 150 kD. Preliminary data from a histomorphometric analysis (n = 3/experimental group) indicated that the number of emigrated (extravascular) leukocytes after ischemia reperfusion was markedly reduced in Daflon 500 mg-treated animals as compared to controls. These data indicate that Daflon 500 mg prevents leakage of the macromolecular tracer FITC-dextran 150 kD from postcapillary venules after postischemic reperfusion, presumably through an inhibitory action on the emigration of activated leukocytes. PMID:9477038

Nolte, D; Pickelman, S; Schütze, E; Möllmann, M; Messmer, K

1997-01-01

47

Biomarkers for ischemic preconditioning: finding the responders.  

PubMed

Ischemic preconditioning is emerging as an innovative and novel cytoprotective strategy to counter ischemic vascular disease. At the root of the preconditioning response is the upregulation of endogenous defense systems to achieve ischemic tolerance. Identifying suitable biomarkers to show that a preconditioning response has been induced remains a translational research priority. Preconditioning leads to a widespread genomic and proteonomic response with important effects on hemostatic, endothelial, and inflammatory systems. The present article summarizes the relevant preclinical studies defining the mechanisms of preconditioning, reviews how the human preconditioning response has been investigated, and which of these bioresponses could serve as a suitable biomarker. Human preconditioning studies have investigated the effects of preconditioning on coagulation, endothelial factors, and inflammatory mediators as well as on genetic expression and tissue blood flow imaging. A biomarker for preconditioning would significantly contribute to define the optimal preconditioning stimulus and the extent to which such a response can be elicited in humans and greatly aid in dose selection in the design of phase II trials. Given the manifold biologic effects of preconditioning a panel of multiple serum biomarkers or genomic assessments of upstream regulators may most accurately reflect the full spectrum of a preconditioning response. PMID:24643082

Koch, Sebastian; Della-Morte, David; Dave, Kunjan R; Sacco, Ralph L; Perez-Pinzon, Miguel A

2014-06-01

48

Cardiac genomic response following preconditioning stimulus  

Microsoft Academic Search

This review focuses on the genomic response following a preconditioning stimulus. Initial studies demonstrated that classical ischemic preconditioning mediated by cyclic episodes of short durations of reversible ischemia and reperfusion could result in the reprogramming of gene expression. Some of these genes are translated into proteins during the late preconditioning or so-called ''second window of protection''. Subsequent studies determined a

Dipak K. Das; Nilanjana Maulik

2006-01-01

49

Effects of angiotensin II AT1-receptor blockade on coronary dynamics, function, and structure in postischemic heart failure in rats.  

PubMed

Angiotensin II AT1-receptor blockers (AT1-s) prolong survival in experimental postischemic (coronary artery ligation) heart failure (CHF) in rats. The goal of this study was to investigate whether potential beneficial effects of short- and/or long-term treatment with AT1-s on coronary dynamics, function, and structure develop along with the drug-induced survival prolongation in this model. Coronary blood flow was measured (fluorescent microspheres) in conscious sham, untreated, and irbesartan-treated (50 mg/kg daily for 6 weeks or 6 months, starting 8 days after surgery) CHF rats at baseline and at maximal vasodilatation induced by dipyridamole, and coronary dilatation reserve (CDR) was calculated as the ratio of maximal to baseline coronary flow. Coronary endothelial function was assessed in vitro by measuring the coronary relaxant responses to acetylcholine in the three groups of animals. Finally, cardiac hypertrophy and pericoronary fibrosis also were investigated. In CHF rats, left (LV) and right (RV) ventricular CDR were markedly depressed at both 7 weeks and 6 months after ligation, whereas coronary endothelial function was significantly impaired only after 6 months. Short-term AT1-receptor blockade with irbesartan did not prevent CDR deterioration at 7 weeks, nor did it significantly oppose cardiac hypertrophy and pericoronary fibrosis development. Prolonged AT1-receptor blockade prevented both RV CDR deterioration and coronary endothelial function impairment. It also limited significantly the increase in LV end diastolic pressure and the development of cardiac hypertrophy and pericoronary fibrosis. In conclusion, in postischemic CHF in rats, alterations of CDR precede those of coronary endothelial function. Long-, but not short-term AT1-receptor blockade prevents endothelial function degradation, opposes RV CDR impairment, prevents pericoronary fibrosis development, and improves systemic hemodynamics. These effects of AT1-s on coronary dynamics, function, and structure (i.e., on myocardial perfusion) may contribute to the drug-induced survival prolongation in this model. PMID:10975590

Gervais, M; Fornes, P; Richer, C; Nisato, D; Giudicelli, J F

2000-09-01

50

Hypoxic preconditioning protects rat hearts against ischemia-reperfusion injury via the arachidonate12-lipoxygenase/transient receptor potential vanilloid 1 pathway.  

PubMed

Hypoxic preconditioning (HPC) protects rat hearts against ischemia-reperfusion (IR) injury. However, the role of transient receptor potential vanilloid 1 (TRPV1) in HPC-mediated cardioprotection remains unknown. TRPV1 is activated by endovanilloid 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], which is synthesized by arachidonate 12-lipoxygenase (ALOX12). Therefore, we examined whether HPC protects the myocardium against IR via the ALOX12/TRPV1 pathway. Compared to hearts of rats kept in room air, the hearts of rats kept in air with 10 % oxygen for 4 weeks had better post-ischemic recovery and less tissue damage when subjected to 30-min global ischemia and 4-h reflow in a Langendorff apparatus. Capsazepine, a specific TRPV1 blocker, administered 5 min before reperfusion markedly attenuated the effects of HPC, confirming that TRPV1 is a downstream effector in HPC-mediated cardioprotection. HPC resulted in the upregulation of ALOX12 and myocardial 12(S)-HETE, and prevented IR-induced 12(S)-HETE reduction. In addition, sarcolemmal ALOX12 expression in HPC hearts mainly co-localized with TRPV1 expression. Blockade of ALOX12 by cinnamyl-3,4-dihydroxy-?-cyanocinnamate or baicalein abrogated the effects of HPC, baicalein also decreased 12(S)-HETE expression. Mimicking HPC by given 12(S)-HETE or capsaicin to baicalien-treated hearts enhanced cardiac recovery during reperfusion. The cardiac protein kinase C (PKC) isoforms ?, ?, ?, and ? were preferentially expressed in the sarcolemmal membrane of HPC-treated hearts, indicating their high intrinsic activation state. Capsazepine or co-treatment with baicalein attenuated translocation of PKC?, PKC? and PKC?, but not that of PKC?. We conclude that HPC reduces heart susceptibly to IR via ALOX12/TRPV1/PKC pathway, as shown by increased 12(S)-HETE expression in HPC hearts. PMID:24816396

Lu, Ming-Jen; Chen, Yih-Sharng; Huang, Ho-Shiang; Ma, Ming-Chieh

2014-07-01

51

Intestinal injury can be reduced by intra-arterial postischemic perfusion with hypertonic saline  

PubMed Central

AIM: To investigate the effect of local intestinal perfusion with hypertonic saline (HTS) on intestinal ischemia-reperfusion injury (IRI) in both ex vivo and in vivo rat models. METHODS: All experiments were performed on male Wistar rats anesthetized with pentobarbital sodium given intraperitoneally at a dose of 60 mg/kg. Ex vivo vascularly perfused rat intestine was subjected to 60-min ischemia and either 30-min reperfusion with isotonic buffer (controls), or 5 min with HTS of 365 or 415 mOsm/L osmolarity (HTS365mOsm or HTS415mOsm, respectively) followed by 25-min reperfusion with isotonic buffer. The vascular intestinal perfusate flow (IPF) rate was determined by collection of the effluent from the portal vein in a calibrated tube. Spontaneous intestinal contraction rate was monitored throughout. Irreversible intestinal injury or area of necrosis (AN) was evaluated histochemically using 2.3.5-triphenyltetrazolium chloride staining. In vivo, 30-min ischemia was followed by either 30-min blood perfusion or 5-min reperfusion with HTS365mOsm through the superior mesenteric artery (SMA) followed by 25-min blood perfusion. Arterial blood pressure (BP) was measured in the common carotid artery using a miniature pressure transducer. Histological injury was evaluated in both preparations using the Chui score. RESULTS: Ex vivo, intestinal IRI resulted in a reduction in the IPF rate during reperfusion (P < 0.05 vs sham). The postischemic recovery of the IPF rate did not differ between the controls and the HTS365mOsm group. In the HTS415mOsm group, postischemic IPF rates were lower than in the controls and the HTS365mOsm group (P < 0.05). The intestinal contraction rate was similar at baseline in all groups. An increase in this parameter was observed during the first 10 min of reperfusion in the control group as compared to the sham-treated group, but no such increase was seen in the HTS365mOsm group. In controls, AN averaged 14.8% ± 5.07% of the total tissue volume. Administration of HTS365mOsm for 5 min after 60-min ischemia resulted in decrease in AN (5.1% ± 1.20% vs controls, P < 0.01). However, perfusion of the intestine with the HTS of greater osmolarity (HTS415mOsm) failed to protect the intestine from irreversible injury. The Chiu score was lower in the HTS365mOsm group in comparison with controls (2.4 ± 0.54 vs 3.2 ± 0.44, P = 0.042), while intestinal perfusion with HTS415mOsm failed to improve the Chiu score. Intestinal reperfusion with HTS365mOsm in the in vivo series secured rapid recovery of BP after its transient fall, whereas in the controls no recovery was seen. The Chiu score was lower in the HTS365mOsm group vs controls (3.1 ± 0.26 and 3.8 ± 0.22, P = 0.0079 respectively,), although the magnitude of the effect was lower than in the ex vivo series. CONCLUSION: Brief intestinal postischemic perfusion with HTS365mOsm through the SMA followed by blood flow restoration is a protective procedure that could be used for the prevention of intestinal IRI.

Kornyushin, Oleg; Galagudza, Michael; Kotslova, Anna; Nutfullina, Gelfia; Shved, Nina; Nevorotin, Alexey; Sedov, Valeriy; Vlasov, Timur

2013-01-01

52

Preconditioning Operators on Unstructured Grids  

NASA Technical Reports Server (NTRS)

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

Nepomnyaschikh, S. V.

1996-01-01

53

NCX1 and NCX3: two new effectors of delayed preconditioning in brain ischemia.  

PubMed

Substantial evidence has established that a short sub-lethal brain ischemia applied before a prolonged harmful ischemic episode confers ischemic neuroprotection, a phenomenon named ischemic preconditioning. Na(+)/Ca(2+) exchanger (NCX) isoforms, NCX1, NCX2, and NCX3, are plasmamembrane ionic transporters widely distributed in the brain, where they are involved in the control of Na(+) and Ca(2+) homeostasis and in the progression of stroke damage. The objective of this study was to evaluate the role of these three proteins in the preconditioning-induced neuroprotection. NCX protein expression was evaluated at different time points in the ischemic temporoparietal cortex of rats subjected to ischemia alone, to ischemic preconditioning alone, or to ischemic preconditioning plus ischemia. NCX1 and NCX3 were up-regulated in those brain regions protected by preconditioning treatment. These changes were mediated by p-AKT, since the p-AKT inhibition prevented the up-regulation of both isoforms. The relevant role of NCX1 and NCX3 during preconditioning was further confirmed when NCX1 and NCX3 silencing, induced by icv infusion of siRNA, partially reverted the preconditioning-induced neuroprotection. The enhancement of NCX1 and NCX3 expression and activity might represent a reasonable strategy to reduce the infarct extension after stroke. PMID:22036625

Pignataro, Giuseppe; Boscia, Francesca; Esposito, Elga; Sirabella, Rossana; Cuomo, Ornella; Vinciguerra, Antonio; Di Renzo, Gianfranco; Annunziato, Lucio

2012-01-01

54

Preconditioning rabbit cardiomyocytes: role of pH, vacuolar proton ATPase, and apoptosis.  

PubMed Central

Ischemic preconditioning signals through protein kinase C (PKC) to protect against myocardial infarction. This protection is characterized by diminished intracellular acidification. Acidification is also a feature of apoptosis, and several agents act to prevent apoptosis by preventing acidification through activation of ion channels and pumps to promote cytoplasmic alkalinization. We characterized metabolic inhibition, recovery, and preconditioning through a PKC-dependent pathway in cardiomyocytes isolated from adult rabbit hearts. Preconditioning reduced loss of viability assessed by morphology and reduced DNA nicking. Blockade of the vacuolar proton ATPase (VPATPase) prevented the effect of preconditioning to reduce metabolic inhibition-induced acidosis, loss of viability, and DNA nicking. The beneficial effect of Na+/H+ exchange inhibition, which is thought to be effective through reduced intracellular Na+ and Ca++, was also abrogated by VPATPase blockade, suggesting that acidification even in the absence of Na+/H+ exchange may lead to cell death. We conclude that a target of PKC in mediating preconditioning is activation of the VPATPase with resultant attenuation of intracellular acidification during metabolic inhibition. Inhibition of the "death protease," interleukin-1-beta converting enzyme or related enzymes, also protected against the injury that followed metabolic inhibition. This observation, coupled with the detection of DNA nicking in cells subjected to metabolic inhibition, suggests that apoptotic cell death may be preventable in this model of ischemia/reperfusion injury.

Gottlieb, R A; Gruol, D L; Zhu, J Y; Engler, R L

1996-01-01

55

Preconditioning mesenchymal stem cells with transforming growth factor-alpha improves mesenchymal stem cell-mediated cardioprotection.  

PubMed

Mesenchymal stem cells (MSCs) are a promising therapy for acute organ ischemia in part due to their paracrine production of growth factors. However, transplanted cells encounter an inflammatory environment that mitigates their function and survival, and treating the cells with exogenous agents during ex vivo expansion before transplantation is one strategy for overcoming this limitation by enhancing paracrine function. We hypothesized that preconditioning bone marrow MSCs with TGF-alpha would 1) increase MSC production of the critical paracrine factor, vascular endothelial growth factor (VEGF), via a p38 mitogen-activated protein kinase (MAPK)-dependent mechanism and 2) enhance myocardial functional recovery in a rat model of acute myocardial I/R injury. To study this, bone marrow MSCs were harvested from adult male mice (C57BL/6J) and treated in vitro for 24 h according to the following groups: 1) control, 2) TGF-alpha (250 ng mL (-1)), 3) TNF-alpha (50 ng mL (-1)), 4) TGF-alpha + TNF-alpha, 5) hypoxia, and 6) TGF-alpha + hypoxia. For the isolated heart perfusion experiments, adult male Sprague-Dawley rat hearts were isolated, perfused via the Langendorff model, and subjected to I/R. Vehicle or MSCs with or without TGF-alpha preconditioning were infused immediately before ischemia. Mesenchymal stem cells were also treated with TGF-alpha alone or in combination with a p38 MAPK inhibitor (SB202190). In vitro, TGF-alpha increased MSC VEGF production alone (157.9 +/- 1.11 - 291.0 +/- 3.74 pg 10 (-5); P < 0.05) and, to a greater extent, in combination with TNF-alpha or hypoxia (364.5 +/- 0.868 and 342.0 +/- 7.92 pg 10(-5) cells, respectively; P < 0.05 vs. TGF-alpha alone). Postischemic myocardial functional recovery was greater in hearts infused with TGF-alpha-preconditioned MSCs compared with untreated MSCs or vehicle. Myocardial IL-1beta and TNF-alpha production and activation of caspase 3 were significantly decreased after infusion of both cell groups. p38 MAPK inhibition suppressed TGF-alpha-stimulated MSC VEGF production and postischemic myocardial recovery. These results suggest that TGF-alpha stimulates MSC VEGF production in part via a p38 MAPK-dependent mechanism, and preconditioning MSCs with TGF-alpha may enhance their ability to protect myocardium during I/R injury. PMID:19996917

Herrmann, Jeremy L; Wang, Yue; Abarbanell, Aaron M; Weil, Brent R; Tan, Jiangning; Meldrum, Daniel R

2010-01-01

56

Preconditioning Techniques in Computational Fluid Dynamics  

Microsoft Academic Search

An overview of preconditioning for the steady-state compressible inviscid fluid dynamic equations is presented. Extensions to the Navier-Stokes equations are also considered. These preconditioners are necessary for many algorithms in order to have the correct behavior at low speeds and to converge to the solution of the incompressible equations as the Mach number goes to zero. In addition, the preconditioning

E. Turkel

1999-01-01

57

Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity.  

PubMed

The clinical importance of vascular reactivity as an early marker of atherosclerosis has been well established, and a number of established and emerging techniques have been employed to provide measurements of peripheral vascular reactivity. However, relations between these methodologies are unclear as each technique evaluates different physiological aspects related to micro- and macrovascular reactive hyperemia. To address this question, a total of 40 apparently healthy normotensive adults, 19-68 yr old, underwent 5 min of forearm suprasystolic cuff-induced ischemia followed by postischemic measurements. Measurements of vascular reactivity included 1) flow-mediated dilatation (FMD), 2) changes in pulse wave velocity between the brachial and radial artery (DeltaPWV), 3) hyperemic shear stress, 4) reactive hyperemic flow, 5) reactive hyperemia index (RHI) assessed by fingertip arterial tonometry, 6) fingertip temperature rebound (TR), and 7) skin reactive hyperemia. FMD was significantly and positively associated with RHI (r=0.47) and TR (r=0.45) (both P<0.01) but not with reactive hyperemic flow or hyperemic shear stress. There was no correlation between two measures of macrovascular reactivity (FMD and DeltaPWV). Skin reactive hyperemia was significantly associated with RHI (r=0.55) and reactive hyperemic flow (r=0.35) (both P<0.05). There was a significant association between reactive hyperemia and RHI (r=0.30; P<0.05). In more than 75% of cases, vascular reactivity measures were not significantly associated. We concluded that associations among different measures of peripheral micro- and macrovascular reactivity were modest at best. These results suggest that different physiological mechanisms may be involved in changing different measures of vascular reactivity. PMID:18483158

Dhindsa, Mandeep; Sommerlad, Shawn M; DeVan, Allison E; Barnes, Jill N; Sugawara, Jun; Ley, Obdulia; Tanaka, Hirofumi

2008-08-01

58

Preconditioning: from experimental findings to novel therapies in acute kidney injury.  

PubMed

Improving the ability of the kidney to tolerate injury through preconditioning is likely to have important clinical implications. Although a number of preconditioning strategies have been studied, ischemic preconditioning (IP) has been studied the most experimentally. The information gathered has helped us shed more light into the mechanisms responsible for this tissue adaptation that confers to tissues a more resistant status. IP is effective within minutes, suggesting that preformed mediators are involved. This is followed by delayed preconditioning, a phenomenon that is less potent but longer acting. Remote preconditioning occurs also in non-affected tissues and can be transferable. A number of mediators and transcription factors have been implicated including kinases, heat shock proteins, nitric oxide and neurogenic pathways, all of which help change the cell into a more resistant phenotype. There is evidence that IP also occurs in the human environment with lessons learned from myocardial ischemia, hepatic resection and cerebral ischemia. Because of the ethical impediment with intentionally applying organ ischemia, there has been an interest in pharmacological preconditioning lately. Exogenously administered erythropoietin was shown to benefit kidneys subjected to different insults. In addition, mesenchymal stem cells-based approaches for the prevention and treatment of acute kidney injury (AKI) are being studied. Calcineurin inhibitors may represent a viable way to reduce ischemia reperfusion injury in transplantation. Translating the experimental findings to the clinical arena remains a challenge. The discovery of new biomarkers for AKI should help initiate therapy early, when therapy could make a difference. PMID:19773719

Shihab, F S

2009-09-01

59

Preconditioning Strategy in Stem Cell Transplantation Therapy  

PubMed Central

Stem cell transplantation therapy has emerged as a promising regenerative medicine for ischemic stroke and other neurodegenerative disorders. However, many issues and problems remain to be resolved before successful clinical applications of the cell-based therapy. To this end, some recent investigations have sought to benefit from well-known mechanisms of ischemic/hypoxic preconditioning. Ischemic/hypoxic preconditioning activates endogenous defense mechanisms that show marked protective effects against multiple insults found in ischemic stroke and other acute attacks. As in many other cell types, a sub-lethal hypoxic exposure significantly increases the tolerance and regenerative properties of stem cells and progenitor cells. So far, a variety of preconditioning triggers have been tested on different stem cells and progenitor cells. Preconditioned stem cells and progenitors generally show much better cell survival, increased neuronal differentiation, enhanced paracrine effects leading to increased trophic support, and improved homing to the lesion site. Transplantation of preconditioned cells helps to suppress inflammatory factors and immune responses, and promote functional recovery. Although the preconditioning strategy in stem cell therapy is still an emerging research area, accumulating information from reports over the last few years already indicates it as an attractive, if not essential, prerequisite for transplanted cells. It is expected that stem cell preconditioning and its clinical applications will attract more attention in both the basic research field of preconditioning as well as in the field of stem cell translational research. This review summarizes the most important findings in this active research area, covering the preconditioning triggers, potential mechanisms, mediators, and functional benefits for stem cell transplant therapy.

Yu, Shan Ping; Wei, Zheng; Wei, Ling

2013-01-01

60

Glutathione disulfide as an index of oxidative stress during postischemic reperfusion in isolated rat hearts  

Microsoft Academic Search

The objectives of this study were to determine 1) whether reactive oxygen species generated upon postischemic reperfusion lead to oxidative stress in rat hearts, and 2) whether an exogenous prooxidant present in the early phase of reperfusion causes additional injury. Isolated buffer-perfused rat hearts were subjected to 30 min of hypothermic no-flow ischemia followed by 30 min of reperfusion. Increased

Robert J. A. M. Verbunt; Willem G. Dockum; E. M. Lars Bastiaanse; Janneke M. Egas; Arnoud Laarse

1995-01-01

61

Ascorbic acid improves postischemic vasodilatation impaired by infusion of soybean oil into canine iliac artery.  

PubMed

This study was conducted to (a) assess postischemic vasodilatation by changes in the vascular cross-sectional area using simultaneous intravascular two-dimensional and Doppler ultrasound before and after the infusion of Intralipid (Pharmacia & Upjohn, Peapack, NJ, U.S.A.); (b) evaluate how antioxidant ascorbic acid modifies the effects of Intralipid on postischemic vasodilatation: and (c) clarify the changes in plasma nitrite and nitrate (NOx-) levels after the infusion of Intralipid with and without ascorbic acid. Twenty-eight mongrel dogs were used to measure for vascular cross-sectional area and average instantaneous peak velocity in the iliac arteries after the 5-min occlusion of the arteries. Postischemic vasodilatation was impaired after the infusion of Intralipid (20%, 2 ml/kg) and this impaired response was reversed by the co-administration of ascorbic acid (30 mg/kg). NG-monomethyl-L-arginine completely abolished postischemic vasodilatation. Plasma NOx levels were significantly reduced after the infusion of Intralipid compared with baseline (11.6+/-0.4 vs. 12.9+/-0.3 microM, p = 0.025) and after infusion of Intralipid with ascorbic acid compared with baseline (11.8+/-0.5 vs. 13.1+/-0.4 microM, p = 0.047). We concluded that ascorbic acid reverses the endothelial dysfunction induced by Intralipid without increasing plasma NOx- levels and that deactivation of nitric oxide by oxidative stress is a primary contributor to Intralipid-induced impaired vasodilation. PMID:11117366

Osanai, H; Okumura, K; Hayakawa, M; Harada, M; Numaguchi, Y; Mokuno, S; Murase, K; Matsui, H; Toki, Y; Ito, T; Hayakawa, T

2000-12-01

62

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

NASA Astrophysics Data System (ADS)

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

Hejranfar, Kazem; Kamali-Moghadam, Ramin

2012-06-01

63

Laser thermal preconditioning enhances dermal wound repair  

NASA Astrophysics Data System (ADS)

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

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

2008-03-01

64

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.

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

2014-01-01

65

An electrocardiographic sign of ischemic preconditioning.  

PubMed

Ischemic preconditioning is a form of intrinsic cardioprotection where an episode of sublethal ischemia protects against subsequent episodes of ischemia. Identifying a clinical biomarker of preconditioning could have important clinical implications, and prior work has focused on the electrocardiographic ST segment. However, the electrophysiology biomarker of preconditioning is increased action potential duration (APD) shortening with subsequent ischemic episodes, and APD shortening should primarily alter the T wave, not the ST segment. We translated findings from simulations to canine to patient models of preconditioning to test the hypothesis that the combination of increased [delta (?)] T wave amplitude with decreased ST segment elevation characterizes preconditioning. In simulations, decreased APD caused increased T wave amplitude with minimal ST segment elevation. In contrast, decreased action potential amplitude increased ST segment elevation significantly. In a canine model of preconditioning (9 mongrel dogs undergoing 4 ischemia-reperfusion episodes), ST segment amplitude increased more than T wave amplitude during the first ischemic episode [?T/?ST slope = 0.81, 95% confidence interval (CI) 0.46-1.15]; however, during subsequent ischemic episodes the T wave increased significantly more than the ST segment (?T/?ST slope = 2.43, CI 2.07-2.80) (P < 0.001 for interaction of occlusions 2 vs. 1). A similar result was observed in patients (9 patients undergoing 2 consecutive prolonged occlusions during elective percutaneous coronary intervention), with an increase in slope of ?T/?ST of 0.13 (CI -0.15 to 0.42) in the first occlusion to 1.02 (CI 0.31-1.73) in the second occlusion (P = 0.02). This integrated analysis of the T wave and ST segment goes beyond the standard approach to only analyze ST elevation, and detects cellular electrophysiology changes of preconditioning. PMID:24778173

Meijs, Loek P B; Galeotti, Loriano; Pueyo, Esther P; Romero, Daniel; Jennings, Robert B; Ringborn, Michael; Warren, Stafford G; Wagner, Galen S; Strauss, David G

2014-07-01

66

Mitochondrial Preconditioning: A Potential Neuroprotective Strategy  

PubMed Central

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

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

2010-01-01

67

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.

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

2012-01-01

68

Further probes into the molecular sites of damage to cerebral adenylate cyclase following postischemic reperfusion  

Microsoft Academic Search

A variety of pharmacological agents were used as experimental probes to determine with greater precision the site(s) of damage\\u000a to cerebral adenylate cyclase as a consequence of postischemic reperfusion in the gerbil. A paradigm of 60-min bilateral ischemia\\u000a followed by 40-min reperfusion results in a decreased sensitivity of the catalytic site of adenylate cyclase to Mn2+. Likewise, the GTP-transducer site

Gene C. Palmer; David J. Jones; S. Jo Palmer; Barbara C. Christie-Pope; Lawrence Poulakos

1986-01-01

69

Contribution of poly(ADP-ribose) polymerase to postischemic blood–brain barrier damage in rats  

Microsoft Academic Search

The nuclear enzyme poly(ADP-ribose) polymerase (PARP) is activated by oxidative stress and plays a significant role in postischemic brain injury. We assessed the contribution of PARP activation to the blood–brain barrier (BBB) disruption and edema formation after ischemia–reperfusion. In male Wistar rats, global cerebral ischemia was achieved by occluding the carotid arteries and lowering arterial blood pressure for 20 mins.

Gábor Lenzsér; Béla Kis; James A Snipes; Tamás Gáspár; Péter Sándor; Katalin Komjáti; Csaba Szabó; David W Busija

2007-01-01

70

Contribution of amino acids in protective solutions to postischemic functional recovery of canine kidneys  

Microsoft Academic Search

Summary Amino acids are known to increase glomerular filtration rate (GFR). There is also an early resumption of filtration following 2-h renal ischemic stress under protection by histidine-buffered histidine-tryptophanketoglutarate solution (HTK), possibly due in part to an amino acid effect. Hence, we have examined the possibility of further enhancing the postischemic GFR by adding 32 (ASP I; 4 mM Mg2+)

G. Kehrer; M. Blech; M. Kallerhoff; M. Langheinrich; H.-J. Bretschneider

1989-01-01

71

The Time of Maximum Post-Ischemic Hyperperfusion Indicates Infarct Growth Following Transient Experimental Ischemia  

PubMed Central

After recanalization, cerebral blood flow (CBF) can increase above baseline in cerebral ischemia. However, the significance of post-ischemic hyperperfusion for tissue recovery remains unclear. To analyze the course of post-ischemic hyperperfusion and its impact on vascular function, we used magnetic resonance imaging (MRI) with pulsed arterial spin labeling (pASL) and measured CBF quantitatively during and after a 60 minute transient middle cerebral artery occlusion (MCAO) in adult rats. We added a 5% CO2 - challenge to analyze vasoreactivity in the same animals. Results from MRI were compared to histological correlates of angiogenesis. We found that CBF in the ischemic area recovered within one day and reached values significantly above contralateral thereafter. The extent of hyperperfusion changed over time, which was related to final infarct size: early (day 1) maximal hyperperfusion was associated with smaller lesions, whereas a later (day 4) maximum indicated large lesions. Furthermore, after initial vasoparalysis within the ischemic area, vasoreactivity on day 14 was above baseline in a fraction of animals, along with a higher density of blood vessels in the ischemic border zone. These data provide further evidence that late post-ischemic hyperperfusion is a sequel of ischemic damage in regions that are likely to undergo infarction. However, it is transient and its resolution coincides with re-gaining of vascular structure and function.

Wegener, Susanne; Artmann, Judith; Luft, Andreas R.; Buxton, Richard B.; Weller, Michael; Wong, Eric C.

2013-01-01

72

Post-ischemic azotemia as a partial 'brake', slowing progressive kidney disease  

PubMed Central

Background Recent experimental work suggests a paradox: although uremia evokes systemic toxicities, in the setting of AKI, it can induce intrarenal cytoprotective and anti-inflammatory effects. Whether these influences can attenuate post-ischemic kidney disease progression remains unknown. Methods To explore this possibility, male CD-1 mice were subjected to a 30-min unilateral (left) kidney ischemia model, previously shown to reduce renal mass by ?50% over 2–3 weeks. Stepwise azotemia/acute uremia was superimposed by inducing different lengths of contralateral (right) kidney ischemia (0, 15, 18, 20 min). Subsequent loss of left renal mass (kidney weight) was assessed 2 weeks later and contrasted with the degree of initial azotemia 24-h BUN. Results A striking correlation between 24-h BUNs and 2-week left renal mass was observed (r, 0.77; P < 0.001). With 20 min of right kidney ischemia, left kidney size was completely preserved. This preservation did not result from increased tubular cell proliferation or decreased microvascular loss, as gauged by KI-67 and CD-34 immunohistochemistry, respectively. Rather, an early reduction in proximal tubule cell dropout (as judged by renal cortical N-acetyl-glucosaminidase content), with a subsequent preservation of tubule mass, was observed. Conclusions In summary, these findings advance a novel concept: acute uremia can confer early post-ischemic cytoprotection resulting in a slowed progression of post-ischemic kidney disease.

Zager, Richard A.; Johnson, Ali C.; Becker, Kirsten

2013-01-01

73

Sound preconditioning therapy inhibits ototoxic hearing loss in mice  

PubMed Central

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

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

2013-01-01

74

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

75

Ligand triggers of classical preconditioning and postconditioning  

Microsoft Academic Search

The cardioprotection afforded by ischemic preconditioning (IPC) and ischemic postconditioning (PC) are receptor mediated. In this review, we will focus on the major ligand classes and receptors that contribute to IPC and PC-induced cardioprotection. Ligand classes discussed include adenosine, bradykinin, opioids, erythropoietin, adrenergics and muscarinics. The cardioprotective therapeutic window of each ligand class will also be summarized, with particular focus

Eric R. Gross; Garrett J. Gross

2006-01-01

76

Interagency Collaboration: Preconditions, Progress, and Pressures.  

ERIC Educational Resources Information Center

The Down East Partnership for Children (DEPC) was established in 1993 to bring together health, education, and social service agencies to address the needs of children and families in two eastern North Carolina counties. Collaboration theory provided a useful lens through which to examine the development of the partnership, recognize preconditions

Bradshaw, Lynn K.

77

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

78

China's Pension Reform: A Precondition Approach  

Microsoft Academic Search

China has a relatively young population, but is about to undergo a remarkable demographic transformation. Given the un-sustainability of the old system, the Chinese authorities have initiated a number of pension reforms since the early 1990s. In this paper, based on latest precondition framework, we analyse and conclude that the initial economic and financial conditions within the reform started in

Yu-Wei Hu

2006-01-01

79

Neuronal plasticity after ischemic preconditioning and TIA-like preconditioning ischemic periods  

Microsoft Academic Search

Transient ischemic attacks (TIAs) have recently become the center of attention since they are thought to share some characteristics\\u000a with experimental ischemic preconditioning (IPC). This phenomenon describes the situation that a brief, per se harmless, cerebral\\u000a ischemic period renders the brain resistant to a subsequent severe and normally damaging ischemia. Preconditioning (PC) is\\u000a not restricted to the brain but also

Clemens Sommer

2009-01-01

80

Postischemic leukocyte/endothelial cell interactions and microvascular barrier dysfunction in skeletal muscle: cellular mechanisms and effect of Daflon 500 mg.  

PubMed

A growing body of evidence indicates that neutrophils play a critical role in disrupting the microvascular barrier in skeletal muscle. Recent studies from our laboratory and by others indicate that administration of antibodies directed against P-selectin, ICAM-1, or the common subunit (CD18) of CD11/CD18 was as effective as neutrophil depletion in attenuating ischemia/reperfusion (I/R)-induced microvascular barrier disruption and edema formation in skeletal muscle. These studies have important implications with regard to the pathogenesis of leg ulceration in view of our more recent work indicating that the increase in tissue pressure induced by edema formation secondary to microvascular barrier disruption may lead to the development of capillary no-reflow. The resulting maldistribution of blood flow during reperfusion exacerbates muscle injury induced by ischemia. Daflon 500 mg is a purified, micronized flavonoid fraction that exhibits a number of anti-inflammatory properties and is used clinically to treat venous insufficiency. In view of these actions and the demonstrated role of neutrophil adhesion in the pathogenesis of I/R, we sought to determine whether this agent would prevent leukocyte adhesion and microvascular barrier disruption in postischemic rat cremaster muscles and small bowel. Rats were treated with Daflon 500 mg (80 mg/kg/day by gavage) or its vehicle for 2 (cremaster studies) or 10 (mesenteric studies) days prior to the experiments. Leukocyte/endothelial cell interactions and venular protein leakage were quantitated using intravital microscopic techniques in rat cremaster muscles and mesenteries subjected to ischemia (60 min for cremaster, 20 min for mesentery) and reperfusion (60 min). The results indicated that Daflon 500 mg was as effective as the anti-adhesive monoclonal antibodies in reducing postischemic leukocyte adhesion and emigration and venular protein leakage in these models. PMID:9477039

Korthuis, R J; Gute, D C

1997-01-01

81

Uncoupling of mitochondrial oxidative phosphorylation alters lipid peroxidation-derived free radical production but not recovery of postischemic rat hearts and post-hypoxic endothelial cells.  

PubMed

The contribution of mitochondrial free radical production towards the initiation of lipid peroxidation (LPO) and functional injury in the post-ischemic heart is unclear. Using the isolated rat heart model, the effects of the uncoupler of mitochondrial oxidative phosphorylation dinitrophenol (DNP, 50 microM final) on post-ischemic lipid peroxidation-derived free radical production and functional recovery were assessed. Hearts were subjected to 30 min total global ischemia followed by 15 min of reperfusion in the presence of DNP. As expected, DNP enhanced oxygen consumption before (11.3 +/- 0.9 mumol/min, p < 0.001) and during reperfusion (at 10 min: 7.9 +/- 0.7 mu umol/min), compared to the heart with control treatment (8.2 +/- 0.5 and 6.7 +/- 0.3, respectively). This effect was only associated with a higher incidence of ventricular tachycardia during reperfusion (80 vs. 50% for control treatment, p < 0.05). Electron spin resonance spectroscopy (ESR) and spin trapping with alpha-phenyl-tert-butylnitrone PBN-radical adducts (untreated: 6.4 +/- 1.0 nM, at 10 min) decreased in the presence of DNP (1.7 +/- 0.4 nM, p < 0.01). The radical concentration inversely correlated with myocardial oxygen consumption. Total liberation of free radical adducts during the initial 10 min of reperfusion was reduced by DNP (0.59 +/- 0.09 nmol, p < 0.01) compared to the respective control treatment (1.26 +/- 0.16 nmol). Similar effects, prevention of PBN adduct formation and unchanged viability in the presence of DNP, were obtained with endothelial cells during post-hypoxic reoxygenation. Since inhibition of mitochondrial phosphorylation can inhibit the formation of LPO-derived free radicals after an ischemic/hypoxic interval, mitochondria may represent an important source of free radicals capable of initiating lipid peroxidative injury during reperfusion/reoxygenation. PMID:8901471

Blasig, I E; Dickens, B F; Weglicki, W B; Kramer, J H

1996-01-01

82

Morphine preconditioning protects against LPS-induced neuroinflammation and memory deficit.  

PubMed

Recent studies show that morphine possesses protective preconditioning effects in different ischemia/reperfusion models. However, there is very little information about the antineuroinflammatory role of morphine and its protective effect against memory deficit. In the present study, we evaluated the role of morphine preconditioning in a model of mild neuroinflammation induced by intraperitoneal lipopolysaccharide (LPS) injection (1 mg/kg). Rats were trained on passive avoidance apparatus and challenged with LPS 20 h later. Four hours after LPS, rats were subjected to passive avoidance testing and then for the assessments of inflammatory and apoptotic cell death mediators in the hippocampus. LPS significantly increased the nuclear NF-?B and expression of COX-2, IL-1?, and TNF-?, augmented the activity of caspase-3 and PARP cleavage, and in parallel shortened the latencies to enter the dark compartment. Although morphine injection in a noninflammatory context was able to induce a neuroinflammatory response and memory loss, morphine preconditioning at the dose of 4 mg/kg significantly prevented the LPS-induced neuroinflammation and memory deficit. Morphine preconditioning was abolished by naloxone and, therefore, is dependent on opioid receptors. These results suggest that acute morphine injection, in spite of the induction of a neuroinflammatory response and amnesia per se, exerts an antineuroinflammatory role and protects from cell death and memory deficit in an inflammatory context. PMID:22388653

Rostami, Farzaneh; Oryan, Shahrbanoo; Ahmadiani, Abolhassan; Dargahi, Leila

2012-09-01

83

Progranulin Deficiency Promotes Post-Ischemic Blood-Brain Barrier Disruption  

PubMed Central

Loss-of-function mutations of progranulin (PGRN) have been linked to frontotemporal dementia, but little is known about the effects of PGRN deficiency on the brain in health and disease. PGRN has been implicated in neurovascular development, inflammation, and Wnt signaling, a pathway involved in the formation of the blood–brain barrier (BBB). Because BBB alterations and inflammation contribute to ischemic brain injury, we examined the role of PGRN in the brain damage produced by ischemia-reperfusion. PGRN+/? and PGRN?/? mice underwent middle cerebral artery occlusion (MCAO) with monitoring of cerebral blood flow. Infarct volume and motor deficits were assessed 72 h later. Post-ischemic inflammation was examined by expression of inflammatory genes and flow cytometry. BBB structure and permeability were examined by electron microscopy (EM) and Evans blue (EB) extravasation, respectively. MCAO resulted in ?60% larger infarcts in PGRN+/? and PGRN?/? mice, an effect independent of hemodynamic factors or post-ischemic inflammation. Rather, massive hemorrhages and post-ischemic BBB disruption were observed, unrelated to degradation of tight junction (TJ) proteins or matrix metalloproteinases (MMPs). By EM, TJ were 30–52% shorter, fewer, and less interlocking, suggesting a weaker seal between endothelial cells. Intracerebral injection of platelet-derived growth factor-CC (PDGF-CC), which increases BBB permeability, resulted in a more severe BBB breakdown in PGRN+/? and PGRN?/? than wild-type mice. We describe a previously unrecognized involvement of PGRN in the expression of key ultrastructural features of the BBB. Such a novel vasoprotective role of PGRN may contribute to brain dysfunction and damage in conditions associated with reduced PGRN function.

Jackman, Katherine; Kahles, Timo; Lane, Diane; Garcia-Bonilla, Lidia; Abe, Takato; Capone, Carmen; Hochrainer, Karin; Voss, Henning; Zhou, Ping; Ding, Aihao; Anrather, Josef

2013-01-01

84

Postischemic cerebral blood flow recovery in the female: effect of 17 beta-estradiol.  

PubMed

Female reproductive hormones are considered to be protective agents in atherosclerotic vascular disease and stroke. The present study determined if there are unique cerebrovascular responses in female animals to global cerebral ischemia and if 17 beta-estradiol is important to postischemic outcome in brain. Three groups of anesthetized, sexually mature rabbits were treated with normotensive four-vessel occlusion (6 min) and 3 h of reperfusion: females chronically instrumented with 17 beta-estradiol implants (EFEM; n = 8, plasma estradiol level = 365 +/- 48 pg/ml), untreated females (FEM; n = 8, estradiol = 13 +/- 3 pg/ml), and untreated males (M; n = 8, estradiol < limit of radioimmunoassay). CBF (microspheres) and somatosensory evoked potential (SEP) amplitude were measured during ischemia/reperfusion. Baseline hemispheric blood flow and regional flow distribution were not altered by chronic estradiol treatment. Hemispheric blood flow was equivalently reduced during ischemia in FEM and M (6 +/- 1 and 9 +/- 2 ml min-1 100 g-1, respectively); however postischemic hyperemia was greater in FEM than M (CBF = 257 +/- 27 and 183 +/- 27 ml min-1 100 g-1. However, EFEM experienced higher CBF during ischemia (e.g., 13 +/- 2 ml min-1 100 g-1) and less hyperemia (134 +/- 4 ml min-1 100 g-1 in hemispheres) in numerous brain regions than FEM. CBF at 3 h reperfusion was not different among the groups. Recovery of SEPs was incomplete and similar in all groups. We conclude that chronic exogenous 17 beta-estradiol treatment increases CBF during global incomplete ischemia and ameliorates postischemic hyperemia in the female animal. PMID:7790416

Hurn, P D; Littleton-Kearney, M T; Kirsch, J R; Dharmarajan, A M; Traystman, R J

1995-07-01

85

Intranasal delivery of HMGB1-binding heptamer peptide confers a robust neuroprotection in the postischemic brain.  

PubMed

High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In a previous report, we showed that HMGB1 is massively released during NMDA-induced acute damaging process in the postischemic brain and triggers inflammatory processes and induces neuronal apoptosis. We have also reported a robust neuroprotection of intranasally delivered HMGB1 siRNA in the postischemic rat brain (middle cerebral artery occlusion (MCAO), 60 min). In the present study, we investigated the therapeutic efficacy of intranasally delivered HMGB1 binding heptamer peptide (HBHP; HMSKPVQ), which was selected using a phage display approach, in the same stroke animal model. A pull-down assay using biotin-labeled HBHP showed that HBHP binds directly to HMGB1, specifically to HMGB1 A box, confirming HMGB1/HBHP interaction. HBHP significantly suppressed HMGB1-mediated neuronal cell death in primary cortical cultures and HMGB1/HBHP binding was detected in NMDA-conditioned culture media. However, a heptamer peptide composed of a scrambled sequence of the seven amino acids in HBHP failed to bind HMGB1 and had no protective effect. Furthermore, HBHP (300 ng) delivered intranasally at 30 min before MCAO significantly suppressed infarct volume in the postischemic rat brain (maximal reduction by 41.8±5.4%) and ameliorated neurological and behavioral deficits. In contrast, scrambled heptamer peptide had no protective effect at the same dose. Together these results suggest that intranasal HBHP ameliorates neuronal damage in the ischemic brain by binding HMGB1, which might inhibit the function of HMGB1 as an endogenous danger signal molecule. PMID:22877697

Kim, Il-Doo; Shin, Joo-Hyun; Lee, Hye-Kyung; Jin, Yin-Chuan; Lee, Ja-Kyeong

2012-09-13

86

A multigrid preconditioned Newton-Krylov method  

SciTech Connect

The authors study multigrid preconditioning of matrix-free Newton-Krylov methods as a means of developing more efficient nonlinear iterative methods for large scale simulation. Newton-Krylov methods have proven dependable in solving nonlinear systems while not requiring the explicit formation or storage of the complete Jacobian. However, the standard algorithmic scaling of Krylov methods is nonoptimal, with increasing linear system dimension. This motivates the use of multigrid-based preconditioning. It is demonstrated that a simple multigrid-based preconditioner can effectively limit the growth of Krylov iterations as the dimension of the linear system is increased. Different performance aspects of the proposed algorithm are investigated on three nonlinear, nonsymmetric, boundary value problems. The goal is to develop a hybrid methodology which has Newton-Krylov nonlinear convergence properties and multigrid-like linear convergence scaling for large scale simulation.

Knoll, D.A.; Rider, W.J.

1999-10-01

87

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

88

Metabolic monitoring of postischemic myocardium during intermittent warm-blood cardioplegic administration.  

PubMed

In 12 patients undergoing elective myocardial revascularization with intermittent administration of warm-blood cardioplegic solution for myocardial protection, we analyzed metabolic changes by assay of global ischemia indicators (pH, lactate, glucose, and potassium), which we measured in the coronary sinus and arterial blood during the ischemic and postischemic periods. A typical cumulative ischemic pattern with progressively decreasing pH values and progressively increasing lactate values could not be observed in all patients. It was not the degree of lactate washout, but the lactate concentration at the end of each reperfusion, that correlated significantly with global metabolic recovery time, which suggests the importance of effective reperfusion. PMID:20401291

Borowski, Andreas; Kurt, Muhammed; Calvo, Sanchez; Paprotny, Gerrit; Godehardt, Erhard; Fraessdorf, Jan; Ghodsizad, Ali

2010-01-01

89

Pediatric cerebral stroke: susceptibility-weighted imaging may predict post-ischemic malignant edema.  

PubMed

Susceptibility-weighted imaging (SWI) is an advanced MRI technique providing information on the blood oxygenation level. Deoxyhemoglobin is increased in hypoperfused tissue characterized by SWI-hypointensity, while high oxyhemoglobin concentration within hyperperfused tissue results in a SWI iso- or hyperintensity compared to healthy brain tissue. We describe a child with a stroke, where SWI in addition to excluding hemorrhage and delineating the thrombus proved invaluable in determining regions of hyperperfusion or luxury perfusion, which contributed further to the prognosis including an increased risk of developing post-ischemic malignant edema. PMID:24199819

Bosemani, Thangamadhan; Poretti, Andrea; Orman, Gunes; Meoded, Avner; Huisman, Thierry A G M

2013-10-01

90

Metabolic Monitoring of Postischemic Myocardium during Intermittent Warm-Blood Cardioplegic Administration  

PubMed Central

In 12 patients undergoing elective myocardial revascularization with intermittent administration of warm-blood cardioplegic solution for myocardial protection, we analyzed metabolic changes by assay of global ischemia indicators (pH, lactate, glucose, and potassium), which we measured in the coronary sinus and arterial blood during the ischemic and postischemic periods. A typical cumulative ischemic pattern with progressively decreasing pH values and progressively increasing lactate values could not be observed in all patients. It was not the degree of lactate washout, but the lactate concentration at the end of each reperfusion, that correlated significantly with global metabolic recovery time, which suggests the importance of effective reperfusion.

Borowski, Andreas; Kurt, Muhammed; Calvo, Sanchez; Paprotny, Gerrit; Godehardt, Erhard; Fraessdorf, Jan; Ghodsizad, Ali

2010-01-01

91

A multigrid preconditioned Newton-Krylov method  

Microsoft Academic Search

The authors study multigrid preconditioning of matrix-free Newton-Krylov methods as a means of developing more efficient nonlinear iterative methods for large scale simulation. Newton-Krylov methods have proven dependable in solving nonlinear systems while not requiring the explicit formation or storage of the complete Jacobian. However, the standard algorithmic scaling of Krylov methods is nonoptimal, with increasing linear system dimension. This

D. A. Knoll; W. J. Rider

1999-01-01

92

Mechanism of Cardioprotection by Early Ischemic Preconditioning  

Microsoft Academic Search

A series of brief ischemia\\/reperfusion cycles (termed ischemic preconditioning, IPC) limits myocardial injury produced by\\u000a a subsequent prolonged period of coronary artery occlusion and reperfusion. Over the last 2 decades our understanding of IPC’s\\u000a mechanism has increased exponentially. Hearts exposed to IPC have a better metabolic and ionic status during prolonged ischemia\\u000a compared to naïve hearts. However, this difference is

Xiulan Yang; Michael V. Cohen; James M. Downey

2010-01-01

93

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

94

A critical role of NO/cGMP/PKG dependent pathway in hippocampal post-ischemic LTP: modulation by zonisamide.  

PubMed

Nitric oxide (NO) is an intercellular retrograde messenger involved in several physiological processes such as synaptic plasticity, hippocampal long-term potentiation (LTP), and learning and memory. Moreover NO signaling is implicated in the pathophysiology of brain ischemia. In this study, we have characterized the role of NO/cGMP signaling cascade in the induction and maintenance of post-ischemic LTP (iLTP) in rat brain slices. Moreover, we have investigated the possible inhibitory action of zonisamide (ZNS) on this pathological form of synaptic plasticity as well as the effects of this antiepileptic drug (AED) on physiological activity-dependent LTP. Finally, we have characterized the possible interaction between ZNS and the NO/cGMP/PKG-dependent pathway involved in iLTP. Here, we provided the first evidence that an oxygen and glucose deprivation episode can induce, in CA1 hippocampal slices, iLTP by modulation of the NO/cGMP/PKG pathway. Additionally, we found that while ZNS application did not affect short-term synaptic plasticity and LTP induced by high-frequency stimulation, it significantly reduced iLTP. This reduction was mimicked by bath application of NO synthase inhibitors and a soluble guanyl cyclase inhibitor. The effect of ZNS was prevented by either the application of a NO donor or drugs increasing intracellular levels of cGMP and activating PKG. These findings are in line with the possible use of AEDs, such as ZNS, as a possible neuroprotective strategy in brain ischemia. Moreover, these findings strongly suggest that NO/cGMP/PKG intracellular cascade might represent a physiological target for neuroprotection in pathological forms of synaptic plasticity such as hippocampal iLTP. PMID:21749921

Costa, Cinzia; Tozzi, Alessandro; Siliquini, Sabrina; Galletti, Francesca; Cardaioli, Gabriela; Tantucci, Michela; Pisani, Francesco; Calabresi, Paolo

2011-11-01

95

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.

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

2013-01-01

96

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.

Kaucsar, Tamas; Bodor, Csaba; Godo, Maria; Szalay, Csaba; Revesz, Csaba; Nemeth, Zalan; Mozes, Miklos; Szenasi, Gabor; Rosivall, Laszlo; Soti, Csaba; Hamar, Peter

2014-01-01

97

Toward the Optimal Preconditioned Eigensolver: Locally Optimal Block Preconditioned Conjugate Gradient Method  

Microsoft Academic Search

We describe new algorithms of the locally optimal block preconditioned conjugate gradient (LOBPCG) method for symmetric eigenvalue problems, based on a local optimization of a three-term recurrence, and suggest several other new methods. To be able to compare numerically different methods in the class, with different preconditioners, we propose a common system of model tests, using random preconditioners and initial

Andrew V. Knyazev

2001-01-01

98

Endothelial nitric oxide synthase (NOS3) knockout decreases NOS2 induction, limiting hyperoxygenation and conferring protection in the postischemic heart.  

PubMed

Although it has been shown that endothelial nitric oxide synthase (eNOS)-derived nitric oxide downregulates mitochondrial oxygen consumption during early reperfusion, its effects on inducible NOS (iNOS) induction and myocardial injury during late reperfusion are unknown. Wild-type (WT) and eNOS(-/-) mice were subjected to 30 min of coronary ligation followed by reperfusion. Expression of iNOS mRNA and protein levels and peroxynitrite production were lower in postischemic myocardium of eNOS(-/-) mice than levels in WT mice 48 h postreperfusion. Significantly improved hemodynamics (+/-dP/dt, left ventricular systolic pressure, mean arterial pressure), increased rate pressure product, and reduced myocardial infarct size (18 +/- 2.5% vs. 31 +/- 4.6%) were found 48 h after reperfusion in eNOS(-/-) mice compared with WT mice. Myocardial infarct size was also significantly decreased in WT mice treated with the specific iNOS inhibitor 1400W (20.5 +/- 3.4%) compared with WT mice treated with PBS (33.9 +/- 5.3%). A marked reperfusion-induced hyperoxygenation state was observed by electron paramagnetic resonance oximetry in postischemic myocardium, but Po(2) values were significantly lower from 1 to 72 h in eNOS(-/-) than in WT mice. Cytochrome c-oxidase activity and NADH dehydrogenase activity were significantly decreased in postischemic myocardium in WT and eNOS(-/-) mice compared with baseline control, respectively, and NADH dehydrogenase activity was significantly higher in eNOS(-/-) than in WT mice. Thus deficiency of eNOS exerted a sustained beneficial effect on postischemic myocardium 48 h after reperfusion with preserved mitochondrial function, which appears to be due to decreased iNOS induction and decreased iNOS-derived peroxynitrite in postischemic myocardium. PMID:17114245

Zhao, Xue; Chen, Yeong-Renn; He, Guanglong; Zhang, Aiwen; Druhan, Lawrence J; Strauch, Arthur R; Zweier, Jay L

2007-03-01

99

ISOFLURANE PRECONDITIONING AND POSTCONDITIONING IN RAT HIPPOCAMPAL NEURONS  

PubMed Central

The volatile anesthetic isoflurane is capable of inducing preconditioning and postconditioning effects in the brain. However, the mechanisms for these neuroprotective effects are not fully understood. Here, we showed that rat hippocampal neuronal cultures exposed to 2% isoflurane for 30 min at 24 h before a 1-h oxygen-glucose deprivation (OGD) and a 24-h simulated reperfusion had a reduced lactate dehydrogenase release. Similarly, this OGD and simulated reperfusion-induced lactate dehydrogenase release was attenuated by exposing the neuronal cultures to 2% isoflurane for 1 h at various times after the onset of the simulated reperfusion (isoflurane postconditioning). The combination of isoflurane preconditioning and postconditioning induced a better neuroprotection than either alone. Inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII), inhibition of N-methyl D-aspartate (NMDA) receptors, or activation of adenosine A2A receptors resulted in reduction of the OGD and simulated reperfusion-induced cell injury. The combination of CaMKII inhibition and isoflurane preconditioning or postconditioning did not provide better protection than CaMKII inhibition, isoflurane preconditioning, or isoflurane postconditioning alone. The combination of NMDA receptor inhibition and isoflurane postconditioning was not better than NMDA receptor inhibition or isoflurane postconditioning alone for neuroprotection. However, the combination of adenosine A2A receptor activation with either isoflurane preconditioning or isoflurane postconditioning induced a better neuroprotective effect than adenosine A2A receptor activation, isoflurane preconditioning, or isoflurane postconditioning alone. The combination of NMDA receptor inhibition and isoflurane preconditioning caused a better neuroprotective effect than NMDA receptor inhibition or isoflurane preconditioning alone. These results suggest that isoflurane preconditioning- and postconditioning-induced neuroprotection can be additive. Isoflurane preconditioning and isoflurane postconditioning may involve CaMKII inhibition, but may not involve adenosine A2A receptor activation. Inhibition of NMDA receptors may mediate the effects of isoflurane postconditioning, but not isoflurane preconditioning.

McMurtrey, Richard J.; Zuo, Zhiyi

2010-01-01

100

Effects of Postconditioning, Preconditioning and Perfusion of L-carnitine During Whole Period of Ischemia/ Reperfusion on Cardiac Hemodynamic Functions and Myocardial Infarction Size in Isolated Rat Heart  

PubMed Central

Objective(s): In the present work, the effects of L-carnitine (LC) on postischemic cardiac hemodynamic functions and infarction size were studied in isolated rat heart. Materials and Methods: The hearts were subjected to 30 min regional ischemia followed by 120 min reperfusion. Then they were perfused by a drug-free or LC-enriched Krebs–Henseleit (K/H) solution during ischemia/ reperfusion (I/R) (Protocol 1), 10 min before ischemia induction (Protocol 2; preconditioning group) or the first 10 min of reperfusion (Protocol 3; postconditioning group). Results: The perfusion of LC in protocol 1 significantly reduced left ventricular end diastolic pressure (LVEDP) (P<0.05), and increased left ventricular developed pressure (LVDP) (P<0.05), rate pressure product (RPP) (P<0.01) and coronary flow rate (CFR) (P<0.05). The short-term preischemic administration of LC in protocol 2 improved RPP, CFR and decreased the extent of LVEDP elevation. However, protective effects of LC in this protocol were low compared to the whole period perfusion. In protocol 3, LC preserved postischemic cardiac functions not as much as the other protocols. In addition, infarct size significantly decreased by LC in all protocols as opposed to the control group (P<0.001). Conclusion: The results of the present work showed that LC produced protective effects against I/R injury. These protective actions were reversed by concomitant use of etomoxir (a CPT-I inhibitor), suggesting that the efficacy of LC could be due to its mitochondrial action, probably related to the raise in glucose oxidation of the reperfused hearts.

Najafi, Moslem

2013-01-01

101

Preconditioning an Entire Stope Block for Rock Burst Control.  

National Technical Information Service (NTIS)

Rock preconditioning in advance of mining has been an effective means of rock-burst control based on small-scale field demonstrations. The objective of this investigation was to test the effectiveness of rock preconditioning on a larger scale and to deter...

W. Blake

1980-01-01

102

The multigrid preconditioned conjugate gradient method  

NASA Technical Reports Server (NTRS)

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

Tatebe, Osamu

1993-01-01

103

Preconditioning Newton-Krylor Methods for Variably Saturated Flow  

SciTech Connect

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

Woodward, C.; Jones, J

2000-01-07

104

Remote renal preconditioning-induced cardioprotection: a key role of hypoxia inducible factor-prolyl 4-hydroxylases.  

PubMed

Remote preconditioning is a unique phenomenon in which brief episodes of ischemia and reperfusion to remote organ protect the target organ against sustained ischemia-reperfusion (I/R)-induced injury. Protective effects of remote renal preconditioning (RRPC) are well established in heart, but their mechanisms still remain to be elucidated. So, the present study was designed to investigate the possible role of oxygen-sensing hypoxia inducible factor-prolyl 4-hydroxylases (HIF-P4Hs) in RRPC-induced cardioprotection in rats. Remote renal preconditioning was performed by four episodes of 5 min renal artery occlusion and reperfusion. Isolated rat hearts were perfused on Langendorff apparatus and were subjected to global ischemia for 30 min followed by 120 min reperfusion. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in coronary effluent to assess the degree of myocardial injury. Extent of myocardial infarct size and coronary flow rate was also measured. Ethyl 3,4-dihydroxybenzoate (EDHB) and alpha-ketoglutarate (alpha-KG) were employed as HIF-P4Hs inhibitor and activator, respectively. Diethyldithiocarbamic acid (DDCA) was employed as NFkB inhibitor. Remote renal preconditioning prevented I/R-induced myocardial injury and produced cardioprotective effects. Pharmacological preconditioning with EDHB (100 mg kg(-1) i.p.) mimicked the cardioprotective effects of RRPC. However, alpha-KG (200 mg kg(-1) i.p.) and DDCA (150 mg kg(-1) i.p.) abolished cardioprotective effects of RRPC and EDHB. So, it may be concluded that inhibition of HIF-P4H has a key role in RRPC-induced cardioprotection. Further, remote preconditioning-induced HIF-P4H inhibition may have triggered a transduction pathway involving activation of NFkB. PMID:18273560

Kant, Ravi; Diwan, Vishal; Jaggi, Amteshwar Singh; Singh, Nirmal; Singh, Dhandeep

2008-05-01

105

Remote preconditioning in normal and hypertrophic rat hearts  

PubMed Central

Background The aim of our study was to investigate whether remote preconditioning (RPC) improves myocardial function after ischemia/reperfusion injury in both normal and hypertrophic isolated rat hearts. This is the first time in world literature that cardioprotection by RPC in hypertrophic myocardium is investigated. Methods Four groups of 7 male Wistar rats each, were used: Normal control, normal preconditioned, hypertrophic control and hypertrophic preconditioned groups. Moderate cardiac hypertrophy was induced by fludrocortisone acetate and salt administration for 30 days. Remote preconditioning of the rat heart was achieved by 20 minutes transient right hind limb ischemia and 10 minutes reperfusion of the anaesthetized animal. Isolated Langendorff-perfused animal hearts were then subjected to 30 minutes of global ischemia and reperfusion for 60 minutes. Contractile function and heart rhythm were monitored. Preconditioned groups were compared to control groups. Results Left ventricular developed pressure (LVDP) and the product LVDP × heart rate (HR) were significantly higher in the hypertrophic preconditioned group than the hypertrophic control group while left ventricular end diastolic pressure (LVEDP) and severe arrhythmia episodes did not differ. Variances between the normal heart groups were not significantly different except for the values of the LVEDP in the beginning of reperfusion. Conclusions Remote preconditioning seems to protect myocardial contractile function in hypertrophic myocardium, while it has no beneficial effect in normal myocardium.

2011-01-01

106

Mitochondria: The Missing Link Between Preconditioning and Neuroprotection  

PubMed Central

The quote “what does not kill you makes you stronger” perfectly describes the preconditioning phenomenon – a paradigm that affords robust brain tolerance in the face of neurodegenerative insults. Over the last few decades, many attempts have been made to identify the molecular mechanisms involved in preconditioning-induced protective responses, and recent data suggests that many of these mechanisms converge on the mitochondria, positing mitochondria as master regulators of preconditioning-triggered endogenous neuroprotection. In this review, we critically discuss evidence for the involvement of mitochondria within the preconditioning paradigm. We will highlight the crucial targets and mediators by which mitochondria are integrated into neuroprotective signaling pathways that underlie preconditioning, putting focus on mitochondrial respiratory chain and mitochondrial reactive oxygen species, mitochondrial ATP-sensitive potassium channels, mitochondrial permeability transition pore, uncoupling proteins, and mitochondrial antioxidant enzyme manganese superoxide dismutase. We also discuss the role of mitochondria in the induction of hypoxia-inducible factor-1, a transcription factor engaged in preconditioning-mediated neuroprotective effects. The identification of intrinsic mitochondrial mechanisms involved in preconditioning will provide new insights which can be translated into potential pharmacological interventions aimed at counteracting neurodegeneration.

Correia, Sonia C.; Santos, Renato X.; Perry, George; Zhu, Xiongwei; Moreira, Paula I.; Smith, Mark A.

2010-01-01

107

Sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia.  

PubMed

Brain ischemic tolerance is an endogenous protective mechanism activated by a preconditioning stimulus that is closely related to N-methyl-d-aspartate receptor (NMDAR). Glycine transporter type 1 (GlyT-1) inhibitors potentiate NMDAR and suggest an alternative strategy for brain preconditioning. The aim of this work was to evaluate the effects of brain preconditioning induced by sarcosine, a GlyT-1 inhibitor, against global cerebral ischemia and its relation to NMDAR. Sarcosine was administered over 7days (300 or 500mg/kg/day, ip) before the induction of a global cerebral ischemia model in Wistar rats (male, 8-week-old). It was observed that sarcosine preconditioning reduced cell death in rat hippocampi submitted to cerebral ischemia. Hippocampal levels of glycine were decreased in sarcosine-treated animals, which was associated with a reduction of [(3)H] glycine uptake and a decrease in glycine transporter expression (GlyT-1 and GlyT-2). The expression of glycine receptors and the NR1 and NR2A subunits of NMDAR were not affected by sarcosine preconditioning. However, sarcosine preconditioning reduced the expression of the NR2B subunits of NMDAR. In conclusion, these data demonstrate that sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia and this neuroprotective state is associated with changes in glycine transport and reduction of NR2B-containing NMDAR expression. PMID:24797328

Pinto, M C X; Simão, F; da Costa, F L P; Rosa, D V; de Paiva, M J N; Resende, R R; Romano-Silva, M A; Gomez, M V; Gomez, R S

2014-06-20

108

The preconditioning of major sudden stratospheric warmings  

NASA Astrophysics Data System (ADS)

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

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

2012-02-01

109

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.

2013-01-01

110

Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia.  

PubMed

Perinatal hypoxia-ischemia is a major cause of acute mortality in newborns and cognitive and motor impairments in children. Cerebral hypoxia-ischemia leads to excitotoxicity and necrotic and apoptotic cell death, in which mitochondria play a major role. Increased resistance against major damage can be achieved by preconditioning triggered by subtle insults. CO, a toxic molecule that is also generated endogenously, may have a role in preconditioning as low doses can protect against inflammation and apoptosis. In this study, the role of CO-induced preconditioning on neurons was addressed in vitro and in vivo. The effect of 1 h of CO treatment on neuronal death (plasmatic membrane permeabilization and chromatin condensation) and bcl-2 expression was studied in cerebellar granule cells undergoing to glutamate-induced apoptosis. CO's role was studied in vivo in the Rice-Vannucci model of neonatal hypoxia-ischemia (common carotid artery ligature +75 min at 8% oxygen). Apoptotic cells, assessed by Nissl staining were counted with a stereological approach and cleaved caspase 3-positive profiles in the hippocampus were assessed. Apoptotic hallmarks were analyzed in hippocampal extracts by Western Blot. CO inhibited excitotoxicity-induced cell death and increased Bcl-2 mRNA in primary cultures of neurons. In vivo, CO prevented hypoxia-ischemia induced apoptosis in the hippocampus, limited cytochrome c released from mitochondria and reduced activation of caspase-3. Still, Bcl-2 protein levels were higher in hippocampus of CO pre-treated rat pups. Our results show that CO preconditioning elicits a molecular cascade that limits neuronal apoptosis. This could represent an innovative therapeutic strategy for high-risk cerebral hypoxia-ischemia patients, in particular neonates. PMID:22952602

Queiroga, Cláudia S F; Tomasi, Simone; Widerøe, Marius; Alves, Paula M; Vercelli, Alessandro; Vieira, Helena L A

2012-01-01

111

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 202kPa 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 608kPa, 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 608kPa, latency to CNS-OT increased from 12.8 to 22.4min 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

112

The protective roles of autophagy in ischemic preconditioning.  

PubMed

Autophagy, a process for the degradation of protein aggregates and dysfunctional organelles, is required for cellular homeostasis and cell survival in response to stress and is implicated in endogenous protection. Ischemic preconditioning is a brief and nonlethal episode of ischemia, confers protection against subsequent ischemia-reperfusion through the up-regulation of endogenous protective mechanisms. Emerging evidence shows that autophagy is associated with the protective effect of ischemic preconditioning. This review summarizes recent progress in research on the functions and regulations of the autophagy pathway in preconditioning-induced protection and cellular survival. PMID:23603984

Yan, Wen-jun; Dong, Hai-long; Xiong, Li-ze

2013-05-01

113

Preconditioned Minimal Residual Methods for Chebyshev Spectral Caluclations  

NASA Technical Reports Server (NTRS)

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

Canuto, C.; Quarteroni, A.

1983-01-01

114

Insulin inhibits myocardial ischemia-induced apoptosis and alleviates chronic adverse changes in post-ischemic cardiac structure and function  

Microsoft Academic Search

Insulin has been shown to possess significant anti-apoptotic effect in myocardial ischemia\\/reperfusion (MI\\/R). However, the\\u000a contribution by this protection of insulin to the prolonged cardiac function in rats subjected to ischemia remains unclear.\\u000a The present study attempted to test whether early insulin treatment influences adverse prolonged post-ischemic cardiac structural\\u000a and functional changes. Adult male rats were subjected to left anterior

Wenjuan Xing; Wenjun Yan; Feng Fu; Yulan Jin; Lele Ji; Wenchong Liu; Li Wang; Anlin Lv; Yunyan Duan; Jun Zhang; Haifeng Zhang; Feng Gao

2009-01-01

115

Biodegradable gelatin microspheres enhance the neuroprotective potency of osteopontin via quick and sustained release in the post-ischemic brain.  

PubMed

Gelatin microspheres (GMSs) are widely used as drug carriers owing to their excellent biocompatibilities and toxicologically safe degradation products. The drug release profile is easily tailored by controlling the cross-linking density and surface-to-volume ratio, i.e. size, of the GMS. In this study, we employed GMSs which are 25?m in diameter and cross-linked with 0.03125% glutaraldehyde, to enable rapid initial and a subsequent sustained release. Therapeutic potency of human recombinant osteopontin (rhOPN) with or without encapsulation into GMSs was investigated after administrating them to rat stroke model (Sprague-Dawley; middle cerebral artery occlusion, MCAO). The administration of rhOPN/GMS (100ng/100?g) at 1h post-MCAO reduced the mean infarct volume by 81.8% of that of the untreated MCAO control and extended the therapeutic window at least to 12h post-MCAO, demonstrating a markedly enhanced therapeutic potency for the use of OPN in the post-ischemic brain. Scanning electron microscopy micrographs revealed that GMSs maintained the three-dimensional shape for more than 5days in normal brain but were degraded rapidly in the post-ischemic brain, presumably due to high levels of gelatinase induction. After encapsulation with GMS, the duration of OPN release was markedly extended; from the period of 2days to 5days in normal brain, and from 2days to 4days in the post-ischemic brain; these encompass the critical period for recovery processes, such as vascularization, and controlling inflammation. Together, these results indicate that GMS-mediated drug delivery has huge potential when it was used in the hyperacute period in the post-ischemic brain. PMID:24607857

Jin, Yinchuan; Kim, In-Yong; Kim, Il-Doo; Lee, Hye-Kyung; Park, Jin-Young; Han, Pyung-Lim; Kim, Kyekyoon Kevin; Choi, Hyungsoo; Lee, Ja-Kyeong

2014-07-01

116

A randomized, placebo-controlled trial of IGF-1 for delayed graft function: A human model to study postischemic ARF  

Microsoft Academic Search

A randomized, placebo-controlled trial of IGF-1 for delayed graft function: A human model to study postischemic ARF.BackgroundInsulin-like growth factor (IGF-1) has been shown in animal models to accelerate recovery from acute renal failure (ARF). However, a therapeutic trial of recombinant human (rh) IGF-1 in patients with ARF in the intensive care unit (ICU) failed to demonstrate efficacy1. Such patients often

Michelle A. Hladunewich; Geraldine Corrigan; Geraldine C. Derby; Deepa Ramaswamy; Neeraja Kambham; John D. Scandling; Bryan D. Myers

2003-01-01

117

Beneficial Effects of Angiotensin I Converting Enzyme Inhibitor on Post-ischemic Contractile Function of Perfused Rat Heart  

Microsoft Academic Search

The present study was undertaken to determine whether trandolaprilat, an active form of angiotensin I converting enzyme (ACE) inhibitor, may improve ischemia\\/reperfusion-induced contractile dysfunction and metabolic derangement of isolated rat hearts. Ischemia (25 min) and subsequent 60-min reperfusion resulted in a small recovery of post-ischemic left ventricular developed pressure (LVDP), a sustained increase in left ventricular end-diastolic pressure, an increase

Kouichi Tanonaka; Toru Kamiyama; Aya Takezono; Kimiko Sakai; Satoshi Takeo

1996-01-01

118

Differential activation of heat shock and nuclear factor kappaB transcription factors in postischemic reperfused rat liver  

Microsoft Academic Search

The aim of this study was to investigate the behavior of the transcription factors, heat-shock factor (HSF) and nuclear factor kappaB (NF-kappaB), in postischemic reperfused liver, with particular attention paid to possible differences in the time-course and mechanism of activation, which may help in defining their role in the response of the liver to reperfusion. Ischemia was induced by clamping

L Tacchini; L Radice; G Pogliaghi; A Bernelli-Zazzera

1997-01-01

119

Free radical production and ischemic brain damage: influence of postischemic oxygen tension.  

PubMed

It is now becoming increasingly clear that free radicals contribute to brain damage in several conditions, such as hyperoxia and trauma. It has been more difficult to prove that free radical production mediates ischemic brain damage, but it has often been suggested that it may be a major contributor to reperfusion damage, observed following transient ischemia. Recent results demonstrate that cerebral ischemia of long duration, particularly when followed by reperfusion, leads to enhanced production of partially reduced oxygen species, notably hydrogen peroxide (H2O2). It has also been suggested that postischemic hyperoxia, e.g. an increased oxygen tension during the recirculation period, adversely affects recovery following transient ischemia. Other data support the notion that brain damage caused by permanent ischemia (stroke) is significantly influenced by production of free radicals. The present study, however, fails to show that recirculation following brief periods of ischemia (15 min) leads to an enhanced H2O2 production, and that hyperoxia aggravates the ischemic damage. This study was undertaken to reveal whether variations in oxygen supply in the postischemic period following forebrain ischemia in rats affect free radical production and the brain damage incurred. To that end, rats ventilated on N2O/O2 (70:30) were subjected to 15 min of transient ischemia. Normoxic animals were ventilated with the N2O/O2 mixture, hyperoxic animals with 100% O2, and hypoxic ones with about 10% O2 (balance either N2O/N2 or N2) during the recirculation. At the end of this period, the animals were decapitated for assessment of H2O2 production with the aminotriazole/catalase method. This method is based on the notion that aminotriazole interacts with H2O2 to inactivate catalase; thus, the rate of inactivation of catalase in aminotriazole treated animals reflects H2O2 production. In a parallel series, animals ventilated with one of the three gas mixtures in the early recirculation period, respectively, were allowed to recover for 7 days, with subsequent perfusion-fixation of brain tissues and light microscopical evaluation of the brain damage. Animals given aminotriazole, whether rendered ischemic or not, showed a reduced tissue catalase activity, reflecting H2O2 production in the brain. Hyperoxic animals failed to show increased tissue H2O2 production, while hypoxic ones showed a tendency towards decreased production. However, all three groups (hypo, normo- and hyperoxic) had similar density and distribution of neuronal damage. These results suggest that although postischemic oxygen tensions may determine the rates of H2O2 production, variations in oxygen tensions do not influence the final brain damage incurred.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2058415

Agardh, C D; Zhang, H; Smith, M L; Siesjö, B K

1991-01-01

120

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

121

40 CFR 86.1232-96 - Vehicle preconditioning.  

Code of Federal Regulations, 2013 CFR

...Vehicle preconditioning. (a) Fuel tank cap(s) of gasoline...damage to the components and the integrity of the fuel system. A replacement canister...damage to the components and the integrity of the fuel system. A replacement...

2013-07-01

122

40 CFR 86.132-96 - Vehicle preconditioning.  

Code of Federal Regulations, 2013 CFR

...Vehicle preconditioning. (a) Fuel tank cap(s) of gasoline...damage to the components and the integrity of the fuel system. A replacement canister...damage to the components and the integrity of the fuel system. A replacement...

2013-07-01

123

Preconditioning in Cardiomyocytes Protects by Attenuating Oxidant Stress at Reperfusion  

Microsoft Academic Search

Cardiomyocyte death after ischemia\\/reperfusion correlates with oxidant stress, and antioxidants confer protection in that model. Preconditioning (PC) with hypoxia or adenosine also confers protection, leading us to hypothesize that PC protects by attenuating oxidant generation during subsequent ischemia\\/reperfusion. Chick cardiomyocytes were preconditioned with 10 minutes of hypoxia or adenosine (100 mmol\\/L), followed by 1 hour of simulated ischemia and 3

Terry L. Vanden Hoek; Lance B. Becker; Zuo-Hui Shao; Chang-Qing Li; Paul T. Schumacker

124

Omapatrilat Limits Infarct Size and Lowers the Threshold for Induction of Myocardial Preconditioning Through a Bradykinin Receptor-Mediated Mechanism  

Microsoft Academic Search

Bradykinin is an important endogenous trigger of myocardial ischemic preconditioning (IPC). Through simultaneous inhibition\\u000a of neutral endopeptidase and angiotensin converting enzyme, omapatrilat prevents enzymatic degradation of bradykinin. The\\u000a aim of this study was to investigate if omapatrilat, through its ability to augment bradykinin levels, can augment a subthreshold\\u000a IPC stimulus (Sub-IPC) and to compare the action of omapatrilat with the

Z. Ebrahim; G. F. Baxter; D. M. Yellon

2004-01-01

125

Ischemic Preconditioning in the Younger and Aged Heart  

PubMed Central

Ischemic preconditioning is the effect of brief ischemic episodes which protect the heart from the following more prolonged ischemic episode. This mechanism is effective in younger but not in aged heart. The age-related reduction of ischemic preconditioning has been demonstrated in experimental models and in elderly patients. Preinfarction angina, a clinical equivalent of ischemic preconditioning, reduces mortality in adult but not in elderly patients with acute myocardial infarction. Physical activity or caloric restriction is partially capable to preserve the cardioprotective effect of ischemic preconditioning in the aging heart. More importantly, physical activity and caloric restriction in tandem action completely preserve the protective mechanism of ischemic preconditioning. Accordingly, the protective mechanism of preinfarction angina is preserved in elderly patients with a high grade of physical activity or a low body-mass index. Thus, both physical activity and caloric restriction are confirmed as powerful anti-aging interventions capable to restore age-dependent reduction of a critical endogenous protective mechanism such as ischemic preconditioning.

Abete, Pasquale; Testa, Gianluca; Cacciatore, Francesco; Della-Morte, David; Galizia, Gianluigi; Langellotto, Assunta; Rengo, Franco

2011-01-01

126

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

PubMed Central

Background Cerebral ischemic preconditioning (IPC) protects brain against ischemic injury. Activation of Toll-like receptor 3 (TLR3) signaling can induce neuroprotective mediators, but whether astrocytic TLR3 signaling is involved in IPC-induced ischemic tolerance is not known. Methods IPC was modeled in mice with three brief episodes of bilateral carotid occlusion. In vitro, IPC was modeled in astrocytes by 1-h oxygen-glucose deprivation (OGD). Injury and components of the TLR3 signaling pathway were measured after a subsequent protracted ischemic event. A neutralizing antibody against TLR3 was used to evaluate the role of TLR3 signaling in ischemic tolerance. Results IPC in vivo reduced brain damage from permanent middle cerebral artery occlusion in mice and increased expression of TLR3 in cortical astrocytes. IPC also reduced damage in isolated astrocytes after 12-h OGD. In astrocytes, IPC or 12-h OGD alone increased TLR3 expression, and 12-h OGD alone increased expression of phosphorylated NF?B (pNF?B). However, IPC or 12-h OGD alone did not alter the expression of Toll/interleukin receptor domain-containing adaptor-inducing IFN? (TRIF) or phosphorylated interferon regulatory factor 3 (pIRF3). Exposure to IPC before OGD increased TRIF and pIRF3 expression but decreased pNF?B expression. Analysis of cytokines showed that 12-h OGD alone increased IFN? and IL-6 secretion; 12-h OGD preceded by IPC further increased IFN? secretion but decreased IL-6 secretion. Preconditioning with TLR3 ligand Poly I:C increased pIRF3 expression and protected astrocytes against ischemic injury; however, cells treated with a neutralizing antibody against TLR3 lacked the IPC- and Poly I:C-induced ischemic protection and augmentation of IFN?. Conclusions The results suggest that IPC-induced ischemic tolerance is mediated by astrocytic TLR3 signaling. This reprogramming of TLR3 signaling by IPC in astrocytes may play an important role in suppression of the post-ischemic inflammatory response and thereby protect against ischemic damage. The mechanism may be via activation of the TLR3/TRIF/IRF3 signaling pathway.

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

2014-01-01

127

The Effects of Remote Ischemic Preconditioning and N-Acetylcysteine with Remote Ischemic Preconditioning in Rat Hepatic Ischemia Reperfusion Injury Model  

PubMed Central

Background. Remote ischemic preconditioning (RIP) and pharmacological preconditioning are the effective methods that can be used to prevent ischemia reperfusion (IR) injury. The aim of this study was to evaluate the effects of RIP and N-Acetylcysteine (NAC) with RIP in the rat hepatic IR injury model. Materials and Methods. 28 rats were divided into 4 groups. Group I (sham): only laparotomy was performed. Group II (IR): following 30 minutes of hepatic pedicle occlusion, 4 hours of reperfusion was performed. Group III (RIP + IR): following 3 cycles of RIP, hepatic IR was performed. Group IV (RIP + NAC + IR): following RIP and intraperitoneal administration of NAC (150?mg/kg), hepatic IR was performed. All the rats were sacrificed after blood samples were taken for the measurements of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver was processed for conventional histopathology. Results. The hepatic histopathological injury scores of RIP + IR and RIP + NAC + IR groups were significantly lower than IR group (P = 0.006, P = 0.003, resp.). There were no significant differences in AST and ALT values between the IR, RIP + IR, and RIP + NAC + IR groups. Conclusions. In the present study, it was demonstrated histopathologically that RIP and RIP + NAC decreased hepatic IR injury significantly.

Uysal, Ali Ihsan; Ozkardesler, Sevda; Ergur, Bekir Ugur; Guneli, Ensari; Kume, Tuncay; Unal Togrul, Belgin

2014-01-01

128

Brain mitochondrial responses to postischemic reperfusion: a role for calcium and hydrogen peroxide?  

PubMed

During early recirculation following global brain ischemia, mitochondria are exposed to markedly elevated Ca(2+) concentrations and a short-lived production of reactive oxygen species, including hydrogen peroxide (H(2)O(2)). A brief increase in mitochondrial Ca(2+) and a subsequent increase in mitochondrial glutathione content have been observed. In the present study, we have confirmed the increase in mitochondrial glutathione in a rat model of global forebrain ischemia. This change was not inhibited by treatment of the rats with FK506, contrasting with our previous finding that cyclosporin A partially blocked the increase. These results suggest that induction of the mitochondrial permeability transition may be necessary for the increase in glutathione content in these organelles. To further investigate possible mitochondrial responses during early postischemic reperfusion, mitochondria isolated from normal brain were exposed to Ca(2+) and H(2)O(2), under conditions similar to those in intact cells. Respiratory activity was substantially modified when the mitochondria were exposed to Ca(2+) and H(2)O(2) together. Two distinct and largely noninteracting mechanisms apparently accounted for the responses to these agents. The effects of Ca(2+), but not H(2)O(2), were inhibited by cyclosporin A, again implicating the permeability transition in some of the mitochondrial changes. PMID:11111152

Sims, N R; Anderson, M F; Hobbs, L M; Powell, J A; Zaidan, E

2000-01-01

129

The Use of NeuroAiD (MLC601) in Postischemic Stroke Patients  

PubMed Central

Aim. We aimed to assess the efficacy of MLC601 on functional recovery in patients given MLC601 after an ischemic stroke. Methods. This is a retrospective cohort study comparing poststroke patients given open-label MLC601 (n = 30; 9 female) for three months and matching patients who did not receive MLC601 from our Stroke Data Bank. Outcome assessed was modified Rankin Scale (mRS) at three months and analyzed according to: (1) achieving a score of 0-2, (2) achieving a score of 0-1, and (3) mean change in scores from baseline. Results. At three months, 21 patients on MLC601 became independent as compared to 17 patients not on MLC601 (OR 1.79; 95% CI 0.62–5.2; P = 0.29). There were twice as many patients (n = 16) on MLC601 who attained mRS scores similar to their prestroke state than in the non-MLC601 group (n = 8) (OR 3.14; 95% CI 1.1–9.27; P = 0.038). Mean improvement in mRS from baseline was better in the MLC601 group than in the non-MLC601 group (?1.7 versus ?0.9; mean difference ?0.73; 95% CI ?1.09 to ?0.38; P < 0.001). Conclusion. MLC601 improves functional recovery at 3 months postischemic stroke. An ongoing large randomized control trial of MLC601 will help validate these results.

Navarro, Jose C.; Molina, Mark C.; Baroque II, Alejandro C.; Lokin, Johnny K.

2012-01-01

130

Backleak, tight junctions, and cell- cell adhesion in postischemic injury to the renal allograft.  

PubMed Central

Postischemic injury in recipients of 3-7-d-old renal allografts was classified into sustained (n = 19) or recovering (n = 20) acute renal failure (ARF) according to the prevailing inulin clearance. Recipients of optimally functioning, long-standing allografts and living donors undergoing nephrectomy served as functional (n = 14) and structural controls (n = 10), respectively. Marked elevation above control of fractional clearance of dextrans of graded size was consistent with transtubular backleak of 57% of filtrate (inulin) in sustained ARF. No backleak was detected in recovering ARF. To explore a structural basis for backleak, allograft biopsies were taken intraoperatively, 1 h after reperfusion in all recipients, and again on day 7 after transplant in a subset (n = 10). Electron microscopy revealed disruption of both apical and basolateral membranes of proximal tubule cells in both sustained and recovering ARF, but cell exfoliation and tubule basement membrane denudation were negligible. Histochemical analysis of membrane-associated adhesion complexes confirmed an abnormality of proximal but not distal tubule cells, marked in sustained ARF but not in recovering ARF. Staining for the zonula occludens complex (ZO-1) and adherens complex (alpha, beta, and gamma catenins) revealed diminished intensity and redistribution of each cytoskeletal protein from the apico-lateral membrane boundary. We conclude that impaired integrity of tight junctions and cell-cell adhesion in the proximal tubule provides a paracellular pathway through which filtrate leaks back in sustained allograft ARF.

Kwon, O; Nelson, W J; Sibley, R; Huie, P; Scandling, J D; Dafoe, D; Alfrey, E; Myers, B D

1998-01-01

131

Losartan Improved Antioxidant Defense, Renal Function and Structure of Postischemic Hypertensive Kidney  

PubMed Central

Ischemic acute renal failure (ARF) is a highly complex disorder involving renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and generation of reactive oxygen species. Due to this complexity, the aim of our study was to explore effects of Angiotensin II type 1 receptor (AT1R) blockade on kidney structure and function, as well as oxidative stress in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. Experiments were performed on anaesthetized adult male SHR in the model of ARF with 40 minutes clamping the left renal artery. The right kidney was removed and 40 minutes renal ischemia was performed. Experimental groups received AT1R antagonist (Losartan) or vehicle (saline) in the femoral vein 5 minutes before, during and 175 minutes after the period of ischemia. Biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. ARF significantly decreased creatinine and urea clearance, increased LDL and lipid peroxidation in plasma. Treatment with losartan induced a significant increase of creatinine and urea clearance, as well as HDL. Lipid peroxidation in plasma was decreased and catalase enzyme activity in erythrocytes was increased after losartan treatment. Losartan reduced cortico-medullary necrosis and tubular dilatation in the kidney. High expression of pro-apoptotic Bax protein in the injured kidney was downregulated after losartan treatment. Our results reveal that angiotensin II (via AT1R) mediates the most postischemic injuries in hypertensive kidney through oxidative stress enhancement. Therefore, blockade of AT1R may have beneficial effects in hypertensive patients who have developed ARF.

Ivanov, Milan; Mihailovic-Stanojevic, Nevena; Grujic Milanovic, Jelica; Jovovic, ?ur?ica; Markovic-Lipkovski, Jasmina; Cirovic, Sanja; Miloradovic, Zoran

2014-01-01

132

Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia  

PubMed Central

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

2014-01-01

133

Reduction in postsystolic wall thickening during late preconditioning.  

PubMed

Brief coronary artery occlusion (CAO) and reperfusion induce myocardial stunning and late preconditioning. Postsystolic wall thickening (PSWT) also develops with CAO and reperfusion. However, the time course of PSWT during stunning and the regional function pattern of the preconditioned myocardium remain unknown. The goal of this study was to investigate the evolution of PSWT during myocardial stunning and its modifications during late preconditioning. Dogs were chronically instrumented to measure (sonomicrometry) systolic wall thickening (SWT), PSWT, total wall thickening (TWT = SWT + PSWT), and maximal rate of thickening (dWT/dt(max)). Two 10-min CAO (circumflex artery) were performed 24 h apart (day 0 and day 1, n = 7). At day 0, CAO decreased SWT and increased PSWT. During the first hours of the subsequent stunning, evolution of PSWT was symmetrical to that of SWT. At day 1, baseline SWT was similar to day 0, but PSWT was reduced (-66%), while dWT/dt(max) and SWT/TWT ratio increased (+48 and +14%, respectively). After CAO at day 1, stunning was reduced, indicating late preconditioning. Simultaneously vs. day 0, PSWT was significantly reduced, and dWT/dt(max) as well as SWT/TWT ratio were increased, i.e., a greater part of TWT was devoted to ejection. Similar decrease in PSWT was observed with a nonischemic preconditioning stimulus (rapid ventricular pacing, n = 4). In conclusion, a major contractile adaptation occurs during late preconditioning, i.e., the rate of wall thickening is enhanced and PWST is almost abolished. These phenotype adaptations represent potential approaches for characterizing stunning and late preconditioning with repetitive ischemia in humans. PMID:16920813

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

2007-01-01

134

Green Tea Polyphenols Precondition against Cell Death Induced by Oxygen-Glucose Deprivation via Stimulation of Laminin Receptor, Generation of Reactive Oxygen Species, and Activation of Protein Kinase C?  

PubMed Central

As the development of synthetic drugs for the prevention of stroke has proven challenging, utilization of natural products capable of preconditioning neuronal cells against ischemia-induced cell death would be a highly useful complementary approach. In this study using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in PC12 cells, we show that 2-day pretreatment with green tea polyphenols (GTPP) and their active ingredient, epigallocatechin-3-gallate (EGCG), protects cells from subsequent OGD/R-induced cell death. A synergistic interaction was observed between GTPP constituents, with unfractionated GTPP more potently preconditioning cells than EGCG. GTPP-induced preconditioning required the 67-kDa laminin receptor (67LR), to which EGCG binds with high affinity. 67LR also mediated the generation of reactive oxygen species (ROS) via activation of NADPH oxidase. An exogenous ROS-generating system bypassed 67LR to induce preconditioning, suggesting that sublethal levels of ROS are indeed an important mediator in GTPP-induced preconditioning. This role for ROS was further supported by the fact that antioxidants blocked GTPP-induced preconditioning. Additionally, ROS induced an activation and translocation of protein kinase C (PKC), particularly PKC? from the cytosol to the membrane/mitochondria, which was also blocked by antioxidants. The crucial role of PKC in GTPP-induced preconditioning was supported by use of its specific inhibitors. Preconditioning was increased by conditional overexpression of PKC? and decreased by its knock-out with siRNA. Collectively, these results suggest that GTPP stimulates 67LR and thereby induces NADPH oxidase-dependent generation of ROS, which in turn induces activation of PKC, particularly prosurvival isoenzyme PKC?, resulting in preconditioning against cell death induced by OGD/R.

Gundimeda, Usha; McNeill, Thomas H.; Elhiani, Albert A.; Schiffman, Jason E.; Hinton, David R.; Gopalakrishna, Rayudu

2012-01-01

135

Myocardial remote ischemic preconditioning: from pathophysiology to clinical application.  

PubMed

Short periods of myocardial ischemia followed by reperfusion induce a cardioprotective mechanism when the myocardium is subsequently subjected to a prolonged period of ischemia, a phenomenon known as ischemic preconditioning. As well as its application in the myocardium, ischemic preconditioning can also be induced by brief interruptions of blood flow to other organs, particularly skeletal muscle. Transient ischemia induced noninvasively by inflating a cuff on a limb, followed by reperfusion, helps reduce the damage caused to the myocardium by interruption of the coronary circulation. Remote ischemic preconditioning involves activation of humoral and/or neural pathways that open mitochondrial ATP-sensitive potassium channels in the myocardium and close mitochondrial permeability transition pores, making cardiomyocytes less vulnerable to ischemia-induced cell death. This cardioprotective mechanism is now being translated into clinical practice, with positive results in several clinical trials in coronary artery bypass surgery, surgical repair of abdominal aortic aneurysms, valve replacement surgery and percutaneous coronary intervention. However, certain factors weaken the subcellular mechanisms of preconditioning - age, comorbidities, medication, anesthetic protocol - and appear to explain the heterogeneity of results in some studies. Detailed understanding of the pathways involved in cardioprotection induced by ischemic preconditioning is expected to lead to the development of new drugs to reduce the consequences of prolonged ischemia. PMID:24120469

Costa, José F; Fontes-Carvalho, Ricardo; Leite-Moreira, Adelino F

2013-11-01

136

Heat shock proteins, end effectors of myocardium ischemic preconditioning?  

PubMed Central

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

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

2006-01-01

137

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.

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

2011-01-01

138

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

139

Preconditioning with Physiological Levels of Ethanol Protect Kidney against Ischemia/Reperfusion Injury by Modulating Oxidative Stress  

PubMed Central

Background Oxidative stress due to excessive production of reactive oxygen species (ROS) and subsequent lipid peroxidation plays a critical role in renal ischemia/reperfusion (IR) injury. The purpose of current study is to demonstrate the effect of antecedent ethanol exposure on IR-induced renal injury by modulation of oxidative stress. Materials and Methods Bilateral renal warm IR was induced in male C57BL/6 mice after ethanol or saline administration. Blood ethanol concentration, kidney function, histological damage, inflammatory infiltration, cytokine production, oxidative stress, antioxidant capacity and Aldehyde dehydrogenase (ALDH) enzymatic activity were assessed to evaluate the impact of antecedent ethanol exposure on IR-induced renal injury. Results After bilateral kidney ischemia, mice preconditioned with physiological levels of ethanol displayed significantly preserved renal function along with less histological tubular damage as manifested by the reduced inflammatory infiltration and cytokine production. Mechanistic studies revealed that precondition of mice with physiological levels of ethanol 3 h before IR induction enhanced antioxidant capacity characterized by significantly higher superoxidase dismutase (SOD) activities. Our studies further demonstrated that ethanol pretreatment specifically increased ALDH2 activity, which then suppressed lipid peroxidation by promoting the detoxification of Malondialdehyde (MDA) and 4-hydroxynonenal (HNE). Conclusions Our results provide first line of evidence indicating that antecedent ethanol exposure can provide protection for kidneys against IR-induced injury by enhancing antioxidant capacity and preventing lipid peroxidation. Therefore, ethanol precondition and ectopic ALDH2 activation could be potential therapeutic approaches to prevent renal IR injury relevant to various clinical conditions.

Zeng, Li; Liu, Fang; Ding, Guoshan; Kang, Yindong; Mao, Jingyan; Cai, Ming; Zhu, Youhua; Wang, Quan-xing

2011-01-01

140

Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats.  

PubMed Central

BACKGROUND: Acute renal failure is a dose-limiting factor of cisplatin chemotherapy. Here, we show the protective effect of ozone oxidative preconditioning against cisplatin-induced renal dysfunction in rats. Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-pro-oxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in various in vivo and in vitro experimental models. AIMS: To analyze the protective role of ozone oxidative preconditioning against cisplatin-induced nephrotoxicity. METHODS: Male Sprague-Dawley rats were pretreated with 15 intrarectal applications of ozone/oxygen mixture at 0.36, 0.72, 1.1, 1.8 and 2.5 mg/kg before cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were extracted and analyzed 5 days after cisplatin treatment for determinations of the renal content of glutathione, thiobarbituric acid-reactive substances, renal concentration and enzymatic activities of catalase, superoxide dismutase and glutathione peroxidase. RESULTS: Ozone pretreatment prevented the increase in serum creatinine levels, the glutathione depletion and the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric acid-reactive substances was decreased by ozone therapy. These protective effects of ozone were dose dependent. CONCLUSIONS: Intrarectal ozone therapy prevented effectively the renal antioxidant unbalance induced by cisplatin treatment.

Borrego, Aluet; Zamora, Zullyt B; Gonzalez, Ricardo; Romay, Cheyla; Menendez, Silvia; Hernandez, Frank; Montero, Teresita; Rojas, Enys

2004-01-01

141

The use of Stronger Neo-Minophagen C, a glycyrrhizin-containing preparation, in robust neuroprotection in the postischemic brain  

PubMed Central

Stronger Neo-Minophagen C (SNMC) is a glycyrrhizin-containing preparation that is approved in Japan for the treatment of chronic hepatic diseases and is marketed in Japan, China, Korea, Taiwan, and India. Glycyrrhizin, a triterpene present in the roots and rhizomes of licorice (Glycyrrhiza glabra) has been shown to have anti-inflammatory, anti-oxidative, and anti-viral effects. In the present study, we demonstrated the marked neuroprotective effects of SNMC in the postischemic rat brain after middle cerebral artery occlusion (MCAO). We used 1 ml/kg of SNMC, which is within the dose range used for the treatment of patients with chronic hepatic disease. The administration of SNMC intravenously at 30 minutes before or 30 minutes and 3 hours after MCAO (60 minutes) reduces mean infarct volumes to 27.0±4.2%, 37.1±12.4%, and 67.8±5.8% of that of untreated controls, respectively. This neuroprotective effect is accompanied by improvements in motor impairment and neurological deficits. The administration of SNMC is shown to suppress microglia activation and neutrophil infiltration in the postischemic brain. In addition, SNMC suppresses lipopolysaccharide-induced nitrite production and proinflammatory cytokine induction in a microglia cell line, BV2. This indicates that the neuroprotective effect of SNMC might be due, at least in part, to an anti-inflammatiory effect. Interestingly, SNMC shows significantly higher neuroprotective potency compared to an equivalent dose of pure glycyrrhizin, in terms of reducing infarct volume and improving neurological deficits. Together these results indicate that SNMC, a glycyrrhizin-containing preparation developed for chronic liver disease, has a marked neuroprotective function in the postischemic brain via its anti-inflammatory effects.

Kim, Seung-Woo; Lim, Chae-Moon; Lee, Hye-Kyung

2011-01-01

142

The use of Stronger Neo-Minophagen C, a glycyrrhizin-containing preparation, in robust neuroprotection in the postischemic brain.  

PubMed

Stronger Neo-Minophagen C (SNMC) is a glycyrrhizin-containing preparation that is approved in Japan for the treatment of chronic hepatic diseases and is marketed in Japan, China, Korea, Taiwan, and India. Glycyrrhizin, a triterpene present in the roots and rhizomes of licorice (Glycyrrhiza glabra) has been shown to have anti-inflammatory, anti-oxidative, and anti-viral effects. In the present study, we demonstrated the marked neuroprotective effects of SNMC in the postischemic rat brain after middle cerebral artery occlusion (MCAO). We used 1 ml/kg of SNMC, which is within the dose range used for the treatment of patients with chronic hepatic disease. The administration of SNMC intravenously at 30 minutes before or 30 minutes and 3 hours after MCAO (60 minutes) reduces mean infarct volumes to 27.0±4.2%, 37.1±12.4%, and 67.8±5.8% of that of untreated controls, respectively. This neuroprotective effect is accompanied by improvements in motor impairment and neurological deficits. The administration of SNMC is shown to suppress microglia activation and neutrophil infiltration in the postischemic brain. In addition, SNMC suppresses lipopolysaccharide-induced nitrite production and proinflammatory cytokine induction in a microglia cell line, BV2. This indicates that the neuroprotective effect of SNMC might be due, at least in part, to an anti-inflammatiory effect. Interestingly, SNMC shows significantly higher neuroprotective potency compared to an equivalent dose of pure glycyrrhizin, in terms of reducing infarct volume and improving neurological deficits. Together these results indicate that SNMC, a glycyrrhizin-containing preparation developed for chronic liver disease, has a marked neuroprotective function in the postischemic brain via its anti-inflammatory effects. PMID:22254159

Kim, Seung-Woo; Lim, Chae-Moon; Lee, Hye-Kyung; Lee, Ja-Kyeong

2011-12-01

143

Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure  

PubMed Central

After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1? (3.8X) and TNF-? (6.0X). IFN-? was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.

Lachtermacher, S.; Esporcatte, B.L.B.; Montalvao, F.; Costa, P.C.; Rodrigues, D.C.; Belem, L.; Rabischoffisky, A.; Neto, H.C.C. Faria; Vasconcellos, R.; Iacobas, S.; Iacobas, D.A.; Dohmann, H.F.R.; Spray, D.C.; Goldenberg, R.C.S.; Campos-de-Carvalho, A.C.

2011-01-01

144

Enteral arginine modulates inhibition of AP1\\/c-Jun by SP600125 in the postischemic gut  

Microsoft Academic Search

We previously demonstrated that enteral arginine increased c-Jun\\/activator protein-1 (AP-1) DNA-binding activity and iNOS\\u000a expression in a rodent model of mesenteric ischemia\\/reperfusion (I\\/R). The objective of this study was to specifically investigate\\u000a the role of AP-1 in arginine’s deleterious effect on the postischemic gut. We hypothesized that AP-1 inhibition would mitigate\\u000a the effects of arginine. Using a rodent model of

Kechen Ban; Rachel Santora; Rosemary A. Kozar

2011-01-01

145

Reproductive Senescence Blunts Response of Estrogen Receptor-? Expression to Estrogen Treatment in Rat Post-Ischemic Cerebral Microvessels  

PubMed Central

Background Several studies demonstrate that estrogen treatment improves cerebral blood flow in ischemic brain regions of young ovariectomized (OVX) rats. Estrogen receptor-? (ER-?) may mediate estrogen’s beneficial actions via its effects on the cerebral microvasculature. However, estrogen-derived benefit may be attenuated in aged, reproductively senescent (RS) rats. Our goal was to determine the effects of aging, estrogen deprivation and estrogen repletion with oral conjugated estrogens (CE) on postischemic cerebral microvascular protein expression of ER-? and ER-?. Methods Fisher-344 (n?=?37) female rats were randomly divided into the following groups: OVX, OVX CE-treated, RS untreated, and RS CE-treated. After 30 days pretreatment with CE (0.01 mg/kg) rats were subjected to15 min. transient global cerebral ischemia. Non-ischemic naïve, OVX and RS rats were used as controls. Expression of ER-? and ER-? in isolated cortical cerebral microvessels (20 to 100 µm in diameter) was assessed using Western blot and immunohistochemistry techniques. Results Age and reproductive status blunted nonischemic ER-? expression in microvessels of OVX rats (0.31±0.05) and RS rats (0.33±0.06) compared to naïve rats (0.45±0.02). Postischemic microvascular expression of ER-? in OVX rats (0.01±0.0) was increased by CE treatment (0.04±0.01). Expression of ER-? in microvessels of RS rats (0.03±0.02) was unaffected by CE treatment (0.01±0.02). Western blot data are presented as a ratio of ER-? or ER-? proteins to ?-actin and. Oral CE treatment had no effect on ER-? expression in postischemic microvessels of OVX and RS rats. Statistical analysis was performed by One-Way ANOVA and a Newman-Keuls or Student’s post-hoc test. Conclusion Chronic treatment with CE increases ER-? but not ER-? expression in cerebral microvessels of OVX rats. Aging appears to reduce the normal ability of estrogen to increase ER-? expression in postischemic cerebral microvessels.

Zeynalov, Emil; Rezvani, Niloofar; Miyazaki, Chikao; Liu, Xiaoguang; Littleton-Kearney, Marguerite T.

2014-01-01

146

CD38 Exacerbates Focal Cytokine Production, Postischemic Inflammation and Brain Injury after Focal Cerebral Ischemia  

PubMed Central

Background Converging evidence suggests that inflammatory processes significantly influence brain injury and clinical impairment in ischemic stroke. Although early studies suggested a key role of lymphocytes, recent data has emphasized the orchestrating function of innate immunity, i.e., macrophages and microglia. The bifunctional receptor and ectoenzyme CD38 synthesizes calcium-mobilizing second messengers (e.g., cyclic ADP-ribose), which have been shown to be necessary for activation and migration of myeloid immune cells. Therefore, we investigated the dynamics of CD38 in stroke and the impact of CD38-deficiency on cytokine production, inflammation and cerebral damage in a mouse model of cerebral ischemia-reperfusion. Methodology/Principal Findings We show that the local expression of the chemokine MCP-1 was attenuated in CD38-deficient mice compared with wildtype mice after focal cerebral ischemia and reperfusion. In contrast, no significant induction of MCP-1 expression was observed in peripheral blood after 6 hours. Flow cytometry analysis revealed less infiltrating macrophages and lymphocytes in the ischemic hemisphere of CD38-deficient mice, whereas the amount of resident microglia was unaltered. An up-regulation of CD38 expression was observed in macrophages and CD8+ cells after focal cerebral ischemia in wildtype mice, whereas CD38 expression was unchanged in microglia. Finally, we demonstrate that CD38-deficiency decreases the cerebral ischemic injury and the persistent neurological deficit after three days of reperfusion in this murine temporary middle cerebral artery occlusion (tMCAO) model. Conclusion/Significance CD38 is differentially regulated following stroke and its deficiency attenuates the postischemic chemokine production, the immune cell infiltration and the cerebral injury after temporary ischemia and reperfusion. Therefore CD38 might prove a therapeutic target in ischemic stroke.

Gelderblom, Mathias; Ludewig, Peter; Leypoldt, Frank; Koch-Nolte, Friedrich; Gerloff, Christian; Magnus, Tim

2011-01-01

147

Losartan improved antioxidant defense, renal function and structure of postischemic hypertensive kidney.  

PubMed

Ischemic acute renal failure (ARF) is a highly complex disorder involving renal vasoconstriction, filtration failure, tubular obstruction, tubular backleak and generation of reactive oxygen species. Due to this complexity, the aim of our study was to explore effects of Angiotensin II type 1 receptor (AT1R) blockade on kidney structure and function, as well as oxidative stress in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. Experiments were performed on anaesthetized adult male SHR in the model of ARF with 40 minutes clamping the left renal artery. The right kidney was removed and 40 minutes renal ischemia was performed. Experimental groups received AT1R antagonist (Losartan) or vehicle (saline) in the femoral vein 5 minutes before, during and 175 minutes after the period of ischemia. Biochemical parameters were measured and kidney specimens were collected 24h after reperfusion. ARF significantly decreased creatinine and urea clearance, increased LDL and lipid peroxidation in plasma. Treatment with losartan induced a significant increase of creatinine and urea clearance, as well as HDL. Lipid peroxidation in plasma was decreased and catalase enzyme activity in erythrocytes was increased after losartan treatment. Losartan reduced cortico-medullary necrosis and tubular dilatation in the kidney. High expression of pro-apoptotic Bax protein in the injured kidney was downregulated after losartan treatment. Our results reveal that angiotensin II (via AT1R) mediates the most postischemic injuries in hypertensive kidney through oxidative stress enhancement. Therefore, blockade of AT1R may have beneficial effects in hypertensive patients who have developed ARF. PMID:24796787

Ivanov, Milan; Mihailovi?-Stanojevi?, Nevena; Gruji? Milanovi?, Jelica; Jovovi?, Dur?ica; Markovi?-Lipkovski, Jasmina; Cirovi?, Sanja; Miloradovi?, Zoran

2014-01-01

148

Microvessel changes after post-ischemic benign and malignant hyperemia: experimental study in rats  

PubMed Central

Background The present investigation was designed to elucidate the use of dynamic contrast enhanced perfusion MR imaging (DCE pMRI) in characterizing hyperemia, including microvessel changes, and to examine whether DCE pMRI can predict benign or malignant hyperemia. Methods Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO) by intraluminal suture placement. All rats were randomized to 4 groups: MCAO for 0.5 hours followed by saline treatment (10 ml/kg; group 1); MCAO for 3 hours followed by treatment with saline (group 2) or urokinase (25000 IU/kg; group 3); and MCAO for 6 hours followed by urokinase treatment (group 4). Relative cerebral blood volume (rCBV) and relative maximum slope of increase of the signal intensity time curve (rMSI) were quantitatively analyzed from MRI. Microvessel diameter and blood-brain barrier disruption obtained by laser scanning confocal microscopy (LSCM) as well as transmission electron microscopy (TEM) were obtained for correlative study. Results Benign hyperemia was noticed only in group 1; malignant hyperemia was seen in group 3. Although the rCBV of malignant hyperemia was slightly higher than in benign hyperemia (P > 0.05), the rMSI, on the other hand, was significantly lower (P < 0.05). Fluoro-isothiocyanate dextran (FITC-dextran) extravasations, marked glial end-foot process swelling, and significant vasodilatation were seen in malignant hyperemia, while no or mild leakage of FITC-dextran and slight glial end-foot process swelling occurred in benign hyperemia. Conclusion Our findings indicate that DCE pMRI can characterize post-ischemic hyperemia and correlates well with microvascular damage.

2010-01-01

149

Thallium 201 kinetics in stunned myocardium characterized by severe postischemic systolic dysfunction  

SciTech Connect

The hypothesis tested in this study was that despite the presence of severe postischemic myocardial dysfunction (stunning), the extraction and subsequent intracellular washout of thallium 201 should be preserved as long as irreversible sarcolemmal membrane injury was avoided. To produce myocardial stunning, 19 open-chested dogs with a critical left anterior descending coronary artery (LAD) stenosis underwent 10 5-minute periods of total LAD occlusion, each interspersed by 10 minutes of reperfusion by reflow through the critical stenosis. In another 12 control dogs observed for the same time period, no LAD occlusions were performed after placement of the critical stenosis. Hemodynamics, regional myocardial thickening by quantitative two-dimensional echocardiography, and microsphere-determined regional blood flows were serially measured. In 18 stunned dogs, systolic thickening in the LAD zone was markedly reduced to 0.4 +/- 2.4% at 40 minutes after the 10th reperfusion period compared with 32.5 +/- 2.2% thickening (p less than 0.001) in 12 control dogs at a matched time. The 201Tl first-pass extraction fraction determined by a double-isotope method using intracoronary 201Tl administration was comparable after the 10th reflow in a subgroup of 13 stunned (0.78) and six control (0.79) dogs. The T1/2 for the intracellular washout rate was also not significantly different in another group of six stunned (60 +/- 13 minutes) and six control (53 +/- 14 minutes) dogs, nor was the percentage of the 201Tl dose initially distributed in the interstitial compartment (11 +/- 3% vs. 7 +/- 2%). Systemic hemodynamics and regional flows were comparable in the two groups at 40 minutes after the 10th reflow. No dog had evidence of myocardial necrosis by triphenyl tetrazolium chloride staining.

Moore, C.A.; Cannon, J.; Watson, D.D.; Kaul, S.; Beller, G.A. (Univ. of Virginia Health Sciences Center, Charlottesville (USA))

1990-05-01

150

[Effects of FO-1561 on postischemic cerebral functional and metabolic recovery in experimental cerebral ischemia].  

PubMed

Effects of S-adenosyl-L-methionine sulfate tosylate (FO-1561) on postischemic cerebral functional and metabolic recovery in experimental cerebral ischemia were investigated. Severe bilateral forebrain ischemia in rats was induced by four-vessel occlusion with reducing the mean arterial pressure to 100-110 mmHg. After forebrain ischemia had been maintained for 30 minutes, recirculation was started by removal of the arterial clamps of bilateral common carotid arteries and by increasing systemic arterial pressure to the preischemic level. The EEG was continuously recorded from gold-coated screws inserted bilaterally in the parietal bones with the tips in extradural position, against a reference inserted prefrontal bone. Analysis of power spectrum of EEG activity was done by Berg Fourier Analyser. The brains were frozen in situ with liquid nitrogen before, during and after ischemia and then chiselled out during irrigation with liquid nitrogen. Concentrations of ATP in brain tissue were determined with high performance liquid chromatography. FO-1561, 100 mg/kg, was given intravenously, immediately after recirculation. After recirculation there was a tendency that EEG power spectrum in FO-1561-treated animals contained higher percentage of beta wave compared to that in control animals, while delta wave was lesser in FO-1561-treated animals. At 90 minutes following recirculation, ATP level in control animals was 2.17 +/- 0.05 mumol/g (mean +/- SE) and 2.42 +/- 0.03 mumol/g (mean +/- SE) in FO-1561-treated animals. Thus, recovery of ATP level was significantly better in FO-1561-treated animals than in control animals (p less than 0.01). PMID:3814437

Mabe, H; Ohara, S; Nagai, H

1986-11-01

151

Mechanical reperfusion is associated with post-ischemic hemorrhage in rat brain.  

PubMed

A major complication of recanalization therapy after an acute arterial occlusion in brain is hemorrhagic transformation (HT). Although it is known that prolonged ischemia is important in the development of HT, the role of reperfusion in ischemia-reperfusion induced HT is less well studied. To address the effect of reperfusion on HT, we assessed the incidence and severity of hemorrhage in rats after 5 h of middle cerebral artery occlusion (MCAO) followed by 19-hour reperfusion compared to rats with permanent occlusion (PMCAO) at the same 24-hour time point. The incidence and amount of hemorrhage, neurological function, and mortality rates were measured. MCAO (5 h) with 19-hour reperfusion was associated with a significantly higher incidence of cortical hemorrhage compared to PMCAO (81.8% vs 18.2%, p<0.05). Hemorrhage scores were higher in the 5-hour MCAO/reperfusion group compared to PMCAO rats (17.6+/-11.5 vs 2.4+/-5.3 in cortex, 20.4+/-4.6 vs 9.7+/-4.5 in striatum, p<0.01). Neurological function was worse in the ischemia-reperfusion group compared to PMCAO (p<0.05) and mortality rates were insignificantly higher in the 5-hour MCAO/reperfusion group vs PMCAO group (54.5% vs 18.1%; p<0.08). The results suggest that reperfusion after prolonged ischemia is associated with increased hemorrhagic transformation and neurological deterioration as compared to permanent ischemia. Whether pharmacological treatments prior to reperfusion attenuate post-ischemic HT requires further study. PMID:19162014

Lu, Aigang; Clark, Joseph F; Broderick, Joseph P; Pyne-Geithman, Gail J; Wagner, Kenneth R; Khatri, Pooja; Tomsick, Thomas; Sharp, Frank R

2009-04-01

152

Hyperbaric oxygen preconditioning reduces the incidence of decompression sickness in rats via nitric oxide.  

PubMed

Divers are at risk of decompression sickness (DCS) when the ambient pressure decrease exceeds a critical threshold. Hyperbaric oxygen (HBO2) preconditioning has been used to prevent various injuries, but the protective effect on DCS has not been well explored. To investigate the prophylactic effect of HBO2 on DCS, rats were pretreated with HBO2 (250 kPa-60 minutes) (all the pressures described here are absolute pressure) for 18 hours before a simulated air dive (700 kPa-100 minutes) with fast decompression to the surface at the rate of 200 kPa/min (n=33). During the following 30 minutes, the rats walked in a 3 m/minute rotating cage and were monitored for signs of DCS. The control rats were pretreated with normobaric air (n=30), normoxic hyperbaric nitrox (250 kPa, 8.4% O2) (n=13), or N(G)-nitro-L-arginine methyl ester (L-NAME) 30 minutes before HBO2 exposure (n=13). Nitric oxide (NO) levels were recorded immediately and 18 hours after HBO2 exposure in the brain and spinal cord. The incidence of DCS in rats pretreated with HBO2 was 30.3%, which was significantly lower than those treated with normobaric air (63.3%) (p<0.05) or hyperbaric nitrox (61.5%) (p<0.05). The onset time of DCS of the rats pretreated with HBO2 was significantly delayed compared with those treated with air (p<0.05). L-NAME nullified the HBO2 preconditioning effect. HBO2 increased NO level in the rat brain and spinal cord right after exposure; this effect was inhibited by L-NAME. Taken together, HBO2 preconditioning reduced the incidence of DCS in rats, and NO was involved in the prophylactic effect. PMID:20568547

Fan, Dan-Feng; Liu, Kan; Xu, Wei-Gang; Zhang, Rong-Jia; Liu, Yun; Kang, Zhi-Min; Sun, Xue-Jun; Li, Run-Ping; Tao, Heng-Yi; Zhang, Jian-Lin

2010-01-01

153

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

NASA Technical Reports Server (NTRS)

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

Wong, G. S.

1973-01-01

154

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

155

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.

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

2014-01-01

156

The Role of Ionospheric Outflow Preconditioning in Determining Storm Geoeffectiveness  

NASA Astrophysics Data System (ADS)

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

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

2012-12-01

157

Newton-preconditioned Krylov subspace solvers for system of nonlinear equations: A numerical experiment  

Microsoft Academic Search

In this paper, we present a numerical comparative study of the Newton-preconditioned Lanczos algorithms and Newton-preconditioned CG-like methods, with respect to convergence speed and CPU-time, by considering appropriate test problems.

S. Sundar; B. K. Bhagavan; S. Prasad

2001-01-01

158

40 CFR 92.125 - Pre-test procedures and preconditioning.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Pre-test procedures and preconditioning. 92.125 Section...POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.125 Pre-test procedures and preconditioning. (a)...

2013-07-01

159

40 CFR 85.2218 - Preconditioned idle test-EPA 91.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 ...Emission Control System Performance Warranty Short Tests § 85.2218 Preconditioned idle testâEPA 91. (a) General requirements...

2013-07-01

160

Ischemic preconditioning for cell-based therapy and tissue engineering.  

PubMed

Cell- and tissue-based therapies are innovative strategies to repair and regenerate injured hearts. Despite major advances achieved in optimizing these strategies in terms of cell source and delivery method, the clinical outcome of cell-based therapy remains unsatisfactory. The non-genetic approach of ischemic/hypoxic preconditioning to enhance cell- and tissue-based therapies has received much attention in recent years due to its non-invasive drug-free application. Here we discuss the current development of hypoxic/ischemic preconditioning to enhance stem cell-based cardiac repair and regeneration. PMID:24321597

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

2014-05-01

161

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

162

Moxonidine prevents ischemia/reperfusion-induced renal injury in rats.  

PubMed

Enhancement of renal sympathetic nerve activity during renal ischemia and its consequent effect on norepinephrine overflow from nerve endings after reperfusion play important roles in the development of ischemic acute kidney injury. In the present study, we evaluated whether moxonidine, an alpha(2)-adrenaline/I(1)-imidazoline receptor agonist which is known to elicit sympathoinhibitory action, would prevent the post-ischemic renal injury. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Intravenous (i.v.) injection of moxonidine at a dose of 360 nmol/kg to ischemic acute kidney injury rats suppressed the enhanced renal sympathetic nerve activity during the ischemic period, to a degree similar to findings with intracerebroventricular (i.c.v.) injection of moxonidine at a dose of 36 nmol/kg. On the other hand, suppressive effects of the i.v. treatment on renal venous norepinephrine overflow, renal dysfunction and tissue injury in the post-ischemic kidney were significantly greater than those elicited by the i.c.v. treatment. These results suggest that renoprotective effects of moxonidine on ischemic acute kidney injury probably result from its suppressive action on the ischemia-enhanced renal sympathetic nerve activity followed by norepinephrine spillover from the nerve endings of the post-ischemic kidney. PMID:19101535

Tsutsui, Hidenobu; Sugiura, Takahiro; Hayashi, Kentaro; Ohkita, Mamoru; Takaoka, Masanori; Yukimura, Tokihito; Matsumura, Yasuo

2009-01-28

163

Protein kinase C isoform–dependent myocardial protection by ischemic preconditioning and potassium cardioplegia  

Microsoft Academic Search

Objective: Ischemic preconditioning combined with potassium cardioplegia does not always confer additive myocardial protection. This study tested the hypothesis that the efficacy of ischemic preconditioning under potassium cardioplegia is dependent on protein kinase C isoform. Methods: Isolated and crystalloid-perfused rat hearts underwent 5 cycles of 1 minute of ischemia and 5 minutes of reperfusion (low-grade ischemic preconditioning) or 3 cycles

Kejie Lu; Hajime Otani; Tadashi Yamamura; Yoshihisa Nakao; Reiji Hattori; Hideki Ninomiya; Motohiko Osako; Hiroji Imamura

2001-01-01

164

Protection of the Liver by Ischemic Preconditioning: A Review of Mechanisms and Clinical Applications  

Microsoft Academic Search

Ischemic preconditioning refers to the endogenous mechanism of protection against a sustained ischemic insult following an initial, brief ischemic stimulus. Ischemia-reperfusion injury of the liver is a major cause of morbidity and mortality in liver surgery and transplantation and ischemic preconditioning is a promising strategy for improving the outcome of liver surgery. The preconditioning phenomenon was first described in a

Rahul S. Koti; Alexander M. Seifalian; Brian R. Davidson

2003-01-01

165

Preconditioning decreases ischemia\\/reperfusion-induced release and activation of matrix metalloproteinase-2  

Microsoft Academic Search

Release and activation of matrix metalloproteinases (MMPs) significantly contribute to myocardial stunning injury immediately after ischemia and reperfusion, however, their role in preconditioning remains unknown. We therefore examined the effects of preconditioning and subsequent ischemia\\/reperfusion on MMP activity in isolated rat hearts. Hearts were subjected to a preconditioning protocol (three consecutive 5-min periods of global ischemia interspersed with 5min of

Manoj M Lalu; Csaba Csonka; Zoltán Giricz; Tamás Csont; Richard Schulz; Péter Ferdinandy

2002-01-01

166

Preconditioning of swine heart with monophosphoryl lipid A improves myocardial preservation  

Microsoft Academic Search

Background. Ischemic preconditioning has been proven to be a powerful tool for myocardial protection in the setting of ischemia and reperfusion. A new drug to provide pharmacologic preconditioning, monophosphoryl lipid A (MLA), was administered 24 hours before an acute coronary occlusion in pigs to determine the effect on pharmacologic preconditioning.Methods. Two studies were completed. In the first, swine were distributed

Tetsuya Yoshida; Richard M Engelman; Daniel T Engelman; John A Rousou; Nilanjana Maulik; Motoaki Sato; Gary T Elliott; Dipak K Das

2000-01-01

167

Chronic intermittent hypoxic preconditioning suppresses pilocarpine-induced seizures and associated hippocampal neurodegeneration.  

PubMed

Mild brief hypoxia can protect against neuronal damage induced by epileptic seizures, at least in part by inhibiting apoptosis. Further elucidation of the antiepileptic mechanisms and optimization of the conditioning protocols are required before this strategy can be considered for clinical intervention. In this study, we compared the effects of different hypoxic preconditioning protocols on spontaneous recurrent seizures (SRS), intracellular free calcium concentration ([Ca(2+)]i), and apoptosis rate following pilocarpine-induced status epilepticus (SE). Male Sprague Dawley rats were subjected to either chronic intermittent hypobaric hypoxia (CIHH) or chronic intermittent normobaric hypoxia (CINH) (both for 6h/day×28 consecutive days) prior to pilocarpine-induced SE. The possible anticonvulsant and neuroprotective effects of CIHH and CINH were compared by video monitoring of behavioral seizure activity (frequency, delay), Nissl staining and Fluoro-Jade B (FJB) staining to examine changes in the morphology of hippocampal pyramidal neurons, and flow cytometry to detect the quantification of [Ca(2+)]i and cell apoptosis. Both hypoxic preconditioning protocols reduced the frequency and severity of SRS, suppressed post-ictal [Ca(2+)]i elevations, and inhibited neuronal apoptosis in the rat hippocampus compared to pilocarpine alone, but CIHH was more effective than CINH. Thus, mild hypoxic pretreatment, particularly when delivered as CIHH, may be a novel strategy for the clinical prevention and treatment of epilepsy. PMID:24680745

Zhen, Jun-Li; Wang, Wei-Ping; Zhou, Jing-Jing; Qu, Zhen-Zhen; Fang, Hai-Bo; Zhao, Ran-Ran; Lu, Yan; Wang, Hong-Chao; Zang, Hong-Min

2014-05-14

168

Elimination of the delayed postischemic energy deficit in cerebral cortex and hippocampus of aged rats with a dried, deproteinized blood extract (Actovegin).  

PubMed

In this study, the effect of Actovegin (AC) on glucose and energy metabolism of cerebral cortex and hippocampus after 15 minute complete cerebral ischemic (cci) and postischemic recirculation periods of 60 min, 24 h, 48 h, 72 and 96 h was investigated. The study was performed on 2-year-old male Wistar rats which may be designated as aged. Actovegin is a dried, deproteinized extract of calf blood which acts on mitochondrial respiration and energy metabolism. After cci, the metabolic abnormalities measured as concentrations of glucose, lactate, creatine phosphate (CrP), and adenosine triphosphate (ATP) normalized rapidly. After 48 h and 72 h postischemic recirculation, however, an imbalance in energy metabolism became manifest in cerebral cortex, and even earlier (24 h), longer (96 h), and more severely in hippocampus. AC (1 ml diluted with 1 ml distilled water/day; 1 ml AC contains 40 mg dried deproteinized extract) counterbalanced the postischemic abnormalities in cerebral cortex and hippocampus. This drug may be able to reduce the detrimental effects to the neuron during postischemic recirculation and may thus help the neuron to survive during this critical period. PMID:2589918

Hoyer, S; Betz, K

1989-01-01

169

Characteristic changes in T 2-value, apparent diffusion coefficient, and ultrastructure of substantia nigra evolving exofocal postischemic neuronal death in rats  

Microsoft Academic Search

To correlate the magnetic resonance (MR) imaging characteristics of exofocal postischemic neuronal death (EPND) in the substantia nigra (SN) with associated histologic changes, we occluded the left middle cerebral artery of rats for 1, 4, 7, or 12 days. Day 1 (post-occlusion) T2-weighted images revealed high signal intensity indicative of infarction in the ipsilateral caudate nucleus, putamen, and cortex but

Fengyu Zhao; Toshihiko Kuroiwa; Naoyuki Miyasaka; Tsukasa Nagaoka; Makoto Nakane; Akira Tamura; Hidehiro Mizusawa

2001-01-01

170

Ischemic Preconditioning: A Novel Target for Neuroprotective Therapy  

Microsoft Academic Search

Ischemic preconditioning involves a brief exposure to ischemia in order to develop a tolerance to injurious effects of prolonged ischemia. The molecular mechanisms of neuroprotection that lead to ischemic tolerance are not yet completely understood. However, it seems that two distinct phases are involved. Firstly, a cellular defense function against ischemia may be developed by the mechanisms inherent to neurons

Miguel Blanco; Ignacio Lizasoain; Tomás Sobrino; José Vivancos; José Castillo

2006-01-01

171

40 CFR 86.132-00 - Vehicle preconditioning.  

Code of Federal Regulations, 2013 CFR

...highway, US06 or SC03 test cycles. (ii) [Reserved] (iii) If a manufacturer has concerns about fuel effects on adaptive memory systems, a manufacturer may precondition a test vehicle on test fuel and the US06 cycle. Upon request from a...

2013-07-01

172

Toward Knowledge Preconditions for Composition of SemanticWeb Services  

Microsoft Academic Search

Several researches have been proposed to formalize the knowledge preconditions problem; an action or a plan is epistemically feasible. However, since the feasibility is only checked at design-time and is assumed that it also will be carried out at run-time, it is not suitable in the context of Web services composition, where the transaction is important in the distributed environment.

Sang-kyun Kim; Taekyung Lee; Kyu-chul Lee

2005-01-01

173

Redox Signaling Pathways Involved in Neuronal Ischemic Preconditioning  

PubMed Central

There is extensive evidence that the restoration of blood flow following cerebral ischemia contributes greatly to the pathophysiology of ischemia mediated brain injury. The initiating stimulus of reperfusion injury is believed to be the excessive production of reactive oxygen (ROS) and nitrogen (RNS) species by the mitochondria. ROS and RNS generation leads to mitochondrial protein, lipid and DNA oxidation which impedes normal mitochondrial physiology and initiates cellular death pathways. However not all ROS and RNS production is detrimental. It has been demonstrated that low levels of ROS production are protective and may serve as a trigger for activation of ischemic preconditioning. Ischemic preconditioning is a neuroprotective mechanism which is activated upon a brief sublethal ischemic exposure and is sufficient to provide protection against a subsequent lethal ischemic insult. Numerous proteins and signaling pathways have been implicated in the ischemic preconditioning neuroprotective response. In this review we examine the origin and mechanisms of ROS and RNS production following ischemic/reperfusion and the role of free radicals in modulating proteins associated with ischemic preconditioning neuroprotection.

Thompson, John W; Narayanan, Srinivasan V; Perez-Pinzon, Miguel A

2012-01-01

174

Application of Dijkstra's weakest precondition calculus to Dining Philosophers problem  

Microsoft Academic Search

Dijkstra's weakest precondition calculus is used to model the well known Dining Philosophers problem. Process and state definitions are done in such a manner that only the deadlock property of the system is highlighted. Care has been taken to choose the proper details such that it is not too elaborate to obscure the requirements also not be too abstract to

Jayasri Banerjee; Anup Kumar Bandyopadhyay; Ajit Kumar Mandal

2007-01-01

175

Weighted graph based ordering techniques for preconditioned conjugate gradient methods  

Microsoft Academic Search

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,

SIMON S. CLIFTIand; Wei-Pai Tang

1995-01-01

176

A component decomposition preconditioning for 3D stress analysis problems  

Microsoft Academic Search

SUMMARY A preconditioning methodology for an iterative solution of discrete stress analysis problems based on a space decomposition and subspace correction framework is analysed in this paper. The principle idea of our approach is the decomposition of a global discrete system into the ser ies of subproblems that correspond to the different Cartesian coordinates of the solution (displacement) vect or.

M. D. Mihajlovic; S. Mijalkovic

177

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

178

Autophagy Induced by Ischemic Preconditioning is Essential for Cardioprotection  

PubMed Central

Based on growing evidence linking autophagy to preconditioning, we tested the hypothesis that autophagy is necessary for cardioprotection conferred by ischemic preconditioning (IPC). We induced IPC with three cycles of 5 min regional ischemia alternating with 5 min reperfusion and assessed the induction of autophagy in mCherry-LC3 transgenic mice by imaging of fluorescent autophagosomes in cryosections. We found a rapid and significant increase in the number of autophagosomes in the risk zone of the preconditioned hearts. In Langendorff-perfused hearts subjected to an IPC protocol of 3?×?5 min ischemia, we also observed an increase in autophagy within 10 min, as assessed by Western blotting for p62 and cadaverine dye binding. To establish the role of autophagy in IPC cardioprotection, we inhibited autophagy with Tat-ATG5K130R, a dominant negative mutation of the autophagy protein Atg5. Cardioprotection by IPC was reduced in rat hearts perfused with recombinant Tat-ATG5K130R. To extend the potential significance of autophagy in cardioprotection, we also assessed three structurally unrelated cardioprotective agents—UTP, diazoxide, and ranolazine—for their ability to induce autophagy in HL-1 cells. We found that all three agents induced autophagy; inhibition of autophagy abolished their protective effect. Taken together, these findings establish autophagy as an end-effector in ischemic and pharmacologic preconditioning.

Huang, Chengqun; Yitzhaki, Smadar; Perry, Cynthia N.; Liu, Wayne; Giricz, Zoltan; Mentzer, Robert M.

2010-01-01

179

Towards bulk based preconditioning for quantum dot computations  

Microsoft Academic Search

This article describes how to accelerate the con- vergence of Preconditioned Conjugate Gradient (PCG) type eigensolvers for the computation of several states around the band gap of colloidal quantum dots. Our new approach uses the Hamiltonian from the bulk materials constituent for the quantum dot to design an efficient preconditioner for the folded spectrum PCG method. The technique described shows

Jack Dongarra; Julien Langou; Stanimire Tomov; Christof V; Lin-Wang Wang

180

Time-derivative preconditioning method for multicomponent flow  

NASA Astrophysics Data System (ADS)

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

Housman, Jeffrey Allen

181

The Role of Preconditioning on Thermosphere Mass Density (Invited)  

NASA Astrophysics Data System (ADS)

The ability to determine the amount of change expected in thermosphere mass density at a specific altitude in response to solar and geomagnetic disturbances is of major importance in predicting how low-earth orbiting satellites will be affected by atmospheric drag. It is also of importance in understanding how energy deposited in the thermosphere results in a certain change in thermosphere mass density. The response at a particular altitude will depend on the type of energy input, the altitude distribution of energy input, the internal processing of the energy input, and the state properties of the thermosphere gas (i.e. density, temperature, composition, winds) prior to the energy input - that is, the preconditioned state. As an example of preconditioning, the mass density at an altitude a few scale heights above the altitude where a fixed amount of energy is deposited will have a greater relative change when the initial state of the thermosphere exospheric temperature is cold. Thus, the preconditioned state of the thermosphere must be described properly in order to adequately predict the mass density response to a given energy input. Furthermore, the preconditioned composition structure will be important and can also cause the level of response in mass density to vary with altitude. The solar EUV flux is the major contributor in establishing the preconditioned state of thermosphere and the recent solar cycle with its extreme solar minimum EUV flux has resulted in an unprecedented cold and contracted thermosphere. High-resolution mass density observations inferred from accelerometer measurements on the CHAMP and GRACE satellites are used to demonstrate the role of preconditioning in mass density response to geomagnetic disturbances. Temperature and composition conditions are evaluated to explain observed changes in mass density. In particular, the dynamic action of the oxygen to helium transition region in both latitude and altitude is used to explain complex behaviors in the mass density at altitudes near 500 km throughout the extended solar minimum from 2007 to 2010. Consequently it will be shown that the level of response of the thermosphere mass density will vary with altitude that depends on the thermosphere preconditioned state, with significant contributions provided by the relative dynamics of the thermosphere composition.

Thayer, J. P.; Liu, X.

2013-12-01

182

Metabolomic Analysis of Two Different Models of Delayed Preconditioning  

PubMed Central

Recently we described an ischemic preconditioning induced by repetitive coronary stenosis, which is induced by 6 episodes of non-lethal ischemia over 3 days, and which also resembles the hibernating myocardium phenotype. When compared with traditional second window of ischemic preconditioning using DNA microarrays, many genes which differed in the repetitive coronary stenosis appeared targeted to metabolism. Accordingly, the goal of this study was to provide a more in depth analysis of changes in metabolism in the different models of delayed preconditioning, i.e., second window and repetitive coronary stenosis. This was accomplished using a metabolomic approach based on liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques. Myocardial samples from the ischemic section of porcine hearts subjected to both models of late preconditioning were compared against sham controls. Interestingly, although both models involve delayed preconditioning, their metabolic signatures were radically different; of the total number of metabolites that changed in both models (135 metabolites) only 7 changed in both models, and significantly more, p<0.01, were altered in the repetitive coronary stenosis (40%) than in the second window (8.1%). The most significant changes observed were in energy metabolism, e.g., phosphocreatine was increased 4 fold and creatine kinase activity increased by 27.2%, a pattern opposite from heart failure, suggesting that the repetitive coronary stenosis and potentially hibernating myocardium have enhanced stress resistance capabilities. The improved energy metabolism could also be a key mechanism contributing to the cardioprotection observed in the repetitive coronary stenosis and in hibernating myocardium.

Bravo, Claudio; Kudej, Raymond K.; Yuan, Chujun; Yoon, Seonghun; Ge, Hui; Park, Ji Yeon; Tian, Bin; Stanley, William C.; Vatner, Stephen F.; Vatner, Dorothy E.; Yan, Lin

2013-01-01

183

AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury  

Microsoft Academic Search

AMP-activated protein kinase (AMPK) is an important regulator of diverse cellular pathways in the setting of energetic stress. Whether AMPK plays a critical role in the metabolic and functional responses to myo- cardial ischemia and reperfusion remains uncertain. We examined the cardiac consequences of long-term inhibition of AMPK activity in transgenic mice expressing a kinase dead (KD) form of the

Raymond R. Russell III; Ji Li; David L. Coven; Marc Pypaert; Christoph Zechner; Monica Palmeri; Frank J. Giordano; James Mu; Morris J. Birnbaum; Lawrence H. Young

2004-01-01

184

Critical role for nitric oxide signaling in cardiac and neuronal ischemic preconditioning and tolerance.  

PubMed

Preconditioning to ischemic tolerance is a phenomenon in which brief episodes of a subtoxic insult induce a robust protection against the deleterious effects of subsequent, prolonged, lethal ischemia. The subtoxic stimuli that constitute the preconditioning event are quite diverse, ranging from brief ischemic episodes, spreading depression or potassium depolarization, chemical inhibition of oxidative phosphorylation, exposure to excitotoxins and cytokines. The beneficial effects of preconditioning were first demonstrated in the heart; it is now clear that preconditioning can induce ischemic tolerance in a variety of organ systems including brain, heart, liver, small intestine, skeletal muscle, kidney, and lung. There are two temporally and mechanistically distinct types of protection afforded by preconditioning stimuli, acute and delayed preconditioning. The signaling cascades that initiate the acute and delayed preconditioning responses may have similar biochemical components. However, the protective effects of acute preconditioning are protein synthesis-independent, mediated by post-translational protein modifications, and are short-lived. The effects of delayed preconditioning require new protein synthesis and are sustained for days to weeks. Elucidation of the molecular mechanisms that are involved in preconditioning and ischemic tolerance and identification of drugs that mimic this protective response have the potential to improve the prognosis of patients at risk for ischemic injury. This article focuses on recent findings on the effects of ischemic preconditioning in the cardiac and nervous systems and discusses potential targets for a successful therapeutic approach to limit ischemia-reperfusion injury. PMID:11303032

Nandagopal, K; Dawson, T M; Dawson, V L

2001-05-01

185

ISOFLURANE PRECONDITIONING NEUROPROTECTION IN EXPERIMENTAL FOCAL STROKE IS ANDROGEN-DEPENDENT IN MALE MICE  

PubMed Central

Isoflurane preconditioning neuroprotection in experimental stroke is male-specific. The role of androgens in the ischemic sensitivity of isoflurane preconditioned male brain and whether androgen effects are androgen receptor dependent were assessed. Male C57BL/6 mice were implanted with flutamide (androgen receptor antagonist), or castrated and implanted with testosterone, dihydrotestosterone, flutamide, letrozole (aromatase inhibitor), or vehicle 7–13 days before preconditioning. P450 estrogen aromatase wild-type and knockout mice were also evaluated. All mice were preconditioned for 4 h with 0% (sham preconditioning) or 1% isoflurane (isoflurane preconditioning) and recovered for 24 h. Mice then underwent 2 h of middle cerebral artery occlusion and were evaluated 22 h later for infarct volume. For neurobehavioral outcomes, sham and isoflurane preconditioned castrated male±dihydrotestosterone groups underwent 1 h of middle cerebral artery occlusion followed by 9 days of reperfusion. Isoflurane preconditioning neuroprotection relative to infarct volume outcomes were testosterone and dihydrotestosterone dose-specific and androgen receptor-dependent. Relative to long-term neurobehavioral outcomes, front paw sensorimotor function improved in isoflurane preconditioned mice regardless of androgen status while androgen replacement independently improved sensorimotor function. In contrast, isoflurane preconditioning improved cognitive function in castrates lacking endogenous androgens, but this improvement was absent in androgen replaced mice. Our findings suggest that androgen availability during isoflurane preconditioning may influence infarct volume and neurobehavioral outcomes in male mice following experimental stroke.

ZHU, W.; WANG, L.; ZHANG, L.; PALMATEER, J. M.; LIBAL, N. L.; HURN, P. D.; HERSON, P. S.; MURPHY, S. J.

2010-01-01

186

Acute preconditioning of cardiac progenitor cells with hydrogen peroxide enhances angiogenic pathways following ischemia-reperfusion injury.  

PubMed

There are a limited number of therapies available to prevent heart failure following myocardial infarction. One novel therapy that is currently being pursued is the implantation of cardiac progenitor cells (CPCs); however, their responses to oxidative stress during differentiation have yet to be elucidated. The objective of this study was to determine the effect of hydrogen peroxide (H2O2) treatment on CPC differentiation in vitro, as well as the effect of H2O2 preconditioning before implantation following ischemia-reperfusion (I/R) injury. CPCs were isolated and cloned from adult rat hearts, and then cultured in the absence or presence of H2O2 for 2 or 5 days. CPC survival was assessed with Annexin V, and cellular differentiation was evaluated through mRNA expression for cardiogenic genes. We found that 100??M H2O2 decreased serum withdrawal-induced apoptosis by at least 45% following both 2 and 5 days of treatment. Moreover, 100??M H2O2 treatment for 2 days significantly increased endothelial and smooth muscle markers compared to time-matched untreated CPCs. However, continued H2O2 treatment significantly decreased these markers. Left ventricular cardiac function was assessed 28 days after I/R and I/R with the implantation of Luciferase/GFP(+) CPCs, which were preconditioned with 100??M H2O2 for 2 days. Hearts implanted with Luciferase/GFP(+) CPCs had significant improvement in both positive and negative dP/dT over I/R. Furthermore, cardiac fibrosis was significantly decreased in the preconditioned cells versus both I/R alone and I/R with control cells. We also observed a significant increase in endothelial cell density in the preconditioned CPC hearts compared to untreated CPC hearts, which also coincided with a higher density of Luciferase(+) vessels. These findings suggest that preconditioning of CPCs with H2O2 for 2 days stimulates neoangiogenesis in the peri-infarct area following I/R injury and could be a viable therapeutic option to prevent heart failure. PMID:23544670

Pendergrass, Karl D; Boopathy, Archana V; Seshadri, Gokulakrishnan; Maiellaro-Rafferty, Kathryn; Che, Pao Lin; Brown, Milton E; Davis, Michael E

2013-09-01

187

Hydrogen Sulfide Preconditioning Protects Rat Liver against Ischemia/Reperfusion Injury by Activating Akt-GSK-3? Signaling and Inhibiting Mitochondrial Permeability Transition  

PubMed Central

Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R) injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC) or sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups. To establish a model of segmental (70%) warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 ?mol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 ?mol/kg) did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP) opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3?) and B-cell lymphoma-2 (Bcl-2) and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3? signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury.

Zhang, Hao; Xu, Fengying; Zou, Zui; Liu, Meng; Wang, Quanxing; Miao, Mingyong; Shi, Xueyin

2013-01-01

188

Preconditioning: a paradigm shift in the biology of myocardial ischemia  

PubMed Central

The discovery of preconditioning (PC) has arguably been the single most important development in the field of ischemic biology in the past 20 years. The significance of this phenomenon transcends cardiovascular medicine, since it is ubiquitously observed in virtually every tissue of the body. This article reviews the pathophysiology and molecular basis of myocardial PC, with particular emphasis on the late phase of this cardioprotective adaptation. The article also discusses the exploitation of late PC for the development of novel gene therapy strategies aimed at inducing a permanently preconditioned cardiac phenotype (prophylactic cardioprotection). Besides its conceptual interest, deciphering the mechanism of late PC has considerable therapeutic reverberations, since transfer of the genes that underlie late PC would be expected to emulate the salubrious effects of this response of the heart to stress.

Bolli, Roberto

2011-01-01

189

Is There a Place for Cerebral Preconditioning in the Clinic?  

Microsoft Academic Search

Preconditioning (PC) describes a phenomenon whereby a sub-injury-inducing stress can protect against a later injurious stress.\\u000a Great strides have been made in identifying the mechanisms of PC-induced protection in animal models of brain injury. While\\u000a these may help elucidate potential therapeutic targets, there are questions over the clinical utility of cerebral PC, primarily\\u000a because of questions over the need to

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

2010-01-01

190

Can preconditioning reduce laparoscopy-induced tissue injury?  

Microsoft Academic Search

Background: Pneumoperitoneum (P) created to facilitate laparoscopy (L) is associated with splanchnic perfusion, ischemia\\/reperfusion (I\\/R) injury, and oxidative stress. In this randomized controlled experimental study with blind outcome assessment, we evaluated the effect of preconditioning (PRE) on L-induced I\\/R injury. Methods: The subjects were 40 Sprague-Dawley male rats. P was created in all except controls, using carbondioxide (CO 2) insufflation

S. Yilmaz; T. Koken; C. Tokyol; A. Kahraman; G. Akbulut; M. Serteser; C. Polat; C. Gokce; O. Gokce

2003-01-01

191

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.

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

2012-01-01

192

Pharmacological preconditioning with diazoxide slows energy metabolism during sustained ischemia.  

PubMed

Ischemic preconditioning (PC) is associated with slower destruction of the adenine nucleotide pool ( summation operatorAd) and slower rate of anaerobic glycolysis during ischemic stress. These changes are concordant with the preconditioned state, supporting an essential role of lowered energy demand in the cardioprotective mechanism of PC. Although pharmacological PC induced by the activation of mitochondrial K(ATP) channels also limits infarct size, its effect on energy metabolism during sustained ischemia is unknown. Using metabolite levels found at baseline and after a 15 min test episode of regional ischemia, the effect of a cardioprotective dose of diazoxide on metabolic features associated with PC was tested in barbital-anesthetized, open-chest dogs. Diazoxide (3.5 mg/kg at an intravenous rate of 1 mL/min) infused before a test episode of ischemia had no effect on baseline metabolic indices. However, during ischemic stress, treated hearts exhibited less destruction of ATP, less degradation of the summation operatorAd into nucleosides and bases, as well as less lactate production than control hearts subjected only to ischemic stress. Thus, diazoxide mimics the metabolic alterations observed in PC tissue. This supports the hypothesis that a reduction in energy demand, which is now equated with an increased ATP to ADP ratio in the sarcoplasm, is a critical component of the mechanism of cardioprotection in preconditioned myocardium. It is hypothesized that during PC or diazoxide treatment, the passage of the summation operatorAd into and out of the mitochondria is slowed, limiting the level of ATP available to the mitochondrial ATPase and preserving ATP and the total summation operatorAd. Altered ischemic mitochondrial metabolism plays an important role in establishing and maintaining the preconditioned state. PMID:18650995

Schwartz, Lisa M; Reimer, Keith A; Crago, Mark S; Jennings, Robert B

2007-01-01

193

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

194

Preconditioned conjugate gradient methods for the Navier-Stokes equations  

NASA Technical Reports Server (NTRS)

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

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

1994-01-01

195

Preconditioning the bidomain model with almost linear complexity  

NASA Astrophysics Data System (ADS)

The bidomain model is widely used in electro-cardiology to simulate spreading of excitation in the myocardium and electrocardiograms. It consists of a system of two parabolic reaction diffusion equations coupled with an ODE system. Its discretisation displays an ill-conditioned system matrix to be inverted at each time step: simulations based on the bidomain model therefore are associated with high computational costs. In this paper we propose a preconditioning for the bidomain model either for an isolated heart or in an extended framework including a coupling with the surrounding tissues (the torso). The preconditioning is based on a formulation of the discrete problem that is shown to be symmetric positive semi-definite. A block LU decomposition of the system together with a heuristic approximation (referred to as the monodomain approximation) are the key ingredients for the preconditioning definition. Numerical results are provided for two test cases: a 2D test case on a realistic slice of the thorax based on a segmented heart medical image geometry, a 3D test case involving a small cubic slab of tissue with orthotropic anisotropy. The analysis of the resulting computational cost (both in terms of CPU time and of iteration number) shows an almost linear complexity with the problem size, i.e. of type nlog ?( n) (for some constant ?) which is optimal complexity for such problems.

Pierre, Charles

2012-01-01

196

Post-ischemic estradiol treatment reduced glial response and triggers distinct cortical and hippocampal signaling in a rat model of cerebral ischemia  

PubMed Central

Background Estradiol has been shown to exert neuroprotective effects in several neurodegenerative conditions, including cerebral ischemia. The presence of this hormone prior to ischemia attenuates the damage associated with such events in a rodent model (middle cerebral artery occlusion (MCAO)), although its therapeutic value when administered post-ischemia has not been assessed. Hence, we evaluated the effects of estradiol treatment after permanent MCAO (pMCAO) was induced in rats, studying the PI3K/AKT/GSK3/?-catenin survival pathway and the activation of SAPK-JNK in two brain areas differently affected by pMCAO: the cortex and hippocampus. In addition, we analyzed the effect of estradiol on the glial response to injury. Methods Male rats were subjected to pMCAO and estradiol (0.04?mg/kg) was administered 6, 24, and 48?h after surgery. The animals were sacrificed 6?h after the last treatment, and brain damage was evaluated by immunohistochemical quantification of ‘reactive gliosis’ using antibodies against GFAP and Iba1. In addition, Akt, phospho-AktSer473, phospho-AktThr308, GSK3, phospho-GSK3Ser21/9, ?-catenin, SAPK-JNK, and pSAPK-JNKThr183/Tyr185 levels were determined in western blots of the ipsilateral cerebral cortex and hippocampus, and regional differences in neuronal phospho-Akt expression were determined by immunohistochemistry. Results The increases in the percentage of GFAP- (5.25-fold) and Iba1- (1.8-fold) labeled cells in the cortex and hippocampus indicate that pMCAO induced ‘reactive gliosis’. This effect was prevented by post-ischemic estradiol treatment; diminished the number of these cells to those comparable with control animals. pMCAO down-regulated the PI3K/AkT/GSK3/?-catenin survival pathway to different extents in the cortex and hippocampus, the activity of which was restored by estradiol treatment more efficiently in the cerebral cortex (the most affected region) than in the hippocampus. No changes in the phosphorylation of SAPK-JNK were observed 54?h after inducing pMCAO, whereas pMCAO did significantly decrease the phospho-AktSer473 in neurons, an effect that was reversed by estradiol. Conclusion The present study demonstrates that post-pMCAO estradiol treatment attenuates ischemic injury in both neurons and glia, events in which the PI3K/AKT/GSK3/?-catenin pathway is at least partly involved. These findings indicate that estradiol is a potentially useful treatment to enhance recovery after human ischemic stroke.

2012-01-01

197

Preconditioning improves cardioplegia-related coronary microvascular smooth muscle hypercontractility: Role of KATP channels  

Microsoft Academic Search

Objectives: The effect of preconditioning before hyperkalemic cardioplegia on the coronary smooth muscle remains to be elucidated. We tested the hypothesis that hypoxic preconditioning could protect coronary smooth muscle against subsequent hyperkalemic cardioplegia-induced coronary vasospasm and that this preconditioning effect could be mediated by KATP channels. Methods: Rat coronary arterioles (endothelium-denuded) were studied in a pressurized, no-flow, normothermic state. Simultaneous

Naruto Matsuda; Kathleen G. Morgan; Frank W. Sellke

1999-01-01

198

Effects of sevoflurane preconditioning and postconditioning on rat myocardial stunning in ischemic reperfusion injury  

Microsoft Academic Search

Ischemic preconditioning and postconditioning distinctly attenuate ventricular arrhythmia after ischemia without affecting\\u000a the severity of myocardial stunning. Therefore, we report the effects of sevoflurane preconditioning and postconditioning\\u000a on stunned myocardium in isolated rat hearts. Isolated rat hearts were underwent 20 min of global ischemia and 40 min of reperfusion.\\u000a After an equilibration period (20 min), the hearts in the preconditioning

An-lu Dai; Li-hua Fan; Feng-jiang Zhang; Mei-juan Yang; Jing Yu; Jun-kuan Wang; Tao Fang; Gang Chen; Li-na Yu; Min Yan

2010-01-01

199

Neuroprotective effects of the dopamine D 2\\/D 3 agonist pramipexole against postischemic or methamphetamine-induced degeneration of nigrostriatal neurons  

Microsoft Academic Search

We have examined the neuroprotective efficacy of the selective dopamine (DA) D2\\/D3 receptor agonist pramipexole in two models of nigrostriatal (NS) degeneration. The first involves the delayed (28-day) postischemic retrograde NS degeneration that takes place in gerbils following a 10-min episode of bilateral carotid arterial occlusion-induced forebrain ischemia. In vehicle (40% hydroxypropyl cyclodextrin)-treated male gerbils, there was a 40–45% loss

Edward D Hall; Paula K Andrus; Jo A Oostveen; John S Althaus; Philip F Von Voigtlander

1996-01-01

200

Hepatic Branch Vagus Nerve Plays a Critical Role in the Recovery of Post-Ischemic Glucose Intolerance and Mediates a Neuroprotective Effect by Hypothalamic Orexin-A  

PubMed Central

Orexin-A (a neuropeptide in the hypothalamus) plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve) is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse) administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve) with orexin-1 receptor and c-Fos (activated neural cells marker). These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A.

Harada, Shinichi; Yamazaki, Yui; Koda, Shuichi; Tokuyama, Shogo

2014-01-01

201

The effect of magnesium added to secondary cardioplegia on postischemic myocardial metabolism and contractile function —a 31 P NMR spectroscopy and functional study in the isolated pig heart  

Microsoft Academic Search

This study investigated whether increasing the magnesium concentration during secondary cardioplegia improves postischemic myocardial recovery. Twenty-four isolated pig hearts were divided into four groups. All hearts were initially subjected to control perfusion with modified Krebs-Henseleit solution for 30 min, followed by a single infusion of St. Thomas' solution #2. The hearts were then maintained without perfusion at 12°C for 4h.

G. Tian; G. P. Biro; B. Xiang; K. W. Butler; R. Deslauriers

1992-01-01

202

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.

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

2014-01-01

203

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.

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

2014-01-01

204

Resveratrol preconditioning increases methionine sulfoxide reductases A expression and enhances resistance of human neuroblastoma cells to neurotoxins.  

PubMed

Methionine sulfoxide reductases A (MsrA) has been postulated to act as a catalytic antioxidant system involved in the protection of oxidative stress-induced cell injury. Recently, attention has turned to MsrA in coupling with the pathology of Parkinson's disease, which is closely related to neurotoxins that cause dopaminergic neuron degeneration. Here, we firstly provided evidence that pretreatment with a natural polyphenol resveratrol (RSV) up-regulated the expression of MsrA in human neuroblastoma SH-SY5Y cells. It was also observed that the expression and nuclear translocation of forkhead box group O 3a (FOXO3a), a transcription factor that activates the human MsrA promoter, increased after RSV pretreatment. Nicotinamide , an inhibitor of silent information regulator 1 (SIRT1), prevented RSV-induced elevation of FOXO3a and MsrA expression, indicating that the effect of RSV was mediated by a SIRT1-dependent pathway. RSV preconditioning increased methionine sulfoxide(MetO)-reducing activity in SH-SY5Y cells and enhanced their resistance to neurotoxins, including chloramine-T and 1-methyl-4-phenyl-pyridinium. In addition, the enhancement of cell resistance to neurotoxins caused by RSV preconditioning can be largely prevented by MsrA inhibitor dimethyl sulfoxide. Our findings suggest that treatment with polyphenols such as RSV can be used as a potential regulatory strategy for MsrA expression and function. PMID:23022493

Wu, Peng-Fei; Xie, Na; Zhang, Juan-Juan; Guan, Xin-Lei; Zhou, Jun; Long, Li-Hong; Li, Yuan-Long; Xiong, Qiu-Ju; Zeng, Jian-Hua; Wang, Fang; Chen, Jian-Guo

2013-06-01

205

Corticosterone reduces brain mitochondrial function and expression of mitofusin, BDNF in depression-like rodents regardless of exercise preconditioning.  

PubMed

Both chronic mild stress and an injection of corticosterone induce depression-like states in rodents. To further link mitochondrial dysfunction to the pathophysiology of major depression, here we describe two rat models of a depressive-like state induced by chronic unpredictable mild stress (CUMS) or corticosterone treatment (CORT). It is also a model that allows the simultaneous study of effects of exercise preconditioning on behavioral, electrophysiological, biochemical and molecular markers in the same animal. Exercise preconditioning ahead of CUMS and CORT treatment prevents many behavioral abnormalities resulted from CUMS. The changes in mitochondrial activity in brain and reduced expressions of superoxide dismutase (SOD1, SOD2), mitofusin (Mfn1, Mfn2) as well as brain-derived neurotrophic factor (BDNF) suggest that both CORT and CUMS may impair mitochondrial function and/or expressions of mitofusion and antioxidant enzymes that, in turn, may increase oxidative stress and reduce energy production in brain with depression-like behaviors. These findings suggest an underlying mechanism by which CORT, as well as CUMS, induces brain mitochondrial dysfunction that is associated with depressive-like states. Remarkably, physical exercise is identified as a helpful and preventive measure to promote mitochondrial function and expressions of mitofusin, BDNF and antioxidant enzymes in brain, so as to protect brain energy metabolism against CUMS, rather than the compound of corticosterone. PMID:22244747

Liu, Weina; Zhou, Chenglin

2012-07-01

206

Neurovascular protection by post-ischemic intravenous injections of the lipoxin A4 receptor agonist, BML-111, in a rat model of ischemic stroke.  

PubMed

Resolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA4 ) is an anti-inflammatory, pro-resolution lipid mediator with high affinity binding to ALX, the lipoxin A4 receptor. Since LXA4 is rapidly inactivated, potent analogs have been created, including the ALX agonist BML-111. We hypothesized that post-ischemic intravenous administration of BML-111 would provide protection to the neurovascular unit and reduce neuroinflammation in a rat stroke model. Animals were subjected to 90 min of middle cerebral artery occlusion (MCAO) and BML-111 was injected 100 min and 24 h after stroke onset and animals euthanized at 48 h. Post-ischemic treatment with BML-111 significantly reduced infarct size, decreased vasogenic edema, protected against blood-brain barrier disruption, and reduced hemorrhagic transformation. Matrix metalloproteinase-9 and matrix metalloproteinase-3 were significantly reduced following BML-111 treatment. Administration of BML-111 dramatically decreased microglial activation, as seen with CD68, and neutrophil infiltration and recruitment, as assessed by levels of myeloperoxidase and intracellular adhesion molecule-1. The tight junction protein zona occludens-1 was protected from degradation following treatment with BML-111. These results indicate that post-ischemic activation of ALX has pro-resolution effects that limit the inflammatory damage in the cerebral cortex and helps maintain blood-brain barrier integrity after ischemic stroke. PMID:24225006

Hawkins, Kimberly E; DeMars, Kelly M; Singh, Jonathan; Yang, Changjun; Cho, Henry S; Frankowski, Jan C; Doré, Sylvain; Candelario-Jalil, Eduardo

2014-04-01

207

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.

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

2010-01-01

208

Preconditioned Conjugate Gradient methods for low speed flow calculations  

NASA Technical Reports Server (NTRS)

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

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

1993-01-01

209

The SDF-1/CXCR4 axis in stem cell preconditioning.  

PubMed

We review the pivotal role of the stromal derived factor (SDF)-1 chemokine in tissue ischaemia and how it orchestrates the rapid revascularization of injured, ischaemic, and regenerating tissues via the CXC chemokine receptors CXCR4 and CXCR7. Furthermore, we discuss the effects of preconditioning (PC), which is a well-known protective phenomenon for tissue ischaemia. The positive effect of both hypoxic and acidic PC on progenitor cell therapeutic potential is reviewed, while stressing the role of the SDF-1/CXCR4 axis in this process. PMID:22451511

Cencioni, Chiara; Capogrossi, Maurizio C; Napolitano, Monica

2012-06-01

210

Preconditioning a product of matrices arising in trust region subproblems  

SciTech Connect

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

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

1996-03-01

211

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

212

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

213

Glycyrrhizic acid affords robust neuroprotection in the postischemic brain via anti-inflammatory effect by inhibiting HMGB1 phosphorylation and secretion.  

PubMed

High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In a previous report, we showed that HMGB1 is massively released during NMDA-induced acute damaging process in the postischemic brain and triggers inflammatory processes, like microglial activation. siRNA-mediated HMGB1 knockdown markedly reduced infarct volumes, confirming the crucial role played by HMGB1 in the postischemic brain. In the present study, we showed neuroprotective effects of glycyrrhizin (GL) in the postischemic rat brain after middle cerebral artery occlusion (MCAO). GL, a triterpene present in the roots and rhizomes of licorice, Glycyrrhiza glabra, has been shown to have anti-inflammatory and anti-viral effects. It has been reported that GL binds directly to HMGB1, and inhibits its chemoattractant and mitogenic activities. The administration of GL (10mg/kg) intravenously at 3 or 6h after MCAO reduced infarct volumes to 12.9±4.2% and 46.2±9.9%, respectively, of untreated control. This neuroprotective effect was accompanied by improvements in motor impairment and neurological deficits and suppressions of microglia activation and proinflammatory cytokine induction. Interestingly, GL almost completely blocked HMGB1 secretion in the postischemic brain and in lipopolysaccharide (LPS)-treated microglia cells. Furthermore, HMGB1 phosphorylation, which is the initial step for HMGB1 secretion, and the interaction between HMGB1 and protein kinase C (PKC) or calcium/calmodulin-dependent protein kinase IV (CaMKIV) were suppressed dose-dependently by GL. Here, we hypothesized that the blockage for the putative phosphorylation sites in HMGB1 by GL might be attributed to this suppression. In addition to the anti-inflammatory effects, we found that GL has anti-excitotoxic and anti-oxidative effects in neurons. Together these results indicate that GL has neuroprotective efficacy in the postischemic brain via its anti-inflammatory, anti-excitotoxic, and anti-oxidative effects and in particular, it exerts anti-inflammatory effect, at least in part, by inhibiting HMGB1 secretion. PMID:22266336

Kim, Seung-Woo; Jin, Yinchuan; Shin, Joo-Hyun; Kim, Il-Doo; Lee, Hye-Kyung; Park, Sunghyouk; Han, Pyung-Lim; Lee, Ja-Kyeong

2012-04-01

214

Global and Ocular Hypothermic Preconditioning Protect the Rat Retina from Ischemic Damage  

PubMed Central

Retinal ischemia could provoke blindness. At present, there is no effective treatment against retinal ischemic damage. Strong evidence supports that glutamate is implicated in retinal ischemic damage. We investigated whether a brief period of global or ocular hypothermia applied 24 h before ischemia (i.e. hypothermic preconditioning, HPC) protects the retina from ischemia/reperfusion damage, and the involvement of glutamate in the retinal protection induced by HPC. For this purpose, ischemia was induced by increasing intraocular pressure to 120 mm Hg for 40 min. One day before ischemia, animals were submitted to global or ocular hypothermia (33°C and 32°C for 20 min, respectively) and fourteen days after ischemia, animals were subjected to electroretinography and histological analysis. Global or ocular HPC afforded significant functional (electroretinographic) protection in eyes exposed to ischemia/reperfusion injury. A marked alteration of the retinal structure and a decrease in retinal ganglion cell number were observed in ischemic retinas, whereas global or ocular HPC significantly preserved retinal structure and ganglion cell count. Three days after ischemia, a significant decrease in retinal glutamate uptake and glutamine synthetase activity was observed, whereas ocular HPC prevented the effect of ischemia on these parameters. The intravitreal injection of supraphysiological levels of glutamate induced alterations in retinal function and histology which were significantly prevented by ocular HPC. These results support that global or ocular HPC significantly protected retinal function and histology from ischemia/reperfusion injury, probably through a glutamate-dependent mechanism.

Salido, Ezequiel M.; Dorfman, Damian; Bordone, Melina; Chianelli, Monica; Gonzalez Fleitas, Maria Florencia; Rosenstein, Ruth E.

2013-01-01

215

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

PubMed Central

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

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

2011-01-01

216

Preconditioning with diosgenin and treadmill exercise preserves the cardiac toxicity of isoproterenol in rats.  

PubMed

This study was aimed to evaluate the preventive effect of diosgenin and exercise on tissue antioxidant status in isoproterenol-induced myocardial infarction (MI) in male Wistar rats. Levels of lipid peroxides, reduced glutathione (GSH), and the activities of glutathione-dependent antioxidant enzymes (glutathione peroxidise and glutathione reductase) and antiperoxidative enzymes (catalase and superoxide dismutase) in the plasma and the heart tissue of experimental groups of rats were determined. Pretreatment with diosgenin and exercise exerted an antioxidant effect against isoproterenol-induced myocardial infarction by blocking the induction of lipid peroxidation. A tendency to prevent the isoproterenol-induced alterations in the level of GSH, in the activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes was also observed. Histopathological findings of the myocardial tissue showed a protective role for combination of diosgenin and exercise in isoproterenol (ISO)-treated rats. Thus, the present study reveals that preconditioning with diosgenin and exercise exerts cardioprotective effect against ISO-induced MI due to its free radical scavenging and antioxidant effects, which maintains the tissue defense system against myocardial damage. PMID:22956342

Salimeh, Afshin; Mohammadi, Mustafa; Rashidi, Bahman

2013-06-01

217

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

Code of Federal Regulations, 2013 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...

2013-07-01

218

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

219

Does fucose or piracetam modify the effect of hypoxia preconditioning against pentylenetetrazol-induced seizures?  

Microsoft Academic Search

To clarify the question whether the duration of hypoxia exposure has an influence on the point in time or the strength of hypoxic preconditioning, hypoxia exposure of rats lasting 1 and 8 h was tested regarding the modification of susceptibility to acute pentylenetetrazol-induced seizures. Following the short-lasting (1 h) hypoxia, the maximum level of preconditioning action was observed 7 days

Christine Rauca; Hannelore Jantze; Manfred Krug

2000-01-01

220

Late ischemic preconditioning of the myocardium alters the expression of genes involved in inflammatory response  

Microsoft Academic Search

Myocardial ischemic preconditioning (IPC) is a potent endogenous mechanism of cardioprotection against ischemia–reperfusion injury. In this study we focused on the second phase of IPC as the most interesting in terms of therapeutic implementations. We aimed at the detection of genes, which are differentially expressed at 16 h after reperfusion. Preconditioning of canine myocardium was initiated by 5 min occlusion

Dmitrij Zubakov; Jörg D Hoheisel; Franz-Werner Kluxen; Marian Brändle; Thomas Ehring; Bernd Hentsch; Marcus Frohme

2003-01-01

221

Superlinearly convergent CG methods via equivalent preconditioning for nonsymmetric elliptic operators  

Microsoft Academic Search

Summary. The convergence of the conjugate gradient method is studied for preconditioned linear operator equations with nonsymmetric normal operators, with focus on elliptic convection-diffusion operators in Sobolev space. Superlinear convergence is proved first for equations whose preconditioned form is a compact perturbation of the identity in a Hilbert space. Then the same convergence result is verified for elliptic convection-diffusion equations

O. Axelsson; J. Karátson

2004-01-01

222

Effects of Ischemic Preconditioning of Different Intraoperative Ischemic Times of Vascularized Bone Graft Rabbit Models  

PubMed Central

Background Ischemic preconditioning has been shown to improve the outcomes of hypoxic tolerance of the heart, brain, lung, liver, jejunum, skin, and muscle tissues. However, to date, no report of ischemic preconditioning on vascularized bone grafts has been published. Methods Sixteen rabbits were divided into four groups with ischemic times of 2, 6, 14, and 18 hours. Half of the rabbits in each group underwent ischemic preconditioning. The osteomyocutaneous flaps consisted of the tibia bone, from which the overlying muscle and skin were raised. The technique of ischemic preconditioning involved applying a vascular clamp to the pedicle for 3 cycles of 10 minutes each. The rabbits then underwent serial plain radiography and computed tomography imaging on the first, second, fourth, and sixth postoperative weeks. Following this, all of the rabbits were sacrificed and histological examinations were performed. Results The results showed that for clinical analysis of the skin flaps and bone grafts, the preconditioned groups showed better survivability. In the plain radiographs, except for two non-preconditioned rabbits with intraoperative ischemic times of 6 hours, all began to show early callus formation at the fourth week. The computed tomography findings showed more callus formation in the preconditioned groups for all of the ischemic times except for the 18-hour group. The histological findings correlated with the radiological findings. There was no statistical significance in the difference between the two groups. Conclusions In conclusion, ischemic preconditioning improved the survivability of skin flaps and increased callus formation during the healing process of vascularized bone grafts.

Wan Ahmad Kamal, Wan Syazli Rodzaia; Noor, Norizal Mohd; Abdullah, Shafie

2013-01-01

223

Critical Role for Nitric Oxide Signaling in Cardiac and Neuronal Ischemic Preconditioning and Tolerance  

Microsoft Academic Search

Preconditioning to ischemic tolerance is a phenomenon in which brief episodes of a subtoxic insult induce a robust pro- tection against the deleterious effects of subsequent, pro- longed, lethal ischemia. The subtoxic stimuli that constitute the preconditioning event are quite diverse, ranging from brief isch- emic episodes, spreading depression or potassium depolariza- tion, chemical inhibition of oxidative phosphorylation, exposure to

KRISHNADAS NANDAGOPAL; TED M. DAWSON; VALINA L. DAWSON

224

Factors affecting preconditioning of Trichinella spiralis nativa larvae in musculature to low temperatures.  

PubMed Central

The influence of preconditioning temperature, length of the preconditioning period, host and age of the infection on the survival of Trichinella spiralis nativa larvae in musculature to low temperature refrigeration was investigated. Dogs, foxes, ferrets, mink and guinea pigs were infected with a T. spiralis nativa isolate, killed at various times postinfection, preconditioned at temperature of -10 degrees C, -15 degrees C or -20 degrees C for varying periods of time prior to low temperature refrigeration and subsequent pepsin digestion to determine survival of larvae. The preconditioning temperature played an important role in the subsequent survival of larvae in musculature at low refrigeration temperatures. Under the conditions of this study, survival of larvae was greater as the preconditioning temperature became lower. The minimum period of preconditioning required had an inverse relationship with the refrigeration temperature. Preconditioning of the T. spiralis nativa isolate used occurred in the musculature of guinea pigs, foxes, ferrets, mink and dogs with larvae surviving longer in vulpine and canine musculature than in the other hosts studied. Age of the infection was not a major factor in the survival of preconditioned larvae in musculature at low refrigeration temperatures although survival was slightly longer in older infections.

Smith, H J

1987-01-01

225

Factors affecting preconditioning of Trichinella spiralis nativa larvae in musculature to low temperatures.  

PubMed

The influence of preconditioning temperature, length of the preconditioning period, host and age of the infection on the survival of Trichinella spiralis nativa larvae in musculature to low temperature refrigeration was investigated. Dogs, foxes, ferrets, mink and guinea pigs were infected with a T. spiralis nativa isolate, killed at various times postinfection, preconditioned at temperature of -10 degrees C, -15 degrees C or -20 degrees C for varying periods of time prior to low temperature refrigeration and subsequent pepsin digestion to determine survival of larvae. The preconditioning temperature played an important role in the subsequent survival of larvae in musculature at low refrigeration temperatures. Under the conditions of this study, survival of larvae was greater as the preconditioning temperature became lower. The minimum period of preconditioning required had an inverse relationship with the refrigeration temperature. Preconditioning of the T. spiralis nativa isolate used occurred in the musculature of guinea pigs, foxes, ferrets, mink and dogs with larvae surviving longer in vulpine and canine musculature than in the other hosts studied. Age of the infection was not a major factor in the survival of preconditioned larvae in musculature at low refrigeration temperatures although survival was slightly longer in older infections. PMID:3607648

Smith, H J

1987-04-01

226

Wallrock Reactions to Mining Beyond a Preconditioned Zone at the Star Mine, Burke, Idaho.  

National Technical Information Service (NTIS)

Rock preconditioning in advance of mining has been an effective means of rock-burst control based on the results of field demonstrations carried out on the 7700 level of the Hecla Mining Co.'s Star mine. Mining through the preconditioned zone was characte...

W. Blake

1980-01-01

227

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

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Preconditioned two speed idle test-EPA 91. 85.2220 Section 85.2220...Emission Control System Performance Warranty Short Tests § 85.2220 Preconditioned two speed idle testâEPA 91. (a) General requirements...

2013-07-01

228

Preconditioning decreases ischemia/reperfusion-induced release and activation of matrix metalloproteinase-2.  

PubMed

Release and activation of matrix metalloproteinases (MMPs) significantly contribute to myocardial stunning injury immediately after ischemia and reperfusion, however, their role in preconditioning remains unknown. We therefore examined the effects of preconditioning and subsequent ischemia/reperfusion on MMP activity in isolated rat hearts. Hearts were subjected to a preconditioning protocol (three consecutive 5-min periods of global ischemia interspersed with 5 min of reperfusion) followed by 30 min ischemia and 5 min reperfusion. To measure MMP release, coronary effluent was collected: (a) during aerobic perfusion, (b) in reperfusion following each preconditioning ischemia, and (c) during the final reperfusion following test ischemia. MMP-2 activities could be detected by gelatin zymography in the ventricles and coronary effluent samples from the perfused hearts. The levels of MMP-2 activity in the effluent were markedly increased in effluent following test ischemia from control hearts without preconditioning. This was accompanied by a decrease in corresponding tissue MMP activities. Preconditioning significantly decreased the MMP-2 activity in the coronary effluent following test ischemia/reperfusion and preserved the MMP-2 protein content and activity in the myocardium. Our results demonstrate that classic preconditioning inhibits ischemia/reperfusion induced release and activation of MMP-2. These results suggest that preconditioning may exert part of its cardioprotective effects through the reduction of MMP-2 release. PMID:12200138

Lalu, Manoj M; Csonka, Csaba; Giricz, Zoltán; Csont, Tamás; Schulz, Richard; Ferdinandy, Péter

2002-08-30

229

Effect of heat preconditioning by microwave hyperthermia on human skeletal muscle after eccentric exercise  

Microsoft Academic Search

The purpose of this study was to clarify whether heat precondi- tioning results in less eccentric exercise-induced muscle damage and muscle soreness, and whether the repeated bout effect is enhanced by heat preconditioning prior to eccentric exercise. Nine untrained male volunteers aged 23 ± 3 years participated in this study. Heat preconditioning included treatment with a mi- crowave hyperthermia unit

Norio Saga; Shizuo Katamoto; Hisashi Naito

230

Effect of Thermal Preconditioning Before Excimer Laser Photoablation  

PubMed Central

The purposes of this study were to assess the expression patterns of heat shock proteins (Hsps), after eyeball heating or cooling, and to elucidate their relationships with corneal wound healing and intraocular complications after excimer laser treatment. Experimental mice were grouped into three according to local pretreatment type: heating, cooling, and control groups. The preconditioning was to apply saline eyedrops onto the cornea prior to photoablation. Following photoablation, we evaluated corneal wound healing, corneal opacity and lens opacity. Hsp expression patterns were elucidated with Western blot and immunohistochemical staining. The heating and cooling groups recovered more rapidly, and showed less corneal and lens opacity than the control group. In the heating and cooling groups, there were more expressions of Hsps in the cornea and lens than in the control group. These results were confirmed in the Hsp 70.1 knockout mouse model. Our study showed that Hsps were induced by the heating or cooling preconditioning, and appeared to be a major factor in protecting the cornea against serious thermal damage. Induced Hsps also seemed to play an important role in rapid wound healing, and decreased corneal and lens opacity after excimer laser ablation.

Kim, Joon Mo; Park, Woo Chan; Seo, Jeong-Sun; Chang, Hae Ran

2004-01-01

231

Long-lasting protection in brain trauma by endotoxin preconditioning.  

PubMed

We investigated the occurrence of endotoxin (lipopolysaccharide, LPS) preconditioning in traumatic brain injury (TBI), evaluating the time window of LPS-induced protection, its persistence, and the associated molecular mechanisms. Mice received 0.1?mg/kg LPS or saline intraperitoneally and subsequently TBI (by controlled cortical impact brain injury) at various time intervals. Mice receiving LPS 3, 5, or 7 days before TBI showed attenuated motor deficits at 1 week after injury compared with mice receiving saline. Those receiving LPS 5 days before injury had also a reduced contusion volume (7.9±1.3 versus 12±2.3?mm(3)) and decreased cell death. One month after injury, the protective effect of LPS on contusion volume (14.5±1.2 versus 18.2±1.2?mm(3)) and neurologic function was still present. Traumatic brain injury increased glial fibrillary acidic protein, CD11b, CD68, tumor necrosis factor-?, interleukin (IL)-10, and IL-6 mRNA expression 24?hours after injury. Lipopolysaccharide administered 5 (but not 9) days before injury increased the expression of CD11b (233%) and of interferon ? (500%) in uninjured mice, while it reduced the expression of CD68 (by 46%) and increased that of IL-6 (by 52%) in injured mice. Lipopolysaccharide preconditioning conferred a long-lasting neuroprotection after TBI, which was associated with a modulation of microglia/macrophages activity and cytokine production. PMID:21468087

Longhi, Luca; Gesuete, Raffaella; Perego, Carlo; Ortolano, Fabrizio; Sacchi, Noemi; Villa, Pia; Stocchetti, Nino; De Simoni, Maria-Grazia

2011-09-01

232

Physics-Based Preconditioning for a Radially Compressed FRC Model  

NASA Astrophysics Data System (ADS)

SEL is a parallel code for solving initial-boundary value problems for coupled nonlinear fluid equations, using high-order spectral elements for discretization in 2 spatial dimensions, and a fully-implicit time step. Efficient parallel operation requires a scalable method for solving large, sparse matrices. In previous work, a framework for such a solver has been developed, separated into general-purpose modules for all applications and problem-specific code for each application. The heart of the method is physics-based preconditioning, which reduces the order and enhances the diagonal dominance of the linear systems to be solved. Approximations introduced at this stage are eliminated by matrix-free Newton-Krylov iteration on the full nonlinear system. The details of the approach depend on the coupling of the various physical variables. It has been successfully tested for ideal MHD waves in a doubly periodic plane. The purpose of this presentation is to describe the development and testing of physics-based preconditioning for a more interesting test case, modeling a radially compressed FRC with extend MHD.

Glasser, A. H.; Lukin, V. S.

2009-11-01

233

Stress Preconditioning of Spreading Depression in the Locust CNS  

PubMed Central

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

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

2007-01-01

234

Acute Superoxide Radical Scavenging Reduces Blood Pressure but Does Not Influence Kidney Function in Hypertensive Rats with Postischemic Kidney Injury  

PubMed Central

Acute kidney injury (AKI) is associated with significant morbidity and mortality in hypertensive surroundings. We investigated superoxide radical molecules influence on systemic haemodynamic and kidney function in spontaneously hypertensive rats (SHR) with induced postischemic AKI. Experiment was performed in anesthetized adult male SHR. The right kidney was removed, and left renal artery was subjected to ischemia by clamping for 40 minutes. The treated group received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5 minutes before, during, and 175 minutes after the period of reperfusion, while the control AKI group received the vehicle via the same route. All parameters were measured 24?h after renal reperfusion. TEMPOL treatment significantly decreased mean arterial pressure and total peripheral resistance (P < 0.05) compared to AKI control. It also increased cardiac output and catalase activity (P < 0.05). Lipid peroxidation and renal vascular resistance were decreased in TEMPOL (P < 0.05). Plasma creatinine and kidney morphological parameters were unchanged among TEMPOL treated and control groups. Our study shows that superoxide radicals participate in haemodynamic control, but acute superoxide scavenging is ineffective in glomerular and tubular improvement, probably due to hypertension-induced strong endothelial dysfunction which neutralizes beneficial effects of O2? scavenging.

Miloradovic, Zoran; Ivanov, Milan; Mihailovic-Stanojevic, Nevena; Grujic Milanovic, Jelica; Jovovic, ?ur?ica; Vajic, Una-Jovana; Markovic-Lipkovski, Jasmina

2014-01-01

235

Increased uptake of 18F-fluorodeoxyglucose in postischemic myocardium of patients with exercise-induced angina  

SciTech Connect

Regional myocardial perfusion and exogenous glucose uptake were assessed with rubidium-82 (82Rb) and 18F-2-fluoro-2-deoxyglucose (FDG) in 10 normal volunteers and 12 patients with coronary artery disease and stable angina pectoris by means of positron emission tomography. In patients at rest, the myocardial uptake of /sup 82/Rb and FDG did not differ significantly from that measured in normal subjects. The exercise test performed within the positron camera in eight patients produced typical chest pain and ischemic electrocardiographic changes in all. In each of the eight patients a region of reduced cation uptake was demonstrated in the /sup 82/Rb scan recorded at peak exercise, after which uptake of /sup 82/Rb returned to the control value 5 to 14 min after the end of the exercise. In these patients, FDG was injected in the recovery phase when all the variables that were altered during exercise, including regional myocardial /sup 82/Rb uptake, had returned to control values. In all but one patient, FDG accumulation in the regions of reduced /sup 82/Rb uptake during exercise was significantly higher than that in the nonischemic regions, i.e., the ones with a normal increment of /sup 82/Rb uptake on exercise. In the nonischemic areas, FDG uptake was not significantly different from that found in normal subjects after exercise. In conclusion, myocardial glucose transport and phosphorylation seem to be enhanced in the postischemic myocardium of patients with exercise-induced ischemia.

Camici, P.; Araujo, L.I.; Spinks, T.; Lammertsma, A.A.; Kaski, J.C.; Shea, M.J.; Selwyn, A.P.; Jones, T.; Maseri, A.

1986-07-01

236

Differential effects of soluble epoxide hydrolase inhibition and CYP2J2 overexpression on postischemic cardiac function in aged mice.  

PubMed

Cardioprotective effects of epoxyeicosatrienoic acids (EETs) have been demonstrated in models of young mice with either the cardiomyocyte specific over-expression of cytochrome P450 2J2 (CYP2J2 Tr) or deletion of soluble epoxide hydrolase (sEH null). In this study we examined differences in EET-induced cardioprotection in young (2 months) and aged (12 months) CYP2J2 Tr and sEHnull mice using Langendorff isolated perfused heart model. Improved postischemic functional recovery was observed in both young and aged sEH null mice compared to age matched WT. Conversely, the cardioprotective effect observed in young CYP2J2 Tr was lost in aged CYP2J2 Tr mice. The loss of cardioprotection in aged CYP2J2 Tr was regained following perfusion with the sEH inhibitor t-AUCB. Data demonstrated increased levels of leukotoxin diol (DiHOME) and oxidative stress as well decreased protein phosphatase 2A (PP2A) activation in aged CYP2J2 Tr. In conclusion, inhibition of sEH and EET-induced cardioprotection is maintained in aged mice. However, the loss of protective effects observed in aged CYP2J2 Tr might be attributed to increased levels of DiHOME, oxidative stress and/or decreased PP2A activity. PMID:22922020

Chaudhary, Ketul R; Zordoky, Beshay N M; Edin, Matthew L; Alsaleh, Nasser; El-Kadi, Ayman O S; Zeldin, Darryl C; Seubert, John M

2013-01-01

237

Preconditioning of Trichinella spiralis nativa larvae in musculature to low temperatures.  

PubMed

Preconditioning of a Trichinella spiralis nativa isolate in ferret and fox musculature was carried out by freezing at -15 degrees C from 0 to 322 days prior to low temperature refrigeration at -32 degrees C. A limited number of preconditioned samples of infected fox musculature was also refrigerated at -45 degrees C. Preconditioned larvae were appreciably more resistant than those subjected to the low temperatures directly. Under the conditions of this investigation, the longer the period of preconditioning, the greater the resistance, (i.e., survival of larvae) observed. The larvae in fox musculature were slightly more resistant than those in ferret musculature. Limited infectivity trials indicated that pre-conditioned larvae surviving low temperature refrigeration of -32 degrees C -45 degrees C retained their infectivity for at least 44 and 37 days, respectively. PMID:6441341

Smith, H J

1984-12-01

238

Pharmacological preconditioning with adenosine A1 receptor agonist suppresses cellular immune response by an A2A receptor dependent mechanism.  

PubMed

Under stressful conditions such as ischemia, sepsis, and severe trauma, adenosine levels are elevated and protect the tissue by interaction with G coupled receptors. In a model of peritonitis, we previously found that pharmacological preconditioning (PPC) of mice with a selective adenosine A1 receptor (A1R) agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA), induced the A2AR which reduces cytokine secretion and leukocyte recruitment. In our present study we determined whether mice PPC will moderate cellular immune response by the same mechanism. Similar to the effect on inflammation, PPC reduced the response to lymphocyte mitogens and allogeneic MLR response. The inhibitory effect of PPC on the immune response was A1R and A2AR dependent as illustrated by experiments with antagonists of these receptors and mice with knock down (KO) receptors. In MLR with PPC splenocytes we found reduced levels of pro-inflammatory cytokines (IFN-?, IL-15, TNF-?) and elevation of IL-10, as well as elevation of regulatory T-cell. Our data indicate that PPC is able to remarkably suppress cellular immune response due to the sensitization A2AR. This effect of PPC sheds light on the protective role of adenosine in ischemic preconditioning and makes this treatment candidate for the prevention of graft rejection. PMID:24560904

Naamani, Oshri; Chaimovitz, Cidio; Douvdevani, Amos

2014-05-01

239

Neuroprotection of preconditioning against ischemic brain injury in rat hippocampus through inhibition of the assembly of GluR6-PSD95-mixed lineage kinase 3 signaling module via nuclear and non-nuclear pathways.  

PubMed

Our previous studies showed that the assembly of the GluR6-PSD95-mixed lineage kinase 3 (MLK3) signaling module played an important role in rat ischemic brain injury. In this study, we aimed to elucidate whether ischemic preconditioning could downregulate the assembly of the GluR6-PSD95-MLK3 signaling module and suppress the activation of MLK3, MKK4/7, and c-Jun N-terminal kinase (JNK). As a result, ischemic preconditioning could not only inhibit the assembly of the GluR6-PSD95-MLK3 signaling module, diminish the phosphorylation of the transcription factor c-Jun, downregulate Fas ligand expression, attenuate the phosphorylation of 14-3-3 and Bcl-2 and the translocation of Bax to mitochondria, but also increase the release of cytochrome c and the activation of caspase-3. In contrast, both GluR6 antisense ODNs (oligodeoxynucleotides) and 6,7,8,9-tetrahydro-5-nitro-1 H-benz[g]indole-2,3-dione-3-oxime (NS102), an antagonist of GluR6 receptor, prevented the above effects of preconditioning, which shows that suppressing the expression of GluR6 or inhibiting GluR6 activity contributes negatively to preconditioning-induced ischemia tolerance. Taken together, our results indicate that preconditioning can inhibit the over-assembly of the GluR6-PSD95-MLK3 signaling module and the JNK3 activation. GluR6 subunit-containing kainite receptors play an important role in the preconditioning-induced neuronal survival and provide new insight into stroke therapy. PMID:19328223

Du, Y; Li, C; Hu, W-W; Song, Y-J; Zhang, G-Y

2009-06-30

240

Magnesium supplementation combined with N-acetylcysteine protects against postischemic acute renal failure.  

PubMed

Magnesium is a potent vasodilator whose effects have not been evaluated in renal ischemia. The antioxidant properties of N-acetylcysteine (NAC) partially protect animals from ischemic/reperfusion injury. This study was designed to evaluate magnesium supplementation, alone or combined with NAC, on ischemic acute renal failure. Rats were maintained on normal diets, supplemented or not with MgCl(2).6H(2)O (1% in drinking water) for 23 d, and some rats received NAC (440 mg/kg body wt) on days 20 to 23. On day 21, ischemia was induced by clamping both renal arteries for 30 min. Five groups were studied: Normal, ischemia, ischemia+magnesium, ischemia+NAC, and ischemia+magnesium+NAC. GFR (inulin clearance), renal blood flow (RBF), FEH(2)O, and FENa were determined. Serum magnesium was decreased in ischemia-only rats. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. However, NAC completely restored the tubular damage induced by ischemia/reperfusion. Semiquantitative immunoblotting showed that NAC prevented the decreased expression of Na-K-2Cl co-transporter and aquaporin 2 after renal ischemia/reperfusion. Untreated rats with acute renal failure demonstrated markedly decreased endothelial nitric oxide synthase expression. Significantly, treatment with NAC, magnesium, or both completely inhibited downregulation of endothelial nitric oxide synthase. The tubular necrosis scores were lower in rats that were treated with NAC alone or with the magnesium-NAC combination. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. The NAC protected tubules from ischemia, decreased infiltrating macrophages/lymphocytes, and had a mild protective effect on GFR. In ischemic/reperfusion injury, renal function benefits more from the magnesium-NAC combination than from magnesium alone. PMID:16177005

de Araujo, Magali; Andrade, Lucia; Coimbra, Terezila M; Rodrigues, Adilson C; Seguro, Antonio Carlos

2005-11-01

241

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.

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

2010-01-01

242

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

243

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

PubMed

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)alpha-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 injury. Our studies show that systemic administration of CpG ODN 1826 in advance of brain ischemia (middle cerebral artery occlusion (MCAO)) reduces ischemic damage up to 60% in a dose- and time-dependent manner. We also offer evidence that CpG ODN preconditioning can provide direct protection to cells of the central nervous system, as we have found marked neuroprotection in modeled ischemia in vitro. Finally, we show that CpG preconditioning significantly increases serum TNFalpha levels before MCAO and that TNFalpha is required for subsequent reduction in damage, as mice lacking TNFalpha are not protected against ischemic injury by CpG preconditioning. Our studies show that preconditioning with a TLR9 ligand induces neuroprotection against ischemic injury through a mechanism that shares common elements with LPS preconditioning via TLR4. PMID:18183029

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

2008-05-01

244

Formation of Hydrogen Peroxide and Reduction of Peroxynitrite via Dismutation of Superoxide at Reperfusion Enhances Myocardial Blood Flow and Oxygen Consumption in Postischemic Mouse Heart  

PubMed Central

Reactive oxygen/nitrogen species suppress myocardial oxygen consumption. In this study, we determined that endogenous hydrogen peroxide through dismutation of superoxide enhances postischemic myocardial blood perfusion and oxygen consumption. Electron paramagnetic resonance oximetry was applied to monitor in vivo tissue Po2 in mouse heart subjected to regional ischemia reperfusion. Heart rate, arterial blood pressure, blood flow, infarction, and activities of mitochondrial NADH dehydrogenase and cytochrome c oxidase were measured in six groups of wild-type (WT) and endothelial nitric-oxide synthase knock-out (eNOS?/?) mice treated with phosphate-buffered saline (PBS), superoxide dismutase mimetic (SODm) M40403 [a manganese(II)-bis(cyclohexylpyridine)-substituted macrocyclic superoxide dismutase mimetic, C21H35Cl2MnN5], 10006329 EUK 134 [EUK134, manganese 3-methoxy N,N1-bis(salicyclidene)ethylenediamine chloride], and SODm plus glibenclamide to study the protective effect of hydrogen peroxide via dismutation of superoxide on the activation of sarcolemmal potassium channels. In the PBS group, there was an overshoot of tissue Po2 after reperfusion. Treatment with SODm, EUK134, and SODm + glibenclamide protected mitochondrial enzyme activities, reduced infarct size, and suppressed the post-ischemic hyperoxygenation. In particular, in the SODm-treated group, there was a transient peak of tissue Po2 at 9 min after reperfusion, which was dependent on endogenous hydrogen peroxide but not nitric oxide formation as it appeared in both WT and eNOS?/? mice. Blood flow and rate pressure product were higher in the SODm group than in other groups, which contributed to the transient oxygen peak. Thus, SOD mimetics protected mouse heart from superoxide-induced reperfusion injury. With treatment of different SOD mimetics, it is concluded that endogenous hydrogen peroxide via dismutation of superoxide at reperfusion enhances postischemic myocardial blood perfusion and mitochondrial oxygen consumption, possibly through activation of sarcolemmal ATP-sensitive potassium channels.

Xu, Yi; Liu, Bin; Zweier, Jay L.; He, Guanglong

2008-01-01

245

Formation of hydrogen peroxide and reduction of peroxynitrite via dismutation of superoxide at reperfusion enhances myocardial blood flow and oxygen consumption in postischemic mouse heart.  

PubMed

Reactive oxygen/nitrogen species suppress myocardial oxygen consumption. In this study, we determined that endogenous hydrogen peroxide through dismutation of superoxide enhances postischemic myocardial blood perfusion and oxygen consumption. Electron paramagnetic resonance oximetry was applied to monitor in vivo tissue Po2 in mouse heart subjected to regional ischemia reperfusion. Heart rate, arterial blood pressure, blood flow, infarction, and activities of mitochondrial NADH dehydrogenase and cytochrome c oxidase were measured in six groups of wild-type (WT) and endothelial nitricoxide synthase knock-out (eNOS(-/-)) mice treated with phosphate-buffered saline (PBS), superoxide dismutase mimetic (SOD(m)) M40403 [a manganese(II)-bis(cyclohexylpyridine)-substituted macrocyclic superoxide dismutase mimetic, C21H35Cl2MnN5], 10006329 EUK 134 [EUK134, manganese 3-methoxy N,N(1)-bis(salicyclidene)ethylenediamine chloride], and SOD(m) plus glibenclamide to study the protective effect of hydrogen peroxide via dismutation of superoxide on the activation of sarcolemmal potassium channels. In the PBS group, there was an overshoot of tissue Po2 after reperfusion. Treatment with SOD(m), EUK134, and SOD(m) + glibenclamide protected mitochondrial enzyme activities, reduced infarct size, and suppressed the postischemic hyperoxygenation. In particular, in the SOD(m)-treated group, there was a transient peak of tissue Po2 at 9 min after reperfusion, which was dependent on endogenous hydrogen peroxide but not nitric oxide formation as it appeared in both WT and eNOS(-/-) mice. Blood flow and rate pressure product were higher in the SOD(m) group than in other groups, which contributed to the transient oxygen peak. Thus, SOD mimetics protected mouse heart from superoxide-induced reperfusion injury. With treatment of different SOD mimetics, it is concluded that endogenous hydrogen peroxide via dismutation of superoxide at reperfusion enhances postischemic myocardial blood perfusion and mitochondrial oxygen consumption, possibly through activation of sarcolemmal ATP-sensitive potassium channels. PMID:18685120

Xu, Yi; Liu, Bin; Zweier, Jay L; He, Guanglong

2008-11-01

246

Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model  

PubMed Central

Reperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia–reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twenty-four hours after transplant, the kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen and creatinine compared with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine: P < 0·001 versus control]. A further decrease was observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was decreased significantly in donors treated with immunosuppressants compared with the control group (P < 0·001 versus control). Moreover, the number of apoptotic nuclei in the control group was higher compared with the treated groups (P < 0·001 versus control). Surprisingly, only rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory cytokines, such as tumour necrosis factor (TNF)-? and interleukin (IL)-6, showed lower levels in the graft of those animals that had been pretreated with rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.

Cicora, F; Roberti, J; Vasquez, D; Guerrieri, D; Lausada, N; Cicora, P; Palti, G; Chuluyan, E; Gonzalez, P; Stringa, P; Raimondi, C

2012-01-01

247

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

PubMed Central

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

Saga, Norio; Katamoto, Shizuo; Naito, Hisashi

2008-01-01

248

Hypoxia preconditioned bone marrow mesenchymal stem cells promote liver regeneration in a rat massive hepatectomy model  

PubMed Central

Introduction Bone marrow mesenchymal stem cells (BMMSCs) have been reported to facilitate liver regeneration after toxic injuries. However, the effect of BMMSCs on liver regeneration after massive hepatectomy is barely studied. Here we explored whether infusion of BMMSCs promotes liver regeneration in a rat massive hepatectomy model. Methods Hypoxia preconditioning was achieved by culturing BMMSCs under a hypoxia environment. Then 85% hepatectomy was performed and hypoxia or normoxia preconditioned BMMSCs were infused into the portal vein. A group of rats received vascular endothelial growth factor (VEGF) neutralizing antibody perioperatively, and underwent 85% hepatectomy and a subsequent infusion of hypoxia preconditioned BMMSCs to verify the role of VEGF in the effects of BMMSCs on liver regeneration. Liver samples were collected and liver regeneration was evaluated postoperatively. Results Hypoxia preconditioning enhanced the expression of VEGF in BMMSCs in vitro. Infusion of BMMSCs promoted proliferation of hepatocytes, reflected by elevated cyclin D1 expression and proliferating cell nuclear antigen-positive hepatocytes. However, BMMSC infusion did not improve the serum albumin level, liver weight/body weight ratio, and survival after operation. Infusion of hypoxia preconditioned BMMSCs significantly elevated cyclin D1, proliferating cell nuclear antigen-positive hepatocytes, liver weight/body weight ratio, and survival compared with normoxia preconditioned BMMSCs, accompanied by an increased serum albumin level. The level of VEGF in liver homogenate was much higher in hypoxia preconditioned BMMSC-treated animals than in other groups. In addition, the perioperative injection of VEGF neutralizing antibody significantly blocked the therapeutic effects of hypoxia preconditioned BMMSCs on liver injury and regeneration in this model. Conclusion Hypoxia preconditioned BMMSCs enhanced liver regeneration after massive hepatectomy in rats, possibly by upregulating the level of VEGF.

2013-01-01

249

Effects of R 56865 on postischemic ventricular function in isolated rat working heart preparations obtained from healthy, diabetic and hypertensive animals  

Microsoft Academic Search

The present study was undertaken to evaluate the effects of R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl-N-methyl-2-benzothiazolamine)\\u000a (Fig. 1) on postischemic ventricular function, an inhibitor of the Na+\\/Ca2+ overload, in the working heart preparation of the rat. The hearts were paced at 5 Hz and perfused with Tyrode solution of\\u000a 37°C at a physiological pH.\\u000a \\u000a After 15 min of pretreatment with R 56865, low-flow

A. J. Pijl; M. G. C. Hendriks; K. L. Kam; M. Paffendorf; P. A. van Zwieten

1994-01-01

250

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.

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

2014-01-01

251

Diabetic Inhibition of Preconditioning- and Postconditioning-Mediated Myocardial Protection against Ischemia/Reperfusion Injury  

PubMed Central

Ischemic preconditioning (IPC) or postconditioning (Ipost) is proved to efficiently prevent ischemia/reperfusion injuries. Mortality of diabetic patients with acute myocardial infarction was found to be 2–6 folds higher than that of non-diabetic patients with same myocardial infarction, which may be in part due to diabetic inhibition of IPC- and Ipost-mediated protective mechanisms. Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3? pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3? pathway. Therefore, this review briefly introduced the general features of IPC- and Ipost-mediated myocardial protection and the general pathogenic effects of diabetes on the myocardium. We have collected experimental evidence that indicates the diabetic inhibition of IPC- and Ipost-mediated myocardial protection. Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3? pathway. Therefore any strategy to activate PI3K/Akt and associated GSK-3? pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries.

Yin, Xia; Zheng, Yang; Zhai, Xujie; Zhao, Xin; Cai, Lu

2012-01-01

252

Effects of targeted deletion of A1 adenosine receptors on postischemic cardiac function and expression of adenosine receptor subtypes.  

PubMed

To examine ischemic tolerance in the absence of A(1) adenosine receptors (A(1)ARs), isolated wild-type (WT) and A(1)AR knockout (A(1)KO) murine hearts underwent global ischemia-reperfusion, and injury was measured in terms of functional recovery and efflux of lactate dehydrogenase (LDH). Hearts were analyzed by real-time RT-PCR both at baseline and at intervals during ischemia-reperfusion to determine whether compensatory expression of other adenosine receptor subtypes occurs with either A(1)AR deletion and/or ischemia-reperfusion. A(1)KO hearts had higher baseline coronary flow (CF) and left ventricular developed pressure (LVDP) than WT hearts, whereas heart rate was unchanged by A(1)AR deletion. After 20 min of ischemia, CF was attenuated in A(1)KO compared with WT hearts, and this reduction persisted throughout reperfusion. Final recovery of LVDP was decreased in A(1)KO hearts (54.4 +/- 5.1 vs. WT 81.1 +/- 3.4% preischemic baseline) and correlated with higher diastolic pressure during reperfusion. Postischemic efflux of LDH was greater in A(1)KO compared with WT hearts. Real-time RT-PCR demonstrated the absence of A(1)AR transcript in A(1)KO hearts, and the message for A(2A), A(2B), and A(3) adenosine receptors was similar in uninstrumented A(1)KO and WT hearts. Ischemia-reperfusion increased A(2B) mRNA expression 2.5-fold in both WT and A(1)KO hearts without changing A(1) or A(3) expression. In WT hearts, ischemia transiently doubled A(2A) mRNA, which returned to preischemic level upon reperfusion, a pattern not observed in A(1)KO hearts. Together, these data affirm the cardioprotective role of A(1)ARs and suggest that induced expression of other adenosine receptor subtypes may participate in the response to ischemia-reperfusion in isolated murine hearts. PMID:16679400

Morrison, R Ray; Teng, Bunyen; Oldenburg, Peter J; Katwa, Laxmansa C; Schnermann, Jurgen B; Mustafa, S Jamal

2006-10-01

253

Absence of glutathione peroxidase-1 exacerbates cerebral ischemia-reperfusion injury by reducing post-ischemic microvascular perfusion.  

PubMed

Mice deficient in the anti-oxidant enzyme glutathione peroxidase-1 (Gpx1) have a greater susceptibility to cerebral injury following a localized ischemic event. Much of the response to ischemia-reperfusion is caused by aberrant responses within the microvasculature, including inflammation, diminished endothelial barrier function (increased vascular permeability), endothelial activation, and reduced microvascular perfusion. However, the role of Gpx1 in regulating these responses has not been investigated. Wild-type and Gpx1-/- mice underwent focal cerebral ischemia via mid-cerebral artery occlusion followed by measurement of cerebral perfusion via laser Doppler and intravital microscopy. Post-ischemic brains in wild-type mice displayed significant deficit in microvascular perfusion. However, in Gpx1-/- mice, the deficit in cerebral blood flow was significantly greater than that in wild-type mice, and this was associated with significant increase in infarct size and increased vascular permeability. Ischemia-reperfusion also resulted in expression of matrix metalloproteinase-9 (MMP-9) in endothelial cells. The absence of Gpx1 was associated with marked increase in pro-MMP-9 expression as well as potentiated MMP-9 activity. Pre-treatment of Gpx1-/- mice with the anti-oxidant ebselen restored microvascular perfusion, limited the induction and activation of MMP-9, and attenuated the increases in infarct size and vascular permeability. These findings demonstrate that the anti-oxidant function of Gpx1 plays a critical role in protecting the cerebral microvasculature against ischemia-reperfusion injury by preserving microvascular perfusion and inhibiting MMP-9 expression. PMID:18691391

Wong, Connie H Y; Bozinovski, Steven; Hertzog, Paul J; Hickey, Michael J; Crack, Peter J

2008-10-01

254

Chronic Valproate Treatment Enhances Post-ischemic Angiogenesis and Promotes Functional Recovery in a Rat Model of Ischemic Stroke  

PubMed Central

Background and Purpose Enhanced angiogenesis facilitates neurovascular remodeling processes and promotes brain functional recovery after stroke. Previous studies from our laboratory demonstrated that valproate (VPA), a histone deacetylase (HDAC) inhibitor, protects against experimental brain ischemia. The present study investigated whether VPA could enhance angiogenesis and promote long-term functional recovery after ischemic stroke. Methods Male rats underwent middle cerebral artery occlusion (MCAO) for 60 minutes followed by reperfusion for up to 14 days. Assessed parameters were: locomotor function via rotarod test; infarct volume via T2-weighted magnetic resonance imaging; microvessel density via immunohistochemistry; relative cerebral blood flow (rCBF) via perfusion-weighted imaging; protein levels of pro-angiogenic factors via Western blotting; and matrix metalloproteinase (MMP)-2/9 activities via gelatin zymography. Results Post-ischemic VPA treatment robustly improved the rotarod performance of MCAO rats on days 7 and 14 after ischemia, and significantly reduced brain infarction on day 14. Concurrently, VPA markedly enhanced microvessel density, facilitated endothelial cell proliferation, and increased rCBF in the ipsilateral cortex. The transcription factor hypoxia-inducible factor (HIF)-1? and its downstream pro-angiogenic factors, vascular endothelial growth factor (VEGF) and MMP-2/9, were upregulated after MCAO and significantly potentiated by VPA in the ipsilateral cortex. Acetylation of histone-H3 and H4 was robustly increased by chronic VPA treatment. The beneficial effects of VPA on rotarod performance and microvessel density were abolished by HIF-1? inhibition. Conclusions Chronic VPA treatment enhances angiogenesis and promotes functional recovery after brain ischemia. These effects may involve HDAC inhibition and upregulation of HIF-1? and its downstream pro-angiogenic factors VEGF and MMP-2/9.

Wang, Zhifei; Tsai, Li-Kai; Munasinghe, Jeeva; Leng, Yan; Fessler, Emily Bame; Chibane, Fairouz; Leeds, Peter; Chuang, De-Maw

2012-01-01

255

Hyperbaric oxygen preconditioning protects against traumatic brain injury at high altitude  

Microsoft Academic Search

\\u000a \\u000a Background  Recent studies have shown that preconditioning with hyperbaric oxygen (HBO) can reduce ischemic and hemorrhagic brain injury.\\u000a We investigated effects of HBO preconditioning on traumatic brain injury (TBI) at high altitude and examined the role of matrix\\u000a metalloproteinase-9 (MMP-9) in such protection.\\u000a \\u000a \\u000a \\u000a Methods  Rats were randomly divided into 3 groups: HBO preconditioning group (HBOP; n=13), high-altitude group (HA; n=13), and high-altitude

S. L. Hu; R. Hu; F. Li; Z. Liu; Y. Z. Xia; G. Y. Cui; H. Feng

256

Characteristic time-stepping or local preconditioning of the Euler equations  

NASA Technical Reports Server (NTRS)

A derivation is presented of a local preconditioning matrix for multidimensional Euler equations, that reduces the spread of the characteristic speeds to the lowest attainable value. Numerical experiments with this preconditioning matrix are applied to an explicit upwind discretization of the two-dimensional Euler equations, showing that this matrix significantly increases the rate of convergence to a steady solution. It is predicted that local preconditioning will also simplify convergence-acceleration boundary procedures such as the Karni (1991) procedure for the far field and the Mazaheri and Roe (1991) procedure for a solid wall.

Van Leer, Bram; Lee, Wen-Tzong; Roe, Philip L.

1991-01-01

257

Characteristic time-stepping or local preconditioning of the Euler equations  

NASA Astrophysics Data System (ADS)

A derivation is presented of a local preconditioning matrix for multidimensional Euler equations, that reduces the spread of the characteristic speeds to the lowest attainable value. Numerical experiments with this preconditioning matrix are applied to an explicit upwind discretization of the two-dimensional Euler equations, showing that this matrix significantly increases the rate of convergence to a steady solution. It is predicted that local preconditioning will also simplify convergence-acceleration boundary procedures such as the Karni (1991) procedure for the far field and the Mazaheri and Roe (1991) procedure for a solid wall.

van Leer, Bram; Lee, Wen-Tzong; Roe, Philip L.

258

Postischemic alterations of BDNF, NGF, HSP 70 and ubiquitin immunoreactivity in the gerbil hippocampus: pharmacological approach.  

PubMed

1. We investigated the immunohistochemical alterations of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus 1 h to 14 days after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor pitavastatin against the changes of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus after cerebral ischemia in the hippocampus after ischemia. 2. The transient cerebral ischemia was carried out by clamping the carotid arteries with aneurismal clips for 5 min. 3. In the present study, the alteration of HSP 70 and ubiquitin immunoreactivity in the hippocampal CA1 sector was more pronounced than that of BDNF and NGF immunoreactivity after transient cerebral ischemia. In double-labeled immunostainings, BDNF, NGF and ubiquitin immunostaining was observed both in GFAP-positive astrocytes and MRF-1-positive microglia in the hippocampal CA1 sector after ischemia. Furthermore, prophylactic treatment with pitavastatin prevented the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after ischemia. 4. These findings suggest that the expression of stress protein including HSP 70 and ubiquitin may play a key role in the protection against the hippocampal CA1 neuronal damage after transient cerebral ischemia in comparison with the expression of neurotrophic factor such as BDNF and NGF. The present findings also suggest that the glial BDNF, NGF and ubiquitin may play some role for helping surviving neurons after ischemia. Furthermore, our present study indicates that prophylactic treatment with pitavastatin can prevent the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after transient cerebral ischemia. Thus our study provides further valuable information for the pathogenesis after transient cerebral ischemia. PMID:16810563

Himeda, Toshiki; Tounai, Hiroko; Hayakawa, Natsumi; Araki, Tsutomu

2007-03-01

259

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.

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

2012-01-01

260

Differential Effects of Delta and Epsilon Protein Kinase C in Modulation of Postischemic Cerebral Blood Flow  

PubMed Central

Cerebral ischemia causes cerebral blood flow (CBF) derangements resulting in neuronal damage by enhanced protein kinase C delta (?PKC) levels leading to hippocampal and cortical neuronal death after ischemia. Contrarily, activation of ?PKC mediates ischemic tolerance by decreasing vascular tone providing neuroprotection. However, whether part of this protection is due to the role of differential isozymes of PKCs on CBF following cerebral ischemia remains poorly understood. Rats pretreated with a ?PKC specific inhibitor (?V1-1, 0.5 mg/kg) exhibited attenuation of hyperemia and latent hypoperfusion characterized by vasoconstriction followed by vasodilation of microvessels after two-vessel occlusion plus hypotension. In an asphyxial cardiac arrest (ACA) model, rats treated with ? V1-1 (pre- and postischemia) exhibited improved perfusion after 24 h and less hippocampal CA1 and cortical neuronal death 7 days after ACA. On the contrary, ?PKC-selective peptide activator, conferred neuroprotection in the CA1 region of the rat hippocampus 30 min before induction of global cerebral ischemia and decreased regional CBF during the reperfusion phase. These opposing effects of ? v. ?PKC suggest a possible therapeutic potential by modulating CBF preventing neuronal damage after cerebral ischemia.

Lin, Hung Wen; Della-Morte, David; Thompson, John W.; Gresia, Victoria L.; Narayanan, Srinivasan V.; DeFazio, R. Anthony; Raval, Ami P.; Saul, Isabel; Dave, Kunjan R.; Morris, Kahlilia C.; Si, Min-Liang

2014-01-01

261

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

262

On the Superlinear Convergence Rate of the Preconditioned CGM for Some Nonsymmetric Elliptic Problems  

Microsoft Academic Search

Earlier estimates on the superlinear convergence of the preconditioned conjugate gradient method are completed using singular values of compact operators. Suitable domain independence and an explicit estimate of the magnitude of superlinear convergence are derived.

J. Karátson

2007-01-01

263

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

SciTech Connect

The iterative diagonalization of a sequence of large ill-conditioned generalized eigenvalue problems is a computational bottleneck in quantum mechanical methods employing a nonorthogonal basis for ab initio electronic structure calculations. We propose a hybrid preconditioning scheme to effectively combine global and locally accelerated preconditioners for rapid iterative diagonalization of such eigenvalue problems. In partition-of-unity finite-element (PUFE) pseudopotential density-functional calculations, employing a nonorthogonal basis, we show that the hybrid preconditioned block steepest descent method is a cost-effective eigensolver, outperforming current state-of-the-art global preconditioning schemes, and comparably efficient for the ill-conditioned generalized eigenvalue problems produced by PUFE as the locally optimal block preconditioned conjugate-gradient method for the well-conditioned standard eigenvalue problems produced by planewave methods.

Cai, Yunfeng, E-mail: yfcai@math.pku.edu.cn [LMAM and School of Mathematical Sciences, Peking University, Beijing 100871 (China) [LMAM and School of Mathematical Sciences, Peking University, Beijing 100871 (China); Department of Computer Science, University of California, Davis 95616 (United States); Bai, Zhaojun, E-mail: bai@cs.ucdavis.edu [Department of Computer Science and Department of Mathematics, University of California, Davis 95616 (United States)] [Department of Computer Science and Department of Mathematics, University of California, Davis 95616 (United States); Pask, John E., E-mail: pask1@llnl.gov [Condensed Matter and Materials Division, Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Sukumar, N., E-mail: nsukumar@ucdavis.edu [Department of Civil and Environmental Engineering, University of California, Davis 95616 (United States)

2013-12-15

264

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.

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

265

Energi 2000 - opfoelgningen. Forudsaetninger og beregninger. (Energy 2000 - the followup. Preconditions and calculations).  

National Technical Information Service (NTIS)

A summary of the preconditions involved in the production of the Danish Ministry of Energy's publication of ''Energi-2000 - opfoelgningen'' (Energy 2000 - the followup) wherein specific initiatives are evaluated. A number of the results of calculations ma...

1993-01-01

266

40 CFR 85.2219 - Idle test with loaded preconditioning-EPA 91.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 2013-07-01 false Idle test with loaded preconditioning-EPA 91. 85.2219...Emission Control System Performance Warranty Short Tests § 85.2219 Idle test with loaded preconditioningâEPA 91. (a)...

2013-07-01

267

Preconditioned Iterative Methods for Nonselfadjoint or Indefinite Elliptic Boundary Value Problems.  

National Technical Information Service (NTIS)

We consider a Galerkin-Finite Element approximation to a general linear elliptic boundary value problem which may be nonselfadjoint or indefinite. We show how to precondition the equations so that the resulting systems of linear algebraic equations lead t...

J. H. Bramble J. E. Pasciak

1984-01-01

268

Spatiotemporal characteristics of postischemic hyperperfusion with respect to changes in T1, T2, diffusion, angiography, and blood-brain barrier permeability  

PubMed Central

The spatiotemporal dynamics of postischemic hyperperfusion (HP) remains incompletely understood. Diffusion, perfusion, T2, T1, angiographic, dynamic susceptibility-contrast magnetic resonance imaging (MRI) and magnetic resonance angiography were acquired longitudinally at multiple time points up to 7 days after stroke in rats subjected to 30-, 60-, and 90-minutes middle cerebral artery occlusion (MCAO). The spatiotemporal dynamics of postischemic HP was analyzed and compared with T1, T2 and blood–brain barrier (BBB) changes. No early HP within 3?hours after recanalization was observed. Late (?12?hours) HP was present in all animals of the 30-minute MCAO group (N=20), half of the animals in the 60-minute MCAO group (N=8), and absent in the 90-minute MCAO group (N=9). Dynamic susceptibility-contrast MRI and magnetic resonance angiography corroborated HP. Hyperperfusion preceded T2 increase in some animals, but HP and T2 changes temporally coincided in others. T2 peaked first at 24?hours whereas HP peaked at 48?hours after occlusion, and HP resolved by day 7 in most animals at which point the arteries became tortuous. Pixel-by-pixel tracking analysis showed that tissue did not infarct (migrated from core or mismatch at 30?minutes to normal at 48?hours) showed normal cerebral blood flow (CBF), whereas infarct tissue (migrated from core or mismatch at 30?minutes to infarct at 48?hours) showed exaggerated CBF, indicating that HP was associated with poor outcome.

Shen, Qiang; Du, Fang; Huang, Shiliang; Duong, Timothy Q

2011-01-01

269

POSSIBLE ROLE OF ADRENERGIC COMPONENT AND CARDIAC MAST CELL DEGRANULATION IN PRECONDITIONING-INDUCED CARDIOPROTECTION  

Microsoft Academic Search

The present study was designed to investigate the role of adrenergic component and cardiac mast cell degranulation in the cardioprotective effect of ischaemic preconditioning. Isolated rat hearts were subjected to 30 min of global ischaemia followed by 30 min of reperfusion. Ischaemic\\/norepinephrine (100 ?m) preconditioning markedly reduced ischaemia–reperfusion-induced release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent

VINAY PARIKH; MANJEET SINGH

1999-01-01

270

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

271

A hybrid time-stepping method of local preconditioning on high aspect ratio grids  

Microsoft Academic Search

Time-derivative preconditioning methods have provided robust convergences and accurate solutions for low-speed inviscid flows\\u000a by using local flow properties as the reference scaling parameter in the preconditioning matrix. During viscous or turbulent\\u000a flow calculations, the use of high aspect ratio grids to obtain accurate solutions near the wall often results in stiff convergence\\u000a and nonphysical solutions in the singular regions.

Jae Eun Lee; Yoonsik Kim; Jang Hyuk Kwon

2011-01-01

272

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

273

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

PubMed

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

Xu, Kui; Lamanna, Joseph C

2014-01-01

274

Cardioprotection by multiple preconditioning cycles does not require mitochondrial K(ATP) channels in pigs.  

PubMed

To test whether cardioprotection induced by ischemic preconditioning depends on the opening of mitochondrial ATP-sensitive K(+) (K(ATP)) channels, the effect of channel blockade was studied in barbital-anesthetized open-chest pigs subjected to 30 min of complete occlusion of the left anterior descending coronary artery and 3 h of reflow. Preconditioning was elicited by two cycles of 5-min occlusion plus 10-min reperfusion before the 30-min occlusion period. 5-Hydroxydecanoate (5 mg/kg iv) was injected 15 min before preconditioning or pharmacological preconditioning induced by diazoxide (3.5 mg/kg, 1 ml/min iv). Infarct size (percentage of the area at risk) after 30 min of ischemia was 35.1 +/- 9.9% (n = 7). Preconditioning markedly limited myocardial infarct size (2.7 +/- 1.6%, n = 7), and 5-hydroxydecanoate did not abolish protection (2.4 +/- 0.9%, n = 8). Diazoxide infusion also significantly limited infarct size (14.6 +/- 7.4%, n = 7), and 5-hydroxydecanoate blocked this effect (30.8 +/- 8.0%, n = 7). Thus the opening of mitochondrial K(ATP) channels is cardioprotective in pigs, but these data do not support the hypothesis that opening of mitochondrial K(ATP) channels is required for the endogenous protection afforded by preconditioning. PMID:12234807

Schwartz, Lisa M; Welch, Timothy S; Crago, Mark S

2002-10-01

275

Preconditioned 70S30C bioactive glass foams promote osteogenesis in vivo.  

PubMed

Bioactive glass scaffolds (70S30C; 70% SiO2 and 30% CaO) produced by a sol-gel foaming process are thought to be suitable matrices for bone tissue regeneration. Previous in vitro data showed bone matrix production and active remodelling in the presence of osteogenic cells. Here we report their ability to act as scaffolds for in vivo bone regeneration in a rat tibial defect model, but only when preconditioned. Pretreatment methods (dry, pre-wetted or preconditioned without blood) for the 70S30C scaffolds were compared against commercial synthetic bone grafts (NovaBone® and Actifuse®). Poor bone ingrowth was found for both dry and wetted sol-gel foams, associated with rapid increase in pH within the scaffolds. Bone ingrowth was quantified through histology and novel micro-CT image analysis. The percentage bone ingrowth into dry, wetted and preconditioned 70S30C scaffolds at 11 weeks were 10±1%, 21±2% and 39±4%, respectively. Only the preconditioned sample showed above 60% material-bone contact, which was similar to that in NovaBone and Actifuse. Unlike the commercial products, preconditioned 70S30C scaffolds degraded and were replaced with new bone. The results suggest that bioactive glass compositions should be redesigned if sol-gel scaffolds are to be used without preconditioning to avoid excess calcium release. PMID:23891811

Midha, Swati; Kim, Taek Bo; van den Bergh, Wouter; Lee, Peter D; Jones, Julian R; Mitchell, Christopher A

2013-11-01

276

Simple preconditioning for time-dependent density functional perturbation theory  

NASA Astrophysics Data System (ADS)

By far, the most common use of time-dependent density functional theory is in the linear-reponse regime, where it provides information about electronic excitations. Ideally, the linear-response equations should be solved by a method that avoids the use of the unoccupied Kohn-Sham states -- such as the Sternheimer method -- as this reduces the complexity and increases the precision of the calculation. However, the Sternheimer equation becomes ill-conditioned near and indefinite above the first resonant frequency, seriously hindering the use of efficient iterative solution methods. To overcome this serious limitation, and to improve the general convergence properties of the iterative techniques, we propose a simple preconditioning strategy. In our method, the Sternheimer equation is solved directly as a linear equation using an iterative Krylov subspace method, i.e., no self-consistent cycle is required. Furthermore, the preconditioner uses the information of just a few unoccupied states and requires simple and minimal modifications to existing implementations. In this way, convergence can be reached faster and in a considerably wider frequency range than the traditional approach.

Lehtovaara, Lauri; Marques, Miguel A. L.

2011-07-01

277

Remote Ischemic Preconditioning (RIPC) Modifies Plasma Proteome in Humans  

PubMed Central

Remote Ischemic Preconditioning (RIPC) induced by brief episodes of ischemia of the limb protects against multi-organ damage by ischemia-reperfusion (IR). Although it has been demonstrated that RIPC affects gene expression, the proteomic response to RIPC has not been determined. This study aimed to examine RIPC induced changes in the plasma proteome. Five healthy adult volunteers had 4 cycles of 5 min ischemia alternating with 5 min reperfusion of the forearm. Blood samples were taken from the ipsilateral arm prior to first ischaemia, immediately after each episode of ischemia as well as, at 15 min and 24 h after the last episode of ischemia. Plasma samples from five individuals were analysed using two complementary techniques. Individual samples were analysed using 2Dimensional Difference in gel electrophoresis (2D DIGE) and mass spectrometry (MS). Pooled samples for each of the time-points underwent trypsin digestion and peptides generated were analysed in triplicate using Liquid Chromatography and MS (LC-MS). Six proteins changed in response to RIPC using 2D DIGE analysis, while 48 proteins were found to be differentially regulated using LC-MS. The proteins of interest were involved in acute phase response signalling, and physiological molecular and cellular functions. The RIPC stimulus modifies the plasma protein content in blood taken from the ischemic arm in a cumulative fashion and evokes a proteomic response in peripheral blood.

Hepponstall, Michele; Ignjatovic, Vera; Binos, Steve; Monagle, Paul; Jones, Bryn; Cheung, Michael H. H.; d'Udekem, Yves; Konstantinov, Igor E.

2012-01-01

278

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

279

Positive Indian Ocean Dipole events precondition southeast Australia bushfires  

NASA Astrophysics Data System (ADS)

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

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

2009-10-01

280

Remote ischemic preconditioning in patients with intermittent claudication  

PubMed Central

OBJECTIVE: Remote ischemic preconditioning (RIPC) is a phenomenon in which a short period of sub-lethal ischemia in one organ protects against subsequent bouts of ischemia in another organ. We hypothesized that RIPC in patients with intermittent claudication would increase muscle tissue resistance to ischemia, thereby resulting in an increased ability to walk. METHODS: In a claudication clinic, 52 ambulatory patients who presented with complaints of intermittent claudication in the lower limbs associated with an absent or reduced arterial pulse in the symptomatic limb and/or an ankle-brachial index <0.90 were recruited for this study. The patients were randomly divided into three groups (A, B and C). All of the patients underwent two tests on a treadmill according to the Gardener protocol. Group A was tested first without RIPC. Group A was subjected to RIPC prior to the second treadmill test. Group B was subjected to RIPC prior to the first treadmill test and then was subjected to a treadmill test without RIPC. In Group C (control group), both treadmill tests were performed without RIPC. The first and second tests were conducted seven days apart. Brazilian Clinical Trials: RBR-7TF6TM. RESULTS: Group A showed a significant increase in the initial claudication distance in the second test compared to the first test. CONCLUSION: RIPC increased the initial claudication distance in patients with intermittent claudication; however, RIPC did not affect the total walking distance of the patients.

Saes, Glauco Fernandes; Zerati, Antonio Eduardo; Wolosker, Nelson; Ragazzo, Luciana; Rosoky, Ruben Miguel Ayzin; Ritti-Dias, Raphael Mendes; Cucato, Gabriel Grizzo; Chehuen, Marcelo; Farah, Breno Quintella; Puech-Leao, Pedro

2013-01-01

281

Sca1 Stem Cell Survival and Engraftment in the Infarcted Heart Dual Role for Preconditioning-Induced Connexin43  

Microsoft Academic Search

Background—We report that elevated connexin-43 (Cx-43) in stem cells preconditioned with insulin-like growth factor-1 (IGF-1) is cytoprotective and reprograms the cells for cardiomyogenic differentiation. Methods and Results—Sca-1 cells were preconditioned with 100 nmol\\/L IGF-1 for 30 minutes followed by 8 hours of oxygen glucose deprivation to assess the cytoprotective effects of preconditioning. LDH release assay, cytochrome c release, and mitochondrial

Gang Lu; Husnain K. Haider; Shujia Jiang; Muhammad Ashraf

282

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

PubMed

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

Khan, Mohsin; Ali, Fatima; Mohsin, Sadia; Akhtar, Shoaib; Mehmood, Azra; Choudhery, Mahmood S; Khan, Shaheen N; Riazuddin, Sheikh

2013-05-24

283

Myocardial protection by interferon-? late preconditioning during cardiopulmonary bypass?associated myocardial ischemia-reperfusion in pigs.  

PubMed

The impact of interferon-? (IFN-?) late preconditioning on myocardial ischemia-reperfusion injury during cardiopulmonary bypass (CPB) and the underlying mechanism were investigated. Using a porcine model of myocardial ischemia-reperfusion injury during CPB with a 60-min aorta cross-clamp, 20 pigs (15±0.5 kg) were treated randomly with either a 1-ml (20,000 IU/kg) IFN-? injection (IFN-? group; n=10) or saline solution (control group; n=10) 24 h prior to CPB. Heart rate, blood pressure, left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), creatine kinase isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) were measured before CPB, before aortic clamping, and at post-reperfusion intervals of 10, 30, 60 and 120 min. Heat shock protein 70 (HSP70), Mn-superoxide dismutase (Mn-SOD) and inducible nitric oxide synthase (iNOS) were measured by immunohistochemical staining in pre-CPB myocardial tissues. Myocardial cell apoptosis TUNEL measurement was assessed in samples obtained 60 min following reperfusion. Both groups exhibited no statistical differences in age, weight, gender and preoperative cardiac function, and worsened left ventricular function, and hemodynamic index reductions, and significant cTnI and CK-MB leakage was observed 10 and 30 min after reperfusion. At 10, 30 and 60 min following reperfusion, ventricular function and leakage of the IFN-? group were significantly improved, and expression of HSP70, iNOS and Mn-SOD increased and myocardial cell apoptosis decreased. IFN-? late preconditioning exhibited preventative effects on myocardial tissues in pigs during CPB surgery, likely due to increased HSP70, Mn-SOD and iNOS expression. PMID:24002640

Yan, Xiangang; Qiu, Wanshan; Jia, Bing; Zhong, Hui; Li, Xin; Chen, Zhanggen

2013-11-01

284

Protection against acetaminophen-induced liver injury by allopurinol is dependent on aldehyde oxidase-mediated liver preconditioning.  

PubMed

Acetaminophen (APAP) overdose causes severe and occasionally fatal liver injury. Numerous drugs that attenuate APAP toxicity have been described. However these compounds frequently protect by cytochrome P450 inhibition, thereby preventing the initiating step of toxicity. We have previously shown that pretreatment with allopurinol can effectively protect against APAP toxicity, but the mechanism remains unclear. In the current study, C3HeB/FeJ mice were administered allopurinol 18h or 1h prior to an APAP overdose. Administration of allopurinol 18h prior to APAP overdose resulted in an 88% reduction in liver injury (serum ALT) 6h after APAP; however, 1h pretreatment offered no protection. APAP-cysteine adducts and glutathione depletion kinetics were similar with or without allopurinol pretreatment. The phosphorylation and mitochondrial translocation of c-jun-N-terminal-kinase (JNK) have been implicated in the progression of APAP toxicity. In our study we showed equivalent early JNK activation (2h) however late JNK activation (6h) was attenuated in allopurinol treated mice, which suggests that later JNK activation is more critical for the toxicity. Additional mice were administered oxypurinol (primary metabolite of allopurinol) 18h or 1h pre-APAP, but neither treatment protected. This finding implicated an aldehyde oxidase (AO)-mediated metabolism of allopurinol, so mice were treated with hydralazine to inhibit AO prior to allopurinol/APAP administration, which eliminated the protective effects of allopurinol. We evaluated potential targets of AO-mediated preconditioning and found increased hepatic metallothionein 18h post-allopurinol. These data show metabolism of allopurinol occurring independent of P450 isoenzymes preconditions the liver and renders the animal less susceptible to an APAP overdose. PMID:24345528

Williams, C David; McGill, Mitchell R; Lebofsky, Margitta; Bajt, Mary Lynn; Jaeschke, Hartmut

2014-02-01

285

Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats  

PubMed Central

Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-? levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity.

Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa

2013-01-01

286

Beneficial effects of ischemic preconditioning on pancreas cold preservation.  

PubMed

Ischemic preconditioning (IPC) confers tissue resistance to subsequent ischemia in several organs. The protective effects are obtained by applying short periods of warm ischemia followed by reperfusion prior to extended ischemic insults to the organs. In the present study, we evaluated whether IPC can reduce pancreatic tissue injury following cold ischemic preservation. Rat pancreata were exposed to IPC (10 min of warm ischemia followed by 10 min of reperfusion) prior to ~18 h of cold preservation before assessment of organ injury or islet isolation. Pancreas IPC improved islet yields (964 ± 336 vs. 711 ± 204 IEQ/pancreas; p = 0.004) and lowered islet loss after culture (33 ± 10% vs. 51 ± 14%; p = 0.0005). Islet potency in vivo was well preserved with diabetes reversal and improved glucose clearance. Pancreas IPC reduced levels of NADPH-dependent oxidase, a source of reactive oxygen species, in pancreas homogenates versus controls (78.4 ± 45.9 vs. 216.2 ± 53.8 RLU/?g; p = 0.002). Microarray genomic analysis of pancreata revealed upregulation of 81 genes and downregulation of 454 genes (greater than twofold change) when comparing IPC-treated glands to controls, respectively, and showing a decrease in markers of apoptosis and oxidative stress. Collectively, our study demonstrates beneficial effects of IPC of the pancreas prior to cold organ preservation and provides evidence of the key role of IPC-mediated modulation of oxidative stress pathways. The use of IPC of the pancreas may contribute to increasing the quality of donor pancreas for transplantation and to improving organ utilization. PMID:22305457

Hogan, Anthony R; Doni, Marco; Molano, R Damaris; Ribeiro, Melina M; Szeto, Angela; Cobianchi, Lorenzo; Zahr-Akrawi, Elsie; Molina, Judith; Fornoni, Alessia; Mendez, Armando J; Ricordi, Camillo; Pastori, Ricardo L; Pileggi, Antonello

2012-01-01

287

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

288

Glaciations in response to climate variations preconditioned by evolving topography.  

PubMed

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

Pedersen, Vivi Kathrine; Egholm, David Lundbek

2013-01-10

289

Ex vivo acidic preconditioning enhances bone marrow ckit+ cell therapeutic potential via increased CXCR4 expression  

PubMed Central

Aims The chemokine receptor CXCR4 modulates endothelial progenitor cell migration, homing, and differentiation, and plays a key role in cardiovascular regeneration. Here we examined the effect of ex vivo acidic preconditioning (AP) on CXCR4 expression and on the regenerative potential of mouse bone marrow (BM) ckit+ cells. Methods and results Acidic preconditioning was achieved by exposing BM ckit+ cells to hypercarbic acidosis (pH 7.0) for 24 h; control cells were kept at pH 7.4. Acidic preconditioning enhanced CXCR4 and stromal cell-derived factor 1 (SDF-1) mRNA levels, as well as CXCR4 phosphorylation. Acidic preconditioning ability to modulate CXCR4 expression depended on cytosolic calcium [Ca2+]i mobilization and on nitric oxide (NO), as determined by [Ca2+]i buffering with BAPTA, and by treatment with the NO donor (DETA/NO) and the NO synthase inhibitor (L-NAME). Further, AP increased SDF-1-driven chemotaxis, transendothelial migration, and differentiation toward the endothelial lineage in vitro. In a mouse model of hindlimb ischaemia, control and AP ckit+ cells were transplanted into the ischaemic muscle; AP cells accelerated blood flow recovery, increased capillary, and arteriole number as well as the number of regenerating muscle fibres vs. control. These effects were abolished by treating AP cells with L-NAME. Conclusion Acidic preconditioning represents a novel strategy to enhance BM ckit+ cell therapeutic potential via NO-dependent increase in CXCR4 expression.

Cencioni, Chiara; Melchionna, Roberta; Straino, Stefania; Romani, Marta; Cappuzzello, Claudia; Annese, Valentina; Wu, Joseph C.; Pompilio, Giulio; Santoni, Angela; Gaetano, Carlo; Napolitano, Monica; Capogrossi, Maurizio C.

2013-01-01

290

Preconditioning Mesenchymal Stem Cells With Caspase Inhibition and Hyperoxia Prior to Hypoxia Exposure Increases Cell Proliferation  

PubMed Central

Myocardial infarction is a leading cause of mortality and morbidity worldwide. Occlusion of a coronary artery produces ischemia and myocardial necrosis that leads to left ventricular (LV) remodeling, dysfunction, and heart failure. Stem cell therapy may decrease infarct size and improve LV function; the hypoxic environment, however, following a myocardial infarction may result in apoptosis, which in turn decreases survival of transplanted stem cells. Therefore, the effects of preconditioned mesenchymal stem cells (MSC) with hyperoxia (100% oxygen), Z-VAD-FMK pan-caspase inhibitor (CI), or both in a hypoxic environment in order to mimic conditions seen in cardiac tissue post-myocardial infarction were studied in vitro. MSCs preconditioned with hyperoxia or CI significantly decreased apoptosis as suggested by TUNEL assay and Annexin V analysis using fluorescence assisted cell sorting. These effects were more profound when both, hyperoxia and CI, were used. Additionally, gene and protein expression of caspases 1, 3, 6, 7, and 9 were down-regulated significantly in MSCs preconditioned with hyperoxia, CI, or both, while the survival markers Akt1, NF-?B, and Bcl-2 were significantly increased in preconditioned MSCs. These changes ultimately resulted in a significant increase in MSC proliferation in hypoxic environment as determined by BrdU assays compared to MSCs without preconditioning. These effects may prove to be of great clinical significance when transplanting stem cells into the hypoxic myocardium of post-myocardial infarction patients in order to attenuate LV remodeling and improve LV function.

Saini, Uksha; Gumina, Richard J.; Wolfe, Brian; Kuppusamy, M. Lakshmi; Kuppusamy, Periannan; Boudoulas, Konstantinos Dean

2014-01-01

291

Analysis of physics-based preconditioning for single-phase subchannel equations  

SciTech Connect

The (single-phase) subchannel approximations are used throughout nuclear engineering to provide an efficient flow simulation because the computational burden is much smaller than for computational fluid dynamics (CFD) simulations, and empirical relations have been developed and validated to provide accurate solutions in appropriate flow regimes. Here, the subchannel equations have been recast in a residual form suitable for a multi-physics framework. The Eigen spectrum of the Jacobian matrix, along with several potential physics-based preconditioning approaches, are evaluated, and the the potential for improved convergence from preconditioning is assessed. The physics-based preconditioner options include several forms of reduced equations that decouple the subchannels by neglecting crossflow, conduction, and/or both turbulent momentum and energy exchange between subchannels. Eigen-scopy analysis shows that preconditioning moves clusters of eigenvalues away from zero and toward one. A test problem is run with and without preconditioning. Without preconditioning, the solution failed to converge using GMRES, but application of any of the preconditioners allowed the solution to converge. (authors)

Hansel, J. E.; Ragusa, J. C. [Department of Nuclear Engineering, Texas A and M University, College Station, TX 77840 (United States)] [Department of Nuclear Engineering, Texas A and M University, College Station, TX 77840 (United States); Allu, S.; Berrill, M. A.; Clarno, K. T. [Oak Ridge National Laboratory, 1 Bethel Valley Rd, Oak Ridge, TN 37831 (United States)] [Oak Ridge National Laboratory, 1 Bethel Valley Rd, Oak Ridge, TN 37831 (United States)

2013-07-01

292

Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction  

PubMed Central

Among its many biological roles, fibroblast growth factor-2 (FGF2) acutely protects the heart from dysfunction associated with ischemia/reperfusion (I/R) injury. Our laboratory has demonstrated that this is due to the activity of the low molecular weight (LMW) isoform of FGF2 and that FGF2-mediated cardioprotection relies on the activity of protein kinase C (PKC); however, which PKC isoforms are responsible for LMW FGF2-mediated cardioprotection, and their downstream targets, remain to be elucidated. To identify the PKC pathway(s) that contributes to postischemic cardiac recovery by LMW FGF2, mouse hearts expressing only LMW FGF2 (HMWKO) were bred to mouse hearts not expressing PKC? (PKC?KO) or subjected to a selective PKC? inhibitor (?V1–2) before and during I/R. Hearts only expressing LMW FGF2 showed significantly improved postischemic recovery of cardiac function following I/R (P < 0.05), which was significantly abrogated in the absence of PKC? (P < 0.05) or presence of PKC? inhibition (P < 0.05). Hearts only expressing LMW FGF2 demonstrated differences in actomyosin ATPase activity as well as increases in the phosphorylation of troponin I and T during I/R compared with wild-type hearts; several of these effects were dependent on PKC? activity. This evidence indicates that both PKC? and PKC? play a role in LMW FGF2-mediated protection from cardiac dysfunction and that PKC? signaling to the contractile apparatus is a key step in the mechanism of LMW FGF2-mediated protection against myocardial dysfunction.

Manning, Janet R.; Perkins, Sarah O.; Sinclair, Elizabeth A.; Gao, Xiaoqian; Zhang, Yu; Newman, Gilbert; Pyle, W. Glen

2013-01-01

293

Activation of ?1B-adrenoceptors contributes to intermittent hypobaric hypoxia-improved postischemic myocardial performance via inhibiting MMP-2 activation.  

PubMed

Inhibition of matrix metalloproteinases-2 (MMP-2) activation renders cardioprotection from ischemia/reperfusion (I/R) injury; however, the signaling pathways involved have not been fully understood. Intermittent hypobaric hypoxia (IHH) has been shown to enhance myocardial tolerance to I/R injury via triggering intrinsic adaptive responses. Here we investigated whether IHH protects the heart against I/R injury via the regulation of MMP-2 and how the MMP-2 is regulated. IHH (Po2 = 84 mmHg, 4-h/day, 4 wk) improved postischemic myocardial contractile performance, lactate dehydrogenase (LDH) release, and infarct size in isolated perfused rat hearts. Moreover, IHH reversed I/R-induced MMP-2 activation and release, disorders in the levels of MMP-2 regulators, peroxynitrite (ONOO(-)) and tissue inhibitor of metalloproteinase-4 (TIMP-4), and loss of the MMP-2 targets ?-actinin and troponin I. This protection was mimicked, but not augmented, by a MMP inhibitor doxycycline and lost by the ?1-adrenoceptor (AR) antagonist prazosin. Furthermore, IHH increased myocardial ?1A-AR and ?1B-AR density but not ?1D-AR after I/R. Concomitantly, IHH further enhanced the translocation of PKC epsilon (PKC?) and decreased the release of mitochondrial cytochrome c due to I/R via the activation of ?1B-AR but not ?1A-AR or ?1D-AR. IHH-conferred cardioprotection in the postischemic contractile function, LDH release, MMP-2 activation, and nitrotyrosine as well as TIMP-4 contents were mimicked but not additive by ?1-AR stimulation with phenylephrine and were abolished by an ?1B-AR antagonist chloroethylclonidine and a PKC? inhibitor PKC? V1-2. These findings demonstrate that IHH exerts cardioprotection through attenuating excess ONOO(-) biosynthesis and TIMP-4 loss and sequential MMP-2 activation via the activation of ?1B-AR/PKC? pathway. PMID:24705558

Gao, Ling; Chen, Le; Lu, Zhi-Zhen; Gao, Hong; Wu, Lan; Chen, Yi-Xiong; Zhang, Cai-Mei; Jiang, Yu-Kun; Jing, Qing; Zhang, You-Yi; Yang, Huang-Tian

2014-06-01

294

Effects of the phlebotropic drug Daflon 500 mg on postischemic microvascular disturbances in striated skin muscle: an intravital microscopic study in the hamster.  

PubMed

The objective of this study was to investigate the effects of the micronized purified flavonoid fraction Daflon 500 mg (90% diosmin and 10% hesperidin) on I/R-induced microvascular leukocyte-endothelium interaction and leakage of the high molecular weight plasma tracer FITC-dextran (relative molecular mass, 150 kd) as assessed in the striated skin muscle of the dorsal skin fold chamber model in the hamster. Intravital fluorescence microscopy was used for analysis of microvascular perfusion, leukocyte-endothelium interaction, and macromolecular leakage of FITC-dextran 150 kd in the striated skin muscle of the hamster. A tourniquet ischemia of 4 hours' duration was induced followed by reperfusion. Animals were treated with an oral administration of Daflon 500 mg (n = six) or its vehicle (5% Arabic gum solution, n = six) for 8 days at a daily dose of 30 mg/kg body weight. Measurements in the microcirculation were made before the 8-day feeding protocol before induction of ischemia and at 0.5, 2, and 24 hours of reperfusion. In the absence of I/R, no differences in microvascular perfusion, leukocyte-endothelium interaction, and macromolecular leakage were found in Daflon 500 mg and vehicle-treated control animals before and after administration of the drugs. Induction of ischemia and reperfusion, however, elicited a significant increase in venular leukocyte rolling and sticking in vehicle-treated animals, which was accompanied by enhancement of leakage of FITC-dextran 150 kd into the perivascular tissue. Treatment with Daflon 500 mg had no effect on postischemic leukocyte rolling and sticking, and macromolecular leakage of FITC-dextran 150 kd from arterioles and postcapillary venules was significantly reduced. These data indicate that Daflon 500 mg preserves the endothelial barrier function of striated skin muscle arterioles and venules after I/R, which appears to be independent of an action on postischemic intravascular leukocyte rolling and sticking. PMID:10560947

Nolte, D; Pickelmann, S; Möllmann, M; Schütze, E; Kübler, W; Leiderer, R; Messmer, K

1999-11-01

295

Co-treating mesenchymal stem cells with IL?1? and TNF-? increases VCAM-1 expression and improves post-ischemic myocardial function.  

PubMed

Inflammatory mediators are released by the myocardium following myocardial ischemia as a response to tissue injury, and contribute to cardiac repair and adaptive responses. Treating mesenchymal stem cells (MSCs) with various inflammatory factors activates a series of biological processes that enhance cell-mediated cardioprotection following myocardial infarction (MI). The present study was designed to examine the effect of interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?) treatment on vascular cell adhesion molecule-1 (VCAM-1) expression in MSCs, and to identify whether cytokine-treated MSCs improve post-ischemic myocardial function in a rat model. MSCs were stimulated with IL-1? and/or TNF-? for 24 h, the production of vascular cell adhesion molecule-1 (VCAM-1) and the adhesion ability of MSCs were assessed by flow cytometry, adhesion assays, quantitative polymerase chain reaction and western blot analysis. The cardiac function was examined by two-dimensional echocardiography. The results demonstrated that in treated MSCs, the secretion of VCAM-1 and the cell adhesion ability were significantly increased, thus markedly improving cardiac function compared with that of the control group (P<0.01). Of all the groups, the rats stimulated with a combination of IL-1? and TNF-? exhibited the greatest cardiac improvements. However, there was no significant difference between the 10 and 20 ng/ml groups which were stimulated with one of the cytokines alone (P>0.05). In conclusion, stimulating MSCs with IL-1? and TNF-? promoted the expression of VCAM-1 and improved post-ischemic cardiac function recovery. Treating MSCs with two cytokines in combination may be a useful method to maximize the potential of cell-based therapy for MI. PMID:24840001

Wang, Chun-Miao; Guo, Zeng; Xie, Yang-Jing; Hao, Yu-Yu; Sun, Ji-Min; Gu, Jian; Wang, Ai-Ling

2014-08-01

296

Preconditioning with acute and chronic lithium administration reduces ischemia/reperfusion injury mediated by cyclooxygenase not nitric oxide synthase pathway in isolated rat heart.  

PubMed

Lithium is widely used for the management of neuropsychiatric symptoms in bipolar disorders. A variety of hypotheses have been invoked to explain the mechanism of action of lithium. To determine if lithium exerts direct cardiac protection, in the present study perfused rat heart model was used. The mechanism of lithium-mediated cardioprotection was explored by combined use of lithium and nitro-L-arginine methyl ester (L-NAME, a non-selective nitric oxide synthase inhibitor) or indomethacin (a non-selective cyclooxygenase pathway inhibitor). Rat isolated hearts were used for Langendorff perfusion. Hearts were either non-preconditioned or preconditioned with acute lithium (3 mM) or chronic lithium (600 mg/l in tap water for 4 weeks, 0.265 +/- 0.023 mM in serum) before 30 min global ischemia followed by 90 min reperfusion. Within each of these protocols, hearts were divided into two groups; one group was exposed to L-NAME (0.1 mM) and another group was exposed to indomethacin (10 microM). Infarct size was measured by the triphenyltetrazolium chloride method. Left ventricular function was assessed by left ventricular developed pressure (LVDP), heart rate and coronary flow (CF). In our experiment acute and/or chronic administration of lithium before prolonged ischemia offered significant myoprotective effects in terms of infarct size reduction and improved cardiac function against ischemia/reperfusion injury. The effects of lithium pretreatment were prevented by the administration of indomethacin but not L-NAME. In conclusion, our results demonstrate that preconditioning with acute and/or chronic lithium administration improves recovery of the ventricular function and reduces infarct size via cyclooxygenase (COX) pathway in isolated rat heart. PMID:18789320

Faghihi, Mahdieh; Mirershadi, Fatemeh; Dehpour, Ahmad Reza; Bazargan, Maryam

2008-11-12

297

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

PubMed

It is well known that a brief anoxia or hypoxia episodes can render brain resistant to a subsequent ischemia. Recent investigations indicate that mechanisms of such stimulated endogenous neuroprotection are related to the family of hypoxia-inducible factors (HIF), however there are still little data available on the role of HIF family members in hippocampus-a brain structure, highly sensitive to oxygen deficiency. We have used the model of cultured hippocampal slices and single-cell quantitative RT-PCR to study HIF-1? and HIF-3? mRNA expression following triple 5-min mild anoxia, 30-min oxygen-glucose deprivation and their combination. We also tested the effects of HIF prolyl-hydroxylase inhibition with 2,4-pyridinedicarboxylic acid diethyl ester pre-treatment followed by a 30-min oxygen-glucose deprivation. It was found that neuronal damage induced by oxygen-glucose deprivation was accompanied by a significant decrease in both HIF-1? and HIF-3? mRNA levels in CA1 but not CA3 neurons. Anoxia preconditioning did not affect cell viability and HIF mRNA levels but applied before oxygen-glucose deprivation prevented neuronal damage and suppression of HIF-1? and HIF-3? mRNA expression. It was also found that effects of the prolyl-hydroxylase inhibitor were similar to anoxia preconditioning. These results suggest that anoxia preconditioning increases anti-ischemic neuronal resistance which to a certain extent correlates with the changes of HIF-1? and HIF-3? expression. PMID:21338581

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

2011-04-22

298

Preconditioning bandgap eigenvalue problems in three-dimensional photonic crystals simulations  

SciTech Connect

To explore band structures of three-dimensional photonic crystals numerically, we need to solve the eigenvalue problems derived from the governing Maxwell equations. The solutions of these eigenvalue problems cannot be computed effectively unless a suitable combination of eigenvalue solver and preconditioner is chosen. Taking eigenvalue problems due to Yee's scheme as examples, we propose using Krylov-Schur method and Jacobi-Davidson method to solve the resulting eigenvalue problems. For preconditioning, we derive several novel preconditioning schemes based on various preconditioners, including a preconditioner that can be solved by Fast Fourier Transform efficiently. We then conduct intensive numerical experiments for various combinations of eigenvalue solvers and preconditioning schemes. We find that the Krylov-Schur method associated with the Fast Fourier Transform based preconditioner is very efficient. It remarkably outperforms all other eigenvalue solvers with common preconditioners like Jacobi, Symmetric Successive Over Relaxation, and incomplete factorizations. This promising solver can benefit applications like photonic crystal structure optimization.

Huang, T.-M., E-mail: min@math.ntnu.edu.t [Department of Mathematics, National Taiwan Normal University, Taipei 116, Taiwan (China); Chang, W.-J., E-mail: e4523744@gmail.co [Graduate Institute of Photonics and Optoelectronic, National Taiwan University, Taipei 106, Taiwan (China); Huang, Y.-L., E-mail: liang@mail.nutn.edu.t [Department of Applied Mathematics, National University of Tainan, Tainan 700, Taiwan (China); Lin, W.-W., E-mail: wwlin@math.ntu.edu.t [Department of Mathematics, National Taiwan University, Taipei 106, Taiwan (China); Wang, W.-C., E-mail: wangwc@math.nthu.edu.t [Department of Mathematics, National Tsing Hua University, Hsinchu 300, Taiwan (China); Wang Weichung, E-mail: wwang@math.ntu.edu.t [Department of Mathematics, National Taiwan University, Taipei 106, Taiwan (China)

2010-11-20

299

Preconditioned conjugate gradient technique for the analysis of symmetric anisotropic structures  

NASA Technical Reports Server (NTRS)

An efficient preconditioned conjugate gradient (PCG) technique and a computational procedure are presented for the analysis of symmetric anisotropic structures. The technique is based on selecting the preconditioning matrix as the orthotropic part of the global stiffness matrix of the structure, with all the nonorthotropic terms set equal to zero. This particular choice of the preconditioning matrix results in reducing the size of the analysis model of the anisotropic structure to that of the corresponding orthotropic structure. The similarities between the proposed PCG technique and a reduction technique previously presented by the authors are identified and exploited to generate from the PCG technique direct measures for the sensitivity of the different response quantities to the nonorthotropic (anisotropic) material coefficients of the structure. The effectiveness of the PCG technique is demonstrated by means of a numerical example of an anisotropic cylindrical panel.

Noor, Ahmed K.; Peters, Jeanne M.

1987-01-01

300

Nitroglycerine and sodium trioxodinitrate: from the discovery to the preconditioning effect.  

PubMed

The history began in the 19th century with Ascanio Sobrero (1812-1888), the discoverer of glycerol trinitrate (nitroglycerine, NTG), and with Angelo Angeli (1864-1931), the discoverer of sodium trioxodinitrate (Angeli's salt). It is likely that Angeli and Sobrero never met, but their two histories will join each other more than a century later. In fact, it has been discovered that both NTG and Angeli's salt are able to induce a preconditioning effect. As NTG has a long history as an antianginal drug its newly discovered property as a preconditioning agent has also been tested in humans. Angeli's salt properties as a preconditioning and inotropic agent have only been tested in animals so far. PMID:23695182

Pagliaro, Pasquale; Gattullo, Donatella; Penna, Claudia

2013-10-01

301

How preconditioning affects the measurement of poro-viscoelastic mechanical properties in biological tissues.  

PubMed

It is known that initial loading curves of soft biological tissues are substantially different from subsequent loadings. The later loading curves are generally used for assessing the mechanical properties of a tissue, and the first loading cycles, referred to as preconditioning, are omitted. However, slow viscoelastic phenomena related to fluid flow or collagen viscoelasticity are initiated during these first preconditioning loading cycles and may persist during the actual data collection. When these data are subsequently used for fitting of material properties, the viscoelastic phenomena that occurred during the initial cycles are not accounted for. The aim of the present study is to explore whether the above phenomena are significant for articular cartilage, by evaluating the effect of such time-dependent phenomena by means of computational modeling. Results show that under indentation, collagen viscoelasticity dominates the time-dependent behavior. Under UC, fluid-dependent effects are more important. Interestingly, viscoelastic and poroelastic effects may act in opposite directions and may cancel each other out in a stress-strain curve. Therefore, equilibrium may be apparent in a stress-strain relationship, even though internally the tissue is not in equilibrium. Also, the time-dependent effects of viscoelasticity and poroelasticity may reinforce each other, resulting in a sustained effect that lasts longer than suggested by their individual effects. Finally, the results illustrate that data collected from a mechanical test may depend on the preconditioning protocol. In conclusion, preconditioning influences the mechanical response of articular cartilage significantly and therefore cannot be neglected when determining the mechanical properties. To determine the full viscoelastic and poroelastic properties of articular cartilage requires fitting to both preconditioning and post-preconditioned loading cycles. PMID:23864393

Hosseini, Sayyed Mohsen; Wilson, Wouter; Ito, Keita; van Donkelaar, Corrinus C

2014-06-01

302

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

303

PRECONDITIONED BI-CONJUGATE GRADIENT METHOD FOR RADIATIVE TRANSFER IN SPHERICAL MEDIA  

SciTech Connect

A robust numerical method called the Preconditioned Bi-Conjugate Gradient (Pre-BiCG) method is proposed for the solution of the radiative transfer equation in spherical geometry. A variant of this method called Stabilized Preconditioned Bi-Conjugate Gradient (Pre-BiCG-STAB) is also presented. These are iterative methods based on the construction of a set of bi-orthogonal vectors. The application of the Pre-BiCG method in some benchmark tests shows that the method is quite versatile, and can handle difficult problems that may arise in astrophysical radiative transfer theory.

Anusha, L. S.; Nagendra, K. N. [Indian Institute of Astrophysics, Koramangala, Bangalore 560 034 (India); Paletou, F.; Leger, L. [Laboratoire d'Astrophysique de Toulouse-Tarbes, Universite de Toulouse, CNRS, 14 Ave. E. Belin, 31400 Toulouse (France)

2009-10-10

304

Preconditioned methods for solving the incompressible and low speed compressible equations  

NASA Technical Reports Server (NTRS)

Acceleration methods are presented for solving the steady state incompressible equations. These systems are preconditioned by introducing artificial time derivatives which allow for a faster convergence to the steady state. The compressible equations in conservation form with slow flow are also considered. Two arbitrary functions, alpha and beta, are introduced in the general preconditioning. An analysis of this system is presented and an optimal value for beta is determined given a constant, alpha. It is further shown that the resultant incompressible equations form a symmetric hyperbolic system and so are well posed. Several generalizations to the compressible equations are presented which generalize previous results.

Turkel, E.

1986-01-01

305

Preconditioned upwind methods to solve 3-D incompressible Navier-Stokes equations for viscous flows  

NASA Technical Reports Server (NTRS)

A computational method for calculating low-speed viscous flowfields is developed. The method uses the implicit upwind-relaxation finite-difference algorithm with a nonsingular eigensystem to solve the preconditioned, three-dimensional, incompressible Navier-Stokes equations in curvilinear coordinates. The technique of local time stepping is incorporated to accelerate the rate of convergence to a steady-state solution. An extensive study of optimizing the preconditioned system is carried out for two viscous flow problems. Computed results are compared with analytical solutions and experimental data.

Hsu, C.-H.; Chen, Y.-M.; Liu, C. H.

1990-01-01

306

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

307

Hyperlipidemia attenuates the infarct size-limiting effect of ischemic preconditioning: role of matrix metalloproteinase-2 inhibition.  

PubMed

Hyperlipidemia attenuates the cardioprotective effect of preconditioning via unknown mechanisms. We have reported previously that in normolipidemic rats, preconditioning decreased ischemia-induced activation and release of myocardial matrix metalloproteinase (MMP)-2 into the coronary perfusate. Here, we investigated whether hyperlipidemia interferes with the cardioprotective effect of preconditioning through modulation of MMP-2. Hearts isolated from male Wistar rats fed 2% cholesterol-enriched or control chow for 9 weeks were subjected to a preconditioning protocol (three intermittent periods of ischemia/reperfusion of 5-min duration each) or a time-matched nonpreconditioning protocol. This was followed by a test ischemia/reperfusion (30-min ischemia and 120-min reperfusion) in both groups. Preconditioning decreased infarct size in the control but not the cholesterol-fed group. Cardioprotection in the preconditioned control group but not in the cholesterol-fed group was associated with an 18 +/- 3% (p < 0.05) inhibition of test ischemia/reperfusion-induced activation and release of myocardial MMP-2 into the perfusate. Myocardial protein levels of tissue inhibitors of MMPs [tissue inhibitor of metalloproteinases (TIMP)-2 and TIMP-4] were not changed in either group. A reduction of infarct size in nonpreconditioned hearts from both control and cholesterol-fed group was produced by the MMP inhibitor ilomastat at 0.25 microM, a concentration producing MMP-2 inhibition comparable with that of preconditioning in the control group. We conclude that hyperlipidemia blocks preconditioning-induced cardioprotection, hyperlipidemia abolishes preconditioning-induced inhibition of myocardial MMP-2 activation and release, preconditioning-induced inhibition of MMP-2 activation and release is not mediated by TIMPs, and pharmacological inhibition of MMPs produces cardioprotection in both normal and hyperlipidemic rats. PMID:16166272

Giricz, Zoltán; Lalu, Manoj M; Csonka, Csaba; Bencsik, Péter; Schulz, Richard; Ferdinandy, Péter

2006-01-01

308

Intracoronary administration of the cx ,-receptor agonist, methoxamine, does not reproduce the infarct-limiting effect of ischemic preconditioning in dogs  

Microsoft Academic Search

Background: The cardioprotective effect of ischemic preconditioning has been hypothesized to occur through one or more signalling mechanisms which activate protein kinase C. Stimulation of Q ,-adrenergic receptors by catecholamines released during the precondition- ing episodes of ischemia is one of these putative signalling mechanisms. Methods: To determine whether stimulation of cr,-adrenergic receptors before an ischemic challenge can mimic preconditioning,

Laurent Sebbag; Masayuki Katsuragawa; Steven Verbinski; Robert B. Jennings; Keith A. Reimer

309

Ischemic preconditioning of the liver in rats: Implications of heat shock protein induction to increase tolerance of ischemia-reperfusion injury  

Microsoft Academic Search

It has been reported that ischemic preconditioning of the heart or brain has a possible relevance to heat shock protein (HSP). It is still unknown, however, whether HSP induced by means of ischemic preconditioning of the liver is a direct factor in the acquisition of tolerance to succeeding ischemia-reperfusion injury. In the present study we used ischemic preconditioning of the

Makoto Kume; Yuzo Yamamoto; Stefano Saad; Takashi Gomi; Syuji Kimoto; Takashi Shimabukuro; Toshikazu Yagi; Mikio Nakagami; Yasutsugu Takada; Taisuke Morimoto; Yoshio Yamaoka

1996-01-01

310

Awareness in nine countries: A public health approach to suicide prevention  

Microsoft Academic Search

Suicide is an important public health problem, increasing worldwide, and on a yearly basis accounting for the death of more than one million people, with estimates as high as 10–20 times that many attempting to take their own life. Because successful suicide prevention depends upon recognition of symptoms of mental ill-health, awareness of these signs is a necessary precondition. The

Christina W. Hoven; Danuta Wasserman; Camilla Wasserman; Donald J. Mandell

2009-01-01

311

Time-Domain Calderón Identities and Preconditioning of the Time-Domain EFIE  

Microsoft Academic Search

An analytical preconditioner for the time-domain electric field integral equation (EFIE) has been developed. First, a time-domain operator identity that enables the construction of an analytically preconditioned time domain EFIE is constructed. Second, a procedure for efficiently discretizing this new time domain EFIE is elucidated. Numerical results that demonstrate the performance of the new analytical preconditioner are presented

K. Cools; F. P. Andriulli; E. Michielssen

2006-01-01

312

An anisotropic preconditioning for the Wilson fermion matrix on the lattice  

SciTech Connect

A preconditioning for the Wilson fermion matrix on the lattice is defined which is particularly suited to the case when the temporal lattice spacing is much smaller than the spatial one. Details on the implementation of the scheme are given. The method is tested in numerical studies of QCD on anisotropic lattices.

Balint Joo, Robert G. Edwards, Michael J. Peardon

2010-01-01

313

Preconditioned Implicit Solvers for the Navier-Stokes Equations on Distributed-Memory Machines.  

National Technical Information Service (NTIS)

The GMRES method is parallelized, and combined with local preconditioning to construct an implicit parallel solver to obtain steady-state solutions for the Navier-Stokes equations of fluid flow on distributed-memory machines. The new implicit parallel sol...

K. Ajmani M. Liou R. W. Dyson

1994-01-01

314

Space charge formation in XLPE-the influence of electrodes and pre-conditioning  

Microsoft Academic Search

The authors present space charge profiles for a range of XLPE planar samples under DC stress. Three different types of semiconductor electrodes were investigated, as well as vacuum evaporated Au. The samples were also subjected to three different heating\\/pumping pre-conditioning procedures. The space charge profiles in the unconditioned samples (heterocharge) were consistent with an apparent volume charge originating in a

R. J. Fleming; M. Henriksen; J. T. Holboll

1999-01-01

315

Coronary microembolization does not induce acute preconditioning against infarction in pigs—the role of adenosine  

Microsoft Academic Search

Objective: After coronary microembolization (ME) adenosine is released from ischemic areas of the microembolized myocardium. This adenosine dilates vessels in adjacent nonembolized myocardium and increases coronary blood flow. For ischemic preconditioning (IP) to protect the myocardium against infarction, an increase in the interstitial adenosine concentration (iADO) prior to the subsequent ischemia\\/reperfusion is necessary. We hypothesized that the adenosine release after

Andreas Skyschally; Rainer Schulz; Petra Gres; Ina Konietzka; Claus Martin; Michael Haude; Raimund Erbel; Gerd Heusch

316

Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection  

Microsoft Academic Search

BACKGROUND: Retinal degeneration is a main cause of blindness in humans. Neuroprotective therapies may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1? in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration. To address the molecular mechanisms of the protection, we analyzed the transcriptome of the hypoxic

Markus Thiersch; Wolfgang Raffelsberger; Rico Frigg; Marijana Samardzija; Andreas Wenzel; Olivier Poch; Christian Grimm

2008-01-01

317

Histone preconditioning protects against obstructive jaundice-induced liver injury in rats  

PubMed Central

A major consequence of obstructive jaundice (OJ) in clinical practice is the development of severe liver injury, and at present, no effective treatments have been developed to protect against it. Preconditioning with damage-associated molecular pattern (DAMP) molecules has been demonstrated to protect multiple organs from injury, and histones have been recently identified as DAMP molecules. The aim of the present study was to investigate the protective effect of histone preconditioning against OJ-induced liver injury in rats and the involvement of Toll-like receptors. Rats were administered histone proteins (200 ?g/kg; 1 ml) or physiological saline (1 ml) intraperitoneally 24 h prior to being subjected to bile duct ligation (BDL). The serum levels of liver enzymes and bilirubin, as well as the histopathology were analyzed. The mRNA expression of interleukin-6 (IL-6) in the liver tissue was analyzed using quantitative polymerase chain reaction. BDL in the control group caused severe OJ-induced liver injury, as indicated by the significantly elevated levels of liver enzymes and mRNA levels of IL-6, and confirmed by histopathological alterations. However, histone preconditioning significantly ameliorated the OJ-induced liver injury caused by BDL, as shown by an improvement in the levels of liver enzymes, a suppression of IL-6 production, as well as histopathological alterations. Therefore, these results suggested that histone preconditioning is able to protect against OJ-induced liver injury in rats.

ZHOU, YOU-XING; NI, YONG; LIU, YI-BING; LIU, XIAOHONG

2014-01-01

318

Ultrafast Preconditioned Conjugate Gradient MAP reconstruction for fully 3-D microPET  

Microsoft Academic Search

Iterative 3D PET reconstruction represents a very computational challenge due to the large number of lines of response (LOR) collected for each data set. This iterative 3D reconstruction also needs a lot of iterations to achieve an acceptable PET reconstructed image. A preconditioned conjugate gradient (PCG) method was previously shown to have faster convergence rate than expectation maximization (EM) type

I. K. Hong; Z. Burbar; C. Michel; R. Leahy

2009-01-01

319

The Role of Macrophage Migration Inhibitory Factor in Anesthetic-Induced Myocardial Preconditioning  

PubMed Central

Introduction Anesthetic-induced preconditioning (AIP) is known to elicit cardioprotective effects that are mediated at least in part by activation of the kinases AMPK and PKC? as well as by inhibition of JNK. Recent data demonstrated that the pleiotropic cytokine macrophage migration inhibitory factor (MIF) provides cardioprotection through activation and/or inhibition of kinases that are also known to mediate effects of AIP. Therefore, we hypothesized that MIF could play a key role in the AIP response. Methods Cardiomyocytes were isolated from rats and subjected to isoflurane preconditioning (4 h; 1.5 vol. %). Subsequently, MIF secretion and alterations in the activation levels of protective kinases were compared to a control group that was exposed to ambient air conditions. MIF secretion was quantified by ELISA and AIP-induced activation of protein kinases was assessed by Western blotting of cardiomyocyte lysates after isoflurane treatment. Results In cardiomyocytes, preconditioning with isoflurane resulted in a significantly elevated secretion of MIF that followed a biphasic behavior (30 min vs. baseline: p?=?0.020; 24 h vs. baseline p?=?0.000). Moreover, quantitative polymerase chain reaction demonstrated a significant increase in MIF mRNA expression 8 h after AIP. Of note, activation of AMPK and PKC? coincided with the observed peaks in MIF secretion and differed significantly from baseline. Conclusions These results suggest that the pleiotropic mediator MIF is involved in anesthetic-induced preconditioning of cardiomyocytes through stimulation of the protective kinases AMPK and PKC?.

Rossaint, Rolf; Bleilevens, Christian; Dollo, Florian; Siry, Laura; Rajabi-Alampour, Setareh; Beckers, Christian; Soppert, Josefin; Lue, Hongqi; Rex, Steffen; Bernhagen, Jurgen; Stoppe, Christian

2014-01-01

320

Antiarrhythmic Effect of Ischemic Preconditioning in Recent Unstable Angina Patients Undergoing Coronary Artery Bypass Grafting  

Microsoft Academic Search

Coronary artery bypass grafting (CABG) for unstable angina pectoris patients results in a higher incidence of arrhythmia and higher arrhythmic cardiac mortality. Ischemic preconditioning (IP) has proved effective in suppressing ischemia reperfusion arrhythmias in animals and in humans. The purpose of the present study was to investigate whether IP protects against postoperative arrhythmias in recent unstable angina patients undergoing urgent

Zhong-Kai Wu; Tiina Iivainen; Erkki Pehkonen; Jari Laurikka; Matti R. Tarkka

2004-01-01

321

Analysis of Off-Board Powered Thermal Preconditioning in Electric Drive Vehicles: Preprint  

SciTech Connect

Following a hot or cold thermal soak, vehicle climate control systems (air conditioning or heat) are required to quickly attain a cabin temperature comfortable to the vehicle occupants. In a plug-in hybrid electric or electric vehicle (PEV) equipped with electric climate control systems, the traction battery is the sole on-board power source. Depleting the battery for immediate climate control results in reduced charge-depleting (CD) range and additional battery wear. PEV cabin and battery thermal preconditioning using off-board power supplied by the grid or a building can mitigate the impacts of climate control. This analysis shows that climate control loads can reduce CD range up to 35%. However, cabin thermal preconditioning can increase CD range up to 19% when compared to no thermal preconditioning. In addition, this analysis shows that while battery capacity loss over time is driven by ambient temperature rather than climate control loads, concurrent battery thermal preconditioning can reduce capacity loss up to 7% by reducing pack temperature in a high ambient temperature scenario.

Barnitt, R. A.; Brooker, A. D.; Ramroth, L.; Rugh , J.; Smith, K. A.

2010-12-01

322

Dynamic inference of likely data preconditions over predicates by tree learning  

Microsoft Academic Search

We present a technique to infer likely data preconditions for procedures written in an imperative programming lan- guage. Given a procedure and a set of predicates over its in- puts, our technique enumerates di!erent truth assignments to the predicates, deriving test cases from each feasible truth assignment. The predicates themselves are derived auto- matically using simple heuristics. The enumeration of

Sriram Sankaranarayanan; Swarat Chaudhuri; Franjo Ivancic; Aarti Gupta

2008-01-01

323

40 CFR 1065.590 - PM sampling media (e.g., filters) preconditioning and tare weighing.  

Code of Federal Regulations, 2010 CFR

...2009-07-01 false PM sampling media (e.g., filters) preconditioning and tare weighing. 1065...in mass to an unused sample medium (e.g., filter). A 47 mm PTFE membrane filter will typically have a mass in the range of...

2009-07-01

324

40 CFR 1065.590 - PM sampling media (e.g., filters) preconditioning and tare weighing.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false PM sampling media (e.g., filters) preconditioning and tare weighing. 1065...in mass to an unused sample medium (e.g., filter). A 47 mm PTFE membrane filter will typically have a mass in the range of...

2010-07-01

325

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

PubMed Central

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.

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

2013-01-01

326

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

327

Fully 3D PET image reconstruction using a Fourier preconditioned conjugate-gradient algorithm  

Microsoft Academic Search

Since the data sixes in fully 3D PET imaging are very large, iterative image reconstruction algorithms must converge in very few iterations to be useful. One can improve the convergence rate of the conjugate-gradient (CG) algorithm by incorporating preconditioning operators that approximate the inverse of the Hessian of the objective function. If the 3D cylindrical PET geometry were not truncated

Jeffrey A. Fessler; Edward P. Ficaro

1996-01-01

328

Role of Inducible Nitric Oxide Synthase in Pharmacological “Preconditioning” with Monophosphoryl Lipid A  

Microsoft Academic Search

Pretreatment with monophosphoryl lipid A (MLA) can pharmacologically mimic the second window of ischemic preconditioning (SWOP) to protect the heart from prolonged ischemia and reperfusion injury. Based on the delayed time course for development of MLA associated cardioprotection, this study was designed to test if MLA's cardioprotective effect is mediated by signalling through production of inducible nitric oxide synthase (iNOS),

Lin Zhao; Patricia A. Weber; Jerry R. Smith; Malissa L. Comerford; Gary T. Elliott

1997-01-01

329

Application of DA-Preconditioned FINN for Electric Power System Fault Detection  

Microsoft Academic Search

This paper proposes a hybrid method of Deterministic Annealing (DA) and Fuzzy Inference Neural Network (FINN) for electric power system fault detection. It extracts features of input data with two-staged precondition of Fast Fourier Transform (FFT) and DA. FFT is useful for extracting the features of fault currents while DA plays a key role to classify input data into clusters

Tadahiro Itagaki; Hiroyuki Mori; Takeshi Yamada; Shoichi Urano

2006-01-01

330

Experience with Fine-Grain Synchronization in MIMD Machines for Preconditioned Conjugate Gradient  

Microsoft Academic Search

This paper discusses our experience with fine-grain synchroniza- tion for a variant of the preconditioned conjugate gradient method. This algorithm represents a large class of algorithms that have been widely used but traditionally difficult to implement efficiently on vector and parallel machines. Through a series of experiments conducted using a simulator of a distributed shared-memory multi- processor, this paper addresses

Donald Yeung; Anant Agarwal

1993-01-01

331

A dispersion minimizing finite difference scheme and preconditioned solver for the 3D Helmholtz equation  

NASA Astrophysics Data System (ADS)

In this paper, a new 27-point finite difference method is presented for solving the 3D Helmholtz equation with perfectly matched layer (PML), which is a second order scheme and pointwise consistent with the equation. An error analysis is made between the numerical wavenumber and the exact wavenumber, and a refined choice strategy based on minimizing the numerical dispersion is proposed for choosing weight parameters. A full-coarsening multigrid-based preconditioned Bi-CGSTAB method is developed for solving the linear system stemming from the Helmholtz equation with PML by the finite difference scheme. The shifted-Laplacian is extended to precondition the 3D Helmholtz equation, and a spectral analysis is given. The discrete preconditioned system is solved by the Bi-CGSTAB method, with a multigrid method used to invert the preconditioner approximately. Full-coarsening multigrid is employed, and a new matrix-based prolongation operator is constructed accordingly. Numerical results are presented to demonstrate the efficiency of both the new 27-point finite difference scheme with refined parameters, and the preconditioned Bi-CGSTAB method with the 3D full-coarsening multigrid.

Chen, Zhongying; Cheng, Dongsheng; Wu, Tingting

2012-10-01

332

Ischemic preconditioning by brief extremity ischemia before flap ischemia in a rat model.  

PubMed

Ischemic preconditioning is a protective endogenous mechanism to reduce ischemia/reperfusion injury and is defined as a brief period of ischemia the authors term "preclamping." This is followed by tissue reperfusion and is believed to increase the ischemic tolerance. The objective of this study was to determine whether acute remote ischemic preconditioning, which has been reported to be successful for other organs, such as the heart, kidney, intestine, and liver, will also result in an enhancement of survival in flaps, and whether remote ischemic preconditioning is as effective as preclamping. Forty male Wistar rats were divided into four experimental groups. An extended epigastric adipocutaneous flap (6 x 10 cm) was raised, based on the left superficial epigastric artery and vein. In the control group, a 3-hour flap ischemia was induced. In the preclamping group, a brief ischemia of 10 minutes was induced by clamping the flap pedicle, followed by 30 minutes of reperfusion. Ischemia of the right hind limb was induced in the femoral ischemia group by clamping the femoral artery and vein for 10 minutes after flap elevation. The limb was then reperfused for 30 minutes. Thereafter, flap ischemia was induced as in the control group. A similar protocol was used in the tourniquet group. A tourniquet was used to induce hind-limb ischemia. The experiment was then performed as in the femoral ischemia group. Mean flap necrosis area was assessed for all groups on the fifth postoperative day using planimetry software. Average flap necrosis area was 68.2 +/- 18.1 percent in the control group, 11 +/- 8.38 percent in the preclamping group, 12.5 +/- 5.83 percent in the femoral ischemia group, and 24 +/- 11.75 percent in the tourniquet group. All preconditioned animals demonstrated a significantly lower area of flap necrosis than the control group (p < 0.001, one-way analysis of variance, post hoc Tukey's test). The data show that ischemic preconditioning and enhancement of flap survival can be achieved not only by preclamping of the flap pedicle but also by induction of an ischemia/reperfusion event in a body area distant from the flap before harvest. These findings indicate that remote ischemic preconditioning is a systemic phenomenon, leading to an enhancement of flap survival. The exact mechanism is not yet completely understood. The data suggest that remote ischemic preconditioning could be performed simultaneously with flap harvest in the clinical setting, resulting in an improved flap survival without prolongation of the operation. This may decrease the rate of partial flap loss or fat necrosis, especially in high-risk groups such as smokers, those with irradiated tissues, and obese patients. PMID:12045567

Küntscher, Markus V; Schirmbeck, Eva U; Menke, Henrik; Klar, Ernst; Gebhard, Martha Maria; Germann, Günter

2002-06-01

333

Osteopontin protects against cardiac ischemia-reperfusion injury through late preconditioning.  

PubMed

Osteopontin (OPN) has been considered as a proinflammatory cytokine. A protective role for OPN in ischemic injury was demonstrated recently. Because proinflammatory cytokines play an important role in induction of late preconditioning, we deduce that OPN may induce late preconditioning in myocardium. Fifty consecutive patients scheduled for mitral valve replacement (MVR) were investigated. Osteopontin and high-sensitivity C-reactive protein levels in plasma before surgery were determined. Nuclear factor kappa B and signal transducer and activator of transcription 3 (STAT3), two main transcription factors involved in late preconditioning, were investigated by electrophoretic mobility shift assay. The effector proteins in late preconditioning, including inducible nitric oxide synthase and cyclooxygenase-2, were evaluated by immunoblotting. Cardioprotective effects were assessed by creatine kinase MB (CK-MB) and cardiac troponin T (cTnT) leakage postoperatively. The protective effects of OPN on neonatal cardiomyocytes against anoxia-reoxygenation-induced injury were also tested. The protein synthesis inhibitor cycloheximide (CH) was used in this model to test if new protein synthesis was necessary for its cardioprotective effects. There was no perioperative death in the groups. We found that patients with higher plasma OPN levels (167 +/- 35 ng/ml vs 63 +/- 13 ng/ml) had more activated extent of transcription factors, higher expression of effector proteins, and better cardioprotective effects, assessed by CK-MB and cTnT. An in vitro experiment also revealed that OPN had a cardioprotective effect 24 h after pretreatment. However, the protective effect was blocked by the protein synthesis inhibitor CH. Osteopontin can protect against cardiac ischemia-reperfusion injury through late preconditioning. PMID:19337795

Wang, Yongyi; Chen, Baofu; Shen, Dafu; Xue, Song

2009-03-01

334

Lipopolysaccharide preconditioning attenuates apoptotic processes and improves neuropathologic changes after spinal cord injury in rats.  

PubMed

We have shown earlier that administration of low-dose lipopolysaccharide (LPS) significantly contributed to recovery of motor function after traumatic spinal cord injury in the adult female rat. Using the same standardized animal model, we have now designed a set of experiments to test the hypothesis that LPS preconditioning attenuates stress-related apoptotic processes early after spinal cord trauma. The lower thoracic spinal cord injury in adult female Sprague-Dawley rats was caused by a 10 g weight rod drop from 25 mm on the dural surface of the exposed spinal cord at T10. The rats were randomly assigned to three groups: Sham injury, control (received normal saline alone), and LPS preconditioning (0.2 mg/kg, ip; 72 h prior to the injury). The animals were euthanized at 72 h postinjury. Neuropathologic changes were assessed using hematoxylin and eosin staining. SCI-induced apoptosis were observed by transmission electron microscopy. Caspase-3, cleaved caspase-3, Bax, and Bcl-2 were examined with immunohistochemistry or Western blotting. Compared with the control group, LPS preconditioning group showed significant improvement in the SCI-induced morphology changes. Furthermore, LPS preconditioning reduced the expressions of apoptotic markers caspase-3, cleaved caspase-3, and Bax, upregulated the expression of antiapoptotic marker Bcl-2 in the samples of spinal cord. Low-dose LPS attenuated the recruitment of inflammatory cells and the proliferation of glial cells in the site of injury. LPS preconditioning has neuroprotective effects against TSCI in rats due to its antiapoptosis properties as shown by the inhibition of caspase pathway and the upregulation of antiapoptotic protein. PMID:24205811

Li, Wei-Chao; Jiang, Rong; Jiang, Dian-Ming; Zhu, Feng-Chen; Su, Bao; Qiao, Bo; Qi, Xiao-Tong

2014-08-01

335

Preconditioning to mild oxidative stress mediates astroglial neuroprotection in an IL-10-dependent manner.  

PubMed

Oxidative stress plays an important role in the pathogenesis of various brain insults, including stroke. Astroglia are the main glial cells that play a fundamental role in maintaining the homeostasis of the CNS. They are important for protection from injury and aid the brain in functional recovery after injuries. It has been shown that the brain can be prepared to withstand an oxidative stress insult by a process known as preconditioning. We used primary astroglial cell culture to investigate whether preconditioning to mild oxidative stress and glucose deprivation (OSGD) can increase both astroglia survival and neuroprotective features. We found that preconditioning astroglia to mild OSGD increases astroglial survival of a second insult through activation of the NF-E2-related factor-2 (Nrf-2) pathway. Moreover, we found that Nrf-2 is highly expressed in adult brain astroglia and that preconditioning to OSGD in vivo, such as in a murine model of ischemic stroke, leads to a significant increase in astroglial Nrf-2 expression. Furthermore, we discovered an increase in neuroprotection, as measured by increased neuronal cell survival, following OSGD in the presence of medium from astroglia exposed to a mild OSGD condition. Interestingly, we discovered a significant increase in astroglial secretion of the anti-inflammatory cytokine IL-10 vs. the pro-inflammatory cytokine IL-1? in mild vs. severe oxidative stress, respectively. We demonstrated that preconditioning astroglia to mild oxidative stress increases neuroprotection in an IL-10-dependent manner. By using tert-butylhydroquinone (tBHQ), a known specific activator of Nrf-2, we found that Nrf-2 can enhance IL-10 expression. Further studies of Nrf-2-mediated cellular pathways in astroglia through IL-10 may provide useful insights into the development of therapeutic interventions following oxidative stress insults such as ischemic stroke. PMID:23313057

Segev-Amzaleg, Niva; Trudler, Dorit; Frenkel, Dan

2013-05-01

336

Marked hyperglycemia attenuates anesthetic preconditioning in human induced pluripotent stem cell-derived cardiomyocytes  

PubMed Central

Introduction Anesthetic preconditioning protects cardiomyocytes from oxidative stress-induced injury, but it is ineffective in patients with diabetes mellitus. To address the role of hyperglycemia in the inability of diabetic individuals to be preconditioned, we used human cardiomyocytes differentiated from induced pluripotent stem cells generated from patients with or without type 2 diabetes mellitus (DM-iPSC- and N-iPSC-CMs, respectively) to investigate the efficacy of preconditioning in varying glucose conditions (5, 11, and 25 mM). Methods Induced pluripotent stem cells were induced to generate cardiomyocytes by directed differentiation. For subsequent studies, cardiomyocytes were identified by genetic labeling with enhanced green fluorescent protein driven by a cardiac-specific promoter. Cell viability was analyzed by lactate dehydrogenase assay. Confocal microscopy was utilized to measure opening of the mitochondrial permeability transition pore and the mitochondrial adenosine-5?-triphosphate-sensitive potassium channels. Results Isoflurane (0.5 mM) preconditioning protected N-iPSC- and DM-iPSC-CMs from oxidative stress-induced lactate dehydrogenase release and mitochondrial permeability transition pore opening in 5 mM and 11 mM glucose. Isoflurane triggered mitochondrial adenosine-5?-triphosphate-sensitive potassium channel opening in N-iPSC-CMs in 5 mM and 11 mM glucose and in DM-iPSC-CMs in 5 mM glucose. 25 mM glucose disrupts anesthetic preconditioning-mediated protection in DM-iPSC- and N-iPSC-CMs. Conclusions The opening of mitochondrial adenosine-5?-triphosphate-sensitive potassium channels are disrupted in DM-iPSC-CMs in 11 mM and 25 mM glucose and in N-iPSC-CMs in 25 mM glucose. Cardiomyocytes derived from healthy donors and patients with a specific disease, such as diabetes in this study, open possibilities in studying genotype and phenotype related pathologies in a human relevant model.

Canfield, Scott G.; Sepac, Ana; Sedlic, Filip; Muravyeva, Maria Y.; Bai, Xiaowen; Bosnjak, Zeljko J.

2012-01-01

337

Cerebral ischemic preconditioning reduces glutamate excitotoxicity by up-regulating the uptake activity of GLT-1 in rats.  

PubMed

Our previous study has shown that cerebral ischemic preconditioning (CIP) can up-regulate the expression of glial glutamate transporter-1 (GLT-1) during the induction of brain ischemic tolerance in rats. The present study was undertaken to further explore the uptake activity of GLT-1 in the process by observing the changes in the concentration of extracellular glutamate with cerebral microdialysis and high-performance liquid chromatography. The results showed that a significant pulse of glutamate concentration reached the peak value of sevenfold of the basal level after lethal ischemic insult, which was associated with delayed neuronal death in the CA1 hippocampus. When the rats were pretreated 2 days before the lethal ischemic insult with CIP which protected the pyramidal neurons against delayed neuronal death, the peak value of glutamate concentration decreased to 3.9 fold of the basal level. Furthermore, pre-administration of dihydrokainate, an inhibitor of GLT-1, prevented the protective effect of CIP on ischemia-induced CA1 cell death. At the same time, compared with the CIP + Ischemia group, the peak value of glutamate concentration significantly increased and reached sixfold of the basal level. These results indicate that CIP induced brain ischemic tolerance via up-regulating GLT-1 uptake activity for glutamate and then decreasing the excitotoxicity of glutamate. PMID:24643365

Gong, Jianxue; Gong, Shujuan; Zhang, Min; Zhang, Lianwei; Hu, Yuyan; Liu, Yixian; Li, Wenbin

2014-06-01

338

Expression profiling and ontology analysis of long noncoding RNAs in post-ischemic heart and their implied roles in ischemia/reperfusion injury.  

PubMed

Long noncoding RNAs (lncRNAs) play important regulatory roles in cellular physiology. The contributions of lncRNAs to ischemic heart disease remain largely unknown. The aim of this study was to investigate the profile of myocardial lncRNAs and their potential roles at early stage of reperfusion. lncRNAs and mRNAs were profiled by microarray and the expression of some highly-dysregulated lncRNAs was further validated using polymerase chain reaction. Our results revealed that 64 lncRNAs were up-regulated and 87 down-regulated, while 50 mRNAs were up-regulated and 60 down-regulated in infarct region at all reperfusion sampled. Gene ontology analysis indicated that dysregulated transcripts were associated with immune response, spermine catabolic process, taxis, chemotaxis, polyamine catabolic process, spermine metabolic process, chemokine activity and chemokine receptor binding. Target gene-related pathway analysis showed significant changes in cytokine-cytokine receptor interaction, the chemokine signaling pathway and nucleotide oligomerization domain (NOD)-like receptor signaling pathway which have a close relationship with myocardial ischemia/reperfusion injury (MI/RI). Besides, a gene co-expression network was constructed to identify correlated targets of 10 highly-dysregulated lncRNAs. These lncRNAs may play their roles by this network in post-ischemic heart. Such results provide a foundation for understanding the roles and mechanisms of myocardial lncRNAs at early stage of reperfusion. PMID:24726549

Liu, Youbin; Li, Guangnan; Lu, Huimin; Li, Wei; Li, Xianglu; Liu, Huimin; Li, Xingda; Li, Tianyu; Yu, Bo

2014-06-10

339

S{sub 2}SA preconditioning for the S{sub n} equations with strictly non negative spatial discretization  

SciTech Connect

Preconditioners based upon sweeps and diffusion-synthetic acceleration have been constructed and applied to the zeroth and first spatial moments of the 1-D S{sub n} transport equation using a strictly non negative nonlinear spatial closure. Linear and nonlinear preconditioners have been analyzed. The effectiveness of various combinations of these preconditioners are compared. In one dimension, nonlinear sweep preconditioning is shown to be superior to linear sweep preconditioning, and DSA preconditioning using nonlinear sweeps in conjunction with a linear diffusion equation is found to be essentially equivalent to nonlinear sweeps in conjunction with a nonlinear diffusion equation. The ability to use a linear diffusion equation has important implications for preconditioning the S{sub n} equations with a strictly non negative spatial discretization in multiple dimensions. (authors)

Bruss, D. E.; Morel, J. E.; Ragusa, J. C. [Department of Nuclear Engineering, Texas A and M University, 3133 TAMU, College Station, TX 77843-3133 (United States)] [Department of Nuclear Engineering, Texas A and M University, 3133 TAMU, College Station, TX 77843-3133 (United States)

2013-07-01

340

Role of autophagy in protection afforded by hypoxic preconditioning against MPP +-induced neurotoxicity in SH-SY5Y cells  

Microsoft Academic Search

A sublethal preconditioning has been proposed as a neuroprotective strategy against several CNS neurodegenerative diseases. In this study, the involvement of autophagy in the protection provided by hypoxic preconditioning against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity was studied in SH-SY5Y neuroblastoma cells. In contrast to the cytotoxicity of 0.1% oxygen, 1% oxygen hypoxia for 24h did not cause significant cell death. A transient

Y. W. Tzeng; L. Y. Lee; P. L. Chao; H. C. Lee; R. T. Wu; A. M. Y. Lin

2010-01-01

341

High-Temperature Preconditioning and Thermal Shock Imposition Affects Water Relations, Gas Exchange and Root Hydraulic Conductivity in Tomato  

Microsoft Academic Search

Potted tomato plants (Lycopersicon esculentum Mill. cv. Amalia) were submitted to three different treatments: control (C) plants were maintained at day\\/night temperature\\u000a of 25\\/18 °C; preconditioned plants (PS) were submitted to two consecutive periods of 4 d each, of 30\\/23 and 35\\/28 °C before\\u000a being exposed to a heat stress (40\\/33 °C lasting 4 d) and non-preconditioned (S) plants were

D. Morales; P. Rodríguez; J. Dell'Amico; E. Nicolás; A. Torrecillas; M. J. Sánchez-Blanco

2003-01-01

342

Dinitrophenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection  

Microsoft Academic Search

Background: Recent studies have postulated that mitochondrial ATP-sensitive potassium (mitoK ) channel activation may modulate ATP mitochondrial function with the resultant induction of a preconditioning phenotype in the heart. We hypothesized that the modulation of mitochondrial homeostasis might confer preconditioning-like cardioprotection. Methods: We used a model of regional ischemia in Langendorff-perfused isolated rat hearts. Short-term administration of 2,4-dinitrophenol (DNP), an

Jan Minners; Ewout J. van den Bos; Derek M. Yellon; Herzl Schwalb; Lionel H. Opie; Michael N. Sack

343

Remote renal preconditioning-induced cardioprotection: a key role of hypoxia inducible factor-prolyl 4-hydroxylases  

Microsoft Academic Search

Remote preconditioning is a unique phenomenon in which brief episodes of ischemia and reperfusion to remote organ protect\\u000a the target organ against sustained ischemia–reperfusion (I\\/R)-induced injury. Protective effects of remote renal preconditioning\\u000a (RRPC) are well established in heart, but their mechanisms still remain to be elucidated. So, the present study was designed\\u000a to investigate the possible role of oxygen-sensing hypoxia

Ravi Kant; Vishal Diwan; Amteshwar Singh Jaggi; Nirmal Singh; Dhandeep Singh

2008-01-01

344

Preconditioned resistance to oxygen–glucose deprivation-induced cortical neuronal death: alterations in vesicular GABA and glutamate release  

Microsoft Academic Search

Central neurons exposed to several types of sublethal stress, including ischemia, acquire resistance to injury induced by subsequent ischemic insults, a phenomenon called ischemic preconditioning. We modeled this phenomenon in vitro, utilizing exposure to 45 mM KCl to reduce the vulnerability of cultured murine cortical neurons to subsequent oxygen–glucose deprivation. Twenty-four hours after preconditioning, cultures exhibited enhanced depolarization-induced, tetanus toxin-sensitive

M. C Grabb; D Lobner; D. M Turetsky; D. W Choi

2002-01-01

345

Ischemic Preconditioning Increases iNOS Transcript Levels in Conscious Rabbits via a Nitric Oxide-dependent Mechanism  

Microsoft Academic Search

Recent studies implicate iNOS as the mediator of the late phase of ischemic preconditioning (PC). However, it is unknown whether induction of iNOS activity is mediated by transcriptional, post-transcriptional, translational, or post-translational mechanisms. To address this issue, we isolated and sequenced a partial iNOS cDNA expressed in preconditioned rabbit myocardium. Using a rabbit-specific probe generated from this sequence, we measured

W. Keith Jones; Michael P. Flaherty; Xian-Liang Tang; Hitoshi Takano; Yumin Qiu; Supratim Banerjee; Traci Smith; Roberto Bolli

1999-01-01

346

P426Delayed preconditioning-like protection against ischemia/reperfusion injury in the rat heart is associated with PPAR-alpha-mediated changes in metabolic genes and non-metabolic effects.  

PubMed

Ischemia alters the balance between fatty acids (FA) and glucose utilization as the main ATP-producing pathways in the heart that may dramatically affect myocardial salvage upon ischemia/reperfusion (I/R). Genes encoding enzymes involved in metabolic processes are transcriptionally regulated by nuclear peroxisome proliferator-activated receptors (PPAR). PPAR-alpha isoform is mainly responsible for FA uptake/transport, beta-oxidation (FAO) and glucose transport/oxidation. During ischemia, it modulates substrates switch aimed at the adequate energy production to preserve cardiac function. However, the role of PPAR-mediated metabolic shifts in protective effects of preconditioning (PC) is relatively less investigated. We explored the effects of PPAR-alpha activation in a setting simulating a delayed PC in the rat heart and potential downstream genomic and non-genomic mechanisms involved. Animals were given PPAR-alpha agonist WY-14643 (WY, 1 mg/kg, i.p.) with or without PPAR-alpha antagonist MKK-886 (MKK), 24 hr prior to 30-min global ischemia/2-h reperfusion in Langendorff-perfused hearts. Sampling for measurement of the expression of PPAR-alpha and its target genes (MCAD, PDK-4, mCPT-1, GLUT-4) and gene of heme oxygenase-1 (HO-1) as a key antioxidative enzyme (real-time RT-PCR), as well as for the determination of levels and phosphorylation of survival proteins (Akt, eNOS) and markers of apoptosis (Bax, Bcl-2, caspase-3) was performed at baseline (prior to ischemia) and after I/R (WB analysis). Pretreatment with WY attenuated postischemic contractile dysfunction, reduced the severity of ventricular arrhythmias and limited the extent of lethal injury (infarct size). These cardioprotective effects were blunted by inhibitor of NO synthase L-NAME and reversed by MKK treatment indicating a PPAR-alpha-dependent response. Administration of WY remarkably enhanced the expression of PPAR-alpha and its target genes promoting FAO (MCAD, PDK-4 and mCPT-1) coupled with reduced expression of GLUT-4 responsible for glucose metabolism and with up-regulation of HO-1. In addition, enhanced Akt phosphorylation and eNOS expression, as well as changes in pro- and antiapoptotic markers (increased Bcl-2/Bax ratio, reduced caspase-3 cleavage) were observed in the WY-treated hearts. Up-regulation of PPAR-alpha target metabolic genes regulating FAO may underlie delayed protection in the rat heart. Potential non-metabolic effects of PPAR-alpha-mediated cardioprotection may involve activation of PI3K/Akt and its downstream targets, such as eNOS, and modulation of oxidative stress and apoptosis. PMID:25020809

Ravingerova, T; Carnicka, S; Ledvenyiova, V; Barlaka, E; Galatou, E; Mandikova, P; Chytilova, A; Nemcekova, M; Kolar, F; Lazou, A

2014-07-15

347

On linearization and preconditioning for radiation diffusion coupled to material thermal conduction equations  

SciTech Connect

Jacobian-free Newton–Krylov (JFNK) method is an effective algorithm for solving large scale nonlinear equations. One of the most important advantages of JFNK method is that there is no necessity to form and store the Jacobian matrix of the nonlinear system when JFNK method is employed. However, an approximation of the Jacobian is needed for the purpose of preconditioning. In this paper, JFNK method is employed to solve a class of non-equilibrium radiation diffusion coupled to material thermal conduction equations, and two preconditioners are designed by linearizing the equations in two methods. Numerical results show that the two preconditioning methods can improve the convergence behavior and efficiency of JFNK method.

Feng, Tao, E-mail: fengtao2@mail.ustc.edu.cn [School of Mathematical Sciences, University of Science and Technology of China, Hefei 230052 (China) [School of Mathematical Sciences, University of Science and Technology of China, Hefei 230052 (China); Graduate School of China Academy Engineering Physics, Beijing 100083 (China); An, Hengbin, E-mail: an_hengbin@iapcm.ac.cn [National Key Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing 100094 (China)] [National Key Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing 100094 (China); Yu, Xijun, E-mail: yuxj@iapcm.ac.cn [National Key Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing 100094 (China)] [National Key Laboratory of Computational Physics, Institute of Applied Physics and Computational Mathematics, Beijing 100094 (China); Li, Qin, E-mail: liqin@lsec.cc.ac.cn [Chinese Academy of Mathematics and Systems Science, Beijing 100190 (China)] [Chinese Academy of Mathematics and Systems Science, Beijing 100190 (China); Zhang, Rongpei, E-mail: zhangrongpei@163.com [Graduate School of China Academy Engineering Physics, Beijing 100083 (China)] [Graduate School of China Academy Engineering Physics, Beijing 100083 (China)

2013-03-01

348

The North Pacific High and wintertime pre-conditioning of California current productivity  

NASA Astrophysics Data System (ADS)

Abstract Variations in large-scale atmospheric forcing influence upwelling dynamics and ecosystem productivity in the California Current System (CCS). In this paper, we characterize interannual variability of the North Pacific High over 40 years and investigate how variation in its amplitude and position affect upwelling and biology. We develop a winter upwelling "<span class="hlt">pre-conditioning</span>" index and demonstrate its utility to understanding biological processes. Variation in the winter NPH can be well described by its areal extent and maximum pressure, which in turn is predictive of winter upwelling. Our winter <span class="hlt">pre-conditioning</span> index explained 64% of the variation in biological responses (fish and seabirds). Understanding characteristics of the NPH in winter is therefore critical to predicting biological responses in the CCS.</p> <div class="credits"> <p class="dwt_author">Schroeder, Isaac D.; Black, Bryan A.; Sydeman, William J.; Bograd, Steven J.; Hazen, Elliott L.; Santora, Jarrod A.; Wells, Brian K.</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-02-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">349</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3652384"> <span id="translatedtitle">The late phase of <span class="hlt">preconditioning</span> and its natural clinical application--gene therapy</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p class="result-summary">There is little doubt that the discovery of ischemic <span class="hlt">preconditioning</span> (PC) has been one of the fundamental milestones in the field of ischemic biology in the past 20 years. The purpose of this article is to review the pathophysiology and molecular basis of the late phase of myocardial PC. The exploitation of late PC for the development of novel gene therapy strategies aimed at inducing a permanently <span class="hlt">preconditioned</span> cardiac phenotype (prophylactic cardioprotection) will also be discussed. Deciphering the mechanism of late PC has not only conceptual interest but also a considerable therapeutic implications, since transfer of the genes that underlie late PC would be expected to replicate the salubrious effects of this response of the heart to stress.</p> <div class="credits"> <p class="dwt_author">Li, Qian-Hong; Tang, Xian-Liang; Guo, Yiru; Xuan, Yu-Ting; Rokosh, Gregg; Dawn, Buddhadeb</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">350</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.osti.gov/scitech/biblio/970636"> <span id="translatedtitle">On Physics-Based <span class="hlt">Preconditioning</span> of the Navier-Stokes Equations</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p class="result-summary">An new and more ecient all-speed flow algorithm is developed. The governing hy- drodynamic equations, in conservative form, are solved implicitly using Jacobian- free Newton-Krylov methods. To overcome numerical stiffness caused by the dis- parity between acoustic and advective modes, the governing hydrodynamic equa- tions are transformed to the primitive variable form in a <span class="hlt">preconditioning</span> step. This transformation enables implicit treatment of distinct physics using traditional semi- implicit and physics-based splitting approaches without a loss of consistency be- tween the original and <span class="hlt">preconditioned</span> systems. The resulting algorithm is capable of solving slow natural circulations (M ~ 10^-4) with signicant heat flux as well as the high-speed (M ~ 1) flows effciently by following dynamical time scales.</p> <div class="credits"> <p class="dwt_author">HyeongKae Park; Robert R. Nourgaliev; Richard C. Martineau; Dana A. Knoll</p> <p class="dwt_publisher"></p> <p class="publishDate">2009-12-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">351</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://adsabs.harvard.edu/abs/2013JCoPh.236...28F"> <span id="translatedtitle">On linearization and <span class="hlt">preconditioning</span> for radiation diffusion coupled to material thermal conduction equations</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p class="result-summary">Jacobian-free Newton-Krylov (JFNK) method is an effective algorithm for solving large scale nonlinear equations. One of the most important advantages of JFNK method is that there is no necessity to form and store the Jacobian matrix of the nonlinear system when JFNK method is employed. However, an approximation of the Jacobian is needed for the purpose of <span class="hlt">preconditioning</span>. In this paper, JFNK method is employed to solve a class of non-equilibrium radiation diffusion coupled to material thermal conduction equations, and two preconditioners are designed by linearizing the equations in two methods. Numerical results show that the two <span class="hlt">preconditioning</span> methods can improve the convergence behavior and efficiency of JFNK method.</p> <div class="credits"> <p class="dwt_author">Feng, Tao; An, Hengbin; Yu, Xijun; Li, Qin; Zhang, Rongpei</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-03-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">352</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://ntrs.nasa.gov/search.jsp?R=19970006601&hterms=finite+elements&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D70%26Ntt%3Dfinite%2Belements"> <span id="translatedtitle">A Note on Substructuring <span class="hlt">Preconditioning</span> for Nonconforming Finite Element Approximations of Second Order Elliptic Problems</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p class="result-summary">In this paper an algebraic substructuring preconditioner is considered for nonconforming finite element approximations of second order elliptic problems in 3D domains with a piecewise constant diffusion coefficient. Using a substructuring idea and a block Gauss elimination, part of the unknowns is eliminated and the Schur complement obtained is <span class="hlt">preconditioned</span> by a spectrally equivalent very sparse matrix. In the case of quasiuniform tetrahedral mesh an appropriate algebraic multigrid solver can be used to solve the problem with this matrix. Explicit estimates of condition numbers and implementation algorithms are established for the constructed preconditioner. It is shown that the condition number of the <span class="hlt">preconditioned</span> matrix does not depend on either the mesh step size or the jump of the coefficient. Finally, numerical experiments are presented to illustrate the theory being developed.</p> <div class="credits"> <p class="dwt_author">Maliassov, Serguei</p> <p class="dwt_publisher"></p> <p class="publishDate">1996-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">353</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://adsabs.harvard.edu/abs/2012AIPC.1487..314B"> <span id="translatedtitle">Parallelization of the <span class="hlt">preconditioned</span> IDR solver for modern multicore computer systems</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p class="result-summary">This paper present the analysis, parallelization and optimization approach for the large sparse matrix solver CNSPACK for modern multicore microprocessors. CNSPACK is an advanced solver successfully used for coupled solution of stiff problems arising in multiphysics applications such as CFD, semiconductor transport, kinetic and quantum problems. It employs iterative IDR algorithm with ILU <span class="hlt">preconditioning</span> (user chosen ILU <span class="hlt">preconditioning</span> order). CNSPACK has been successfully used during last decade for solving problems in several application areas, including fluid dynamics and semiconductor device simulation. However, there was a dramatic change in processor architectures and computer system organization in recent years. Due to this, performance criteria and methods have been revisited, together with involving the parallelization of the solver and preconditioner using Open MP environment. Results of the successful implementation for efficient parallelization are presented for the most advances computer system (Intel Core i7-9xx or two-processor Xeon 55xx/56xx).</p> <div class="credits"> <p class="dwt_author">Bessonov, O. A.; Fedoseyev, A. I.</p> <p class="dwt_publisher"></p> <p class="publishDate">2012-10-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">354</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.osti.gov/scitech/biblio/989166"> <span id="translatedtitle">Microglial ablation and lipopolysaccharide <span class="hlt">preconditioning</span> affects pilocarpine-induced seizures in mice</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p class="result-summary">Activated microglia have been associated with neurodegeneration in patients and in animal models of Temporal Lobe Epilepsy (TLE), however their precise functions as neurotoxic or neuroprotective is a topic of significant investigation. To explore this, we examined the effects of pilocarpine-induced seizures in transgenic mice where microglia/macrophages were conditionally ablated. We found that unilateral ablation of microglia from the dorsal hippocampus did not alter acute seizure sensitivity. However, when this procedure was coupled with lipopolysaccharide (LPS) <span class="hlt">preconditioning</span> (1 mg/kg given 24 h prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activation in the ipsilateral hippocampus during acute seizures, and could be attributed to activity in the mossy fiber pathway. These findings reveal that <span class="hlt">preconditioning</span> with LPS 24 h prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation.</p> <div class="credits"> <p class="dwt_author">Mirrione, M.M.; Mirrione, M.M.; Konomosa, D.K.; Ioradanis, G.; Dewey, S.L.; Agzzid, A.; Heppnerd, F.L.; Tsirka, St.E.</p> <p class="dwt_publisher"></p> <p class="publishDate">2010-04-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">355</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/19202436"> <span id="translatedtitle">Donor <span class="hlt">preconditioning</span> with a calcineurin inhibitor improves outcome in rat syngeneic kidney transplantation.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">Ischemia-reperfusion injury (IRI) in the early posttransplant period affects immediate graft function and late allograft dysfunction. This study determines the influence of pharmacologic <span class="hlt">preconditioning</span> with a calcineurin inhibitor on IRI in a syngeneic F344 rat kidney transplant model. Donor rats were pretreated with one dose of cyclosporine (10 mg/kg) or tacrolimus (1 mg/kg) administered at 24 hr or 7 days before being subjected to 2 hr of cold ischemia and then transplanted. Pharmacologic <span class="hlt">preconditioning</span> significantly improved renal function, as assessed by serum creatinine and inulin clearance, and histologic score versus vehicle-treated rats. There were no differences between cyclosporine and tacrolimus in the measured outcomes. This renoprotective effect, although not complete, was seen with only one dose of calcineurin inhibitor, and the effect was sustained for at least 7 days before IRI. This approach may represent a viable pharmacologic intervention to decrease IRI at the time of organ transplantation. PMID:19202436</p> <div class="credits"> <p class="dwt_author">Shihab, Fuad S; Bennett, William M; Andoh, Takeshi F</p> <p class="dwt_publisher"></p> <p class="publishDate">2009-02-15</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">356</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.cdc.gov/Features/PreventingSuicide/"> <span id="translatedtitle"><span class="hlt">Preventing</span> Suicide</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p class="result-summary">... for self-inflicted injuries. September 10th is World Suicide <span class="hlt">Prevention</span> Day. Help <span class="hlt">prevent</span> suicide in your community. Suicide ( ... is having thoughts of suicide, contact the National Suicide <span class="hlt">Prevention</span> Lifeline at 1-800-273-TALK (1-800- ...</p> <div class="credits"> <p class="dwt_author"></p> <p class="dwt_publisher"></p> <p class="publishDate"></p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">357</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/40956823"> <span id="translatedtitle">Water stress <span class="hlt">preconditioning</span> to improve drought resistance in young apricot plants</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">The effect of water stress <span class="hlt">preconditioning</span> was studied in 1-year-old apricot plants (Prunus armeniaca L., cv. Búlida). Plants were submitted to different treatments, T-0 (control treatment) and T-1, drip irrigated daily; T-2 and T-3, irrigated daily at 50% and 25% of T-0, respectively; T-4 and T-5, irrigated to field capacity every 3 and 6 days, respectively. After 30 days, irrigation</p> <div class="credits"> <p class="dwt_author">M. C Ruiz-Sánchez; R Domingo; A Torrecillas; A Pérez-Pastor</p> <p class="dwt_publisher"></p> <p class="publishDate">2000-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">358</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/1793862"> <span id="translatedtitle">PredictorCorrector <span class="hlt">Preconditioned</span> Newton-Krylov Method For Cavity Flow</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">\\u000a The Newton-Krylov method is used to solve the incompressible Navier-Stokes equations. In the present study, two numerical\\u000a schemes are considered for the method: employing the predictor-corrector method as preconditioner, and solving the equations\\u000a without the preconditioner. The standard driven cavity flow is selected as the test problem to demonstrate the efficiency\\u000a and the reliability of the present <span class="hlt">preconditioned</span> method. It</p> <div class="credits"> <p class="dwt_author">Jianwei Ju; Giovanni Lapenta</p> <p class="dwt_publisher"></p> <p class="publishDate">2005-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">359</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/50963167"> <span id="translatedtitle">Progress toward a stabilization and <span class="hlt">preconditioning</span> protocol for polycrystalline thin-film photovoltaic modules</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">Cadmium telluride (CdTe) and copper indium gallium diselenide (CIGS) thin-film photovoltaic (PV) modules can exhibit substantial variation in measured performance depending on prior exposure history. We studied the metastable performance changes in these PV modules with the goal of establishing standard <span class="hlt">preconditioning</span> or stabilization exposure procedures to mitigate measured variations prior to current-voltage (IV) measurements. We present the results of</p> <div class="credits"> <p class="dwt_author">Joseph A. del Cueto; Chris A. Deline; Steve R. Rummel; Allan Anderberg</p> <p class="dwt_publisher"></p> <p class="publishDate">2010-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">360</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3915687"> <span id="translatedtitle"><span class="hlt">Preconditioning</span> methods influence tumor property in an orthotopic bladder urothelial carcinoma rat model</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p class="result-summary">Urothelial carcinoma (UC) is an extremely common type of cancer that occurs in the bladder. It has a particularly high rate of recurrence. Therefore, preclinical studies using animal models are essential to determine effective forms of treatment. In the present study, in order to establish an orthotopic bladder UC animal model with clinical relevance, the effects of <span class="hlt">preconditioning</span> methods on properties of the developed tumor were evaluated. The bladder cavity was pretreated with phosphate-buffered saline (PBS), acid-base, trypsin (TRY) or poly (L-lysine) (PLL) and then rat UC cells (AY-27) (4×106 cells) were inoculated. The results demonstrated that, two weeks later, the tumorigenic rate (88%) and tumor count (2.3 per rat) were not significantly different among the <span class="hlt">preconditioning</span> methods, whereas tumor volume and invasion depth into bladder tissue were significantly different. Average tumor volumes were >50 mm3 in the PBS and acid-base-treated groups and <10 mm3 in the TRY- and PLL-treated groups. The percentage of invasive tumors (T2 or more advanced stage) was ?75% of total tumors in the PBS- and acid-base-treated groups, whereas the percentages were reduced in the TRY- and PLL-treated groups (58 and 32%, respectively). Non-invasive tumors (Ta or T1) accounted for 54% of tumors in the PLL-treated group, which was 2-5-fold higher than the percentages in the remaining groups. Properties of the developed tumor in the rat orthotopic UC model were different depending on <span class="hlt">preconditioning</span> methods. Therefore, different animal models suitable for a discrete preclinical examination may be established by using the appropriate <span class="hlt">preconditioning</span> condition.</p> <div class="credits"> <p class="dwt_author">MIYAZAKI, KOZO; MORIMOTO, YUJI; NISHIYAMA, NOBUHIRO; SATOH, HIROYUKI; TANAKA, MASAMITSU; SHINOMIYA, NARIYOSHI; ITO, KEIICHI</p> <p class="dwt_publisher"></p> <p class="publishDate">2014-01-01</p> </div> </div> </div> </div> <div id="filter_results_form" class="filter_results_form floatContainer" style="visibility: visible;"> <div style="width:100%" id="PaginatedNavigation" class="paginatedNavigationElement"> <a id="FirstPageLink" onclick='return showDiv("page_1");' href="#" title="First Page"> <img id="FirstPageLinkImage" class="Icon" src="http://www.science.gov/scigov/images/icon.first.18x20.png" alt="First Page" /></a> <a id="PreviousPageLink" onclick='return showDiv("page_17");' href="#" title="Previous Page"> <img id="PreviousPageLinkImage" class="Icon" 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<a onClick='return showDiv("page_6");' href="#">6</a> <a onClick='return showDiv("page_7");' href="#">7</a> <a onClick='return showDiv("page_8");' href="#">8</a> <a onClick='return showDiv("page_9");' href="#">9</a> <a onClick='return showDiv("page_10");' href="#">10</a> <a onClick='return showDiv("page_11");' href="#">11</a> <a onClick='return showDiv("page_12");' href="#">12</a> <a onClick='return showDiv("page_13");' href="#">13</a> <a onClick='return showDiv("page_14");' href="#">14</a> <a onClick='return showDiv("page_15");' href="#">15</a> <a onClick='return showDiv("page_16");' href="#">16</a> <a onClick='return showDiv("page_17");' href="#">17</a> <a onClick='return showDiv("page_18");' href="#">18</a> <a style="font-weight: bold;">19</a> <a onClick='return showDiv("page_20");' href="#">20</a> <a onClick='return showDiv("page_21");' href="#">21</a> <a onClick='return showDiv("page_22");' href="#">22</a> <a onClick='return showDiv("page_23");' href="#">23</a> <a onClick='return showDiv("page_24");' href="#">24</a> <a onClick='return showDiv("page_25");' href="#">25</a> </span> </span> <a id="NextPageLink" onclick='return showDiv("page_20");' href="#" title="Next Page"> <img id="NextPageLinkImage" class="Icon" src="http://www.science.gov/scigov/images/icon.next.18x20.png" alt="Next Page" /></a> <a id="LastPageLink" onclick='return showDiv("page_25.0");' href="#" title="Last Page"> <img id="LastPageLinkImage" class="Icon" src="http://www.science.gov/scigov/images/icon.last.18x20.png" alt="Last Page" /></a> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">361</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/61248903"> <span id="translatedtitle"><span class="hlt">Preconditioning</span> of nonconforming finite element methods for second-order elliptic boundary value problems</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">This thesis deals with the condition numbers and singular value distribution of the <span class="hlt">preconditioned</span> operators B[sub h][sup [minus]1]A[sub h] and A[sub h]B[sub h][sup [minus]1], where A[sub h] and B[sub h] are nonconforming finite element discretizations of second-order elliptic operators A and B. It generalizes the works of Manteuffel and Parter, Goldstein, Manteuffel and Parter, as well as Parter and Wong.</p> <div class="credits"> <p class="dwt_author"></p> <p class="dwt_publisher"></p> <p class="publishDate">1992-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">362</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3615821"> <span id="translatedtitle">Voltage <span class="hlt">Preconditioning</span> Allows Modulated Gene Expression in Neurons Using PEI-complexed siRNA</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p class="result-summary">We present here a high efficiency, high viability siRNA-delivery method using a voltage-controlled chemical transfection strategy to achieve modulated delivery of polyethylenimine (PEI) complexed with siRNA in an in vitro culture of neuro2A cells and neurons. Low voltage pulses were applied to adherent cells before the administration of PEI-siRNA complexes. Live assays of neuro2a cells transfected with fluorescently tagged siRNA showed an increase in transfection efficiency from 62 ± 14% to 98 ± 3.8% (after ?1?V). In primary hippocampal neurons, transfection efficiencies were increased from 30 ± 18% to 76 ± 18% (after ?1?V). Negligible or low-level transfection was observed after <span class="hlt">preconditioning</span> at higher voltages, suggesting an inverse relationship with applied voltage. Experiments with propidium iodide ruled out the role of electroporation in the transfection of siRNAs suggesting an alternate electro-endocytotic mechanism. In addition, image analysis of <span class="hlt">preconditioned</span> and transfected cells demonstrates siRNA uptake and loading that is tuned to <span class="hlt">preconditioning</span> voltage levels. There is approximately a fourfold increase in siRNA loading after <span class="hlt">preconditioning</span> at ?1?V compared with the same at ±2–3?V. Modulated gene expression is demonstrated in a functional knockdown of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in neuro2A cells using siRNA. Cell density and dendritic morphological changes are also demonstrated in modulated knockdown of brain derived neurotrophic factor (BDNF) in primary hippocampal neurons. The method reported here has potential applications in the development of high-throughput screening systems for large libraries of siRNA molecules involving difficult-to-transfect cells like neurons.</p> <div class="credits"> <p class="dwt_author">Sridharan, Arati; Patel, Chetan; Muthuswamy, Jit</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">363</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.osti.gov/scitech/biblio/6979656"> <span id="translatedtitle">Chebyshev pseudospectral solution of advection-diffusion equations with mapped finite difference <span class="hlt">preconditioning</span></span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p class="result-summary">A new Chebyshev pseudo-spectral algorithm with finite difference <span class="hlt">preconditioning</span> is proposed for the solution of advection-diffusion equations. A mapping technique is introduced which allows good convergence for any Peclet number both for one-dimensional and two-dimensional problems. Numerical results show that first-order Lagrange polynomials are the optimal mapping procedure for the one-dimensional problem and second-order Lagrange polynomials, for the two-dimensional one. 8 refs., 22 figs., 4 tabs.</p> <div class="credits"> <p class="dwt_author">Pinelli, A.; Benocci, C. (Von Karman Institute for Fluid Dynamics, Rhode-St-Genese (Belgium)); Deville, M. (Universite Catholique de Louvain, Louvain-La-Neuve (Belgium))</p> <p class="dwt_publisher"></p> <p class="publishDate">1994-05-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">364</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/23536200"> <span id="translatedtitle">Anti-caspase-3 <span class="hlt">preconditioning</span> increases proinsulin secretion and deteriorates posttransplant function of isolated human islets.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">Human islet isolation is associated with adverse conditions inducing apoptosis and necrosis. The aim of the present study was to assess whether antiapoptotic <span class="hlt">preconditioning</span> can improve in vitro and posttransplant function of isolated human islets. A dose-finding study demonstrated that 200 ?mol/L of the caspase-3 inhibitor Ac-DEVD-CMK was most efficient to reduce the expression of activated caspase-3 in isolated human islets exposed to severe heat shock. Ac-DEVD-CMK-pretreated or sham-treated islets were transplanted into immunocompetent or immunodeficient diabetic mice and subjected to static glucose incubation to measure insulin and proinsulin secretion. Antiapoptotic pretreatment significantly deteriorated graft function resulting in elevated nonfasting serum glucose when compared to sham-treated islets transplanted into diabetic nude mice (p < 0.01) and into immunocompetent mice (p < 0.05). Ac-DEVD-CMK pretreatment did not significantly change basal and glucose-stimulated insulin release compared to sham-treated human islets but increased the proinsulin release at high glucose concentrations (20 mM) thus reducing the insulin-to-proinsulin ratio in <span class="hlt">preconditioned</span> islets (p < 0.05). This study demonstrates that the caspase-3 inhibitor Ac-DEVD-CMK interferes with proinsulin conversion in <span class="hlt">preconditioned</span> islets reducing their potency to cure diabetic mice. The mechanism behind this phenomenon is unclear so far but may be related to the ketone CMK linked to the Ac-DEVD molecule. Further studies are required to identify biocompatible caspase inhibitors suitable for islet <span class="hlt">preconditioning</span>. PMID:23536200</p> <div class="credits"> <p class="dwt_author">Brandhorst, Daniel; Brandhorst, Heide; Maataoui, Vidya; Maataoui, Adel; Johnson, Paul R V</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-06-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">365</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://web.lmd.jussieu.fr/~flott/articles/JPO_96.pdf"> <span id="translatedtitle">Large-Scale <span class="hlt">Preconditioning</span> of Deep-Water Formation in the Northwestern Mediterranean Sea</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">The large-scale processes <span class="hlt">preconditioning</span> the winter deep-water formation in the northwestern Mediterranean Sea are investigated with a primitive equation numerical model where convection is parameterized by a non- penetrative convective adjustment algorithm. The ocean is forced by momentum and buoyancy fluxes that have the gross features of mean winter forcing found in the MEDOC area. The wind-driven barotropic circulation appears</p> <div class="credits"> <p class="dwt_author">Gurvan Madec; François Lott; Pascale Delecluse; Michel Crépon</p> <p class="dwt_publisher"></p> <p class="publishDate">1996-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">366</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/23936589"> <span id="translatedtitle">Effects of ischemic <span class="hlt">preconditioning</span> and iloprost on myocardial ischemia-reperfusion damage in rats.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">This study investigates the effects of cardiac ischemic <span class="hlt">preconditioning</span> 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 <span class="hlt">preconditioning</span> (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic <span class="hlt">preconditioning</span> + 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 <span class="hlt">preconditioning</span>, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes. PMID:23936589</p> <div class="credits"> <p class="dwt_author">Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">367</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/12216964"> <span id="translatedtitle">Ischemic <span class="hlt">preconditioning</span> and nicotinamide in spinal cord protection in an experimental model of transient aortic occlusion</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">Objectives: Spinal cord injury is a devastating complication after aortic surgery. The aim of the present study is to examine the effects of ischemic <span class="hlt">preconditioning</span> (IPC) and nicotinamide containing perfusate in transient aortic occlusion in the rat. Methods: Thirty-two male Spraque–Dawley rats under general anesthesia were randomly assigned to four groups (n=8 in each group). The infrarenal aortas were clamped</p> <div class="credits"> <p class="dwt_author">C. Selim Isbir; Koray Aka; Ozlem Kurtkaya; Ümit Zeybek; Serdar Akgün; Bernd W. Scheitauer; Aydin Sav; Adnan Cobanoglu</p> <p class="dwt_publisher"></p> <p class="publishDate">2003-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">368</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3731182"> <span id="translatedtitle">Effects of ischemic <span class="hlt">preconditioning</span> and iloprost on myocardial ischemia-reperfusion damage in rats</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p class="result-summary">This study investigates the effects of cardiac ischemic <span class="hlt">preconditioning</span> 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 <span class="hlt">preconditioning</span> (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic <span class="hlt">preconditioning</span> + 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 <span class="hlt">preconditioning</span>, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes.</p> <div class="credits"> <p class="dwt_author">Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">369</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/22929656"> <span id="translatedtitle">Impact of <span class="hlt">preconditioning</span> pulse on lesion formation during high-intensity focused ultrasound histotripsy.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">Therapeutic applications with high-intensity focused ultrasound (HIFU) fall into two classifications-one using thermal effect for coagulation or ablation while generally avoiding cavitation and the other using cavitation-mediated mechanical effects while suppressing heating. Representative of the latter, histotripsy uses HIFU at low duty factor to create energetic bubble clouds inside tissue to liquefy a region and has the advantages in real-time monitoring and lesion fidelity to treatment planning. We explored the impact of a <span class="hlt">preconditioning</span>/heating pulse on histotripsy lesion formation in porcine muscle samples. During sonication, a targeted square region 9 mm wide (lateral to the focal plane) was scanned in a raster pattern with a step size of 0.75 mm. The 20-s exposure at each treatment location consisted of a 5-s duration <span class="hlt">preconditioning</span> burst at spatial-peak intensities from 0-1386 W/cm² followed by 5000 tone bursts at high intensity (with spatial-peak pulse-average intensity of 47.34 kW/cm², spatial-peak temporal-average intensity of 284 W/cm², peak compressional pressure of 102 MPa and peak rarefactional pressure of 17 MPa). The temperature increase for all exposures was measured using a thermal imager immediately after each exposure. Lesion volume increased with increasing amplitude of the <span class="hlt">preconditioning</span> pulse until coagulation was observed, but lesion width/area did not change significantly with the amplitude. In addition, the lesion dimensions became smaller when the global tissue temperature was raised before applying the histotripsy pulsing sequence. Therefore, the benefit of the <span class="hlt">preconditioning</span> pulse was not caused by global heating. PMID:22929656</p> <div class="credits"> <p class="dwt_author">Xu, Jin; Bigelow, Timothy A; Riesberg, Grant M</p> <p class="dwt_publisher"></p> <p class="publishDate">2012-11-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">370</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/49178615"> <span id="translatedtitle">Critical investigation of <span class="hlt">preconditioned</span> GMRES via incomplete LU factorization applied to power flow simulation</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">For solving the power flow sublinear problem efficiently by the GMRES <span class="hlt">preconditioned</span> via incomplete LU factorization (ILU), this paper investigates causes associated to the preconditioner low quality and proposes a method to improve it and the GMRES convergence rate as well. The goal is provide a well-organized ILU-GMRES for solving linear systems of difficult solution comprising ill-conditioned coefficient matrices, normally</p> <div class="credits"> <p class="dwt_author">José Eduardo O. Pessanha; Carlos Portugal; Ricardo Prada; Alex R. Paz</p> <p class="dwt_publisher"></p> <p class="publishDate">2011-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">371</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/1502276"> <span id="translatedtitle">Multiple scattering among vias in planar waveguides using <span class="hlt">preconditioned</span> SMCG method</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">Full-wave modeling for cylindrical vias in planar waveguides is formulated using Foldy-Lax multiple scattering equations. Recently, a sparse-matrix canonical-grid method based on fast Fourier transform and an iterative algorithm was proposed to solve a large-scale via problem. In this paper, we further improve computational efficiency by a <span class="hlt">preconditioning</span> scheme based on the dominant information contained in the near field. We</p> <div class="credits"> <p class="dwt_author">Chung-Chi Huang; Leung Tsang; Chi Hou Chan; Kung-Hau Ding</p> <p class="dwt_publisher"></p> <p class="publishDate">2004-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">372</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/26963919"> <span id="translatedtitle">Algebraic Multigrid <span class="hlt">Preconditioned</span> Krylov Subspace Methods for Fluid Flow and Heat Transfer on Unstructured Meshes</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">A numerical tool, Thermoflow, is developed for simulating the three-dimensional incompressible viscous flow and heat transfer on unstructured meshes. It is based on a cell-centered, collocated finite-volume method. The velocity–pressure coupling is treated using the SIMPLE\\/C algorithm. An agglomerated multigrid method (AgMG) and the AgMG <span class="hlt">preconditioned</span> Krylov subspace methods are implemented to solve the linearized partial differential equations. Their performances</p> <div class="credits"> <p class="dwt_author">Qinghua Wang; Yogendra Joshi</p> <p class="dwt_publisher"></p> <p class="publishDate">2006-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">373</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://louisville.edu/medschool/cardiology/Publications/previouspubs/Circ103-2935.pdf"> <span id="translatedtitle">Delayed <span class="hlt">Preconditioning</span>-Mimetic Action of Nitroglycerin in Patients Undergoing Coronary Angioplasty</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">Background—Experimental studies suggest that the cardioprotective effects of the late phase of ischemic <span class="hlt">preconditioning</span> (PC) can be mimicked pharmacologically. However, to date, no drug has been tested with respect to its ability to elicit a late PC effect in humans. As a consequence, clinical exploitation of the powerful anti-stunning and anti-infarct actions of late PC has been elusive thus far.</p> <div class="credits"> <p class="dwt_author">Massoud A. Leesar; Marcus F. Stoddard; Buddhadeb Dawn; Venu G. Jasti; Ronald Masden; Roberto Bolli</p> <p class="dwt_publisher"></p> <p class="publishDate">2010-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">374</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/20609912"> <span id="translatedtitle">Methods for studying redox cycling of thioredoxin in mediating <span class="hlt">preconditioning</span>-induced survival genes and proteins.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">Recent advances in molecular biology provide methods and tools for studying cell signaling pathways underlying hormetic mechanisms produced by radiation hormesis, ischemic, remote ischemic, and chemical <span class="hlt">preconditioning</span> as well as withholding of nutrients and/or trophic factors. Most of the proposed key signaling pathways of hormetic mechanisms remain to be elucidated. For the investigation of possible role of thiol redox signaling systems in hormesis, a serum deprivation <span class="hlt">preconditioned</span> human cell model, free radical assays, and molecular biological methods are employed for studying whether free radicals, the NO-cGMP-PKG cell signaling pathway, and the redox protein thioredoxin (Trx) play any roles in the hormetic mechanism against cytotoxicity caused by serum deprivation and also neurotoxin 1-methyl-4-phenyltetrahydropyridinium ion (MPP(+)). This NO-dependent cell signaling pathway of the redox protein Trx may play a key role in the cellular protective mechanism of several potential neuroprotective agents such as S-nitrosoglutathione (GSNO), 17beta-estradiol, selegiline as well as ebeselen, sildenafil, and rasagiline. Consistently, exogenously administrated Trx (<1 microM) provides a concentration-dependent protection for human neuroblasts against MPP(+)-induced oxidative injury. This newly discovered role of the redox protein of Trx in <span class="hlt">preconditioning</span>-induced cell signaling and protection could lead to the development of new lead compounds for upregulation of Trx and related thiol redox proteins for cell survival, repair, proliferation, and neuronal plasticity. PMID:20609912</p> <div class="credits"> <p class="dwt_author">Chiueh, Chuang C</p> <p class="dwt_publisher"></p> <p class="publishDate">2010-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">375</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://adsabs.harvard.edu/abs/2009JCoPh.228.9131P"> <span id="translatedtitle">On physics-based <span class="hlt">preconditioning</span> of the Navier-Stokes equations</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p class="result-summary">We develop a fully implicit scheme for the Navier-Stokes equations, in conservative form, for low to intermediate Mach number flows. Simulations in this range of flow regime produce stiff wave systems in which slow dynamical (advective) modes coexist with fast acoustic modes. Viscous and thermal diffusion effects in refined boundary layers can also produce stiffness. Implicit schemes allow one to step over the fast wave phenomena (or unresolved viscous time scales), while resolving advective time scales. In this study we employ the Jacobian-free Newton-Krylov (JFNK) method and develop a new physics-based preconditioner. To aid in overcoming numerical stiffness caused by the disparity between acoustic and advective modes, the governing equations are transformed into the primitive-variable form in a <span class="hlt">preconditioning</span> step. The physics-based <span class="hlt">preconditioning</span> incorporates traditional semi-implicit and physics-based splitting approaches without a loss of consistency between the original and <span class="hlt">preconditioned</span> systems. The resulting algorithm is capable of solving low-speed natural circulation problems (M˜10-4) with significant heat flux as well as intermediate speed (M˜1) flows efficiently by following dynamical (advective) time scales of the problem.</p> <div class="credits"> <p class="dwt_author">Park, HyeongKae; Nourgaliev, Robert R.; Martineau, Richard C.; Knoll, Dana A.</p> <p class="dwt_publisher"></p> <p class="publishDate">2009-12-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">376</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3558717"> <span id="translatedtitle">Emulsified Isoflurane <span class="hlt">Preconditioning</span> Protects Isolated Rat Kupffer Cells against Hypoxia/Reoxygenation-Induced Injury</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p class="result-summary">Objective: To investigate the protective effect of emulsified isoflurane (EI) <span class="hlt">preconditioning</span> on isolated rat Kupffer cells (KCs) subjected to hypoxia/reoxygenation (H/R)-induced injury. Materials and methods: KCs were isolated by collagenase digestion and purified by Percoll density gradient centrifugation. Primary cultured KCs were divided into five groups: control, H/R plus 0.1% lipid <span class="hlt">preconditioning</span>, and H/R plus 0.05%, 0.1% or 0.2% emulsified isoflurane <span class="hlt">preconditioning</span> groups. H/R was induced by 4 h of hypoxia followed by 6 h of reoxygenation. Reactive oxygen species (ROS) production in the KCs and the concentration of tumor necrosis factor-? (TNF-?) in the KC culture media were measured, and the apoptosis of KCs was assayed concomitantly. Results: ROS and TNF-? production were markedly induced in the H/R + lipid group, and lower in the 0.2% and 0.1% EI groups (P<0.05). The apoptotic rate in the H/R + lipid group was significantly higher than that in the 0.2% and 0.1% EI groups (P<0.05). Conclusions: Emulsified isoflurane protects isolated rat KCs against H/R induced injury by decreasing the production of ROS and TNF-? and attenuating apoptosis in KCs.</p> <div class="credits"> <p class="dwt_author">Wang, Zhenmeng; Lv, Hao; Song, Shaohua; Shen, Xiaoyun; Yang, Liqun; Yu, Weifeng</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">377</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/24771476"> <span id="translatedtitle">Cerebellar cytokine expression in a rat model for fetal asphyctic <span class="hlt">preconditioning</span> and perinatal asphyxia.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">Asphyctic brain injury is a major cause of neuronal inflammation in the perinatal period. Fetal asphyctic <span class="hlt">preconditioning</span> has been shown to modulate the cerebral inflammatory cytokine response, hereby protecting the brain against asphyctic injury at birth. This study was designated to examine the effects of perinatal asphyxia and fetal asphyctic <span class="hlt">preconditioning</span> on the inflammatory cytokine response in the cerebellum. Fetal asphyxia was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global perinatal asphyxia was induced by placing the uterine horns in saline for 19 min. Pro- and anti-inflammatory cytokine expression were assessed by real-time PCR and immunohistochemistry in cerebella of newborn rats. We found that tumor necrosis factor alpha and interleukin-10 mRNA were increased 12 h after fetal asphyxia, while the inflammatory cytokine response was decreased 96 h postfetal asphyxia. When applied as <span class="hlt">preconditioning</span> stimulus, fetal asphyxia attenuates the cerebellar cytokine response. These results indicate that sublethal fetal asphyxia may protect the cerebellum from perinatal asphyxia-induced damage via inhibition of inflammation. PMID:24771476</p> <div class="credits"> <p class="dwt_author">Vlassaks, Evi; Brudek, Tomasz; Pakkenberg, Bente; Gavilanes, Antonio W D</p> <p class="dwt_publisher"></p> <p class="publishDate">2014-08-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">378</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://adsabs.harvard.edu/abs/2013SPIE.9067E..1ZY"> <span id="translatedtitle">Completeness set proof of <span class="hlt">precondition</span> and post-condition types of activity in any EPM</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p class="result-summary">Software evolution process model (EPM) is created in terms of a formal evolution process meta-model (EPMM) and semi-formal approach to modeling based on EPMM [1]. In order to better manage and control the software evolution process and make the best of existing software technology, the method to transform any EPM to its execution model based logic programming has been proposed. Completeness of conversion depends on completeness of the rules, that is, all the expressions of the original model are found the correspondence in the target model. Since transformation rules are proposed based on <span class="hlt">precondition</span> or post-condition types of activities in anyone EPM, this need to prove that activity type set in anyone EPM is completeness set. To this end, the <span class="hlt">precondition</span> and post-condition of activities in EPM are classified based on analyzing all expressions in EPMs and the semantics of the activity execution. Type completeness set of activity's <span class="hlt">precondition</span> and its post-condition is presented. Lastly we prove that the activity type set in anyone EPM is completeness set by mathematical induction.</p> <div class="credits"> <p class="dwt_author">Yu, Qian; Li, Tong; Liu, JinZhuo; Zhang, Xuan; Yu, Yong</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-12-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">379</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/11693187"> <span id="translatedtitle">Effects of dietary polyunsaturated fatty acids and hepatic steatosis on the functioning of isolated working rat heart under normoxic conditions and during <span class="hlt">post-ischemic</span> reperfusion.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">The purpose of this study was to modify the amount of 22:4 n-6, 22:5 n-6 and 20:5 n-3 in cardiac phospholipids and to evaluate the influence of these changes on the functioning of working rat hearts and mitochondrial energy metabolism under normoxic conditions and during <span class="hlt">postischemic</span> reperfusion. The animals were fed one of these four diets: (i) 10% sunflower seed oil (SSO); (ii) 10% SSO + 1% cholesterol; (iii) 5% fish oil (FO, EPAX 3000TG, Pronova) + 5% SSO; (iv) 5% FO + 5% SSO + 1% cholesterol. Feeding n-3 PUFA decreased n-6 PUFA and increased n-3 PUFA in plasma lipids. In the phospholipids of cardiac mitochondria, this dietary modification also induced a decrease in the n-6/n-3 PUFA ratio. Cholesterol feeding induced marked hepatic steatosis (HS) characterized by the whitish appearance of the liver. It also brought about marked changes in the fatty acid composition of plasma and mitochondrial phospholipids. These changes, characterized by the impairment of deltaS- and delta6-desaturases, were more obvious in the SSO-fed rats, probably because of the presence of the precursor of the n-6 family (linoleate) in the diet whereas the FO diet contained large amounts of eicosapentaenoic and docosahexaenoic acids. In the mitochondrial phospholipids of SSO-fed rats, the (22:4 n-6 + 22:5 n-6) to 18:2 n-6 ratio was decreased by HS, without modification of the proportion of 20:4 n-6. In the mitochondrial phospholipids of FO-fed rats, the amount of 20:5 n-3 tended to be higher (+56%). Cardiac functioning was modulated by the diets. Myocardial coronary flow was enhanced by HS in the SSO-fed rats, whereas it was decreased in the FO-fed animals. The rate constant k012 representing the activity of the adenylate kinase varied in the opposite direction, suggesting that decreased ADP concentrations could cause oxygen wasting through the opening of the permeability transition pore. The recovery of the pump function tended to be increased by n-3 PUFA feeding (+22%) and HS (+45%). However, the release of ascorbyl free radical during reperfusion was not significantly modified by the diets. Conversely, energy production was increased by ischemia/reperfusion in the SSO group, whereas it was not modified in the FO group. This supports greater ischemia/reperfusion-induced calcium accumulation in the SSO groups than in the FO groups. HS did not modify the mitochondrial energy metabolism during ischemia/reperfusion. Taken together, these data suggest that HS- and n-3 PUFA-induced decrease in 22:4 and 22:5 n-6 and increase in 20:5 n-3 favor the recovery of mechanical activity during <span class="hlt">post-ischemic</span> reperfusion. PMID:11693187</p> <div class="credits"> <p class="dwt_author">Demaison, L; Moreau, D; Vergely-Vandriesse, C; Grégoire, S; Degois, M; Rochette, L</p> <p class="dwt_publisher"></p> <p class="publishDate">2001-08-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">380</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/10560948"> <span id="translatedtitle">Effects of the phlebotropic drug Daflon 500 mg on <span class="hlt">postischemic</span> reperfusion injury in striated skin muscle: a histomorphologic study in the hamster.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">The objective of this study was to investigate the effects of the purified, micronized, flavonoid fraction Daflon 500 mg (S 5682, 90% diosmin and 10% hesperidin) on tissue damage and leukocyte emigration in striated skin muscle after ischemia-reperfusion, as assessed by histomorphometric analysis. The experimental model used was the transparent dorsal skin fold chamber in the awake Syrian golden hamster. Sixty-four animals were randomly allotted to two treatment groups and time points of investigation. Animals were fed with 30 mg kg(-1) body weight Daflon 500 mg (n = 32) or its vehicle, 5% Arabic gum solution (n = 32), as control 8 hours before ischemia. Before induction of a tourniquet ischemia of 4 hours' duration and at 0.5, 2, and 24 hours of reperfusion, tissue sections were preserved for light and electron microscopic analysis (n = seven or eight animals per time point). The number of intravascular and extravascular leukocytes was determined by light microscopic analysis of esterase-positive leukocytes. For quantitative analysis of ischemia-induced endothelial cell damage, the endothelial thickness of capillaries was calculated by a computer-assisted imaging system, whereas the ischemic tissue damage was assessed by means of a score system (grade 0-3) by an independent investigator. The number of emigrated leukocytes was significantly reduced in Daflon 500 mg-treated animals compared with numbers found in control animals. The histomorphologic muscle fiber damage increased after reperfusion in both groups but was significantly reduced in the Daflon 500 mg-treated animals 2 and 24 hours after reperfusion. These results suggest that the emigration of leukocytes plays an important role in the development of <span class="hlt">postischemic</span> reperfusion injury of striated skin muscle. PMID:10560948</p> <div class="credits"> <p class="dwt_author">Pickelmann, S; Nolte, D; Leiderer, R; Möllmann, M; Schütze, E; Messmer, K</p> <p class="dwt_publisher"></p> <p class="publishDate">1999-11-01</p> </div> </div> </div> </div> <div id="filter_results_form" class="filter_results_form floatContainer" style="visibility: visible;"> <div style="width:100%" id="PaginatedNavigation" class="paginatedNavigationElement"> <a id="FirstPageLink" onclick='return showDiv("page_1");' href="#" title="First Page"> <img id="FirstPageLinkImage" class="Icon" src="http://www.science.gov/scigov/images/icon.first.18x20.png" alt="First Page" /></a> <a id="PreviousPageLink" onclick='return showDiv("page_18");' href="#" title="Previous Page"> <img id="PreviousPageLinkImage" class="Icon" src="http://www.science.gov/scigov/images/icon.previous.18x20.png" alt="Previous Page" /></a> <span id="PageLinks" class="pageLinks"> <span> <a onClick='return showDiv("page_1");' href="#">1</a> <a onClick='return 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title="Next Page"> <img id="NextPageLinkImage" class="Icon" src="http://www.science.gov/scigov/images/icon.next.18x20.png" alt="Next Page" /></a> <a id="LastPageLink" onclick='return showDiv("page_25.0");' href="#" title="Last Page"> <img id="LastPageLinkImage" class="Icon" src="http://www.science.gov/scigov/images/icon.last.18x20.png" alt="Last Page" /></a> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">381</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/23869939"> <span id="translatedtitle">Grafts enriched with subamnion-cord-lining mesenchymal stem cell angiogenic spheroids induce <span class="hlt">post-ischemic</span> myocardial revascularization and preserve cardiac function in failing rat hearts.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">A crucial question in <span class="hlt">post-ischemic</span> cell therapy refers to the ideal method of cell delivery to the heart. We hypothesized that epicardial implantation of subamnion-cord-lining mesenchymal stem cells (CL-MSC) angiogenic spheroids embedded within fibrin grafts (SASG) facilitates donor cell survival and enhances cardiac function in failing rat hearts. Furthermore, we compared the efficacy of this approach applied through two delivery methods. Spheroids made of 1.5×10(4) human CL-MSC coated with 2×10(3) human umbilical vein endothelial cells were self-assembled in hanging drops. SASG were constructed by embedding 150 spheroids in fibrin matrix. Except for untreated rats (MI, n=8), grafts were implanted 2 weeks after myocardial infarction upon confirmation of ensued heart failure through thoracotomy: SASG (n=8) and fibrin graft (FG, n=8); or video-assisted thoracoscopic surgery (VATS): SASG-VATS (n=8) and FG-VATS (n=7). In vivo CL-MSC survival was comparable between both SASG-treated groups throughout the study. SASG and SASG-VATS animals had decreased left ventricular end-diastolic pressure relative to untreated animals, and increased fractional shortening compared to MI and FG controls, 4 weeks after treatment. A 14.1% and 6.2% enhancement in ejection fraction from week 2 to 6 after injury was observed in SASG/SASG-VATS, paralleled by improvement in cardiac output. Treated hearts had smaller scar size, and more blood vessels than MI, while donor CL-MSC contributed to arteriogenesis within the graft and infarct areas. Taken together, our data suggest that SASG treatment has the potential to restore failing hearts by preserving cardiac function and inducing myocardial revascularization, while attenuating cardiac fibrosis. Furthermore, we introduce a method for minimally invasive in situ graft assembly. PMID:23869939</p> <div class="credits"> <p class="dwt_author">Martinez, Eliana C; Vu, Duc-Thang; Wang, Jing; Lilyanna, Shera; Ling, Lieng H; Gan, Shu U; Tan, Ai Li; Phan, Thang T; Lee, Chuen N; Kofidis, Theo</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-12-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">382</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/18946646"> <span id="translatedtitle">[Surgical management of talipes equinovarus as sequelae of a compartment and/or <span class="hlt">postischemic</span> syndrome of the deep flexor compartment of the lower leg].</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">Cases of posttraumatic pes equinovarus after compartment syndrome have become more frequent in the last 3 decades because limb-saving procedures like compartment splitting, vascular repair, and microvascular free flaps have become well established in trauma surgery, thus reducing early below knee amputations. But if the deep flexor compartment is not split completely or if the muscles are crushed by direct trauma severe necrosis and subsequent muscle contractures result in a very severe clubfoot deformity. Metatarsalgia of fifth, fourth, and third metatarsal head even in well-fitted orthopaedic shoes occurs as well as painful bunions and fatigue fractures of the fifth metatarsal. Infected ulcers below the fifth/fourth metatarsal bone in a numb plantar sole often require head resection because of osteomyelitis.From 1994 to 2007 a total of 24 patients with severe pes equinovarus after compartment and/or <span class="hlt">postischemic</span> syndrome were treated operatively. Only in 5 cases was a triple, Chopart, or Lisfranc arthrodesis necessary; 19 cases however could be treated only by soft tissue procedures like tenolysis, tendon lengthening, medial release of the scarred flexor retinacula and contracted capsules of the posterior ankle, subtalar and talonavicular joint to reorientate all axes of the foot. By temporary K-wire transfixation (6 weeks), initial external tibiotarsal transfixation of the foot (10 days), and additional tendon transfer for active foot elevation excellent and good long-term (5 years) results are achievable.The results according to the McKay Score are not significantly different regarding the triple arthrodesis group versus the pure soft tissue release group. Nevertheless, saving joints in the latter group seems to be very important. PMID:18946646</p> <div class="credits"> <p class="dwt_author">Zwipp, H; Sabauri, G; Amlang, M</p> <p class="dwt_publisher"></p> <p class="publishDate">2008-10-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">383</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3703900"> <span id="translatedtitle">Comparison of the Direct Effects of Human Adipose- and Bone-Marrow-Derived Stem Cells on <span class="hlt">Postischemic</span> Cardiomyoblasts in an In Vitro Simulated Ischemia-Reperfusion Model</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p class="result-summary">Regenerative therapies hold a promising and exciting future for the cure of yet untreatable diseases, and mesenchymal stem cells are in the forefront of this approach. However, the relative efficacy and the mechanism of action of different types of mesenchymal stem cells are still incompletely understood. We aimed to evaluate the effects of human adipose- (hASC) and bone-marrow-derived stem cells (hBMSCs) and adipose-derived stem cell conditioned media (ACM) on the viability of cardiomyoblasts in an in vitro ischemia-reperfusion (I-R) model. Flow cytometric viability analysis revealed that both cell treatments led to similarly increased percentages of living cells, while treatment with ACM did not (I-R model: 12.13 ± 0.75%; hASC: 24.66 ± 2.49%; hBMSC: 25.41 ± 1.99%; ACM: 13.94 ± 1.44%). Metabolic activity measurement (I-R model: 0.065 ± 0.033; hASC: 0.652 ± 0.089; hBMSC: 0.607 ± 0.059; ACM: 0.225 ± 0.013; arbitrary units) and lactate dehydrogenase assay (I-R model: 0.225 ± 0.006; hASC: 0.148 ± 0.005; hBMSC: 0.146 ± 0.004; ACM: 0.208 ± 0.009; arbitrary units) confirmed the flow cytometric results while also indicated a slight beneficial effect of ACM. Our results highlight that mesenchymal stem cells have the same efficacy when used directly on <span class="hlt">postischemic</span> cells, and differences found between them in preclinical and clinical investigations are rather related to other possible causes such as their immunomodulatory or angiogenic properties.</p> <div class="credits"> <p class="dwt_author">Szepes, Monika; Benko, Zsolt; Cselenyak, Attila; Kompisch, Kai Michael; Schumacher, Udo; Lacza, Zsombor; Kiss, Levente</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">384</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/35860205"> <span id="translatedtitle">Ginkgolides mimic the effects of hypoxic <span class="hlt">preconditioning</span> to protect C6 cells against ischemic injury by up-regulation of hypoxia-inducible factor-1 alpha and erythropoietin</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">Hypoxic <span class="hlt">preconditioning</span> can play a significant neuroprotective role. However, it has not been employed clinically because of safety concerns. To find a safer <span class="hlt">preconditioning</span> stimulus that is both practical and effective, we investigated whether ginkgolides are capable of <span class="hlt">preconditioning</span> as hypoxia to protect C6 cells against ischemic injury. We demonstrated that both ginkgolides (37.5?g\\/mL) and hypoxia (1% O2 for 16h)</p> <div class="credits"> <p class="dwt_author">Wei He; Ming Qian Zhong; Li Zhu; Qian Christopher; Fang Du; Wing Ho Yung; Ya Ke</p> <p class="dwt_publisher"></p> <p class="publishDate">2008-01-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">385</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://academic.research.microsoft.com/Publication/30506689"> <span id="translatedtitle">Hyperthermic <span class="hlt">preconditioning</span> protects astrocytes from ischemia\\/reperfusion injury by up-regulation of HIF-1 alpha expression and binding activity</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://academic.research.microsoft.com/">Microsoft Academic Search </a></p> <p class="result-summary">It has been demonstrated that hypoxia-inducible factor-1 alpha (HIF-1 alpha) mediates ischemic tolerance induced by hypoxia\\/ischemia or pharmacological <span class="hlt">preconditioning</span>. In addition, <span class="hlt">preconditioning</span> stimuli can be cross-tolerant, safeguarding against other types of injury. We therefore hypothesized HIF-1 alpha might also be associated with ischemic tolerance induced by hyperthermic <span class="hlt">preconditioning</span>. In the present study, we demonstrated for the first time that 6h</p> <div class="credits"> <p class="dwt_author">Fang Du; Li Zhu; Zhong-Ming Qian; Xiao-Mei Wu; Wing-Ho Yung; Ya Ke</p> <p class="dwt_publisher"></p> <p class="publishDate">2010-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">386</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.ncbi.nlm.nih.gov/pubmed/24017972"> <span id="translatedtitle">Sulforaphane <span class="hlt">preconditioning</span> of the Nrf2/HO-1 defense pathway protects the cerebral vasculature against blood-brain barrier disruption and neurological deficits in stroke.</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p class="result-summary">Disruption of the blood-brain barrier (BBB) and cerebral edema are the major pathogenic mechanisms leading to neurological dysfunction and death after ischemic stroke. The brain protects itself against infarction via activation of endogenous antioxidant defense mechanisms, and we here report the first evidence that sulforaphane-mediated preactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target heme oxygenase-1 (HO-1) in the cerebral vasculature protects the brain against stroke. To induce ischemic stroke, Sprague-Dawley rats were subjected to 70 min middle cerebral artery occlusion (MCAo) followed by 4, 24, or 72 h reperfusion. Nrf2 and HO-1 protein expression was upregulated in cerebral microvessels of peri-infarct regions after 4-72 h, with HO-1 preferentially associated with perivascular astrocytes rather than the cerebrovascular endothelium. In naïve rats, treatment with sulforaphane increased Nrf2 expression in cerebral microvessels after 24h. Upregulation of Nrf2 by sulforaphane treatment prior to transient MCAo (1h) was associated with increased HO-1 expression in perivascular astrocytes in peri-infarct regions and cerebral endothelium in the infarct core. BBB disruption, lesion progression, as analyzed by MRI, and neurological deficits were reduced by sulforaphane pretreatment. As sulforaphane pretreatment led to a moderate increase in peroxynitrite generation, we suggest that hormetic <span class="hlt">preconditioning</span> underlies sulforaphane-mediated protection against stroke. In conclusion, we propose that pharmacological or dietary interventions aimed to <span class="hlt">precondition</span> the brain via activation of the Nrf2 defense pathway in the cerebral microvasculature provide a novel therapeutic approach for <span class="hlt">preventing</span> BBB breakdown and neurological dysfunction in stroke. PMID:24017972</p> <div class="credits"> <p class="dwt_author">Alfieri, Alessio; Srivastava, Salil; Siow, Richard C M; Cash, Diana; Modo, Michel; Duchen, Michael R; Fraser, Paul A; Williams, Steven C R; Mann, Giovanni E</p> <p class="dwt_publisher"></p> <p class="publishDate">2013-12-01</p> </div> </div> </div> </div> <div class="floatContainer result odd" lang="en"> <div class="resultNumber element">387</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4057195"> <span id="translatedtitle">Pharmacological <span class="hlt">Preconditioning</span> with Vitamin C Attenuates Intestinal Injury via the Induction of Heme Oxygenase-1 after Hemorrhagic Shock in Rats</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p class="result-summary">Pre-induction of heme oxygenase (HO)-1, which is regarded as an effective method of “organ <span class="hlt">preconditioning</span>”, exerts beneficial effects during hemorrhagic shock (HS). However, the available HO-1 inducers exhibit disadvantages such as toxicity or complex technical requirements. Therefore, a safe and convenient HO-1 inducer would be promising and could be exploited in the treatment of foreseeable hemorrhaging, such as prior to major surgery. Here we investigated the effect of vitamin C (VitC), a common antioxidant, on intestinal HO-1 expression and examined whether VitC pretreatment <span class="hlt">prevented</span> HS related intestinal tissue injuries after HO-1 induction. First, we conducted an in vitro study and found that HO-1 expression in rat intestinal epithelial cells (IEC-6) was induced by non-toxic VitC in a time and concentration dependent manner, and the mechanism was related to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Next, we conducted an in vivo study and found that VitC induced intestinal HO-1 protein expression (mainly observed in the intestinal epithelial cells) and HO-1 activity in normal SD rats, and that these HO-1 levels were further enhanced by VitC in a rat model of HS. The HS related intestinal injuries, including histological damage, pro-inflammatory cytokine levels (tumor necrosis factor and interleukin-6), neutrophil infiltration and apoptosis decreased after VitC pretreatment, and this alleviating of organ injuries was abrogated after the inhibition of HO-1 activity by zinc protoporphyrin-IX. It was of note that VitC did little histological damage to the intestine of the sham rats. These data suggested that VitC might be applied as a safe inducer of intestinal HO-1 and that VitC pretreatment attenuated HS related intestinal injuries via the induction of HO-1.</p> <div class="credits"> <p class="dwt_author">Chen, Ying; Ying, Yi-Lin; Ma, Li; Song, Xiao-Qin; Wang, Lu; Chen, Er-Zhen; Mao, En-Qiang</p> <p class="dwt_publisher"></p> <p class="publishDate">2014-01-01</p> </div> </div> </div> </div> <div class="floatContainer result " lang="en"> <div class="resultNumber element">388</div> <div class="resultBody element"> <p class="result-title"><a target="resultTitleLink" href="http://science.gov/scigov/link.html?type=RESULT&redirectUrl=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4080061"> <span id="translatedtitle">Effect of Air Abrasion <span class="hlt">Preconditioning</span> on Microleakage in Class V Restorations Under Cyclic Loading: An In-vitro Study</span></a>  </p> <div class="result-meta"> <p class="source"><a target="_blank" id="logoLink" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p class="result-summary">Background: Microleakage in class V Glass Ionomer Cement(GIC) or composite restorations at enamel or cementum margins has been cited as a reason for their failure. Air abrasion has been used to <span class="hlt">precondition</span> tooth surface for increasing retention of such restorations. This study is done to evaluate the effect of <span class="hlt">preconditioning</span> with air abrasion on microleakage in class V GIC and composite restorations. Materials and Methods: Class V cavities were prepared in 40 freshly extracted teeth. They were categorised into following four groups (n=10) depending on cavity <span class="hlt">preconditioning</span> and restoration. Group I: 10% polyacrylic acid and GI (Ketac molar TM 3M ESPE); Group II: AA and GI; Group III: 35% Phosphoric acid and micro filled composite (MC) (Heliomolar, Ivoclar Vivadent); Group IV: AA and MC. Each group was further divided into subgroups A (no loading) & B (cyclic loadi