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Sample records for preconditioning prevents postischemic

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

    PubMed

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

    2013-08-15

    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 Ca?. 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

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

    PubMed

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

    2015-09-01

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

  3. Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction.

    PubMed

    Korkmaz, Sevil; Atmanli, Ayhan; Li, Shiliang; Radovits, Tams; Heged?s, Peter; Barnucz, Enik?; Hirschberg, Kristf; Loganathan, Sivakkanan; Yoshikawa, Yutaka; Yasui, Hiroyuki; Karck, Matthias; Szab, Gbor

    2015-09-01

    The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia. Rats were pretreated with ASA (75?mg/kg) or Zn(ASA)2 (100?mg/kg) orally for five consecutive days. Isoproterenol (85?mg/kg, subcutaneously [s.c.]) was applied to produce myocardial infarction. After 17-22?h, animals were anesthetized with sodium pentobarbital (60?mg/kg, intraperitoneally [i.p.]) and both electrical and mechanical parameters of cardiac function were evaluated in vivo. Myocardial histological and gene expression analyses were performed. In isoproterenol-treated rats, Zn(ASA)2 treatment normalized significantly impaired left-ventricular contractility index (Emax 2.6??0.7?mmHg/L vs. 4.6??0.5?mmHg/L, P?preventing electrical, mechanical, and histological changes after acute myocardial ischemia. The induction of antioxidant enzymes and the anti-inflammatory cytokine TGF-?1 may play a pivotal role in the mechanism of action of Zn(ASA)2. PMID:25670850

  4. Can endurance exercise preconditioning prevention disuse muscle atrophy?

    PubMed Central

    Wiggs, Michael P.

    2015-01-01

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

  5. Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism.

    PubMed

    Hayakawa, Kazuhide; Mishima, Kenichi; Irie, Keiichi; Hazekawa, Mai; Mishima, Shohei; Fujioka, Masayuki; Orito, Kensuke; Egashira, Nobuaki; Katsurabayashi, Shutaro; Takasaki, Kotaro; Iwasaki, Katsunori; Fujiwara, Michihiro

    2008-12-01

    We examined the cerebroprotective mechanism of cannabidiol, the non-psychoactive component of marijuana, against infarction in a 4-h mouse middle cerebral artery (MCA) occlusion model. Cannabidiol was intraperitoneally administrated immediately before and 3h after cerebral ischemia. Infarct size and myeloperoxidase (MPO) activity, a marker of neutrophil, monocyte/macropharge, were measured at 24h after cerebral ischemia. Activated microglia and astrocytes were evaluated by immunostaining. Moreover, high-mobility group box1 (HMGB1) was also evaluated at 1 and 3 days after MCA occlusion. In addition, neurological score and motor coordination on the rota-rod test were assessed at 1 and 3 days after cerebral ischemia. Cannabidiol significantly prevented infarction and MPO activity at 20h after reperfusion. These effects of cannabidiol were not inhibited by either SR141716 or AM630. Cannabidiol inhibited the MPO-positive cells expressing HMGB1 and also decreased the expression level of HMGB1 in plasma. In addition, cannabidiol decreased the number of Iba1- and GFAP-positive cells at 3 days after cerebral ischemia. Moreover, cannabidiol improved neurological score and motor coordination on the rota-rod test. Our results suggest that cannabidiol inhibits monocyte/macropharge expressing HMGB1 followed by preventing glial activation and neurological impairment induced by cerebral ischemia. Cannabidiol will open new therapeutic possibilities for post-ischemic injury via HMGB1-inhibiting mechanism. PMID:18634812

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

    PubMed

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

    2015-12-15

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

  7. Hydrogen sulfide preconditioning or neutrophil depletion attenuates ischemia-reperfusion-induced mitochondrial dysfunction in rat small intestine.

    PubMed

    Liu, Yajun; Kalogeris, Theodore; Wang, Meifang; Zuidema, Mozow Yusof; Wang, Qun; Dai, Hongyan; Davis, Michael J; Hill, Michael A; Korthuis, Ronald J

    2012-01-01

    The objectives of this study were to determine whether neutrophil depletion with anti-neutrophil serum (ANS) or preconditioning with the hydrogen sulfide (H(2)S) donor NaHS (NaHS-PC) 24 h prior to ischemia-reperfusion (I/R) would prevent postischemic mitochondrial dysfunction in rat intestinal mucosa and, if so, whether calcium-activated, large conductance potassium (BK(Ca)) channels were involved in this protective effect. I/R was induced by 45-min occlusion of the superior mesenteric artery followed by 60-min reperfusion in rats preconditioned with NaHS (NaHS-PC) or a BK(Ca) channel activator (NS-1619-PC) 24 h earlier or treated with ANS. Mitochondrial function was assessed by measuring mitochondrial membrane potential, mitochondrial dehydrogenase function, and cytochrome c release. Mucosal myeloperoxidase (MPO) and TNF-? levels were also determined, as measures of postischemic inflammation. BK(Ca) expression in intestinal mucosa was detected by immunohistochemistry and Western blotting. I/R induced mitochondrial dysfunction and increased tissue MPO and TNF-? levels. Although mitochondrial dysfunction was attenuated by NaHS-PC or NS-1619-PC, the postischemic increases in mucosal MPO and TNF-? levels were not. The protective effect of NaHS-PC or NS-1619-PC on postischemic mitochondrial function was abolished by coincident treatment with BK(Ca) channel inhibitors. ANS prevented the I/R-induced increase in tissue MPO levels and reversed mitochondrial dysfunction. These data indicate that neutrophils play an essential role in I/R-induced mucosal mitochondrial dysfunction. In addition, NaHS-PC prevents postischemic mitochondrial dysfunction (but not inflammation) by a BK(Ca) channel-dependent mechanism. PMID:21921289

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

    PubMed Central

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

    2014-01-01

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

  9. Preconditioning enhances the paracrine effect of mesenchymal stem cells in preventing oxygen-induced neonatal lung injury in rats.

    PubMed

    Waszak, Paul; Alphonse, Rajesh; Vadivel, Arul; Ionescu, Lavinia; Eaton, Farah; Thbaud, Bernard

    2012-10-10

    Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity. Bone marrow derived-mesenchymal stem cells (BM-MSC) prevent lung injury in an O(2)-induced model of BPD. The low level of lung BM-MSC engraftment suggests alternate mechanisms-beyond cell replacement-to account for their therapeutic benefit. We hypothesized that BM-MSC prevent O(2)-induced BPD through a paracrine-mediated mechanism and that preconditioning of BM-MSC would further enhance this paracrine effect. To this end, conditioned medium (CM) from BM-MSC (MSCcm) or preconditioned CM harvested after 24 h of BM-MSC exposure to 95% O(2) (MSC-O2cm) were administrated for 21 days to newborn rats exposed to 95% O(2) from birth until postnatal day (P)14. Rat pups exposed to hyperoxia had fewer and enlarged air spaces and exhibited signs of pulmonary hypertension (PH), assessed by echo-Doppler, right ventricular hypertrophy, and pulmonary artery medial wall thickness. Daily intraperitoneal administration of both CM preserved alveolar growth. MSC-O2cm exerted the most potent therapeutic benefit and also prevented PH. CM of lung fibroblasts (control cells) had no effect. MSCcm had higher antioxidant capacity than control fibroblast CM. Preconditioning did not increase the antioxidant capacity in MSC-O2cm but produced higher levels of the naturally occurring antioxidant stanniocalcin-1 in MSC-O2cm. Ex vivo preconditioning enhances the paracrine effect of BM-MSC and opens new therapeutic options for cell-based therapies. Ex vivo preconditioning may also facilitate the discovery of MSC-derived repair molecules. PMID:22533467

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

    PubMed Central

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

    2011-01-01

    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. PMID:21666111

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

    PubMed

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

    2015-11-15

    Preconditioning refers to exposure to brief episodes of potentially adverse stimuli and protects against injury during subsequent exposures. This was first described in the heart, where episodes of ischemia/reperfusion render the myocardium resistant to subsequent ischemic injury, which is likely caused by reactive oxygen species (ROS) and proinflammatory processes. Protection of the heart was also found when preconditioning was performed in an organ different from the target, which is called remote ischemic preconditioning (RIPC). The mechanisms causing protection seem to include stimulation of nitric oxide (NO) synthase, increase in antioxidant enzymes, and downregulation of proinflammatory cytokines. These pathways are also thought to play a role in high-altitude diseases: high-altitude pulmonary edema (HAPE) is associated with decreased bioavailability of NO and increased generation of ROS, whereas mechanisms causing acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) seem to involve cytotoxic effects by ROS and inflammation. Based on these apparent similarities between ischemic damage and AMS, HACE, and HAPE, it is reasonable to assume that RIPC might be protective and improve altitude tolerance. In studies addressing high-altitude/hypoxia tolerance, RIPC has been shown to decrease pulmonary arterial systolic pressure in normobaric hypoxia (13% O2) and at high altitude (4,342 m). Our own results indicate that RIPC transiently decreases the severity of AMS at 12% O2. Thus preliminary studies show some benefit, but clearly, further experiments to establish the efficacy and potential mechanism of RIPC are needed. PMID:26089545

  12. Postischemic Treatment With Ethyl Pyruvate Prevents Adenosine Triphosphate Depletion, Ameliorates Inflammation, and Decreases Thrombosis in a Murine Model of Hind-Limb Ischemia and Reperfusion

    PubMed Central

    Crawford, Robert S.; Albadawi, Hassan; Atkins, Marvin D.; Jones, John J.; Conrad, Mark F.; Austen, William G.; Fink, Mitchell P.; Watkins, Michael T.

    2011-01-01

    Introduction Experiments were designed to investigate the effects of ethyl pyruvate (EP) in a murine model of hind-limb ischemia-reperfusion (IR) injury. Methods C57BL6 mice underwent 90 minutes of unilateral ischemia followed by 24 hours of reperfusion using two treatment protocols. For the preischemic treatment (pre-I) protocol, mice (n = 6) were given 300 mg/kg EP before ischemia, followed by 150 mg/kg of EP just before reperfusion and at 6 hours and 12 hours after reperfusion. In a postischemic treatment (post-I) protocol, mice (n = 7) were treated with 300 mg/kg EP at the end of the ischemic period, then 15 minutes later, and 2 hours after reperfusion and 150 mg/kg of EP at 4 hours, 6 hours, 10 hours, 16 hours, and 22 hours after reperfusion. Controls mice for both protocols were treated with lactated Ringers alone at time intervals identical to EP. Skeletal muscle levels of adenosine triphosphate (ATP), interleukin-1?, keratinocyte chemoattractant protein, and thrombin antithrombin-3 complex were measured. Skeletal muscle architectural integrity was assessed microscopically. Results ATP levels were higher in mice treated with EP compared with controls under the both treatment protocols (p = 0.02). Interleukin-1?, keratinocyte chemoattractant protein, thrombin antithrombin-3 complex (p < 0.05), and the percentage of injured fibers (p < 0.0001) were significantly decreased in treated versus control mice under the both protocols. Conclusion Muscle fiber injury and markers of tissue thrombosis and inflammation were reduced, and ATP was preserved with EP in pre-I and post-I protocols. Further investigation of the efficacy of EP to modulate IR injury in a larger animal model of IR injury is warranted. PMID:21217488

  13. Polyethylene Glycol Preconditioning: An Effective Strategy to Prevent Liver Ischemia Reperfusion Injury

    PubMed Central

    Pantazi, Eirini; Calvo, Maria; Folch-Puy, Emma; Serafín, Anna; Panisello, Arnau; Adam, René; Roselló-Catafau, Joan

    2016-01-01

    Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proven their effectiveness in various in vivo and in vitro models of tissue injury. The present study aims to investigate whether the intravenous administration of a high molecular weight PEG of 35 kDa (PEG 35) could be an effective strategy for rat liver preconditioning against IRI. PEG 35 was intravenously administered at 2 and 10 mg/kg to male Sprague Dawley rats. Then, rats were subjected to one hour of partial ischemia (70%) followed by two hours of reperfusion. The results demonstrated that PEG 35 injected intravenously at 10 mg/kg protected efficiently rat liver against the deleterious effects of IRI. This was evidenced by the significant decrease in transaminases levels and the better preservation of mitochondrial membrane polarization. Also, PEG 35 preserved hepatocyte morphology as reflected by an increased F-actin/G-actin ratio and confocal microscopy findings. In addition, PEG 35 protective mechanisms were correlated with the activation of the prosurvival kinase Akt and the cytoprotective factor AMPK and the inhibition of apoptosis. Thus, PEG may become a suitable agent to attempt pharmacological preconditioning against hepatic IRI. PMID:26981166

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

    PubMed Central

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

    2015-01-01

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

  15. Menstrual preconditioning for the prevention of major obstetrical syndromes in polycystic ovary syndrome.

    PubMed

    Brosens, Ivo; Benagiano, Giuseppe

    2015-10-01

    The presence of multiple ovarian cysts, anovulation, and endometrial progesterone resistance in the neonate seems remarkably similar to ovarian and endometrial features of the polycystic ovary syndrome (PCOS) of adolescent and adult women. In fact, in the absence of cyclic menstruations after menarche, the neonatal progesterone resistance is likely to persist and adversely affect young women with PCOS at the time of pregnancy after induction of ovulation, because any persisting defect in progesterone response can interfere with the process of decidualization and trophoblast invasion. The primigravid woman with PCOS therefore is likely to be at risk of defective deep placentation as manifested by the increased risk of major obstetric syndromes. A recent, large epidemiologic study has demonstrated that the risk of preeclampsia and preterm delivery is elevated in the 13- to 15-year old group, although it does not persist in the 16- to 17-year old group. It is proposed therefore that induction of ovulation in the infertile nulligravid woman with PCOS should be preceded by a period of progesterone withdrawal bleedings to achieve full endometrial progesterone response by the time of pregnancy. The cyclic administration of clomiphene citrate for a period to be determined by vascular response may be an appropriate tool to reduce the risk of major obstetric syndromes by menstrual preconditioning. PMID:26212182

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Murphy, Elizabeth

    2010-01-01

    As a G protein-coupled receptor, the extracellular Ca2+-sensing receptor (CaSR) responds to changes not only in extracellular Ca2+, but also to many other ligands. CaSR has been found to be expressed in the hearts and cardiovascular system. In this study, we confirmed that CaSR is expressed in mouse cardiomyocytes and showed that it is predominantly localized in caveolae. The goal of this study was to investigate whether CaSR plays a cardioprotective role in ischemic preconditioning (IPC). Hearts from C57BL/6J mice (male, 1216 wk) were perfused in the Langendorff mode and subjected to the following treatments: 1) control perfusion; 2) perfusion with a specific CaSR antagonist, NPS2143; 3) IPC (four cycles of 5 min of global ischemia and 5 min of reperfusion); or 4) perfusion with NPS2143 before and during IPC. Following these treatments, hearts were subjected to 20 min of no-flow global ischemia and 120 min of reperfusion. Compared with control, IPC significantly improved postischemic left ventricular functional recovery and reduced infarct size. Although NPS2143 perfusion alone did not change the hemodynamic function and did not change the extent of postischemic injury, NPS2143 treatment abolished cardioprotection of IPC. Through immunoblot analysis, it was demonstrated that IPC significantly increased the levels of phosphorylated ERK1/2, AKT, and GSK-3?, which were also prevented by NPS2143 treatment. Taken together, the distribution of CaSR in caveolae along with NPS2143-blockade of IPC-induced cardioprotective signaling suggest that the activation of CaSR during IPC is cardioprotective by a process involving caveolae. PMID:20833954

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

    PubMed

    Grenz, Almut; Bauerle, Jessica D; Dalton, Julee H; Ridyard, Douglas; Badulak, Alexander; Tak, Eunyoung; McNamee, Ein 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; Nrnberg, Bernd; Haase, Volker H; Xia, Yang; Sitkovsky, Michail; Eltzschig, Holger K

    2012-02-01

    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. PMID:22269324

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

    NASA Astrophysics Data System (ADS)

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

    2012-05-01

    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.

  20. Sensory preconditioning in honeybees.

    PubMed

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

    2000-04-01

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

  1. Depletion of NADP(H) due to CD38 activation triggers endothelial dysfunction in the postischemic heart.

    PubMed

    Reyes, Levy A; Boslett, James; Varadharaj, Saradhadevi; De Pascali, Francesco; Hemann, Craig; Druhan, Lawrence J; Ambrosio, Giuseppe; El-Mahdy, Mohamed; Zweier, Jay L

    2015-09-15

    In the postischemic heart, coronary vasodilation is impaired due to loss of endothelial nitric oxide synthase (eNOS) function. Although the eNOS cofactor tetrahydrobiopterin (BH4) is depleted, its repletion only partially restores eNOS-mediated coronary vasodilation, indicating that other critical factors trigger endothelial dysfunction. Therefore, studies were performed to characterize the unidentified factor(s) that trigger endothelial dysfunction in the postischemic heart. We observed that depletion of the eNOS substrate NADPH occurs in the postischemic heart with near total depletion from the endothelium, triggering impaired eNOS function and limiting BH4 rescue through NADPH-dependent salvage pathways. In isolated rat hearts subjected to 30 min of ischemia and reperfusion (I/R), depletion of the NADP(H) pool occurred and was most marked in the endothelium, with >85% depletion. Repletion of NADPH after I/R increased NOS-dependent coronary flow well above that with BH4 alone. With combined NADPH and BH4 repletion, full restoration of NOS-dependent coronary flow occurred. Profound endothelial NADPH depletion was identified to be due to marked activation of the NAD(P)ase-activity of CD38 and could be prevented by inhibition or specific knockdown of this protein. Depletion of the NADPH precursor, NADP(+), coincided with formation of 2'-phospho-ADP ribose, a CD38-derived signaling molecule. Inhibition of CD38 prevented NADP(H) depletion and preserved endothelium-dependent relaxation and NO generation with increased recovery of contractile function and decreased infarction in the postischemic heart. Thus, CD38 activation is an important cause of postischemic endothelial dysfunction and presents a novel therapeutic target for prevention of this dysfunction in unstable coronary syndromes. PMID:26297248

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

    PubMed

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

    1992-10-26

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

  3. Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans

    PubMed Central

    Tian, Yi; Li, Haobo; Liu, Peiyu; Xu, Jun-mei; Irwin, Michael G.; Xia, Zhengyuan; Tian, Guogang

    2015-01-01

    Background. Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury. Methods and Results. Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30?min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress. Conclusion. A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation. PMID:26273143

  4. Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of BK channels

    PubMed Central

    Zuidema, Mozow Y.; Yang, Yan; Wang, Meifang; Kalogeris, Theodore; Liu, Yajun; Meininger, Cynthia J.; Hill, Michael A.; Davis, Michael J.

    2010-01-01

    The objectives of this study were to determine the role of calcium-activated, small (SK), intermediate (IK), and large (BK) conductance potassium channels in initiating the development of an anti-inflammatory phenotype elicited by preconditioning with an exogenous hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS). Intravital microscopy was used to visualize rolling and firmly adherent leukocytes in vessels of the small intestine of mice preconditioned with NaHS (in the absence and presence of SK, IK, and BK channel inhibitors, apamin, TRAM-34, and paxilline, respectively) or SK/IK (NS-309) or BK channel activators (NS-1619) 24 h before ischemia-reperfusion (I/R). I/R induced marked increases in leukocyte rolling and adhesion, effects that were largely abolished by preconditioning with NaHS, NS-309, or NS-1619. The postischemic anti-inflammatory effects of NaHS-induced preconditioning were mitigated by BKB channel inhibitor treatment coincident with NaHS, but not by apamin or TRAM-34, 24 h before I/R. Confocal imaging and immunohistochemistry were used to demonstrate the presence of BK? subunit staining in both endothelial and vascular smooth muscle cells of isolated, pressurized mesenteric venules. Using patch-clamp techniques, we found that BK channels in cultured endothelial cells were activated after exposure to NaHS. Bath application of the same concentration of NaHS used in preconditioning protocols led to a rapid increase in a whole cell K+ current; specifically, the component of K+ current blocked by the selective BK channel antagonist iberiotoxin. The activation of BK current by NaHS could also be demonstrated in single channel recording mode where it was independent of a change in intracellular Ca+ concentration. Our data are consistent with the concept that H2S induces the development of an anti-adhesive state in I/R in part mediated by a BK channel-dependent mechanism. PMID:20833953

  5. Fetal brain genomic reprogramming following asphyctic preconditioning

    PubMed Central

    2013-01-01

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

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

    PubMed Central

    YE, JIAN-XI; CHEN, DAO-ZHONG

    2015-01-01

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

  7. Preventing infection of osseointegrated transcutaneous implants: Incorporation of silver into preconditioned fibronectin-functionalized hydroxyapatite coatings suppresses Staphylococcus aureus colonization while promoting viable fibroblast growth in vitro.

    PubMed

    Chimutengwende-Gordon, Mukai; Pendegrass, Catherine; Bayston, Roger; Blunn, Gordon

    2014-09-01

    The success of transcutaneous implants depends on the achievement of a soft tissue seal by enabling fibroblasts to win the race for the surface against bacteria. Fibronectin-functionalized hydroxyapatite coatings (HAFn) have been shown to improve dermal tissue ingrowth and attachment. However, during the early postoperative period before a soft tissue seal has formed, bacterial colonization may occur. This study explored the incorporation of silver, a broad spectrum antimicrobial agent, into HAFn coatings with the aim of reducing bacterial colonization. Silver is known to have dose-dependent cytotoxic effects. Therefore, the effects of silver incorporation into HAFn coatings on both in vitro human dermal fibroblast viability and Staphylococcus aureus colonization were assessed. An electrochemical deposition technique was used to codeposit hydroxyapatite and silver (HAAg) and fibronectin was adsorbed onto this to produce HAAgFn coatings. Surfaces were preconditioned with serum to mimic the in vivo environment. Nonpreconditioned HAAg and HAAgFn coatings suppressed bacterial colonization but were cytotoxic. After serum-preconditioning, more than 90% of fibroblasts that grew on all HAAg and HAAgFn coatings were viable. The highest silver content coatings tested (HAAg100 and HAAgFn100) resulted in a greater than 99% reduction in biofilm and planktonic bacterial numbers compared to HA and HAFn controls. Although HAAg100 had greater antibacterial activity than HAAgFn100, the findings of this study indicate that fibroblasts would win the race for the surface against S aureus on both HAAg100 and HAAgFn100 after serum-preconditioning. PMID:25280851

  8. Cardiac parametric variations in post-ischemic myocardium.

    PubMed

    Li, John K-J; Zhu, Ying; Khaw, Kenneth; Kedem, Joseph

    2004-01-01

    Mechanisms governing post-ischemic ventricular function after episodes of acute myocardial ischemia are still unclear. We investigated this stunned myocardial function with a computer model in conjunction with animal experiments. A modified lumped cardiac muscle model was subjected to parametric changes similar to regionally recorded ventricular parameters. The model was perturbed by alterations in contractility and rates of activation and deactivation. Results show that the cardiac muscle model can mimic many of the physiological changes observed in a stunned myocardium. PMID:17271081

  9. Preconditioned Iterative Solver

    Energy Science and Technology Software Center (ESTSC)

    2002-08-01

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

  10. Post-ischemic inflammation regulates neural damage and protection

    PubMed Central

    Shichita, Takashi; Ito, Minako; Yoshimura, Akihiko

    2014-01-01

    Post-ischemic inflammation is important in ischemic stroke pathology. However, details of the inflammation process, its resolution after stroke and its effect on pathology and neural damage have not been clarified. Brain swelling, which is often fatal in ischemic stroke patients, occurs at an early stage of stroke due to endothelial cell injury and severe inflammation by infiltrated mononuclear cells including macrophages, neutrophils, and lymphocytes. At early stage of inflammation, macrophages are activated by molecules released from necrotic cells [danger-associated molecular patterns (DAMPs)], and inflammatory cytokines and mediators that increase ischemic brain damage by disruption of the blood–brain barrier are released. After post-ischemic inflammation, macrophages function as scavengers of necrotic cell and brain tissue debris. Such macrophages are also involved in tissue repair and neural cell regeneration by producing tropic factors. The mechanisms of inflammation resolution and conversion of inflammation to neuroprotection are largely unknown. In this review, we summarize information accumulated recently about DAMP-induced inflammation and the neuroprotective effects of inflammatory cells, and discuss next generation strategies to treat ischemic stroke. PMID:25352781

  11. Post-ischemic vascular adhesion protein-1 inhibition provides neuroprotection in a rat temporary middle cerebral artery occlusion model

    PubMed Central

    Watcharotayangul, Jittiya; Mao, Lizhen; Xu, Haoliang; Vetri, Francesco; Baughman, Verna L.; Paisansathan, Chanannait; Pelligrino, Dale A.

    2012-01-01

    We examined the neuroprotective efficacy associated with post-ischemic vascular adhesion protein-1 (VAP-1) blockade in rats subjected to transient (1h) middle cerebral artery occlusion (MCAo). We compared saline-treated control rats to rats treated with a highly-selective VAP-1 inhibitor, LJP-1586 [Z-3-fluoro-2-(4-methoxybenzyl) allylamine hydrochloride]. Initial intraperitoneal LJP-1586 (or saline control) treatments were delayed until 6h or 12h reperfusion. At 72h reperfusion, LJP-1586-treated rats displayed 51% and 33% smaller infarct volumes, relative to their controls, in the 6- and 12h-treatment groups, respectively. However, only in the 6h-treatment group was the infarct volume reduction significant (p<0.05). On the other hand, we observed significantly improved neurologic functions in both 6- and 12h-treatment groups, versus their matched controls (p<0.05). Also, the effect of 6h LJP-1586 treatment on post-ischemic leukocyte trafficking in pial venules overlying the ischemic cortex was evaluated using intravital microscopy. These experiments revealed that: 1) LJP-1586 did not affect intravascular leukocyte (largely neutrophil) adhesion, at least out to 12h reperfusion; and 2) the onset of neutrophil extravasation, which occurred between 6-8h reperfusion in control rats, was prevented by LJP-1586-treatment. In conclusion, in rats subjected to transient MCAo, selective VAP-1 pharmacologic blockade provided neuroprotection, with a prolonged therapeutic window of 6 to 12h reperfusion. PMID:23050649

  12. Effects of MK-801 and ganglioside GM1 on postischemic prostanoid release and hippocampal lesion in gerbil brain.

    PubMed

    Lazarewicz, J W; Sali?ska, E; Speina, E; Gadamski, R

    1994-01-01

    In this study Mongolian gerbils were submitted to a normothermic bilateral carotid ligation lasting 5 min. A noncompetitive antagonist of NMDA receptors, MK-801, 0.8 mg/kg, was injected i.p. 30 min before ischemia, or the ganglioside GM1, 30 mg/kg, was given i.p. for 3 days, twice a day. The morphology of the hippocampal CA1 neurones and the brain content of cyclooxygenase metabolites of arachidonic acid: prostaglandin 6-keto PGF1 alpha and thromboxane Tx B2 were studied. Untreated ischemia induced the accumulation in brain of the 6-keto PGF1 alpha and Tx B2 immunoreactive materials, and resulted in a lesion of 70% of CA1 neurones. In the MK-801- and GM1-pretreated groups the postischemic levels of Tx B2 were significantly decreased. However MK-801 and GM1 did not prevent damage to the CA1 neurones in gerbils normothermic after ischemia, whereas a partial neuroprotection was observed in hypothermic, MK-801 treated gerbils. The results of this study indicate that NMDA receptors may participate in the mechanism of postischemic release of eicosanoids in brain. They also confirm a potential modulatory role of gangliosides. These results are discussed in terms of the involvement of cyclooxygenase metabolites of arachidonic acid in the mechanism of a selective delayed neuronal damage to the hippocampus CA1 after ischemia. PMID:7887181

  13. Neuronal Preconditioning by Inhalational Anesthetics

    PubMed Central

    Bantel, Carsten; Maze, Mervyn; Trapp, Stefan

    2010-01-01

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

  14. Hypoxia preconditioning protects corneal stromal cells against induced apoptosis

    PubMed Central

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

    2011-01-01

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

  15. The neuroprotective mechanism of brain ischemic preconditioning

    PubMed Central

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

    2009-01-01

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

  16. Pharmacologic Preconditioning: Translating the Promise

    PubMed Central

    Gidday, Jeffrey M.

    2010-01-01

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

  17. Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

    PubMed

    Zarubina, I V; Shabanov, P D

    2009-03-01

    Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia. PMID:19529857

  18. Preconditioning stress prevents cold restraint stress-induced gastric lesions in rats: roles of COX-1, COX-2, and PLA2.

    PubMed

    Tanaka, Akiko; Hatazawa, Ryo; Takahira, Yuka; Izumi, Nahoko; Filaretova, Ludmila; Takeuchi, Koji

    2007-02-01

    We investigated the protective effect of mild stress on gastric lesions induced by cold-restraint stress, especially concerning prostaglandins (PGs)/cyclo-oxygenase (COX) isozymes. Rats were exposed to severe stress (cold-restraint stress at 10 degrees C for 6 hr) or mild stress (cold-restraint stress at 10 degrees C for 30 min and kept at room temperature for 60 min) followed by severe stress. Severe stress induced gastric lesions, with a concomitant decrease in body temperature (BT). The ulcerogenic response was inhibited by atropine but worsened by indomethacin and SC-560 but not rofecoxib, although none of these agents had any effect on the change in BT. Mild stress suppressed the gastric ulceration and the decrease in BT induced by severe stress, and these effects were reversed by both COX-1 and COX-2 inhibitors. The expression of COX-2 in the stomach was up-regulated from 4 hr after severe stress and this response was slightly expedited by mild stress. COX-2 was also expressed in the hypothalamus under normal and stressed conditions. Quinacrine (phospholipase A(2) inhibitor) attenuated the protective effect of mild stress on the ulceration and decrease in BT caused by severe stress. TA-0910 (TRH analogue) at a low dose also prevented the gastric ulceration and the decrease in BT induced by severe stress. These results suggest that mild stress protects against cold-restraint stress-induced gastric ulceration, and the effect is peripherally and centrally mediated by PGs derived from both COX-1 and COX-2 through the activation of phospholipase A(2). TRH may also be involved in the protective effect of mild stress, probably through regulation of the thermogenic system. PMID:17226073

  19. An improved algorithm of fiber tractography demonstrates postischemic cerebral reorganization

    NASA Astrophysics Data System (ADS)

    Liu, Xiao-dong; Lu, Jie; Yao, Li; Li, Kun-cheng; Zhao, Xiao-jie

    2008-03-01

    In vivo white matter tractography by diffusion tensor imaging (DTI) accurately represents the organizational architecture of white matter in the vicinity of brain lesions and especially ischemic brain. In this study, we suggested an improved fiber tracking algorithm based on TEND, called TENDAS, for tensor deflection with adaptive stepping, which had been introduced a stepping framework for interpreting the algorithm behavior as a function of the tensor shape (linear-shaped or not) and tract history. The propagation direction at each step was given by the deflection vector. TENDAS tractography was used to examine a 17-year-old recovery patient with congenital right hemisphere artery stenosis combining with fMRI. Meaningless picture location was used as spatial working memory task in this study. We detected the shifted functional localization to the contralateral homotypic cortex and more prominent and extensive left-sided parietal and medial frontal cortical activations which were used directly as seed mask for tractography for the reconstruction of individual spatial parietal pathways. Comparing with the TEND algorithms, TENDAS shows smoother and less sharp bending characterization of white matter architecture of the parietal cortex. The results of this preliminary study were twofold. First, TENDAS may provide more adaptability and accuracy in reconstructing certain anatomical features, whereas it is very difficult to verify tractography maps of white matter connectivity in the living human brain. Second, our study indicates that combination of TENDAS and fMRI provide a unique image of functional cortical reorganization and structural modifications of postischemic spatial working memory.

  20. Early postischemic /sup 45/Ca accumulation in rat dentate hilus

    SciTech Connect

    Benveniste, H.; Diemer, N.H.

    1988-10-01

    Several studies have found postischemic regional accumulation of calcium to be time-dependent and coincident with the progression of ischemic cell change. In the most vulnerable cells in the hippocampus one would therefore expect to find a primary and specific early uptake of calcium after ischemia. Autoradiograms of /sup 45/Ca and /sup 3/H-inulin distribution were investigated before and 1 h after 20 min ischemia in the rat hippocampus. Two different methodological approaches were used for administration of /sup 45/Ca: (a) administration via microdialysis probes, (b) intraventricular injection. During control conditions the /sup 45/Ca autoradiograms showed variations in distribution volume in accordance with /sup 3/H-inulin determination of extracellular space size. One hour after ischemia a massive accumulation of /sup 45/Ca was found in the dentate hilus. No change in the distribution pattern of /sup 3/H-inulin could be demonstrated 1 h after ischemia. We suggest that /sup 45/Ca accumulation in dentate hilus 1 h after ischemia is a result of increased Ca/sup 2 +/ uptake before irreversible cell damage occurs and is not due to passive influx of calcium across a leaky plasma membrane.

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

    PubMed Central

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

    2001-01-01

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

  2. Orderings for conjugate gradient preconditionings

    NASA Technical Reports Server (NTRS)

    Ortega, James M.

    1991-01-01

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

  3. Postischemic [Ca2+] repletion improves cardiac performance without altering oxygen demands.

    PubMed

    Yokoyama, H; Julian, J S; Vinten-Johansen, J; Johnston, W E; Smith, T D; McGee, D S; Cordell, A R

    1990-06-01

    The positive inotropism expected with correction of postischemic hypocalcemia might be counterbalanced by potential aggravation of reperfusion injury, in particular by calcium overload. We evaluated the effect of normalizing blood calcium concentration ([Ca2+]) on postischemic left ventricular systolic and diastolic mechanics using oxygen consumption and indices derived from pressure-diameter relations. In 10 open-chest dogs on cardiopulmonary bypass, the hearts underwent 30 minutes of normothermic global ischemia followed by one hour of multidose hypothermic (4 degrees C), hypocalcemic (0.3 mmol/L) blood cardioplegia. After reperfusion, systemic [Ca2+] had decreased to 70% of control (p = 0.017). The left ventricular inotropic state was significantly depressed from baseline (control) values, but was restored to baseline levels by resumption of normocalcemia after one hour of reperfusion. Chamber stiffness increased by 308% (p = 0.006) after hypocalcemic reperfusion but decreased significantly after [Ca2+] correction. Recovery of left ventricular performance with [Ca2+] correction did not augment myocardial oxygen consumption from the postischemic uncorrected state (5.0 +/- 0.3 mL O2/min/100 g versus 5.3 +/- 0.3 mL O2/min/100 g). We conclude that normalizing [Ca2+] after blood cardioplegia improves postischemic left ventricular performance without adversely affecting compliance or oxygen consumption. PMID:2369187

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Liu, Zhangsuo; Gong, Rujun

    2015-11-01

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

  6. Management of Preconditioned Calves and Impacts of Preconditioning.

    PubMed

    Hilton, W Mark

    2015-07-01

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

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

    PubMed Central

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

    2014-01-01

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

  8. The time of maximum post-ischemic hyperperfusion indicates infarct growth following transient experimental ischemia.

    PubMed

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

    2013-01-01

    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. PMID:23741488

  9. Gender disparity in the role of TLR2 in post-ischemic myocardial inflammation and injury

    PubMed Central

    Li, Jilin; Ao, Lihua; Zhai, Yufeng; Cleveland, Joseph C Jr; Fullerton, David A; Meng, Xianzhong

    2015-01-01

    It is unclear whether Toll-like receptor (TLR) 2 plays a role in post-ischemic myocardial inflammatory response and cardiac dysfunction in both males and females. Permanent ischemia was induced in male and female C57BL/6J (wild-type, WT) and TLR2 knockout (KO) mice. Infarct size and left ventricular (LV) function were analyzed at day 7. Myocardial levels of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1), as well as neutrophil infiltration, were assessed at day 3, and mononuclear cell accumulation was determined at day 7. Lower MCP-1 and ICAM-1 levels, and reduced leukocyte accumulation correlated with smaller infarct size and improved LV function in male TLR2 KO mice. Female WT mice exhibited attenuated myocardial inflammatory response and injury, and TLR2 KO in females did not provide a protective effect although myocardial TLR2 levels in female WT mice were unaltered, and their cardiac cells responded to bacterial TLR2 agonist properly. TLR2 KO in male mice reduced post-ischemic myocardial inflammatory response, resulting in smaller infarct sizes and improved cardiac function. However, TLR2 KO was not beneficial in female mice. The gender disparity in the role of TLR2 in post-ischemic myocardial inflammatory response and myocardial injury suggests that interception with TLR2 signaling may have therapeutic potentials only in males. PMID:26379843

  10. Myocardial Po2 does not limit aerobic metabolism in the postischemic heart.

    PubMed

    Chung, Youngran

    2016-01-15

    Reperfused hypertrophic hearts are prone to develop reflow abnormalities, which are likely to impair O2 return to the myocardium. Yet, reflow deficit may not be the only factor determining postischemic oxygenation in the hypertrophic heart. Altered O2 demand may also contribute to hypoxia. In addition, the extent to which myocardial Po2 dictates energy and functional recovery in the reperfused heart remains uncertain. In the present study, moderately hypertrophied hearts from spontaneously hypertensive rats were subjected to ischemia-reperfusion, and the recovery time courses of pH and high-energy phosphates were followed by (31)P NMR. (1)H NMR measurement of intracellular myoglobin assessed tissue O2 levels. The present study found that the exacerbation of hypoxia in the postischemic spontaneously hypertensive rat heart arises mostly from impaired microvascular supply of O2. However, postischemic myocardial Po2, at least when it exceeds ∼18% of the preischemic level, does not limit mitochondrial respiration and high-energy phosphate resynthesis. It only passively reflects changes in the O2 supply-demand balance. PMID:26589325

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

    PubMed Central

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

    2014-01-01

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

  12. 40 CFR 80.52 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  13. Laser thermal preconditioning enhances dermal wound repair

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

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

  14. Progranulin Deficiency Promotes Post-Ischemic Blood–Brain Barrier Disruption

    PubMed Central

    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

    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. PMID:24336722

  15. A mouse model of peripheral postischemic dysesthesia: involvement of reperfusion-induced oxidative stress and TRPA1 channel.

    PubMed

    Sasaki, Atsushi; Mizoguchi, Shizuka; Kagaya, Kenta; Shiro, Mai; Sakai, Akiho; Andoh, Tsugunobu; Kino, Yurika; Taniguchi, Hiroyuki; Saito, Yukako; Takahata, Hiroki; Kuraishi, Yasushi

    2014-12-01

    Peripheral postischemic dysesthesia was examined behaviorally in mice and we investigated the underlying molecular mechanism with a focus on oxidative stress. Hind-paw ischemia was induced by tight compression of the ankle with a rubber band, and reperfusion was achieved by cutting the rubber tourniquet. We found that reperfusion after ischemia markedly provoked licking of the reperfused hind paw, which was significantly inhibited by systemic administration of the antioxidant N-acetyl-l-cysteine and the transient receptor potential (TRP) A1 channel blocker HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide]. Postischemic licking was also significantly inhibited by an intraplantar injection of another antioxidant, phenyl-N-tert-butylnitrone. The TRPV1 channel blocker BCTC [N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide] did not inhibit postischemic licking. An intraplantar injection of hydrogen peroxide elicited hind-paw licking, which was inhibited by N-acetyl-l-cysteine, phenyl-N-tert-butylnitrone, and HC-030031. Postischemic licking was not affected by chemical depletion of sensory C-fibers, but it was inhibited by morphine, which has been shown to inhibit the C- and A?-fiber-evoked responses of dorsal horn neurons. Interestingly, postischemic licking was not inhibited by gabapentin and pregabalin, which have been shown to inhibit the C-fiber- but not A?-fiber-evoked response. The present results suggest that ischemia-reperfusion induces oxidative stress, which activates TRPA1 channels to provoke postischemic licking. It has been suggested that this behavior is mediated by myelinated (probably A?-type) afferent fibers. Oxidative stress and TRPA1 channels may be potential targets to treat peripheral ischemia-associated dysesthesia. PMID:25228635

  16. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure.

    PubMed

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-?. Overexpression of TNF-? in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-? inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-? production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-? overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  17. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    PubMed Central

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-?. Overexpression of TNF-? in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-? inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-? production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-? overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  18. Postischemic canine cerebral blood flow is coupled to cerebral metabolic rate.

    PubMed

    Michenfelder, J D; Milde, J H; Katusi?, Z S

    1991-07-01

    Following complete global cerebral ischemia and reperfusion, a brief period of reactive hyperemia is followed by a prolonged period of low flow commonly referred to as the delayed postischemic hypoperfusion state. It is generally assumed that this low-flow state may be injurious because of inadequate substrate delivery, thus implying that flow is no longer coupled to metabolic needs. This relationship of CBF to CMRO2 was examined in six anesthetized dogs that were subjected to 12 min of complete ischemia induced either by CSF compression or aortic occlusion. Following reperfusion and onset of the low-flow state, which stabilized at 45 min postischemia, control normothermic (37 degrees C) measurements of CBF and CMRO2 were determined. Thereafter, femoral arterial blood was circulated through a heat exchanger (42.5 degrees C), and brain temperature was increased to 40 degrees C and measurements were repeated. The brain was then cooled back to 37 degrees C for a final set of normothermic measurements. Thereafter, brain biopsies were taken to determine the energy state of the brain. CMRO2 changed approximately 6%/degrees C. CBF paralleled the change in CMRO2. Accordingly, the ratio of CBF to CMRO2 remained constant throughout at a value of 8 to 9, demonstrating maintained coupling. The brain energy state was normal at the end of the study. The authors conclude that postischemic CBF is modulated by the brain's metabolic needs. PMID:2050748

  19. Neuroprotective effects of a glutathione depletor in rat post-ischemic reperfusion brain damage.

    PubMed

    Giacomo, Claudia Di; Santangelo, Rosa; Sorrenti, Valeria; Volti, Giovanni L; Acquaviva, Rosaria

    2015-01-01

    The induction of heme oxygenase (HO), the rate-limiting enzyme in heme degradation, occurs as an adaptative response to oxidative stress and is consequent to decrease in cellular glutathione levels. Our previous studies demonstrated significant increase in survival rates of rats treated with glutathione depletors and submitted to transient cerebral ischemia. The aim of the present research was to test the effects of L-Buthionine sulfoximine (BSO), a glutathione depletor, during cerebral post-ischemic reperfusion. Cerebral ischemia was induced by bilateral clamping of common carotid arteries for 20 min. Each sample was used for glutathione ad lipid peroxidation level dosage and for evaluating the expression of heme oxygenase both after a single subcutaneous administration of BSO and without treatment. In the same experimental conditions, endothelial, inducible and neuronal Nitric Oxide Synthase (eNOS, iNOS and nNOS) and Dimethylarginine Dimethyl amine Hydrolases (DDAH-1 and DDAH-2) were also evaluated. Results obtained in the present study suggested that HO-1 over-expression may be implicated in the protective effect of BSO in post-ischemic reperfusion brain damage, although the involvement of other important stress mediators cannot be ruled out. PMID:25613502

  20. Estrogen receptors alpha mediates postischemic inflammation in chronically estrogen-deprived mice.

    PubMed

    Cordeau, Pierre; Lalancette-Hébert, Mélanie; Weng, Yuan Cheng; Kriz, Jasna

    2016-04-01

    Estrogens are known to exert neuroprotective and immuneomodulatory effects after stroke. However, at present, little is known about the role of estrogens and its receptors in postischemic inflammation after menopause. Here, we provide important in vivo evidence of a distinct shift in microglial phenotypes in the model of postmenopause brain. Using a model-system for live imaging of microglial activation in the context of chronic estrogen- and ERα-deficiency associated with aging, we observed a marked deregulation of the TLR2 signals and/or microglial activation in ovariectomized and/or ERα knockout mice. Further analysis revealed a 5.7-fold increase in IL-6, a 4.7-fold increase in phospho-Stat3 levels suggesting an overactivation of JAK/STAT3 pathway and significantly larger infarction in ERα knockouts chronically deprived of estrogen. Taken together, our results suggest that in the experimental model of menopause and/or aging, ERα mediates innate immune responses and/or microglial activation, and ischemia-induced production of IL-6. Based on our results, we propose that the loss of functional ERα may lead to deregulation of postischemic inflammatory responses and increased vulnerability to ischemic injury in aging female brains. PMID:26973103

  1. Epoxyeicosatrienoic acid prevents postischemic electrocardiogram abnormalities in an isolated heart model.

    PubMed

    Batchu, S N; Law, E; Brocks, D R; Falck, J R; Seubert, J M

    2009-01-01

    Cytochrome P450 epoxygenases metabolize arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs) which are in turn converted to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). The main objective of this study was to investigate the protective effects of EETs following ischemic injury using an ex vivo electrocardiogram (EKG) model. Hearts from C57Bl/6, transgenic mice with cardiomyocyte-specific overexpression of CYP2J2 (Tr) and wildtype (WT) littermates were excised and perfused with constant pressure in a Langendorff apparatus. Electrodes were placed superficially at the right atrium and left ventricle to assess EKG waveforms. In ischemic reperfusion experiments hearts were subjected to 20 min of global no-flow ischemia followed by 20 min of reperfusion (R20). The EKG from C57Bl/6 hearts perfused with 1 microM 14,15-EET showed less QT prolongation (QTc) and ST elevation (STE) (QTc=41+/-3, STE=2.3+/-0.3; R20: QTc=42+/-2 ms, STE=1.2+/-0.2mv) than control hearts (QTc=36+/-2, STE=2.3+/-0.2; R20: QTc=53+/-3 ms; STE=3.6+/-0.4mv). Similar results of reduced QT prolongation and ST elevation were observed in EKG recording from CYP2J2 Tr mice (QTc=35+/-1, STE=1.9+/-0.1; R20: QTc=38+/-4 ms, STE=1.3+/-0.2mv) compared to WT hearts. The putative epoxygenase inhibitor MS-PPOH (50 microM) and EET antagonist 14,15-EEZE (10 microM) both abolished the cardioprotective response, implicating EETs in this process. In addition, separate exposure to the K(ATP) channel blockers glibenclamide (1 microM) and HMR1098 (10 microM), or the PKA protein inhibitor H89 (50 nM) during reperfusion abolished the improved repolarization in both the models. Consistent with a role of PKA, CYP2J2 Tr mice had an enhanced activation of the PKAalpha regulatory II subunit in plasma membrane following IR injury. The present data demonstrate that EETs can enhance the recovery of ventricular repolarization following ischemia, potentially by facilitating activation of K(+) channels and PKA-dependent signaling. PMID:18973759

  2. Steps to translate preconditioning from basic research to the clinic

    PubMed Central

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

    2012-01-01

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

  3. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

    SciTech Connect

    Li, Zhao; Jin, Zhu-Qiu

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiac TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in normal mouse heart. IPC preserves the integrity of TJ structure and function that are vulnerable to IR injury.

  4. [L-propionylcarnitine taurine amide induces the metabolic recovery of the isolated postischemic rat heart].

    PubMed

    Lazzarino, G; Corsico, N; Tavazzi, B; di Pierro, D; Arrigoni-Martelli, E; Giardina, B

    1992-10-01

    The effect of reperfusion with L-propionyl-carnitine-taurinammide 1 mM was evaluated on the metabolic recovery of the isolated postischemic rat heart. Data referring to the tissue concentration of the high-energy phosphates, oxypurines, nucleosides, nicotinic coenzymes, lactate and pyruvate indicate that L-propionyl-carnitine-taurinammide significantly improves the metabolism of the reperfused myocardium. In particular, ATP, creatinphosphate, GTP, sum of adenine nucleotides and the energy charge resulted 1.80, 1.83, 3.47, 1.47 and 1.20 times higher respectively than the corresponding values recorded in control reperfused heart (p < 0.01 all). These data, out of supplying the necessary biochemical support to the beneficial effects of L-propionyl-carnitine-taurinammide on hemodynamics obtained in previous studies, suggest that L-propionyl-carnitine-taurinammide might represent a useful tool for the pharmacological treatment of myocardial infarction. PMID:1296879

  5. Revealing Preconditions for Trustful Collaboration in CSCL

    ERIC Educational Resources Information Center

    Gerdes, Anne

    2010-01-01

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

  6. Revealing Preconditions for Trustful Collaboration in CSCL

    ERIC Educational Resources Information Center

    Gerdes, Anne

    2010-01-01

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

  7. 40 CFR 1065.518 - Engine preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  8. Adverse effects of free fatty acid associated with increased oxidative stress in postischemic isolated rat hearts.

    PubMed

    Gambert, Sgolne; Vergely, Catherine; Filomenko, Rodolphe; Moreau, Daniel; Bettaieb, Ali; Opie, Lionel H; Rochette, Luc

    2006-02-01

    The mechanisms of the adverse effects of free fatty acids on the ischemic-reperfused myocardium are not fully understood. Long-chain fatty acids, including palmitate, uncouple oxidative phosphorylation and should therefore promote the formation of oxygen-derived free radicals, with consequent adverse effects. Conversely, the antianginal agent trimetazidine (TMZ), known to inhibit cardiac fatty acid oxidation, could hypothetically lessen the formation of reactive oxygen species (ROS) and thus improve reperfusion mechanical function. Isolated perfused rat hearts underwent 30 min of total global ischemia followed by 30 min of reperfusion. Hearts were perfused with glucose 5.5 mmol/l or palmitate 1.5 mmol/l with or without TMZ (100 micromol/l). Ascorbyl free radical (AFR) release during perfusion periods was measured by electron spin resonance as a marker of oxidative stress. Post-ischemic recovery in the palmitate group of heart was lower than in the glucose group with a marked rise in diastolic tension and reduction in left ventricular developed pressure (Glucose: 85 +/- 11 mmHg; Palmitate: 10 +/- 6 mmHg; p < 0.001). TMZ decreased diastolic tension in both glucose- and in palmitate-perfused hearts. Release of AFR within the first minute of reperfusion was greater in palmitate-perfused hearts and in hearts perfused with either substrate, this marker of oxidative stress was decreased by TMZ (expressed in arbitrary units/ml; respectively: 8.49 +/- 1.24 vs. 1.06 +/- 0.70 p < 0.05; 12.47 +/- 2.49 vs. 3.37 +/- 1.29 p < 0.05). Palmitate increased the formation of ROS and reperfusion contracture. TMZ, a potential inhibitor of palmitate-induced mitochondrial uncoupling, decreased the formation of free radicals and improved postischemic mechanical dysfunction. The novel conclusion is that adverse effects of fatty acids on ischemic-reperfusion injury may be mediated, at least in part, by oxygen-derived free radicals. PMID:16444597

  9. Extracellular brain cortical levels of noradrenaline in ischemia: effects of desipramine and postischemic administration of idazoxan.

    PubMed

    Gustafson, I; Westerberg, E J; Wieloch, T

    1991-01-01

    Using microdialysis, extracellular noradrenaline (NA) levels in the rat cerebral cortex were studied under isoflurane/N2O anaesthesia before, during and for 6 hours following 10 min of forebrain ischemia in a 2-vessel occlusion model. A microdialysis probe was introduced into the parietal cortex and dorsal hippocampus in anaesthetized rats and continuously perfused with Krebs-Ringer-bicarbonate buffer with or without the NA uptake inhibitor desipramine (DMI, 5 microM). Twenty min fractions were collected and the extracellular NA levels were measured in the dialysates using HPLC with electrochemical detection. The basal NA concentration in the dialysate was 10.5 +/- 1.8 (mean +/- SEM) pg/20 min fraction and increased to 39.3 +/- 4.8 pg/20 min fraction after local administration of DMI. During ischemia, NA increased to 38 times the basal level without DMI, and 6 times with DMI included during two hours' perfusion prior to ischemia. After recirculation NA levels returned to, or even transiently decreased below, preischemic values. With DMI present in the dialysis buffer, administration of idazoxan immediately following ischemia delayed the return to preischemic NA levels in the recirculation phase. In the absence of DMI, no effect of idazoxan on postischemic levels of NA was found. Local administration of DMI increases basal extracellular NA levels and reduces the ischemia-induced NA release. The latter effect may be a due to inhibition of the NA uptake system working in a reversed mode, or as a result of decreased synthesis of NA due to activation of presynaptic alpha 2-receptors by the increased synaptic NA levels. Postischemic treatment with the alpha 2-adrenoceptor antagonist idazoxan in combination with DMI prolongs the period of elevated extracellular NA levels, which may be of importance for the protective properties of idazoxan against ischemic cell injury. PMID:1684752

  10. Hyperoxia and transforming growth factor ?1 signaling in the post-ischemic mouse heart

    PubMed Central

    Li, Yuanjing; Cai, Ming; Sun, Qinghua; Liu, Zhenguo; Cardounel, Arturo J.; Swartz, Harold M.; He, Guanglong

    2013-01-01

    Aims Following ischemic injury, myocardial healing and remodeling occur with characteristic myofibroblast trans-differentiation and scar formation. The current study tests the hypothesis that hyperoxia and nitric oxide (NO) regulate TGF-?1 signaling in the post-ischemic myocardium. Main methods C57BL/6 wild-type (WT), endothelial and inducible nitric oxide synthase knockout (eNOS?/? and iNOS?/?) mice were subjected to 30-min left anterior descending coronary artery occlusion followed by reperfusion. Myocardial tissue oxygenation was monitored with electron paramagnetic resonance oximetry. Protein expressions of TGF-?1, receptor-activated small mothers against decapentaplegic homolog (Smad), p21 and ?-smooth muscle actin (?-SMA) were measured with enzyme-linked immunosorbent assay (ELISA), Western immunoblotting, and immunohistochemical staining. Key findings There was a hyperoxic state in the post-ischemic myocardial tissue. Protein expressions of total and active TGF-?1, p-Smad2/3 over t-Smad2/3 ratio, p21, and ?-SMA were significantly increased in WT mice compared to Sham control. Knockout of eNOS or iNOS further increased protein expression of these signals. The expression of ?-SMA was more abundant in the infarct of eNOS?/? and iNOS?/? mice than WT mice. A protein band indicating nitration of TGF-? type-II receptor (TGF?RII) was observed from WT heart. Carbogen (95% O2 plus 5% CO2) treatment increased the ratio of p-Smad2/t-Smad2, which was inhibited by 10006329 EUK (EUK134) and sodium nitroprusside (SNP). In conclusion, hyperoxia up-regulated and NO/ ONOO? inhibited cardiac TGF-?1 signaling and myofibroblast trans-differentiation. Significance These findings may provide new insights in myocardial infarct healing and repair. PMID:23352974

  11. Post-ischemic Reperfusion Causes Smooth Muscle Calcium Sensitization and Vasoconstriction of Parenchymal Arterioles

    PubMed Central

    Cipolla, Marilyn J.; Chan, Siu-Lung; Sweet, Julie; Tavares, Matthew J.; Gokina, Natalia; Brayden, Joseph E.

    2014-01-01

    Background and Purpose Parenchymal arterioles (PAs) are high resistance vessels in the brain that connect pial vessels to the microcirculation. We previously showed that PAs have increased vasoconstriction after ischemia and reperfusion that could increase perfusion deficit. Here, we investigated underlying mechanisms by which early post-ischemic reperfusion causes increased vasoconstriction of PAs. Methods Isolated and pressurized PAs from within the MCA territory were studied in male Wistar rats that were either nonischemic control (CTL; n=34) or after exposure to transient MCAO by filament occlusion for 2 hours with 30 minutes of reperfusion (MCAO; n=38). The relationships between pressure-induced tone, smooth muscle calcium (using Fura 2) and membrane potential were determined. Sensitivity of the contractile apparatus to calcium was measured in permeabilized arterioles using Staphaloccus aureus α-toxin. Reactivity to inhibition of TRPM4 (9-phenanthrol), Rho kinase (Y27632) and protein kinase C (Gö6976) was also measured. Results After MCAO, PAs had increased myogenic tone compared to controls (47±2% vs. 35±2% at 40 mmHg; p<0.01), without an increase in smooth muscle calcium (177±21 vs. 201±16 nmol/L; p>0.05) or membrane depolarization (−38±4 vs. −36±1 mV;p>0.05). In α-toxin permeabilized vessels, MCAO caused increased sensitivity of the contractile apparatus to calcium. MCAO did not affect dilation to TRPM4- or PKC-inhibition, but diminished dilation to Rho kinase inhibition. Conclusions The increased vasoconstriction of PAs during early post-ischemic reperfusion appears to be due to calcium sensitization of smooth muscle and could contribute to infarct expansion and limit neuroprotective agents from reaching their target tissue. PMID:24968928

  12. Condition Number Estimation of Preconditioned Matrices

    PubMed Central

    Kushida, Noriyuki

    2015-01-01

    The present paper introduces a condition number estimation method for preconditioned matrices. The newly developed method provides reasonable results, while the conventional method which is based on the Lanczos connection gives meaningless results. The Lanczos connection based method provides the condition numbers of coefficient matrices of systems of linear equations with information obtained through the preconditioned conjugate gradient method. Estimating the condition number of preconditioned matrices is sometimes important when describing the effectiveness of new preconditionerers or selecting adequate preconditioners. Operating a preconditioner on a coefficient matrix is the simplest method of estimation. However, this is not possible for large-scale computing, especially if computation is performed on distributed memory parallel computers. This is because, the preconditioned matrices become dense, even if the original matrices are sparse. Although the Lanczos connection method can be used to calculate the condition number of preconditioned matrices, it is not considered to be applicable to large-scale problems because of its weakness with respect to numerical errors. Therefore, we have developed a robust and parallelizable method based on Hagers method. The feasibility studies are curried out for the diagonal scaling preconditioner and the SSOR preconditioner with a diagonal matrix, a tri-daigonal matrix and Peis matrix. As a result, the Lanczos connection method contains around 10% error in the results even with a simple problem. On the other hand, the new method contains negligible errors. In addition, the newly developed method returns reasonable solutions when the Lanczos connection method fails with Peis matrix, and matrices generated with the finite element method. PMID:25816331

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

    PubMed

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

    2016-03-01

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

  14. [Postischemic reorganization of dendritic architectonics of the hippocampal CA3 region in albino rats predisposed to seizures].

    PubMed

    Semchenko, V V; Stepanov, S S; Nikel', A E; Akulinin, V A

    2000-01-01

    Total short term ischemia of brain was induced experimentally in albino rats (10 min long clamp of heart vascular bundle). Using Golgi Silver nitrate impregnation geometry of pyramidal neurons dendritic tree was studied in sector of hippocampus in norm, postischemic period (d 1.30 and 90) healthy animals and those predisposed to cramps. Significant reduction of dendrite volume, total length, dendrite territory, parameters of dendrite arborization were shown on the background of stable numerical density of neurons in all animals who survived brain ischemia. The extent of reduction, volume and duration of changes of parameters of dendritic tree geometry was higher in animals predisposed to cramps than in high threshold animals without cramps. Possible mechanisms of postischemic neuron "epileptization" were discussed. PMID:11210456

  15. Preconditioning Stem Cells for In Vivo Delivery

    PubMed Central

    Sart, Sbastien; Ma, Teng

    2014-01-01

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

  16. Preserving Symmetry in Preconditioned Krylov Subspace Methods

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

    We consider the problem of solving a linear system Ax = b when A is nearly symmetric and when the system is preconditioned by a symmetric positive definite matrix M. In the symmetric case, one can recover symmetry by using M-inner products in the conjugate gradient (CG) algorithm. This idea can also be used in the nonsymmetric case, and near symmetry can be preserved similarly. Like CG, the new algorithms are mathematically equivalent to split preconditioning, but do not require M to be factored. Better robustness in a specific sense can also be observed. When combined with truncated versions of iterative methods, tests show that this is more effective than the common practice of forfeiting near-symmetry altogether.

  17. A Hybrid Parallel Preconditioning Algorithm For CFD

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  18. M-step preconditioned conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Adams, L.

    1983-01-01

    Preconditioned conjugate gradient methods for solving sparse symmetric and positive finite systems of linear equations are described. Necessary and sufficient conditions are given for when these preconditioners can be used and an analysis of their effectiveness is given. Efficient computer implementations of these methods are discussed and results on the CYBER 203 and the Finite Element Machine under construction at NASA Langley Research Center are included.

  19. Does intraperitoneal medical ozone preconditioning and treatment ameliorate the methotrexate induced nephrotoxicity in rats?

    PubMed Central

    Aslaner, Arif; ak?r, Tu?rul; elik, Betl; Do?an, U?ur; Mayir, Burhan; Akyz, Cebrail; Polat, Cemal; Ba?trk, Ahmet; Soyer, Vural; Ko, Sleyman; ?ehirli, Ahmet zer

    2015-01-01

    Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-?, IL-1?, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-? and IL-1? (P<0.05) and significant decrease in tissue GSH and histopathology (P<0.05) after Mtx administration. The preconditioning and treatment with medical ozone ameliorated the nephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue. PMID:26550330

  20. On polynomial preconditioning for indefinite Hermitian matrices

    NASA Technical Reports Server (NTRS)

    Freund, Roland W.

    1989-01-01

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

  1. Postischemic cardiac recovery in heme oxygenase-1 transgenic ischemic/reperfused mouse myocardium

    PubMed Central

    Juhasz, Bela; Varga, Balazs; Czompa, Attila; Bak, Istvan; Lekli, Istvan; Gesztelyi, Rudolf; Zsuga, Judit; Kemeny-Beke, Adam; Antal, Miklos; Szendrei, Levente; Tosaki, Arpad

    2011-01-01

    Abstract Heme oxygenase-1 (HO-1) transgenic mice (Tg) were created using a rat HO-1 genomic transgene. Transgene expression was detected by RT-PCR and Western blots in the left ventricle (LV), right ventricle (RV) and septum (S) in mouse hearts, and its function was demonstrated by the elevated HO enzyme activity. Tg and non-transgenic (NTg) mouse hearts were isolated and subjected to ischemia/reperfusion. Significant post-ischemic recovery in coronary flow (CF), aortic flow (AF), aortic pressure (AOP) and first derivative of AOP (AOPdp/dt) were detected in the HO-1 Tg group compared to the NTg values. In HO-1 Tg hearts treated with 50 ?mol/kg of tin protoporphyrin IX (SnPPIX), an HO enzyme inhibitor, abolished the post-ischemic cardiac recovery. HO-1 related carbon monoxide (CO) production was detected in NTg, HO-1 Tg and HO-1 Tg + SnPPIX treated groups, and a substantial increase in CO production was observed in the HO-1 Tg hearts subjected to ischemia/reperfusion. Moreover, in ischemia/reperfusion-induced tissue Na+ and Ca2+ gains were reduced in HO-1 Tg group in comparison with the NTg and HO-1 Tg + SnPPIX treated groups; furthermore K+ loss was reduced in the HO-1 Tg group. The infarct size was markedly reduced from its NTg control value of 37 4% to 20 6% (P < 0.05) in the HO-1 Tg group, and was increased to 47 5% (P < 0.05) in the HO-1 knockout (KO) hearts. Parallel to the infarct size reduction, the incidence of total and sustained ventricular fibrillation were also reduced from their NTg control values of 92% and 83% to 25% (P < 0.05) and 8% (P < 0.05) in the HO-1 Tg group, and were increased to 100% and 100% in HO-1 KO?/? hearts. Immunohistochemical staining of HO-1 was intensified in HO-1 Tg compared to the NTg myocardium. Thus, the HO-1 Tg mouse model suggests a valuable therapeutic approach in the treatment of ischemic myocardium. PMID:20716121

  2. Assessment of myocardial viability in patients with postischemic left ventricular dysfunction: role of myocardial contrast echocardiography.

    PubMed

    Agati, Luciano; De Majo, Francesca; Madonna, Maria Pina; Celani, Flavia; Funaro, Stefania; Tonti, Gianni

    2003-08-01

    The distinction between viable and nonviable dysfunctional left ventricular (LV) segments after acute myocardial infarction is very important, because revascularization increases survival only in patients with viable myocardial tissue. Recent studies have highlighted a mismatch between two highly specific investigations for viability assessment: dobutamine echocardiography, which measures inotropic reserve, and myocardial contrast echocardiography (MCE), which measures microvascular perfusion. Viability and functional reserve are not synonymous. Maintenance of microvascular perfusion, independently of functional reserve, attenuates left ventricular remodelling, reduces the risk of major cardiac events, and increases survival. MCE provides similar perfusion information as myocardial blush, but image quality is much higher. Quantitative analysis of digital data provides more accurate diagnostic MCE information than qualitative analysis of video signal intensity. In a recent study relating MCE findings to histologic data, MCE-derived quantitative data were closely correlated with microvascular density and capillary area, and inversely correlated with collagen content. One of the contrast agents routinely used for MCE is SonoVue, a second generation microbubble contrast agent, which is characterized by high response to ultrasound energy, ease of destruction at high energy, and strong harmonic signal at low energy. Recommendations for the assessment of postischemic LV dysfunction: routine use of MCE, followed by dobutamine echocardiography if perfusion is documented. If MCE is negative, revascularization is not indicated; if both tests are positive, revascularization is strongly recommended; if they are discordant, useful information can be obtained by assessing the extent of 201T1 viability. PMID:23573622

  3. Influence of preischemic hyperglycemia on osmolality and early postischemic edema in the rat brain.

    PubMed

    Gisselsson, L; Smith, M L; Siesj, B K

    1992-09-01

    Preischemic hyperglycemia, which raises tissue lactate content during ischemia, is known to aggravate ischemic brain damage. To explore the possibility that the enhanced lactic acidosis gives rise to osmotic damage, we studied the influence of a varied preischemic plasma glucose concentration on the early postischemic edema. Brain edema was measured by the specific-gravity technique. Brain and plasma osmolality were measured with a vapor pressure osmometer. We examined different brain regions in hyperglycemic and moderately hypoglycemic rats subjected to 15 min of forebrain ischemia, followed by recirculation for 5, 15, and 30 min. The decrease in specific gravity was compared with the increase in osmolality, to study whether the edema formation in the different groups correlated to the increase in tissue osmolality. We found edema formation to be most pronounced in frontoparietal cortex. In this structure and in hippocampus, statistically significant decreases of specific gravity were seen at all recirculation times studied. In caudoputamen, significant edema was seen only in the groups with 5 and 15 min of recirculation. Contrary to expectations, no difference was found between hyperglycemic and hyperglycemic animals. Tissue osmolality increased during ischemia in both the low and high glucose groups, but to a higher level in the latter (hypoglycemia 311 +/- 1 mmol kg-1, hyperglycemia 328 +/- 10 mmol kg-1; mean +/- SD, p less than 0.05). In the hyperglycemic group, brain osmolality remained elevated for the first 15 min of recirculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1506445

  4. Temporal assessment of vascular reactivity and functionality using MRI during postischemic proangiogenenic vascular remodeling.

    PubMed

    Huang, Chien-Hsiang; Shih, Yen-Yu Ian; Siow, Tiing-Yee; Hsu, Yi-Hua; Chen, Chiao-Chi V; Lin, Teng-Nan; Jaw, Fu-Shan; Chang, Chen

    2015-09-01

    Postischemic angiogenesis is an important recovery mechanism. Both arteries and veins are upregulated during angiogenesis, but eventually there are more angiogenic veins than arteries in terms of number and length. It is critical to understand how the veins are modulated after ischemia and then transitioned into angiogenic vessels during the proangiogenic stage to finally serve as a restorative strength to the injured area. Using a rat model of transient focal cerebral ischemia, the hypercapnic blood oxygen level-dependent (BOLD) response was used to evaluate vascular reactivity, while the hyperoxic BOLD and tissue oxygen level-dependent (TOLD) responses were used to evaluate the vascular functionality at 1, 3, and 7days after ischemia. Vessel-like venous signals appeared on R2* maps on days 3 and 7, but not on day 1. The large hypercapnic BOLD responses on days 3 and 7 indicated that these areas have high vascular reactivity. The temporal correlation between vascular reactivity and the immunoreactivity to desmin and VEGF further indicates that the integrity of vascular reactivity is associated with the pericyte coverage as regulated by the VEGF level. Vascular functionality remained low on days 1, 3, and 7, as reflected by the small hyperoxic BOLD and large hyperoxic TOLD responses, indicating the low oxygen consumption of the ischemic tissues. These functional changes in proangiogenic veins may be critical for angiogenesis. PMID:25944092

  5. [Energy corrective and antioxidative actions of cytoflavin during postischemic period of human dermal fibroblasts in vitro].

    PubMed

    Tiuriaeva, I I; Kuranova, M L; Gonchar, I V; Rozanov, Iu M

    2012-01-01

    The influence of metabolic drug Cytoflavin (CF) with antihypoxic and antioxidative properties on human dermal fibroblasts in a model of ischemia-reoxygenation in vitro was studied. It was revealed that the restoration of ATP synthesis in fibroblasts in the postischemic period was considerably accelerated (in 2.1 times) by the addition of CF to the culture medium. The drug had a cell protective effect of reducing cell mortality during the reoxygenation after ischemia by 2-2.7 times. CF effectively reduced the level of reactive oxygen species (ROS) in fibroblasts after H2O2 treatment which allowed maintaining their survival at the level of control cells. Pretreatment of the cells with CF for one day ensured the maintenance of normal levels of ROS during the investigated time period in the fibroblasts subjected to H2O2 treatment, and reduced H2O2-induced cell death by almost a third compared to control cells. The introduction of CF in culture medium after ischemia showed no influence on Hsp70 synthesis, but led to decrease in GRP78 synthesis, raised after ischemia, to the control level, indicating a resolve of the endoplasmic reticulum (ER) stress and functional normalization of ER. PMID:22997734

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

    PubMed Central

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

    2014-01-01

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

  7. Prevention

    MedlinePLUS

    ... provides helpful advice and information. Get Started Heart Attack Risk Calculator Discover your 10-year risk of ... and activities near you. Learn more > Home Tools & Protocols Data & Reports Partners & Progress Learn & Prevent News & Media ...

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Ghosh, A; Paparao, P

    1987-07-15

    Analog electrooptical processors are best suited for applications demanding high computational throughput with tolerance for inaccuracies. Matrix preconditioning is one such application. Matrix preconditioning is a preprocessing step for reducing the condition number of a matrix and is used extensively with gradient algorithms for increasing the rate of convergence and improving the accuracy of the solution. In this paper, we describe a simple parallel algorithm for matrix preconditioning, which can be implemented efficiently on a pipelined optical linear algebra processor. From the results of our numerical experiments we show that the efficacy of the preconditioning algorithm is affected very little by the errors of the optical system. PMID:20489953

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

    NASA Technical Reports Server (NTRS)

    Wong, Yau Shu; Jiang, Hong

    1987-01-01

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

  11. H(curl) Auxiliary Mesh Preconditioning

    SciTech Connect

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

    2006-08-31

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

  12. Controlled Ionospheric Preconditioning and Stimulated Electromagnetic Radiation

    SciTech Connect

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

    1998-06-01

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

  13. The multigrid preconditioned conjugate gradient method

    NASA Technical Reports Server (NTRS)

    Tatebe, Osamu

    1993-01-01

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

  14. 40 CFR 1066.407 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  15. 40 CFR 1066.407 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  16. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  17. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  18. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  19. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  20. A preconditioned formulation of the Cauchy-Riemann equations

    NASA Technical Reports Server (NTRS)

    Phillips, T. N.

    1983-01-01

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

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

    PubMed

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

    2015-09-01

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

  2. AB068. Association between MTHFR C677T and carotid intima medial thickness progression in post-ischemic stroke patient

    PubMed Central

    Pramukarso, Dodik Tugasworo; Faradz, Sultana MH; Sari, Stefani Harum; Hadisaputro, Suharyo

    2015-01-01

    Background and objective Substitution of c.677C > T in methylenetetrahydrofolate reductase (MTHFR) gene contributes to increase blood level of homocysteine (Hcy). Hyperhomocysteinemia is believed to have association with vascular damage leads to atherosclerosis. Defect MTHFR may influence vascular progression in post ischemic stroke. Carotid intima media thickness (c-IMT) has been known as vascular marker for atherosclerosis and predictor for ischemic stroke. The study aims to determine association between MTHFR C677T and c-IMT progression in post-ischemic stroke patients. Methods Seventy one of post-ischemic stroke patients were included in epidemiological prospective observational cohort study. Genotyping MTHFR gene polymorphism was done using PCR-RFLP with HinfI restriction enzyme. Blood Hcy level was determined using enzyme immunoassay (EIA) method. Carotid duplex ultrasound was used to evaluate c-IMT in 1st, 6th, and 12th month after the onset of stroke. Results The genotype distribution of MTHFR C677T in samples was CC (81.9%), CT (13.9%) and TT (4.2%). No significant differences in mean Hcy levels between genotype TT and others (CT and CC) were identified (P=0.250). Mean c-IMT showed no significant differences between genotype TT and others at evaluation in 1st month (P=0.979), 6th month (P=0.670) and 12th month (P=0.770). All samples with genotype TT were observed to have increase c-IMT level at evaluation in 1st, 6th and 12th month. Conclusions The presence of homozygote TT of MTHFR C677T may contribute to increase c-IMT level. However, this study found no association between MTHFR C677T with hyperhomocysteinemia as well as an increase in c-IMT in post-ischemic stroke patients.

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

    PubMed

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

    2010-04-01

    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-1beta (3.8X) and TNF-alpha (6.0X). IFN-gamma 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. PMID:20209379

  4. Is reduced SERCA2a expression detrimental or beneficial to postischemic cardiac function and injury? Evidence from heterozygous SERCA2a knockout mice.

    PubMed

    Talukder, M A Hassan; Kalyanasundaram, Anuradha; Zuo, Li; Velayutham, Murugesan; Nishijima, Yoshinori; Periasamy, Muthu; Zweier, Jay L

    2008-03-01

    Recent studies have demonstrated that increased expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 2a improves myocardial contractility and Ca2+ handling at baseline and in disease conditions, including myocardial ischemia-reperfusion (I/R). Conversely, it has also been reported that pharmacological inhibition of SERCA might improve postischemic function in stunned hearts or in isolated myocardium following I/R. The goal of this study was to test how decreases in SERCA pump level/activity affect cardiac function following I/R. To address this question, we used a heterozygous SERCA2a knockout (SERCA2a+/-) mouse model with decreased SERCA pump levels and studied the effect of myocardial stunning (20-min ischemia followed by reperfusion) and infarction (30-min ischemia followed by reperfusion) following 60-min reperfusion. Our results demonstrate that postischemic myocardial relaxation was significantly impaired in SERCA2a+/- hearts with both stunning and infarction protocols. Interestingly, postischemic recovery of contractile function was comparable in SERCA2a+/- and wild-type hearts subjected to stunning. In contrast, following 30-min ischemia, postischemic contractile function was reduced in SERCA2a+/- hearts with significantly larger infarction. Rhod-2 spectrofluorometry revealed significantly higher diastolic intracellular Ca2+ in SERCA2a+/- hearts compared with wild-type hearts. Both at 30-min ischemia and 2-min reperfusion, intracellular Ca2+ levels were significantly higher in SERCA2a+/- hearts. Electron paramagnetic resonance spin trapping showed a similar extent of postischemic free-radical generation in both strains. These data provide direct evidence that functional SERCA2a level, independent of oxidative stress, is crucial for postischemic myocardial function and salvage during I/R. PMID:18203847

  5. A limited role for regulatory T cells in post-ischemic neovascularization.

    PubMed

    Hellingman, A A; van der Vlugt, L E P M; Lijkwan, M A; Bastiaansen, A J N M; Sparwasser, T; Smits, H H; Hamming, J F; Quax, P H A

    2012-02-01

    Recently, it was demonstrated that arteriogenesis is enhanced in mice deficient in regulatory T cells (CD4(+) CD25(+) FoxP3(+) T cell), which can suppress effector T cell responses. The present study investigates the effects of these regulatory T cells on arteriogenesis in more detail by either specific expanding or depleting regulatory T cells. Hind limb ischemia was induced by electro-coagulation of the femoral artery in mice. Regulatory T cells were either expanded by injecting mice with a complex of interleukin (IL)-2 with the IL-2 monoclonal antibody JES6-1, or depleted by anti-CD25 antibody or diphtheria toxin injections in DEREG mice (depletion of regulatory T cells). Blood flow restoration was monitored using laser Doppler perfusion imaging. Collateral arteries were visualized by immunohistochemistry. Regulatory T cell expansion led to a moderate though significant suppression of blood flow restoration after ischemia induction. Surprisingly, depletion of regulatory T cells resulted in minor increase on blood flow recovery. However, collateral and capillary densities in the post-ischemic skeletal muscle were significantly increased in DEREG mice depleted for regulatory T cells. The presence of regulatory T cells after ischemia induction when analysed in non-depleted DEREG mice could be demonstrated by green fluorescent protein staining only in lymph nodes in the ischemic area, and not in the ischemic muscle tissue. The current study demonstrates that, even under conditions of major changes in regulatory T cell content, the contribution of regulatory T cells to the regulation of the arteriogenic response is only moderate. PMID:21426486

  6. A limited role for regulatory T cells in post-ischemic neovascularization

    PubMed Central

    Hellingman, AA; van der Vlugt, LEPM; Lijkwan, MA; Bastiaansen, AJNM; Sparwasser, T; Smits, HH; Hamming, JF; Quax, PHA

    2012-01-01

    Abstract Recently, it was demonstrated that arteriogenesis is enhanced in mice deficient in regulatory T cells (CD4+CD25+FoxP3+ T cell), which can suppress effector T cell responses. The present study investigates the effects of these regulatory T cells on arteriogenesis in more detail by either specific expanding or depleting regulatory T cells. Hind limb ischemia was induced by electro-coagulation of the femoral artery in mice. Regulatory T cells were either expanded by injecting mice with a complex of interleukin (IL)-2 with the IL-2 monoclonal antibody JES6–1, or depleted by anti-CD25 antibody or diphtheria toxin injections in DEREG mice (depletion of regulatory T cells). Blood flow restoration was monitored using laser Doppler perfusion imaging. Collateral arteries were visualized by immunohistochemistry. Regulatory T cell expansion led to a moderate though significant suppression of blood flow restoration after ischemia induction. Surprisingly, depletion of regulatory T cells resulted in minor increase on blood flow recovery. However, collateral and capillary densities in the post-ischemic skeletal muscle were significantly increased in DEREG mice depleted for regulatory T cells. The presence of regulatory T cells after ischemia induction when analysed in non-depleted DEREG mice could be demonstrated by green fluorescent protein staining only in lymph nodes in the ischemic area, and not in the ischemic muscle tissue. The current study demonstrates that, even under conditions of major changes in regulatory T cell content, the contribution of regulatory T cells to the regulation of the arteriogenic response is only moderate. PMID:21426486

  7. Recovery of postischemic contractile function is depressed by antegrade warm continuous blood cardioplegia.

    PubMed

    Misare, B D; Krukenkamp, I B; Lazer, Z P; Levitsky, S

    1993-01-01

    To assess the effectiveness of warm antegrade continuous blood cardioplegia in the setting of an acute coronary arterial occlusion, we instrumented 19 Yorkshire swine to quantitate left ventricular global, systolic, diastolic, and regional mechanics. Data were acquired before and after 10 minutes of mid-left anterior descending coronary artery occlusion followed by 60 minutes of aortic crossclamping. Cardiac arrest was induced by the antegrade infusion of 20 ml/kg of warm (37 degrees C) or cold (4 degrees C) oxygenated blood cardioplegic solution followed by either continuous warm (75 ml/min, n = 9) or intermittent cold (10 ml/kg every 20 minutes, n = 10) cardioplegic reinfusions. Left anterior descending coronary artery occlusion was released 20 minutes after aortic crossclamping and resulted in warm-arrested hearts developing a 139% increase in global oxygen consumption compared with values obtained with the left anterior descending coronary artery occluded (p < 0.02). Recovery of global left ventricle contractility, quantitated by the linear preload recruitable stroke-work relationship, was significantly worse after warm cardioplegia (52.4% +/- 5.1% versus 68.0% +/- 5.9%, warm versus cold, p < 0.05). Similarly, left anterior descending coronary artery regional ischemic zone contractility recovered 34.5% +/- 7.3% of control function with cold cardioplegia, whereas warm cardioplegia resulted in -11.36% +/- 7.46% functional recovery indicative of dyssynchronous contraction (p < 0.05). Diastolic compliance, calculated with an exponential end-diastolic pressure-versus-volume relationship, was not changed postischemically in either group. These data suggest that warm antegrade blood cardioplegia may potentiate acute ischemic injury and provide inadequate myocardial protection. PMID:8419707

  8. Kinin receptor agonism restores hindlimb postischemic neovascularization capacity in diabetic mice.

    PubMed

    Desposito, Dorinne; Potier, Louis; Chollet, Catherine; Gobeil, Fernand; Roussel, Ronan; Alhenc-Gelas, Francois; Bouby, Nadine; Waeckel, Ludovic

    2015-02-01

    Limb ischemia is a major complication of thromboembolic diseases. Diabetes worsens prognosis by impairing neovascularization. Genetic or pharmacological inactivation of the kallikrein-kinin system aggravates limb ischemia in nondiabetic animals, whereas angiotensin I-converting enzyme/kininase II inhibition improves outcome. The role of kinins in limb ischemia in the setting of diabetes is not documented. We assessed whether selective activation of kinin receptors by pharmacological agonists can influence neovascularization in diabetic mice with limb ischemia and have a therapeutic effect. Selective pseudopeptide kinin B1 or B2 receptor agonists resistant to peptidase action were administered by osmotic minipumps at a nonhypotensive dosage for 14 days after unilateral femoral artery ligation in mice previously rendered diabetic by streptozotocin. Comparison was made with ligatured, nonagonist-treated nondiabetic and diabetic mice. Diabetes reduced neovascularization, assessed by microangiography and histologic capillary density analysis, by roughly 40%. B1 receptor agonist or B2 receptor agonist similarly restored neovascularization in diabetic mice. Neovascularization in agonist-treated diabetic mice was indistinguishable from nondiabetic mice. Both treatments restored blood flow in the ischemic hindfoot, measured by laser-Doppler perfusion imaging. Macrophage infiltration increased 3-fold in the ischemic gastrocnemius muscle during B1 receptor agonist or B2 receptor agonist treatment, and vascular endothelial growth factor (VEGF) level increased 2-fold. Both treatments increased, by 50-100%, circulating CD45/CD11b-positive monocytes and CD34(+)/VEGFR2(+) progenitor cells. Thus, selective pharmacological activation of B1 or B2 kinin receptor overcomes the effect of diabetes on postischemic neovascularization and restores tissue perfusion through monocyte/macrophage mobilization. Kinin receptors are potential therapeutic targets in limb ischemia in diabetes. PMID:25398240

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

    SciTech Connect

    Moore, C.A.; Cannon, J.; Watson, D.D.; Kaul, S.; Beller, G.A. )

    1990-05-01

    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.

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

    PubMed Central

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

    2014-01-01

    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 estrogens 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 nave, OVX and RS rats were used as controls. Expression of ER-? and ER-? in isolated cortical cerebral microvessels (20 to 100 m in diameter) was assessed using Western blot and immunohistochemistry techniques. Results Age and reproductive status blunted nonischemic ER-? expression in microvessels of OVX rats (0.310.05) and RS rats (0.330.06) compared to nave rats (0.450.02). Postischemic microvascular expression of ER-? in OVX rats (0.010.0) was increased by CE treatment (0.040.01). Expression of ER-? in microvessels of RS rats (0.030.02) was unaffected by CE treatment (0.010.02). 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 Students 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. PMID:25010766

  11. NCX1 Exchanger Cooperates with Calretinin to Confer Preconditioning-Induced Tolerance Against Cerebral Ischemia in the Striatum.

    PubMed

    Boscia, Francesca; Casamassa, Antonella; Secondo, Agnese; Esposito, Alba; Pannaccione, Anna; Sirabella, Rossana; Pignataro, Giuseppe; Cuomo, Ornella; Vinciguerra, Antonio; de Rosa, Valeria; Annunziato, Lucio

    2016-03-01

    Recently, the Na(+)/Ca(+2) exchanger NCX1 and the calcium binding protein calretinin have emerged as new molecular effectors of delayed preconditioning in the brain. In the present study, we investigated whether NCX1 and calretinin cooperate within the preconditioned striatum to confer neurons greater resistance to degeneration. Confocal microscopy analysis revealed that NCX1 expression was upregulated in calretinin-positive interneurons in the rat striatum after tolerance induction. Consistently, coimmunoprecipitation assays performed on human SHSY-5Y cells, a neuronal cell line which constitutively expresses calretinin, revealed a binding between NCX1 and calretinin. Finally, silencing of calretinin expression, both in vitro and in vivo, significantly prevented preconditioning-induced neuroprotection. Interestingly, our biochemical and functional studies showed that the selective silencing of calretinin in brain cells significantly prevented not only the preconditioning-induced upregulation of NCX1 expression and activity but also the activation of the prosurvival protein kinase Akt, which is involved in calretinin and NCX1 protective actions. Collectively, our results indicate that the Na(+)/Ca(+2) exchanger NCX1 and the calcium binding protein calretinin cooperate within the striatum to confer tolerance against cerebral ischemia. PMID:25633096

  12. Cellular and Molecular Neurobiology of Brain Preconditioning

    PubMed Central

    Cadet, Jean Lud; Krasnova, Irina N.

    2009-01-01

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

  13. The preconditioning of major sudden stratospheric warmings

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  14. Intranasal delivery of HMGB1 siRNA confers target gene knockdown and robust neuroprotection in the postischemic brain.

    PubMed

    Kim, Il-Doo; Shin, Joo-Hyun; Kim, Seung-Woo; Choi, Sunghyun; Ahn, Junseong; Han, Pyung-Lim; Park, Jong-Sang; Lee, Ja-Kyeong

    2012-04-01

    Noninvasive intranasal drug administration has been noted to allow direct delivery of drugs to the brain. In the present study, the therapeutic efficacy of intranasal small interfering RNA (siRNA) delivery was investigated in the postischemic rat brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA was delivered intranasally in normal adult rats using e-PAM-R, a biodegradable PAMAM dendrimer, as gene carrier. Florescence-tagged siRNA was found in the cytoplasm and processes of neurons and of glial cells in many brain regions, including the hypothalamus, amygdala, cerebral cortex, and striatum, in 1 hour after infusion, and the FITC-fluorescence was continuously detected for at least 12 hours. When siRNA for high mobility group box 1 (HMGB1), which functions as an endogenous danger molecule and aggravates inflammation, was delivered intranasally, the target gene was significantly depleted in many brain regions, including the prefrontal cortex and striatum. More importantly, intranasal delivery of HMGB1 siRNA markedly suppressed infarct volume in the postischemic rat brain (maximal reduction to 42.8 5.6% at 48 hours after 60 minutes middle cerebral artery occlusion (MCAO)) and this protective effect was manifested by recoveries from neurological and behavioral deficits. These results indicate that the intranasal delivery of HMGB1 siRNA offers an efficient means of gene knockdown-mediated therapy in the ischemic brain. PMID:22252450

  15. Application of high-dose propofol during ischemia improves postischemic function of rat hearts: effects on tissue antioxidant capacity.

    PubMed

    Xia, Zhengyuan; Godin, David V; Ansley, David M

    2004-10-01

    Previous studies have shown that reactive oxygen species mediated lipid peroxidation in patients undergoing cardiac surgery occurs primarily during cardiopulmonary bypass. We examined whether application of a high concentration of propofol during ischemia could effectively enhance postischemic myocardial functional recovery in the setting of global ischemia and reperfusion in an isolated heart preparation. Hearts were subjected to 40 min of global ischemia followed by 90 min of reperfusion. During ischemia, propofol (12 microg/mL in saline) was perfused through the aorta at 60 microL/min. We found that application of high-concentration propofol during ischemia combined with low-concentration propofol (1.2 microg/mL) administered before ischemia and during reperfusion significantly improved postischemic myocardial functional recovery without depressing cardiac mechanics before ischemia, as is seen when high-concentration propofol was applied prior to ischemia and during reperfusion. The functional enhancement is associated with increased heart tissue antioxidant capacity and reduced lipid peroxidation. We conclude that high-concentration propofol application during ischemia could be a potential therapeutic and anesthetic strategy for patients with preexisting myocardial dysfunction. PMID:15573153

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

    PubMed Central

    Busija, David W.; Katakam, Prasad V.

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. Pre-Conditioning with Low-Level Laser (Light) Therapy: Light Before the Storm

    PubMed Central

    Agrawal, Tanupriya; Gupta, Gaurav K.; Rai, Vikrant; Carroll, James D.; Hamblin, Michael R.

    2014-01-01

    Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance. PMID:25552961

  19. Pre-conditioning with low-level laser (light) therapy: light before the storm.

    PubMed

    Agrawal, Tanupriya; Gupta, Gaurav K; Rai, Vikrant; Carroll, James D; Hamblin, Michael R

    2014-12-01

    Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance. PMID:25552961

  20. Preconditioning reduces hypoxia-evoked alterations in glutamatergic Ca2+ signaling in rat cortex.

    PubMed

    Semenov, Dmitry G; Samoilov, Mikhail O; Lazarewicz, Jerzy W

    2008-01-01

    The aims of this study were (1) to characterize calcium signaling in rat cortex induced by repeated in vitro application of the glutamatergic agonists L-glutamate, NMDA, AMPA and DHPG, (2) to analyze the influence of transient severe hypobaric hypoxia (180 Torr) administered in vivo on calcium responses to stimulation of glutamate receptors by their agonists, and (3) to evaluate the effects of preconditioning with intermittent mild hypobaric hypoxia (360 Torr) 24 h before the severe hypoxia, on these Ca2+ responses. Intracellular Ca2+ dynamics was studied using the fluorescent probes fura-2 and chlortetracycline to monitor free and bound calcium (Cai and Cab) respectively. In control cortical slices, application of L-glutamate, NMDA and AMPA induced concomitant increases in Cai and Cab, reflecting Ca2+ influx and its intracellular accumulation in neurons. DHPG, an agonist of group I mGlu receptors induced a decrease in Cab accompanied by a rise in Cai levels, indicating Ca2+ mobilization. In cortical slices collected 24 h after severe hypoxia, the responses of Cab to glutamate administration were increased, DHPG-induced shifts were reversed, the increase in Cab after the first application of AMPA was reduced, while after the second, Cab rises were potentiated, and the increases in Cab evoked by NMDA application were slightly suppressed. The alterations of responses in Cab to the selective agonists were completely prevented by preconditioning with mild hypoxia. Our results suggest that protection of normal glutamatergic calcium signaling contributes to tolerance to hypoxia induced by preconditioning. PMID:18511953

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

    PubMed

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

    2014-06-15

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

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

    PubMed

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

    2013-11-01

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

  3. Glutathione preconditioning ameliorates mitochondria dysfunction during warm pulmonary ischemia–reperfusion injury†, ‡

    PubMed Central

    Sommer, Sebastian-Patrick; Sommer, Stefanie; Sinha, Bhanu; Walter, Daniel; Aleksic, Ivan; Gohrbandt, Bernhard; Otto, Christoph; Leyh, Rainer G.

    2012-01-01

    OBJECTIVES: Reduced glutathione (GSH) has been shown to improve pulmonary graft preservation. Mitochondrial dysfunction is regarded to be the motor of ischemia–reperfusion injury (IR) in solid organs. We have shown previously that IR induces pulmonary mitochondrial damage. This study elucidates the impact of GSH preconditioning on the integrity and function of pulmonary mitochondria in the setting of warm pulmonary IR. METHODS: Wistar rats were subjected to control, sham, and to two-study-group conditions (IR30/60 and GSH-IR30/60) receiving IR with or without GSH preconditioning. Rats were anesthetized and received mechanical ventilation. Pulmonary in situ clamping followed by reperfusion generated IR. Mitochondria were isolated from pulmonary tissue. Respiratory chain complexes activities (I–IV) were analyzed by polarography. Mitochondrial viability (Ca2+-induced swelling) and membrane integrity (citrate synthase assay) were determined. Subcellular-fractional cytochrome C-content (Cyt C) was quantified by enzyme-linked immunosorbent assay (ELISA). Mitochondrial membrane potential (ΔΨm) was analyzed by fluorescence-activated cell sorting (FACS) after energizing and uncoupling. Inflammatory activation was determined by myeloperoxidase activity (MPO), matrix-metalloproteinase 9 (MMP-9) activity by gel zymography. RESULTS: Pulmonary IR significantly reduced mitochondrial viability in combination with ΔΨm hyper-polarization. GSH preconditioning improved mitochondrial viability and normalized ΔΨm. Cyt C was reduced after IR; GSH protected from Cyt C liberation. Respiratory chain complex activities (I, II, III) declined during IR; GSH protected complex II function. GSH also protected from MMP-9 and neutrophil sequestration (P > .05). CONCLUSIONS: GSH preconditioning is effective to prevent mitochondrial death and improves complex II function during IR, but not mitochondrial membrane stability. GSH-mediated amelioration of ΔΨm hyper-polarization appears to be the key factor of mitochondrial protection. PMID:21596579

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2011-01-01

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

  6. Platelet aggregation but not activation and degranulation during the acute post-ischemic reperfusion phase in livers with no underlying disease

    PubMed Central

    van Golen, Rowan F.; Stevens, Katarzyna M.; Colarusso, Pina; Jaeschke, Hartmut; Heger, Michal

    2016-01-01

    Background Platelets and P-selectin (CD62P) play an unequivocal role in the pathology of hepatic ischemia/reperfusion (I/R) injury. Inhibition or knock-out of P-selectin or immunodepletion of platelets results in amelioration of post-ischemic inflammation, reduced hepatocellular damage, and improved survival. However, P-selectin expression on platelets and endothelial cells, which concurs with platelet activation, has never been clearly demonstrated in I/R-subjected livers. Aims To determine whether platelets become activated and degranulate in the acute phase of liver I/R and whether the platelets interact with neutrophils. Methods Hepatic I/R was induced in male C57BL/6J mice (N = 12) using 37.5-min ischemia time. Platelets, endothelial cells, and neutrophils were fluorescently labeled by systemic administration of non-blocking antibodies. Cell kinetics were monitored by intravital spinning disk confocal microscopy during 90 min of reperfusion. Image analysis and quantification was performed with dedicated software. Results Platelets adhered to sinusoids more extensively in post-ischemic livers compared to livers not subjected to I/R and formed aggregates, which occurred directly after ischemia. Platelets and endothelial cells did not express P-selectin in post-ischemic livers. There was no interaction between platelets and neutrophils. Conclusions Platelets aggregate but do not become activated and do not degranulate in post-ischemic livers. There is no platelet-neutrophil interplay during the early reperfusion phase in a moderate model of hepatic I/R injury. The mechanisms underlying the biological effects of platelets and P-selectin in this setting warrant further investigation. Relevance for patients I/R in surgical liver patients may compromise outcome due to post-ischemic oxidative stress and sterile inflammation. Both processes are mediated in part by platelets. Understanding platelet function during I/R is key to developing effective interventions for I/R injury and improving clinical outcomes.

  7. 40 CFR 1066.816 - Vehicle preconditioning for FTP testing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  8. Preconditioning methods for improved convergence rates in iterative reconstructions

    SciTech Connect

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

    1993-03-01

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

  9. 40 CFR 86.132-00 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  10. 40 CFR 86.1232-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  11. 40 CFR 86.1232-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  12. Remote ischaemic preconditioning for coronary artery bypass grafting

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Pathomechanisms of ischemia-reperfusion injury as the basis for novel preventive strategies: is it time for the introduction of pleiotropic compounds?

    PubMed

    Menger, M D; Vollmar, B

    2007-03-01

    Ischemia-reperfusion-associated tissue dysfunction and organ failure still represent major complications in transplantation surgery. The pathomechanisms involve microvascular perfusion failure, ie, no-reflow and tissue hypoxia despite reperfusion and reoxygenation. However, postischemic reperfusion also provokes an inflammatory response, ie, reflow paradox, with activation of macrophages, recruitment of leukocytes, and accumulation of platelets, involving surface adhesion molecules such as P-selectin, P-selectin glycoprotein ligand (PSGL)-1, Mac-1, and intercellular adhesion molecule (ICAM)-1. These inflammatory cells produce cytokines, chemokines, lipid mediators, and oxygen radicals, which all may contribute to the manifestation of injury, including apoptosis, necrosis, and necrapoptosis. Although specific inhibition of single mediators, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and oxygen radicals, or distinct molecules, such as P-selectin and ICAM-1, has been shown to be protective in the experimental setting, these single-agent antimediator and antimolecule approaches did not find their way into clinical practice. Clinically, University of Wisconsin (UW) solution for organ preservation is still the major milestone for prevention of ischemia- and reperfusion-associated injury. Characteristically, this treatment strategy does not represent an anti-single mediator approach, but exerts protection by influencing multiple pathways involved in hypoxic and inflammatory injury, potentially restoring the overall homeostasis. This type of pleiotropic action may also be achieved by single pharmacological compounds, such as statins, erythropoietin, hemoxygenase-1, and L-glycine. In recent experimental studies, these compounds have been shown to be effective to reduce post-ischemic-reperfusion injury, and, additionally, to be associated with less side effects. Accordingly, these pleiotropic substances may represent ideal candidates for pharmacological preconditioning in patient treatment, and, thus, should be further evaluated in clinical trials. PMID:17362764

  15. Responsive corneosurfametry following in vivo skin preconditioning.

    PubMed

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

    2003-12-01

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

  16. A Weakest Precondition Approach to Robustness

    NASA Astrophysics Data System (ADS)

    Balliu, Musard; Mastroeni, Isabella

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

  17. Cellular prion protein promotes post-ischemic neuronal survival, angioneurogenesis and enhances neural progenitor cell homing via proteasome inhibition.

    PubMed

    Doeppner, T R; Kaltwasser, B; Schlechter, J; Jaschke, J; Kilic, E; Bhr, M; Hermann, D M; Weise, J

    2015-01-01

    Although cellular prion protein (PrP(c)) has been suggested to have physiological roles in neurogenesis and angiogenesis, the pathophysiological relevance of both processes remain unknown. To elucidate the role of PrP(c) in post-ischemic brain remodeling, we herein exposed PrP(c) wild type (WT), PrP(c) knockout (PrP-/-) and PrP(c) overexpressing (PrP+/+) mice to focal cerebral ischemia followed by up to 28 days reperfusion. Improved neurological recovery and sustained neuroprotection lasting over the observation period of 4 weeks were observed in ischemic PrP+/+ mice compared with WT mice. This observation was associated with increased neurogenesis and angiogenesis, whereas increased neurological deficits and brain injury were noted in ischemic PrP-/- mice. Proteasome activity and oxidative stress were increased in ischemic brain tissue of PrP-/- mice. Pharmacological proteasome inhibition reversed the exacerbation of brain injury induced by PrP-/-, indicating that proteasome inhibition mediates the neuroprotective effects of PrP(c). Notably, reduced proteasome activity and oxidative stress in ischemic brain tissue of PrP+/+ mice were associated with an increased abundance of hypoxia-inducible factor 1? and PACAP-38, which are known stimulants of neural progenitor cell (NPC) migration and trafficking. To elucidate effects of PrP(c) on intracerebral NPC homing, we intravenously infused GFP(+) NPCs in ischemic WT, PrP-/- and PrP+/+ mice, showing that brain accumulation of GFP(+) NPCs was greatly reduced in PrP-/- mice, but increased in PrP+/+ animals. Our results suggest that PrP(c) induces post-ischemic long-term neuroprotection, neurogenesis and angiogenesis in the ischemic brain by inhibiting proteasome activity. PMID:26673668

  18. Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201

    SciTech Connect

    Sinusas, A.J.; Watson, D.D.; Cannon, J.M. Jr.; Beller, G.A. )

    1989-12-01

    The myocardial uptake of a new technetium-99m-labeled myocardial perfusion agent, methoxyisobutyl isonitrile (Tc-99m MIBI), and thallium-201 was correlated with microsphere flow in an open chest canine model of low coronary flow and postischemic dysfunction. Eighteen dogs were given an injection of thallium-201 (0.5 mCi) and Tc-99m MIBI (5 mCi) either after 40 min of partial left anterior descending artery occlusion (Group I, 10 dogs) or during reperfusion after 15 min of left anterior descending artery occlusion (Group II, 8 dogs). Regional dysfunction was documented during injection in both groups by quantitative two-dimensional echocardiography. Regional blood flow was assessed by radiolabeled microspheres. The heart was excised 15 min after radionuclide injection and the left ventricle divided into 96 segments for gamma well counting. Among Group I dogs, central ischemic thallium-201 and Tc-99m MIBI activity (expressed as a percent of the activity in the corresponding nonischemic zone) was comparable, respectively, for endocardial (54 +/- 17% and 52 +/- 17%), mid-wall (71 +/- 20% and 69 +/- 17%) and epicardial (89 +/- 13% and 94 +/- 9%) segments and increased proportionally with flow. There was a good linear correlation among these endocardial segments between flow and both thallium-201 (r = 0.78) and Tc-99m MIBI (r = 0.85) activity. Among Group II dogs, central ischemic endocardial flow (59 +/- 14%) was comparable to thallium-201 (70 +/- 18%) and Tc-99m MIBI (74 +/- 12%) activity. Similarly, relative endocardial flow in the intermediate ischemic region (71 +/- 11%) was comparable to thallium-201 (77 +/- 11%) and Tc-99m MIBI (81 +/- 10%) activity. Thus, myocardial uptake of Tc-99m MIBI and thallium-201 is comparable under conditions of low coronary flow and postischemic dysfunction and closely parallels flow alterations.

  19. Cellular prion protein promotes post-ischemic neuronal survival, angioneurogenesis and enhances neural progenitor cell homing via proteasome inhibition

    PubMed Central

    Doeppner, T R; Kaltwasser, B; Schlechter, J; Jaschke, J; Kilic, E; Bähr, M; Hermann, D M; Weise, J

    2015-01-01

    Although cellular prion protein (PrPc) has been suggested to have physiological roles in neurogenesis and angiogenesis, the pathophysiological relevance of both processes remain unknown. To elucidate the role of PrPc in post-ischemic brain remodeling, we herein exposed PrPc wild type (WT), PrPc knockout (PrP−/−) and PrPc overexpressing (PrP+/+) mice to focal cerebral ischemia followed by up to 28 days reperfusion. Improved neurological recovery and sustained neuroprotection lasting over the observation period of 4 weeks were observed in ischemic PrP+/+ mice compared with WT mice. This observation was associated with increased neurogenesis and angiogenesis, whereas increased neurological deficits and brain injury were noted in ischemic PrP−/− mice. Proteasome activity and oxidative stress were increased in ischemic brain tissue of PrP−/− mice. Pharmacological proteasome inhibition reversed the exacerbation of brain injury induced by PrP−/−, indicating that proteasome inhibition mediates the neuroprotective effects of PrPc. Notably, reduced proteasome activity and oxidative stress in ischemic brain tissue of PrP+/+ mice were associated with an increased abundance of hypoxia-inducible factor 1α and PACAP-38, which are known stimulants of neural progenitor cell (NPC) migration and trafficking. To elucidate effects of PrPc on intracerebral NPC homing, we intravenously infused GFP+ NPCs in ischemic WT, PrP−/− and PrP+/+ mice, showing that brain accumulation of GFP+ NPCs was greatly reduced in PrP−/− mice, but increased in PrP+/+ animals. Our results suggest that PrPc induces post-ischemic long-term neuroprotection, neurogenesis and angiogenesis in the ischemic brain by inhibiting proteasome activity. PMID:26673668

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    1999-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. Incomplete domain decomposition preconditioning for coarse mesh neutron diffusion problems

    SciTech Connect

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

    1995-12-31

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

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2006-02-01

    Xenon attenuates on-going neuronal injury in both in vitro and in vivo models of hypoxic-ischaemic injury when administered during and after the insult. In the present study, we sought to investigate whether the neuroprotective efficacy of xenon can be observed when administered before an insult, referred to as 'preconditioning'. In a neuronal-glial cell coculture, preexposure to xenon for 2 h caused a concentration-dependent reduction of lactate dehydrogenase release from cells deprived of oxygen and glucose 24 h later; xenon's preconditioning effect was abolished by cycloheximide, a protein synthesis inhibitor. Preconditioning with xenon decreased propidium iodide staining in a hippocampal slice culture model subjected to oxygen and glucose deprivation. In an in vivo model of neonatal asphyxia involving hypoxic-ischaemic injury to 7-day-old rats, preconditioning with xenon reduced infarction size when assessed 7 days after injury. Furthermore, a sustained improvement in neurologic function was also evident 30 days after injury. Phosphorylated cAMP (cyclic adenosine 3',5'-monophosphate)-response element binding protein (pCREB) was increased by xenon exposure. Also, the prosurvival proteins Bcl-2 and brain-derived neurotrophic factor were upregulated by xenon treatment. These studies provide evidence for xenon's preconditioning effect, which might be caused by a pCREB-regulated synthesis of proteins that promote survival against neuronal injury. PMID:16034370

  7. Implementation of Preconditioned Dual-Time Procedures in OVERFLOW

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  8. BWR Fuel Thermomechanical Evaluation for Preconditioning Procedures With FEMAXI-V

    SciTech Connect

    Hernandez-Lopez, Hector; Lucatero, Marco A.; Ortiz-Villafuerte, Javier

    2006-07-01

    Burnup limitations are normally set to limit stresses in the fuel assembly components. The defined limits provide guidance to the fuel designer to minimize fuel failure during steady sate operation, and also prevent against some thermal and mechanical phenomena that could occur during overpower transients. In particular, a LHGR limit value is set to take into account physical phenomena that could lead to pellet-cladding interaction. This limit value directly relates to a PCI limit, which may be set based on experimental ramp tests. Thus, to avoid violating the PCI limit, fuel conditioning procedures are still required for both barrier and non-barrier fuel. Simulation of the power ramp procedures to be performed by the reactor operator during startup or power increase maneuvers is advisable as a preventive measure of possible overpower consequences on the fuel thermomechanical behavior. In this paper, the thermomechanical behavior of two different kinds of BWR fuel rods is analyzed for fuel preconditioning procedures. Five different preconditioning computations were performed, each with three different ascending linear power rate ramps. The starting point of the ramps was taken from data of the Cycle 8 of the Unit 1 of the Laguna Verde Nuclear Power Plant, located in Mexico. The top limit of the ramps was the threshold linear power at which failure by PCI could occur, as a function of burnup. The analysis was performed with the FEMAXI-V code. (authors)

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

    PubMed Central

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

    2002-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Fischer, Bernd; Freund, Roland W.

    1992-01-01

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

  11. Operator-Based Preconditioning of Stiff Hyperbolic Systems

    SciTech Connect

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

    2009-02-09

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

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

    NASA Technical Reports Server (NTRS)

    Wong, G. S.

    1973-01-01

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

  13. 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

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

    2014-01-01

    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. PMID:24759941

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  15. A subspace preconditioning algorithm for eigenvector/eigenvalue computation

    SciTech Connect

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

    1996-12-31

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

  16. Choice of Variables and Preconditioning for Time Dependent Problems

    NASA Technical Reports Server (NTRS)

    Turkel, Eli; Vatsa, Verr N.

    2003-01-01

    We consider the use of low speed preconditioning for time dependent problems. These are solved using a dual time step approach. We consider the effect of this dual time step on the parameter of the low speed preconditioning. In addition, we compare the use of two sets of variables, conservation and primitive variables, to solve the system. We show the effect of these choices on both the convergence to a steady state and the accuracy of the numerical solutions for low Mach number steady state and time dependent flows.

  17. Fourier analysis of finite element preconditioned collocation schemes

    NASA Technical Reports Server (NTRS)

    Deville, Michel O.; Mund, Ernest H.

    1990-01-01

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

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

    PubMed

    Babu, Chidambaram Saravana; Ramanathan, Muthiah

    2011-02-01

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

  19. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  20. 40 CFR 1066.405 - Vehicle preparation and preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  1. Dexmedetomidine Preconditioning Attenuates Cisplatin-Induced Ototoxicity in Zebrafish

    PubMed Central

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

    2014-01-01

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

  2. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  3. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  4. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  5. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  6. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  7. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  8. 33 CFR 183.320 - Preconditioning for tests.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  9. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  10. 33 CFR 183.220 - Preconditioning for tests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  11. 40 CFR 86.532-78 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  12. 40 CFR 86.532-78 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  13. 40 CFR 86.232-94 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  14. 40 CFR 86.232-94 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  15. 40 CFR 86.232-94 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  16. 40 CFR 86.1774-99 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  17. 40 CFR 1065.516 - Sample system decontamination and preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  18. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Vehicle preconditioning. 86.132-96 Section 86.132-96 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New...

  19. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Vehicle preconditioning. 86.132-96 Section 86.132-96 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New...

  20. Thrombin Preconditioning in Surgical Brain Injury in Rats.

    PubMed

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

    2016-01-01

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

  1. Numerical simulation of cavitating flows based on preconditioning technique

    NASA Astrophysics Data System (ADS)

    Goncalvs, E.

    2013-10-01

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

  2. In vivo inhibition of the mitochondrial H+-ATP synthase in neurons promotes metabolic preconditioning

    PubMed Central

    Formentini, Laura; Pereira, Marta P; Snchez-Cenizo, Laura; Santacatterina, Fulvio; Lucas, Jos J; Navarro, Carmen; Martnez-Serrano, Alberto; Cuezva, Jos M

    2014-01-01

    A key transducer in energy conservation and signaling cell death is the mitochondrial H+-ATP synthase. The expression of the ATPase inhibitory factor 1 (IF1) is a strategy used by cancer cells to inhibit the activity of the H+-ATP synthase to generate a ROS signal that switches on cellular programs of survival. We have generated a mouse model expressing a mutant of human IF1 in brain neurons to assess the role of the H+-ATP synthase in cell death in vivo. The expression of hIF1 inhibits the activity of oxidative phosphorylation and mediates the shift of neurons to an enhanced aerobic glycolysis. Metabolic reprogramming induces brain preconditioning affording protection against quinolinic acid-induced excitotoxicity. Mechanistically, preconditioning involves the activation of the Akt/p70S6K and PARP repair pathways and Bcl-xL protection from cell death. Overall, our findings provide the first in vivo evidence highlighting the H+-ATP synthase as a target to prevent neuronal cell death. PMID:24521670

  3. Renal osmotic stress-induced cotransporter: expression in the newborn, adult and post-ischemic rat kidney.

    PubMed

    Obermller, N; Krnzlin, B; Verma, R; Gretz, N; Kriz, W; Witzgall, R

    1997-12-01

    The renal osmotic stress-induced cotransporter (ROSIT), a new putative member of a family of organic solute transporters, is highly expressed in the kidney. Our in situ hybridization data now reveal that large amounts of ROSIT mRNA can be found in the S3 segment of the proximal tubule. In the developing kidney, ROSIT mRNA is expressed after the S-shaped body stage. Because the S3 segment is the major site of damage in the post-ischemic kidney, we evaluated alterations in ROSIT mRNA expression after ischemic acute tubular necrosis. Renal osmotic stress-induced cotransporter mRNA levels were already decreased eight hours post-ischemia. At seven days post-ischemia, ROSIT mRNA reappeared in a mosaic pattern in the regenerating S3 segment, being fully expressed three weeks after the insult except for focal areas. The exact localization of this putative osmolyte transporter in the kidney, together with that of other known osmolyte transporter will contribute to a better understanding of the mechanism of medullary osmolyte accumulation and its vectorial transport. PMID:9407504

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

    SciTech Connect

    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

    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.

  5. Intrarenal cells, not bone marrowderived cells, are the major source for regeneration in postischemic kidney

    PubMed Central

    Lin, Fangming; Moran, Ashley; Igarashi, Peter

    2005-01-01

    Ischemic injury to the kidney produces acute tubular necrosis and apoptosis followed by tubular regeneration and recovery of renal function. Although mitotic cells are present in the tubules of postischemic kidneys, the origins of the proliferating cells are not known. Bone marrow cells (BMCs) can differentiate across lineages to repair injured organs, including the kidney. However, the relative contribution of intrarenal cells and extrarenal cells to kidney regeneration is not clear. We produced transgenic mice that expressed enhanced GFP (EGFP) specifically and permanently in mature renal tubular epithelial cells. Following ischemia/reperfusion injury (IRI), EGFP-positive cells showed incorporation of BrdU and expression of vimentin, which provides direct evidence that the cells composing regenerating tubules are derived from renal tubular epithelial cells. In BMC-transplanted mice, 89% of proliferating epithelial cells originated from host cells, and 11% originated from donor BMCs. Twenty-eight days after IRI, the kidneys contained 8% donor-derived cells, of which 8.4% were epithelial cells, 10.6% were glomerular cells, and 81% were interstitial cells. No renal functional improvement was observed in mice that were transplanted with exogenous BMCs. These results show that intrarenal cells are the main source of renal repair, and a single injection of BMCs does not make a significant contribution to renal functional or structural recovery. PMID:16007252

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

    PubMed Central

    Miloradovi?, Zoran; Ivanov, Milan; Mihailovi?-Stanojevi?, Nevena; Gruji? Milanovi?, Jelica; Jovovi?, ?ur?ica; Vaji?, Una-Jovana; Markovi?-Lipkovski, Jasmina

    2014-01-01

    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. PMID:25050356

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  10. Finding Chemical Reaction Paths with a Multilevel Preconditioning Protocol

    PubMed Central

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-01-01

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

  12. Shape reanalysis and sensitivities utilizing preconditioned iterative boundary solvers

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  13. AdipoRon, the first orally active adiponectin receptor activator, attenuates postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signalings.

    PubMed

    Zhang, Yanqing; Zhao, Jianli; Li, Rui; Lau, Wayne Bond; Yuan, Yue-Xing; Liang, Bin; Li, Rong; Gao, Er-He; Koch, Walter J; Ma, Xin-Liang; Wang, Ya-Jing

    2015-08-01

    Adiponectin (APN) is a cardioprotective molecule. Its reduction in diabetes exacerbates myocardial ischemia/reperfusion (MI/R) injury. Although APN administration in animals attenuates MI/R injury, multiple factors limit its clinical application. The current study investigated whether AdipoRon, the first orally active molecule that binds APN receptors, may protect the heart against MI/R injury, and if so, to delineate the involved mechanisms. Wild-type (WT), APN knockout (APN-KO), and cardiomyocyte specific-AMPK dominant negative (AMPK-DN) mice were treated with vehicle or AdipoRon (50 mg/kg, 10 min prior to MI) and subjected to MI/R (30 min/3-24 h). Compared with vehicle, oral administration of AdipoRon to WT mice significantly improved cardiac function and attenuated postischemic cardiomyocyte apoptosis, determined by DNA ladder formation, TUNEL staining, and caspase-3 activation (all P < 0.01). MI/R-induced apoptotic cell death was significantly enhanced in mice deficient in either APN (APN-KO) or AMPK (AMPK-DN). In APN-KO mice, AdipoRon attenuated MI/R injury to the same degree as observed in WT mice. In AMPK-DN mice, AdipoRon's antiapoptotic action was partially inhibited but not lost. Finally, AdipoRon significantly attenuated postischemic oxidative stress, as evidenced by reduced NADPH oxidase expression and superoxide production. Collectively, these results demonstrate for the first time that AdipoRon, an orally active APN receptor activator, effectively attenuated postischemic cardiac injury, supporting APN receptor agonists as a promising novel therapeutic approach treating cardiovascular complications caused by obesity-related disorders such as type 2 diabetes. PMID:26037251

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

    PubMed Central

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

    2012-01-01

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

  15. Parallel Domain Decomposition Preconditioning for Computational Fluid Dynamics

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  16. Effect of HMGB1 on the paracrine action of EPC promotes post-ischemic neovascularization in mice.

    PubMed

    Chen, Chao; Lin, Xiaojie; Wang, Jixian; Tang, Guanghui; Mu, Zhihao; Chen, Xiaoyan; Xu, Jin; Wang, Yongting; Zhang, Zhijun; Yang, Guo-Yuan

    2014-10-01

    Transplantation of endothelial progenitor cells (EPCs) leads to better outcomes in experimental stroke, but the mechanism remains unclear. It was reported that astrocytic-high mobility group box1 (HMGB1) promoted endogenous EPC-mediated neurovascular remodeling during stroke recovery. It is unclear whether HMGB1 involves in exogenous EPC-mediated stroke recovery. In this study, we aim to explore whether microglial HMGB1 contributes to human peripheral blood-derived (hPB)-EPCs-mediated neurovascular remodeling by modulating the paracrine function of exogenous hPB-EPCs. Coculturing hPB-EPCs with lipopolysaccharides stimulated BV2 cells upregulated Interleukin-8 expression in hPB-EPCs; this was blocked by treating BV2 cells with HMGB1 inhibitor Glycyrrhizin. Conditioned medium (CM) of hPB-EPCs cocultured with BV2 cells promoted the viability and tube formation of human umbilical cord vein cells. Inhibiting either HMGB1 or IL-8 could block the effect of hPB-EPCs CM. In vivo study showed hPB-EPCs transplantation improved neurobehavioral outcomes, reduced brain atrophy volume, and enhanced neovascularization in transient middle cerebral artery occlusion (tMCAO) mice. Intraperitoneally administration of HMGB1 inhibitor glycyrrhizin blocked the beneficial effect of hPB-EPC transplantation. We did not observe the integration of green fluorescent protein-labeled hPB-EPCs with microvessels in peri-infarct areas at day-14 after tMCAO. In summary, the result suggested that HMGB1 upregulation in postischemic brain could promote exogenous hPB-EPC-mediated stroke recovery by modulating paracrine function of hPB-EPCs. PMID:24888319

  17. Mitochondria-targeted ROS scavenger improves post-ischemic recovery of cardiac function and attenuates mitochondrial abnormalities in aged rats

    PubMed Central

    Escobales, Nelson; Nuez, Rebeca E.; Jang, Sehwan; Parodi-Rullan, Rebecca; Ayala-Pea, Sylvette; Sacher, Joshua R.; Skoda, Erin M.; Wipf, Peter; Frontera, Walter; Javadov, Sabzali

    2014-01-01

    Mitochondria-generated reactive oxygen species (ROS) play a crucial role in the pathogenesis of aging and age-associated diseases. In this study, we evaluated the effects of XJB-5-131 (XJB), a mitochondria-targeted ROS and electron scavenger, on cardiac resistance to ischemia-reperfusion (IR)-induced oxidative stress in aged rats. Male adult (5-month old, n=17) and aged (29-month old, n=19) Fischer Brown Norway (F344/BN) rats were randomly assigned to the following groups: adult (A), adult+XJB (AX), aged (O), and aged+XJB (OX). XJB was administered 3 times per week (3 mg/kg body weight, IP) for four weeks. At the end of the treatment period, cardiac function was continuously monitored in excised hearts using the Langendorff technique for 30 min, followed by 20-min of global ischemia, and 60-min reperfusion. XJB improved post-ischemic recovery of aged hearts, as evidenced by greater left ventricular developed-pressures and rate-pressure products than the untreated, aged-matched group. The state 3 respiration rates at complexes I, II and IV of mitochondria isolated from XJB-treated aged hearts were 57% (P<0.05), 25% (P<0.05) and 28% (P<0.05), respectively, higher than controls. Ca2+-induced swelling, an indicator of permeability transition pore opening, was reduced in mitochondria of XJB-treated aged rats. In addition, XJB significantly attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as total and mitochondrial ROS levels in cultured cardiomyocytes. This study underlines the importance of mitochondrial ROS in aging-induced cardiac dysfunction and suggests that targeting mitochondrial ROS may be an effective therapeutic approach to protect the aged heart against IR injury. PMID:25451170

  18. Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: role of ET-1-induced peroxynitrite generation

    PubMed Central

    Cipolla, Marilyn J; Sweet, Julie G; Gokina, Natalia I; White, Sheryl L; Nelson, Mark T

    2013-01-01

    The contributions of vasoconstrictors (endothelin-1 (ET-1), peroxynitrite) and endothelium-dependent vasodilatory mechanisms to basal tone were investigated in parenchymal arterioles (PAs) after early postischemic reperfusion. Transient middle cerebral artery occlusion (tMCAO) was induced for 2 hours with 30 minutes reperfusion in male Wistar rats and compared with ischemia alone (permanent MCAO (pMCAO); 2.5 hours) or sham controls. Changes in lumen diameter of isolated and pressurized PAs were compared. Quantitative PCR was used to measure endothelin type B (ETB) receptors. Constriction to intravascular pressure (‘basal tone') was not affected by tMCAO or pMCAO. However, constriction to inhibitors of endothelial cell, small- (SK) and intermediate- (IK) conductance, Ca2+-sensitive K+ channels (apamin and TRAM-34, respectively) were significantly enhanced in PAs from tMCAO compared with pMCAO or sham. Addition of the ETB agonist sarafotoxin caused constriction in PAs from tMCAO but not from sham animals (21±4% versus 3±3% at 1 nmol/L; P<0.01) that was inhibited by the peroxynitrite scavenger FeTMPyP (5,10,15,20-tetrakis (N-methyl-4′-pyridyl) porphinato iron (III) chloride) (100 μmol/L). Expression of ETB receptors was not found on PA smooth muscle, suggesting that constriction to sarafotoxin after tMCAO was due to peroxynitrite and not ETB receptor expression. The maintenance of basal tone in PAs after tMCAO may restrict flow to the ischemic region and contribute to infarct expansion. PMID:23778163

  19. Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: role of ET-1-induced peroxynitrite generation.

    PubMed

    Cipolla, Marilyn J; Sweet, Julie G; Gokina, Natalia I; White, Sheryl L; Nelson, Mark T

    2013-10-01

    The contributions of vasoconstrictors (endothelin-1 (ET-1), peroxynitrite) and endothelium-dependent vasodilatory mechanisms to basal tone were investigated in parenchymal arterioles (PAs) after early postischemic reperfusion. Transient middle cerebral artery occlusion (tMCAO) was induced for 2 hours with 30 minutes reperfusion in male Wistar rats and compared with ischemia alone (permanent MCAO (pMCAO); 2.5 hours) or sham controls. Changes in lumen diameter of isolated and pressurized PAs were compared. Quantitative PCR was used to measure endothelin type B (ETB) receptors. Constriction to intravascular pressure ('basal tone') was not affected by tMCAO or pMCAO. However, constriction to inhibitors of endothelial cell, small- (SK) and intermediate- (IK) conductance, Ca(2+)-sensitive K(+) channels (apamin and TRAM-34, respectively) were significantly enhanced in PAs from tMCAO compared with pMCAO or sham. Addition of the ETB agonist sarafotoxin caused constriction in PAs from tMCAO but not from sham animals (21 4% versus 3 3% at 1 nmol/L; P<0.01) that was inhibited by the peroxynitrite scavenger FeTMPyP (5,10,15,20-tetrakis (N-methyl-4'-pyridyl) porphinato iron (III) chloride) (100 ?mol/L). Expression of ETB receptors was not found on PA smooth muscle, suggesting that constriction to sarafotoxin after tMCAO was due to peroxynitrite and not ETB receptor expression. The maintenance of basal tone in PAs after tMCAO may restrict flow to the ischemic region and contribute to infarct expansion. PMID:23778163

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

    PubMed

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

    2015-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

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

    PubMed Central

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

    2015-01-01

    Abstract Ischemic heart diseases are the leading cause of death with increasing numbers of patients worldwide. Despite advances in revascularization techniques, angiogenic therapies remain highly attractive. Physiological ischemia training, which is first proposed in our laboratory, refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for about 4 weeks for the sake of triggering molecular and cellular mechanisms to promote angiogenesis and formation of collateral vessels and protect remote ischemia areas. Physiological ischemia training therapy augments angiogenesis in the ischemic myocardium by inducing differential expression of proteins involved in energy metabolism, cell migration, protein folding, and generation. It upregulates the expressions of vascular endothelial growth factor, and induces angiogenesis, protects the myocardium when infarction occurs by increasing circulating endothelial progenitor cells and enhancing their migration, which is in accordance with physical training in heart disease rehabilitation. These findings may lead to a new approach of therapeutic angiogenesis for patients with ischemic heart diseases. On the basis of the promising results in animal studies, studies were also conducted in patients with coronary artery disease without any adverse effect in vivo, indicating that physiological ischemia training therapy is a safe, effective and non-invasive angiogenic approach for cardiovascular rehabilitation. Preconditioning is considered to be the most protective intervention against myocardial ischemia-reperfusion injury to date. Physiological ischemia training is different from preconditioning. This review summarizes the preclinical and clinical data of physiological ischemia training and its difference from preconditioning. PMID:26664354

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  4. Islet preconditioning via multimodal microfluidic modulation of intermittent hypoxia

    PubMed Central

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

    2012-01-01

    Simultaneous stimulation of ex vivo pancreatic islets with dynamic oxygen and glucose is a critical technique for studying how hypoxia alters glucose-stimulated response, especially in transplant environments. Standard techniques using a hypoxic chamber cannot provide both oxygen and glucose modulations while monitoring stimulus-secretion coupling factors in real-time. Using novel microfluidic device with integrated glucose and oxygen modulations, we quantified hypoxic impairment of islet response by calcium influx, mitochondrial potentials, and insulin secretion. Glucose-induced calcium response magnitude and phase were suppressed by hypoxia, while mitochondrial hyperpolarization and insulin secretion decreased in coordination. More importantly, hypoxic response was improved by preconditioning islets to intermittent hypoxia (IH, 1min/1min 5%21% cycling for 1 hour), translating to improved insulin secretion. Moreover, blocking mitochondrial KATP channels removed preconditioning benefits of IH, similar to mechanisms in preconditioned cardiomyocytes. Additionally, the multimodal device can be applied to a variety of dynamic oxygen-metabolic studies in other ex vivo tissues. PMID:22296179

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

    PubMed

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

    2015-11-01

    Ischemic heart diseases are the leading cause of death with increasing numbers of patients worldwide. Despite advances in revascularization techniques, angiogenic therapies remain highly attractive. Physiological ischemia training, which is first proposed in our laboratory, refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for about 4 weeks for the sake of triggering molecular and cellular mechanisms to promote angiogenesis and formation of collateral vessels and protect remote ischemia areas. Physiological ischemia training therapy augments angiogenesis in the ischemic myocardium by inducing differential expression of proteins involved in energy metabolism, cell migration, protein folding, and generation. It upregulates the expressions of vascular endothelial growth factor, and induces angiogenesis, protects the myocardium when infarction occurs by increasing circulating endothelial progenitor cells and enhancing their migration, which is in accordance with physical training in heart disease rehabilitation. These findings may lead to a new approach of therapeutic angiogenesis for patients with ischemic heart diseases. On the basis of the promising results in animal studies, studies were also conducted in patients with coronary artery disease without any adverse effect in vivo, indicating that physiological ischemia training therapy is a safe, effective and non-invasive angiogenic approach for cardiovascular rehabilitation. Preconditioning is considered to be the most protective intervention against myocardial ischemia-reperfusion injury to date. Physiological ischemia training is different from preconditioning. This review summarizes the preclinical and clinical data of physiological ischemia training and its difference from preconditioning. PMID:26664354

  6. Preconditioning the bidomain model with almost linear complexity

    NASA Astrophysics Data System (ADS)

    Pierre, Charles

    2012-01-01

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

  7. Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke.

    PubMed

    Ruscher, Karsten; Kuric, Enida; Liu, Yawei; Walter, Helene L; Issazadeh-Navikas, Shohreh; Englund, Elisabet; Wieloch, Tadeusz

    2013-08-01

    After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3(+)) and CD3(+)/CD4(+) T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke. PMID:23632969

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

    PubMed

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

    2013-01-01

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

  9. Morphine-Induced Preconditioning: Involvement of Protein Kinase A and Mitochondrial Permeability Transition Pore

    PubMed Central

    Dorsch, Marianne; Behmenburg, Friederike; Raible, Miriam; Blase, Dominic; Grievink, Hilbert; Hollmann, Markus W.; Heinen, André; Huhn, Ragnar

    2016-01-01

    Background Morphine induces myocardial preconditioning (M-PC) via activation of mitochondrial large conductance Ca2+-sensitive potassium (mKCa) channels. An upstream regulator of mKCa channels is protein kinase A (PKA). Furthermore, mKCa channel activation regulates mitochondrial bioenergetics and thereby prevents opening of the mitochondrial permeability transition pore (mPTP). Here, we investigated in the rat heart in vivo whether 1) M-PC is mediated by activation of PKA, and 2) pharmacological opening of the mPTP abolishes the cardioprotective effect of M-PC and 3) M-PC is critically dependent on STAT3 activation, which is located upstream of mPTP within the signalling pathway. Methods Male Wistar rats were randomised to six groups (each n = 6). All animals underwent 25 minutes of regional myocardial ischemia and 120 minutes of reperfusion. Control animals (Con) were not further treated. Morphine preconditioning was initiated by intravenous administration of 0.3 mg/kg morphine (M-PC). The PKA blocker H-89 (10 μg/kg) was investigated with and without morphine (H-89+M-PC, H-89). We determined the effect of mPTP opening with atractyloside (5 mg/kg) with and without morphine (Atr+M-PC, Atr). Furthermore, the effect of morphine on PKA activity was tested in isolated adult rat cardiomyocytes. In further experiments in isolated hearts we tested the protective properties of morphine in the presence of STAT3 inhibition, and whether pharmacological prevention of the mPTP-opening by cyclosporine A (CsA) is cardioprotective in the presence of STAT3 inhibition. Results Morphine reduced infarct size from 64±5% to 39±9% (P<0.05 vs. Con). H-89 completely blocked preconditioning by morphine (64±9%; P<0.05 vs. M-PC), but H-89 itself had not effect on infarct size (61±10%; P>0.05 vs. Con). Also, atractyloside abolished infarct size reduction of morphine completely (65±9%; P<0.05 vs. M-PC) but had no influence on infarct size itself (64±5%; P>0.05 vs. Con). In isolated hearts STAT3 inhibitor Stattic completely abolished morphine-induced preconditioning. Administration of Stattic and mPTP inhibitor cyclosporine A reduced infarct size to 31±6% (Stat+CsA, P<0.05 vs. Con). Cyclosporine A alone reduced infarct size to 26±7% (CsA P<0.05 vs. Con). In cardiomyocytes, PKA activity was increased by morphine. Conclusion Our data suggest that morphine-induced cardioprotection is mediated by STAT3-activation and inhibition of mPTP, with STA3 located upstream of mPTP. There is some evidence that protein kinase A is involved within the signalling pathway. PMID:26968004

  10. Postischemic hyperperfusion on arterial spin labeled perfusion MRI is linked to hemorrhagic transformation in stroke.

    PubMed

    Yu, Songlin; Liebeskind, David S; Dua, Sumit; Wilhalme, Holly; Elashoff, David; Qiao, Xin J; Alger, Jeffry R; Sanossian, Nerses; Starkman, Sidney; Ali, Latisha K; Scalzo, Fabien; Lou, Xin; Yoo, Bryan; Saver, Jeffrey L; Salamon, Noriko; Wang, Danny J J

    2015-04-01

    The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR) = 4.8, 95% confidence interval (CI) 2.5 to 8.9, P < 0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P<0.001). There was a significant association between having hyperperfusion at any time point and HT (OR = 3.5, 95% CI 2.0 to 6.3, P < 0.001). There was a positive relationship between the grade of HT and time-hyperperfusion with the Spearman's rank correlation of 0.44 (P = 0.003). Arterial spin labeling hyperperfusion may provide an imaging marker of HT, which may guide the management of AIS patients post tissue-type plasminogen activator (tPA) and/or endovascular treatments. Late hyperperfusion should be given more attention to prevent high-grade HT. PMID:25564233

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

    PubMed

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

    2015-08-01

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

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

    PubMed

    Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju

    2016-03-01

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

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

    PubMed

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

    2007-04-01

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

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

    PubMed Central

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

    2012-01-01

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

  15. Calcium preconditioning triggers neuroprotection in retinal ganglion cells

    PubMed Central

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

    2010-01-01

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

  16. Preconditioned Conjugate Gradient methods for low speed flow calculations

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Preconditioning methods for ideal and multiphase fluid flows

    NASA Astrophysics Data System (ADS)

    Gupta, Ashish

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

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

    SciTech Connect

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

    1996-03-01

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

  20. Weighted graph based ordering techniques for preconditioned conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Clift, Simon S.; Tang, Wei-Pai

    1994-01-01

    We describe the basis of a matrix ordering heuristic for improving the incomplete factorization used in preconditioned conjugate gradient techniques applied to anisotropic PDE's. Several new matrix ordering techniques, derived from well-known algorithms in combinatorial graph theory, which attempt to implement this heuristic, are described. These ordering techniques are tested against a number of matrices arising from linear anisotropic PDE's, and compared with other matrix ordering techniques. A variation of RCM is shown to generally improve the quality of incomplete factorization preconditioners.

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

    SciTech Connect

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

    2005-09-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  5. Stress Preconditioning of Spreading Depression in the Locust CNS

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements—(1) Exhaust gas...

  8. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements—(1) Exhaust gas...

  9. 40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Preconditioned two speed idle test-EPA 91. 85.2220 Section 85.2220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General...

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

    ERIC Educational Resources Information Center

    Coureaud, Gerard; Tourat, Audrey; Ferreira, Guillaume

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Coureaud, Gerard; Tourat, Audrey; Ferreira, Guillaume

    2013-01-01

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

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

    PubMed

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

    2006-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  14. 3?phosphoinositide-dependent kinase-1 is essential for ischemic preconditioning of the myocardium

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2015-12-01

    Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, d-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an invitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented. Mammalian hibernation provides a valuable model of tolerance to ischemic stress. Herein, we demonstrate that marked reductions in the phosphorylation of ribosomal protein S6 (rpS6), extracellular signal-regulated kinase family of mitogen-activated protein (MAP) kinase p44/42 (p44/42MAPK) and ribosomal protein S6 kinase (S6K) occur within the brains of both hibernating squirrels and rats, which have undergone an ischemic preconditioning paradigm. We therefore propose that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning, via a suppression of protein synthesis and/or energy consumption. PMID:26375300

  16. Type 2 Diabetes Restricts Multipotency of Mesenchymal Stem Cells and Impairs Their Capacity to Augment Postischemic Neovascularization in db/db Mice

    PubMed Central

    Yan, Jinglian; Tie, Guodong; Wang, Shouying; Messina, Katharine E.; DiDato, Sebastian; Guo, Sujuan; Messina, Louis M.

    2012-01-01

    Background This study tested the hypothesis that type 2 diabetes restricts multipotency of db/db mesenchymal stem cells (MSCs), promotes their terminal differentiation into adipocytes rather than endothelial cells, thereby promotes adipocytic infiltration into ischemic muscles, and reduces their capacity to participate in postischemic neovascularization. Methods and Results To test this hypothesis, we transplanted MSCs from db/db or wild-type (WT) mice into WT recipients after induction of hind limb ischemia. WT recipients of db/db MSCs demonstrated adipocyte infiltration of ischemic muscle and impaired neovascularization; WT recipients of WT MSCs showed no intramuscular adipocyte infiltration and had significantly enhanced neovascularization (P<0.05; n=6). Confocal microscopy showed that the percentage of MSCs that differentiated into an adipocyte phenotype was greater and into an endothelial cell was less in WT recipients transplanted with db/db MSCs than those transplanted with WT MSCs (P<0.05; n=6). In vitro, db/db MSCs exhibited greater oxidant stress, greater adipocyte differentiation, and less endothelial differentiation than WT MSCs, and these differences were reversed by treatment with N-acetylcysteine or Nox4 siRNA (P<0.05; n=6). Insulin increased Nox4 expression, oxidant stress, and adipocyte differentiation in WT MSCs, and these insulin-induced effects were reversed by Nox4 siRNA (P<0.05; n=6). Reversal of db/db MSC oxidant stress by in vivo pretreatment with Nox4 siRNA before transplantation reversed their impaired capacity to augment postischemic neovascularization. Conclusions Type 2 diabetes–induced oxidant stress restricts the multipotency of MSCs and impairs their capacity to increase blood flow recovery after the induction of hind-limb ischemia. Reversal of MSC oxidant stress might permit greater leverage of the therapeutic potential of MSC transplantation in the setting of diabetes. PMID:23316315

  17. Aerodynamic shape optimization using preconditioned conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Burgreen, Greg W.; Baysal, Oktay

    1993-01-01

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

  18. Preconditioned Mixed Spectral Element Methods for Elasticity and Stokes Problems

    NASA Technical Reports Server (NTRS)

    Pavarino, Luca F.

    1996-01-01

    Preconditioned iterative methods for the indefinite systems obtained by discretizing the linear elasticity and Stokes problems with mixed spectral elements in three dimensions are introduced and analyzed. The resulting stiffness matrices have the structure of saddle point problems with a penalty term, which is associated with the Poisson ratio for elasticity problems or with stabilization techniques for Stokes problems. The main results of this paper show that the convergence rate of the resulting algorithms is independent of the penalty parameter, the number of spectral elements Nu and mildly dependent on the spectral degree eta via the inf-sup constant. The preconditioners proposed for the whole indefinite system are block-diagonal and block-triangular. Numerical experiments presented in the final section show that these algorithms are a practical and efficient strategy for the iterative solution of the indefinite problems arising from mixed spectral element discretizations of elliptic systems.

  19. A frequency dependent preconditioned wavelet method for atmospheric tomography

    NASA Astrophysics Data System (ADS)

    Yudytskiy, Mykhaylo; Helin, Tapio; Ramlau, Ronny

    2013-12-01

    Atmospheric tomography, i.e. the reconstruction of the turbulence in the atmosphere, is a main task for the adaptive optics systems of the next generation telescopes. For extremely large telescopes, such as the European Extremely Large Telescope, this problem becomes overly complex and an efficient algorithm is needed to reduce numerical costs. Recently, a conjugate gradient method based on wavelet parametrization of turbulence layers was introduced [5]. An iterative algorithm can only be numerically efficient when the number of iterations required for a sufficient reconstruction is low. A way to achieve this is to design an efficient preconditioner. In this paper we propose a new frequency-dependent preconditioner for the wavelet method. In the context of a multi conjugate adaptive optics (MCAO) system simulated on the official end-to-end simulation tool OCTOPUS of the European Southern Observatory we demonstrate robustness and speed of the preconditioned algorithm. We show that three iterations are sufficient for a good reconstruction.

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

    PubMed

    Lalonde, Franois; Curnier, Daniel Y

    2015-01-01

    Remote ischemic preconditioning (RIPC) provides a substantial benefit for heart protection during surgery. Recent literature on RIPC reveals the potential to benefit the enhancement of sports performance as well. The aim of this study was to investigate the effect of RIPC on anaerobic performance. Seventeen healthy participants who practice regular physical activity participated in the project (9 women and 8 men, mean age 28 8 years). The participants were randomly assigned to an RIPC intervention (four 5-minute cycles of ischemia reperfusion, followed by 5 minutes using a pressure cuff) or a SHAM intervention in a crossover design. After the intervention, the participants were tested for alactic anaerobic performance (6 seconds of effort) followed by a Wingate test (lactic system) on an electromagnetic cycle ergometer. The following parameters were evaluated: average power, peak power, the scale of perceived exertion, fatigue index (in watt per second), peak power (in Watt), time to reach peak power (in seconds), minimum power (in Watt), the average power-to-weight ratio (in watt per kilogram), and the maximum power-to-weight ratio (in watt per kilogram). The peak power for the Wingate test is 794 W for RIPC and 777 W for the control group (p = 0.208). The average power is 529 W (RIPC) vs. 520 W for controls (p = 0.079). Perceived effort for RIPC is 9/10 on the Borg scale vs. 10/10 for the control group (p = 0.123). Remote ischemic preconditioning does not offer any significant benefits for anaerobic performance. PMID:25068802

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

    PubMed

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

    2012-07-01

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

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

    PubMed

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

    2009-02-01

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

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

    PubMed Central

    Chen, Ou; Wu, Miaomiao; Jiang, Liangfu

    2015-01-01

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

  4. Characteristic time-stepping or local preconditioning of the Euler equations

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Yin, Jun-Feng; Hayami, Ken

    2009-04-01

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

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

    NASA Technical Reports Server (NTRS)

    Darmofal, David L.

    1998-01-01

    An analysis of the effect of local preconditioning on boundary conditions for the subsonic, one-dimensional Euler equations is presented. Decay rates for the eigenmodes of the initial boundary value problem are determined for different boundary conditions. Riemann invariant boundary conditions based on the unpreconditioned Euler equations are shown to be reflective with preconditioning, and, at low Mach numbers, disturbances do not decay. Other boundary conditions are investigated which are non-reflective with preconditioning and numerical results are presented confirming the analysis.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    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

    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)-α 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. PMID:22132896

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

    PubMed

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

    1993-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. Effect of Preconditioning and Soldering on Failures of Chip Tantalum Capacitors

    NASA Technical Reports Server (NTRS)

    Teverovsky, Alexander A.

    2014-01-01

    Soldering of molded case tantalum capacitors can result in damage to Ta205 dielectric and first turn-on failures due to thermo-mechanical stresses caused by CTE mismatch between materials used in the capacitors. It is also known that presence of moisture might cause damage to plastic cases due to the pop-corning effect. However, there are only scarce literature data on the effect of moisture content on the probability of post-soldering electrical failures. In this work, that is based on a case history, different groups of similar types of CWR tantalum capacitors from two lots were prepared for soldering by bake, moisture saturation, and longterm storage at room conditions. Results of the testing showed that both factors: initial quality of the lot, and preconditioning affect the probability of failures. Baking before soldering was shown to be effective to prevent failures even in lots susceptible to pop-corning damage. Mechanism of failures is discussed and recommendations for pre-soldering bake are suggested based on analysis of moisture characteristics of materials used in the capacitors' design.

  14. Aggravation of post-ischemic liver injury by overexpression of insulin-like growth factor binding protein 3

    PubMed Central

    Zhou, Lu; Koh, Hyoung-Won; Bae, Ui-Jin; Park, Byung-Hyun

    2015-01-01

    Insulin-like growth factor-1 (IGF-1) is known to inhibit reperfusion-induced apoptosis. IGF-binding protein-3 (IGFBP-3) is the major circulating carrier protein for IGF-1 and induces apoptosis. In this study, we determined if IGFBP-3 was important in the hepatic response to I/R. To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 cDNA (AdIGFBP-3) or an IGFBP-3 mutant devoid of IGF binding affinity but retaining IGFBP-3 receptor binding ability (AdIGFBP-3GGG). Mice subjected to I/R injury showed typical patterns of hepatocellular damage. Protein levels of IGFBP-3 were increased after reperfusion and showed a positive correlation with the extent of liver injury. Prior injection with AdIGFBP-3 aggravated liver injury: serum aminotransferases, prothrombin time, proinflammatory cytokines, hepatocellular necrosis and apoptosis, and neutrophil infiltration were markedly increased compared to control mice. A decrease in antioxidant potential and an upregulation of NADPH oxidase might have caused these aggravating effects of IGFBP-3. Experiments using HepG2 cells and N-acetylcysteine-pretreated mice showed a discernible effect of IGFBP-3 on reactive oxygen species generation. Lastly, AdIGFBP-3 abolished the beneficial effects of ischemic preconditioning and hypothermia. Mice treated with AdIGFBP-3GGG exhibited effects similar to those of AdIGFBP-3, suggesting a ligand-independent effect of IGFBP-3. Our results suggest IGFBP-3 as an aggravating factor during hepatic I/R injury. PMID:26073647

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

    PubMed

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

    2011-09-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

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

    SciTech Connect

    Cai, Yunfeng; Department of Computer Science, University of California, Davis 95616 ; Bai, Zhaojun; Pask, John E.; Sukumar, N.

    2013-12-15

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

  18. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  19. 40 CFR 85.2218 - Preconditioned idle test-EPA 91.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

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

    PubMed

    Sverdlik, A; Lanir, Y

    2002-02-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

    Histotripsy is a non-invasive ablation method that mechanically fractionates tissue by controlling acoustic cavitation. Previous work has revealed that tissue mechanical properties play a significant role in the histotripsy process, with stiffer tissues being more resistant to histotripsy-induced tissue damage. In this study, we propose a thermal pretreatment strategy to precondition tissues before histotripsy. We hypothesize that a thermal pretreatment can be used to alter tissue stiffness by modulating collagen composition, thus changing tissue susceptibility to histotripsy. More specifically, we hypothesize that tissues will soften and become more susceptible to histotripsy when preheated at ?60C because of collagen denaturation, but that tissues will rapidly stiffen and become less susceptible to histotripsy when preheated at ?90C because of collagen contraction. To test this hypothesis, a controlled temperature water bath was used to heat various ex vivo bovine tissues (tongue, artery, liver, kidney medulla, tendon and urethra). After heating, the Young's modulus of each tissue sample was measured using a tissue elastometer, and changes in tissue composition (i.e., collagen structure/density) were analyzed histologically. The susceptibility of tissues to histotripsy was investigated by treating the samples using a 750-kHz histotripsy transducer. Results revealed a decrease in stiffness and an increase in susceptibility to histotripsy for tissues (except urethra) preheated to 58C. In contrast, preheating to 90C increased tissue stiffness and reduced susceptibility to histotripsy for all tissues except tendon, which was significantly softened due to collagen hydrolysis into gelatin. On the basis of these results, a final set of experiments were conducted to determine the feasibility of using high-intensity focused ultrasound to provide the thermal pretreatment. Overall, the results of this study indicate the initial feasibility of a thermal pretreatment strategy to precondition tissue mechanical properties and alter tissue susceptibility to histotripsy. Future work will aim to optimize this thermal pretreatment strategy to determine if this approach is practical for specific clinical applications in vivo without causing unwanted damage to surrounding or overlying tissue. PMID:26318560

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

    PubMed

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

    2015-09-01

    The capacity of tumor cells for nucleotide excision repair (NER) is a major determinant of the efficacy of and resistance to DNA-damaging chemotherapeutics, such as cisplatin. Here, we demonstrate that using lesion-specific monoclonal antibodies, NER capacity is enhanced in human lung cancer cells after preconditioning with DNA-damaging agents. Preconditioning of cells with a nonlethal dose of UV radiation facilitated the kinetics of subsequent cisplatin repair and vice versa. Dual-incision assay confirmed that the enhanced NER capacity was sustained for 2 days. Checkpoint activation by ATR kinase and expression of NER factors were not altered significantly by the preconditioning, whereas association of XPA, the rate-limiting factor in NER, with chromatin was accelerated. In preconditioned cells, SIRT1 expression was increased, and this resulted in a decrease in acetylated XPA. Inhibition of SIRT1 abrogated the preconditioning-induced predominant XPA binding to DNA lesions. Taking these data together, we conclude that upregulated NER capacity in preconditioned lung cancer cells is caused partly by an increased level of SIRT1, which modulates XPA sensitivity to DNA damage. This study provides some insights into the molecular mechanism of chemoresistance through acquisition of enhanced DNA repair capacity in cancer cells. PMID:26317794

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

    PubMed Central

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

    2015-01-01

    The capacity of tumor cells for nucleotide excision repair (NER) is a major determinant of the efficacy of and resistance to DNA-damaging chemotherapeutics, such as cisplatin. Here, we demonstrate that using lesion-specific monoclonal antibodies, NER capacity is enhanced in human lung cancer cells after preconditioning with DNA-damaging agents. Preconditioning of cells with a nonlethal dose of UV radiation facilitated the kinetics of subsequent cisplatin repair and vice versa. Dual-incision assay confirmed that the enhanced NER capacity was sustained for 2 days. Checkpoint activation by ATR kinase and expression of NER factors were not altered significantly by the preconditioning, whereas association of XPA, the rate-limiting factor in NER, with chromatin was accelerated. In preconditioned cells, SIRT1 expression was increased, and this resulted in a decrease in acetylated XPA. Inhibition of SIRT1 abrogated the preconditioning-induced predominant XPA binding to DNA lesions. Taking these data together, we conclude that upregulated NER capacity in preconditioned lung cancer cells is caused partly by an increased level of SIRT1, which modulates XPA sensitivity to DNA damage. This study provides some insights into the molecular mechanism of chemoresistance through acquisition of enhanced DNA repair capacity in cancer cells. PMID:26317794

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

    Xu, Kui; Lamanna, Joseph C

    2014-01-01

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

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

    PubMed Central

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

    1994-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Brandli, Alice

    2015-01-01

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

  11. Cerenkov luminescence tomography based on preconditioning orthogonal matching pursuit

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Concepts of hypoxic NO signaling in remote ischemic preconditioning

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-26

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    2010-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2002-04-01

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

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

    PubMed

    Matsumoto, Yukihisa; Hirashima, Daisuke; Mizunami, Makoto

    2013-03-01

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

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

    PubMed

    Pedersen, Vivi Kathrine; Egholm, David Lundbek

    2013-01-10

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

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

    NASA Astrophysics Data System (ADS)

    Larsson, Elisabeth

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

  1. Super-low Dose Endotoxin Pre-conditioning Exacerbates Sepsis Mortality

    PubMed Central

    Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu

    2015-01-01

    Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditioning with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in contrast to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks. PMID:26029736

  2. Hypoxic Preconditioning Suppresses Glial Activation and Neuroinflammation in Neonatal Brain Insults

    PubMed Central

    Chen, Chien-Yi; Sun, Wei-Zen; Kang, Kai-Hsiang; Chou, Hung-Chieh; Tsao, Po-Nien; Hsieh, Wu-Shiun; Fu, Wen-Mei

    2015-01-01

    Perinatal insults and subsequent neuroinflammation are the major mechanisms of neonatal brain injury, but there have been only scarce reports on the associations between hypoxic preconditioning and glial activation. Here we use neonatal hypoxia-ischemia brain injury model in 7-day-old rats and in vitro hypoxia model with primary mixed glial culture and the BV-2 microglial cell line to assess the effects of hypoxia and hypoxic preconditioning on glial activation. Hypoxia-ischemia brain insult induced significant brain weight reduction, profound cell loss, and reactive gliosis in the damaged hemisphere. Hypoxic preconditioning significantly attenuated glial activation and resulted in robust neuroprotection. As early as 2 h after the hypoxia-ischemia insult, proinflammatory gene upregulation was suppressed in the hypoxic preconditioning group. In vitro experiments showed that exposure to 0.5% oxygen for 4 h induced a glial inflammatory response. Exposure to brief hypoxia (0.5 h) 24 h before the hypoxic insult significantly ameliorated this response. In conclusion, hypoxic preconditioning confers strong neuroprotection, possibly through suppression of glial activation and subsequent inflammatory responses after hypoxia-ischemia insults in neonatal rats. This might therefore be a promising therapeutic approach for rescuing neonatal brain injury. PMID:26273140

  3. Research on the Changes to the Lipid/Polymer Membrane Used in the Acidic Bitterness Sensor Caused by Preconditioning.

    PubMed

    Harada, Yuhei; Noda, Junpei; Yatabe, Rui; Ikezaki, Hidekazu; Toko, Kiyoshi

    2016-01-01

    A taste sensor that uses lipid/polymer membranes can evaluate aftertastes felt by humans using Change in membrane Potential caused by Adsorption (CPA) measurements. The sensor membrane for evaluating bitterness, which is caused by acidic bitter substances such as iso-alpha acid contained in beer, needs an immersion process in monosodium glutamate (MSG) solution, called "MSG preconditioning". However, what happens to the lipid/polymer membrane during MSG preconditioning is not clear. Therefore, we carried out three experiments to investigate the changes in the lipid/polymer membrane caused by the MSG preconditioning, i.e., measurements of the taste sensor, measurements of the amount of the bitterness substance adsorbed onto the membrane and measurements of the contact angle of the membrane surface. The CPA values increased as the preconditioning process progressed, and became stable after 3 d of preconditioning. The response potentials to the reference solution showed the same tendency of the CPA value change during the preconditioning period. The contact angle of the lipid/polymer membrane surface decreased after 7 d of MSG preconditioning; in short, the surface of the lipid/polymer membrane became hydrophilic during MSG preconditioning. The amount of adsorbed iso-alpha acid was increased until 5 d preconditioning, and then it decreased. In this study, we revealed that the CPA values increased with the progress of MSG preconditioning in spite of the decrease of the amount of iso-alpha acid adsorbed onto the lipid/polymer membrane, and it was indicated that the CPA values increase because the sensor sensitivity was improved by the MSG preconditioning. PMID:26891299

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

    PubMed Central

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

    2013-01-01

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

  5. Major Ozonated Autohemotherapy Preconditioning Ameliorates Kidney Ischemia-Reperfusion Injury.

    PubMed

    Sancak, Eyup Burak; Turkön, Hakan; Çukur, Selma; Erimsah, Sevilay; Akbas, Alpaslan; Gulpinar, Murat Tolga; Toman, Huseyin; Sahin, Hasan; Uzun, Metehan

    2016-02-01

    Medical ozone has therapeutic properties as an antimicrobial, anti-inflammatory, modulator of antioxidant defense system. Major ozonated autohemotherapy (MOA) is a new therapeutic approach that is widely used in the treatment of many diseases. The objective of the present study was to determine whether preischemic application of MOA would attenuate renal ischemia-reperfusion injury (IRI) in rabbits. Twenty-four male New Zealand white rabbits were divided into four groups, each including six animals: (1) Sham-operated group, (2) Ozone group (the MOA group without IRI), (3) IR group (60 min ischemia followed by 24 h reperfusion), and (4) IR + MOA group (MOA group). The effects of MOA were examined by use of hematologic and biochemical parameters consisting of neutrophil to lymphocyte ratio (NLR), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), ischemia-modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). In addition, the histopathological changes including the tubular brush border loss (TBBL), tubular cast (TC), tubular necrosis (TN), intertubular hemorrhage and congestion (IHC), dilatation of bowman space (DBS), and interstitial inflammatory cells infiltration (IECI) were evaluated. In the IR group, compared to the Sham group, biochemical parameters indicating oxidative stress, NLR, IL-6, TNF-α, IMA, TOS, and OSI have increased. MOA reduced inflammation and oxidative stress parameters. Although TAS values have decreased in the IR group and increased in the MOA-pretreated group, no significant changes in TAS values were detected between the IR and MOA groups. The total score was obtained by summing all the scores from morphological kidney damage markers. The total score has increased with IR damage when compared with the Sham group (13.83 ± 4.30 vs 1.51 ± 1.71; p = 0.002). But, the total score has decreased significantly after application of MOA (5.01 ± 1.49; p = 0.002; compared with the IR group). MOA preconditioning is effective in reducing tissue damage induced in kidney ischemia-reperfusion injury. The protective effect of MOA is mediated via reducing inflammatory response and regulating of reactive oxygen species (ROS). Renal histology also showed convincing evidence regarding MOA's protective nature against kidney injury induced renal ischemia-reperfusion. Consequently, MOA might be helpful in protecting the kidneys from IR-induced damage in humans, probably through the anti-inflammatory effect and reducing the total oxidant status. PMID:26282390

  6. Peri-operative anaesthetic myocardial preconditioning and protection - cellular mechanisms and clinical relevance in cardiac anaesthesia.

    PubMed

    Kunst, G; Klein, A A

    2015-04-01

    Preconditioning has been shown to reduce myocardial damage caused by ischaemia-reperfusion injury peri-operatively. Volatile anaesthetic agents have the potential to provide myocardial protection by anaesthetic preconditioning and, in addition, they also mediate renal and cerebral protection. A number of proof-of-concept trials have confirmed that the experimental evidence can be translated into clinical practice with regard to postoperative markers of myocardial injury; however, this effect has not been ubiquitous. The clinical trials published to date have also been too small to investigate clinical outcome and mortality. Data from recent meta-analyses in cardiac anaesthesia are also not conclusive regarding intra-operative volatile anaesthesia. These inconclusive clinical results have led to great variability currently in the type of anaesthetic agent used during cardiac surgery. This review summarises experimentally proposed mechanisms of anaesthetic preconditioning, and assesses randomised controlled clinical trials in cardiac anaesthesia that have been aimed at translating experimental results into the clinical setting. PMID:25764404

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

    The preconditioning procedure for generalized finite-rate chemistry and the proper preconditioning for the one-dimensional Navier-Stokes equations are presented. Eigenvalue stiffness is resolved and convergence-rate acceleration is demonstrated over the entire Mach-number range from the incompressible to the hypersonic. Specific benefits are realized at low and transonic flow speeds. The extended preconditioning matrix accounts for thermal and chemical non-equilibrium and its implementation is explained for both explicit and implicit time marching. The effect of higher-order spatial accuracy and various flux splittings is investigated. Numerical analysis reveals the possible theoretical improvements from using proconditioning at all Mach numbers. Numerical results confirm the expectations from the numerical analysis. Representative test cases include flows with previously troublesome embedded high-condition-number regions.

  8. Novel Genes Critical for Hypoxic Preconditioning in Zebrafish Are Regulators of Insulin and Glucose Metabolism.

    PubMed

    Manchenkov, Tania; Pasillas, Martina P; Haddad, Gabriel G; Imam, Farhad B

    2015-06-01

    Severe hypoxia is a common cause of major brain, heart, and kidney injury in adults, children, and newborns. However, mild hypoxia can be protective against later, more severe hypoxia exposure via "hypoxic preconditioning," a phenomenon that is not yet fully understood. Accordingly, we have established and optimized an embryonic zebrafish model to study hypoxic preconditioning. Using a functional genomic approach, we used this zebrafish model to identify and validate five novel hypoxia-protective genes, including irs2, crtc3, and camk2g2, which have been previously implicated in metabolic regulation. These results extend our understanding of the mechanisms of hypoxic preconditioning and affirm the discovery potential of this novel vertebrate hypoxic stress model. PMID:25840431

  9. Wide-field fluorescence molecular tomography with compressive sensing based preconditioning

    PubMed Central

    Yao, Ruoyang; Pian, Qi; Intes, Xavier

    2015-01-01

    Wide-field optical tomography based on structured light illumination and detection strategies enables efficient tomographic imaging of large tissues at very fast acquisition speeds. However, the optical inverse problem based on such instrumental approach is still ill-conditioned. Herein, we investigate the benefit of employing compressive sensing-based preconditioning to wide-field structured illumination and detection approaches. We assess the performances of Fluorescence Molecular Tomography (FMT) when using such preconditioning methods both in silico and with experimental data. Additionally, we demonstrate that such methodology could be used to select the subset of patterns that provides optimal reconstruction performances. Lastly, we compare preconditioning data collected using a normal base that offers good experimental SNR against that directly acquired with optimal designed base. An experimental phantom study is provided to validate the proposed technique. PMID:26713202

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

    PubMed Central

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

    2015-01-01

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

  11. Peri-operative anaesthetic myocardial preconditioning and protection cellular mechanisms and clinical relevance in cardiac anaesthesia

    PubMed Central

    Kunst, G; Klein, A A

    2015-01-01

    Preconditioning has been shown to reduce myocardial damage caused by ischaemiareperfusion injury peri-operatively. Volatile anaesthetic agents have the potential to provide myocardial protection by anaesthetic preconditioning and, in addition, they also mediate renal and cerebral protection. A number of proof-of-concept trials have confirmed that the experimental evidence can be translated into clinical practice with regard to postoperative markers of myocardial injury; however, this effect has not been ubiquitous. The clinical trials published to date have also been too small to investigate clinical outcome and mortality. Data from recent meta-analyses in cardiac anaesthesia are also not conclusive regarding intra-operative volatile anaesthesia. These inconclusive clinical results have led to great variability currently in the type of anaesthetic agent used during cardiac surgery. This review summarises experimentally proposed mechanisms of anaesthetic preconditioning, and assesses randomised controlled clinical trials in cardiac anaesthesia that have been aimed at translating experimental results into the clinical setting. PMID:25764404

  12. Novel Genes Critical for Hypoxic Preconditioning in Zebrafish Are Regulators of Insulin and Glucose Metabolism

    PubMed Central

    Manchenkov, Tania; Pasillas, Martina P.; Haddad, Gabriel G.; Imam, Farhad B.

    2015-01-01

    Severe hypoxia is a common cause of major brain, heart, and kidney injury in adults, children, and newborns. However, mild hypoxia can be protective against later, more severe hypoxia exposure via “hypoxic preconditioning,” a phenomenon that is not yet fully understood. Accordingly, we have established and optimized an embryonic zebrafish model to study hypoxic preconditioning. Using a functional genomic approach, we used this zebrafish model to identify and validate five novel hypoxia-protective genes, including irs2, crtc3, and camk2g2, which have been previously implicated in metabolic regulation. These results extend our understanding of the mechanisms of hypoxic preconditioning and affirm the discovery potential of this novel vertebrate hypoxic stress model. PMID:25840431

  13. Effects of dietary polyunsaturated fatty acids and hepatic steatosis on the functioning of isolated working rat heart under normoxic conditions and during post-ischemic reperfusion.

    PubMed

    Demaison, L; Moreau, D; Vergely-Vandriesse, C; Grgoire, S; Degois, M; Rochette, L

    2001-08-01

    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 postischemic 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 post-ischemic reperfusion. PMID:11693187

  14. Isoflurane's Effect on Protein Conformation as a Proposed Mechanism for Preconditioning

    PubMed Central

    Baker, Michelle R.; Benton, Sean K.; Theisen, Christopher S.; McClintick, Chad A.; Fibuch, Eugene E.; Seidler, Norbert W.

    2011-01-01

    Persistent alteration of protein conformation due to interaction with isoflurane may be a novel molecular aspect of preconditioning. We preincubated human serum albumin with isoflurane, dialyzed to release agent, and assessed protein conformation. Susceptibility to chemical modification by methylglyoxal and nitrophenylacetate was also examined. Isoflurane had a persistent effect on protein conformation. An increase in the susceptibility of surface residues to chemical modification attended this change in conformation. Modification of isoflurane-treated HSA included intra- and intersubunit cross-linking that may be a consequence of anesthetic-induced changes in multimeric subpopulations. This irreversible effect of isoflurane may represent a mechanism for preconditioning. PMID:21918721

  15. Isoflurane's Effect on Protein Conformation as a Proposed Mechanism for Preconditioning.

    PubMed

    Baker, Michelle R; Benton, Sean K; Theisen, Christopher S; McClintick, Chad A; Fibuch, Eugene E; Seidler, Norbert W

    2011-01-01

    Persistent alteration of protein conformation due to interaction with isoflurane may be a novel molecular aspect of preconditioning. We preincubated human serum albumin with isoflurane, dialyzed to release agent, and assessed protein conformation. Susceptibility to chemical modification by methylglyoxal and nitrophenylacetate was also examined. Isoflurane had a persistent effect on protein conformation. An increase in the susceptibility of surface residues to chemical modification attended this change in conformation. Modification of isoflurane-treated HSA included intra- and intersubunit cross-linking that may be a consequence of anesthetic-induced changes in multimeric subpopulations. This irreversible effect of isoflurane may represent a mechanism for preconditioning. PMID:21918721

  16. Propulsion-related flowfields using the preconditioned Navier-Stokes equations

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    A previous time-derivative preconditioning procedure for solving the Navier-Stokes is extended to the chemical species equations. The scheme is implemented using both the implicit ADI and the explicit Runge-Kutta algorithms. A new definition for time-step is proposed to enable grid-independent convergence. Several examples of both reacting and non-reacting propulsion-related flowfields are considered. In all cases, convergence that is superior to conventional methods is demonstrated. Accuracy is verified using the example of a backward facing step. These results demonstrate that preconditioning can enhance the capability of density-based methods over a wide range of Mach and Reynolds numbers.

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

    NASA Technical Reports Server (NTRS)

    Godfrey, Andrew G.

    1993-01-01

    The extension of Van Leer's preconditioning procedure to generalized finite-rate chemistry is discussed. Application to viscous flow is begun with the proper preconditioning matrix for the one-dimensional Navier-Stokes equations. Eigenvalue stiffness is resolved and convergence-rate acceleration is demonstrated over the entire Mach-number range from nearly stagnant flow to hypersonic. Specific benefits are realized at the low and transonic flow speeds typical of complete propulsion-system simulations. The extended preconditioning matrix necessarily accounts for both thermal and chemical nonequilibrium. Numerical analysis reveals the possible theoretical improvements from using a preconditioner for all Mach number regimes. Numerical results confirm the expectations from the numerical analysis. Representative test cases include flows with previously troublesome embedded high-condition-number areas. Van Leer, Lee, and Roe recently developed an optimal, analytic preconditioning technique to reduce eigenvalue stiffness over the full Mach-number range. By multiplying the flux-balance residual with the preconditioning matrix, the acoustic wave speeds are scaled so that all waves propagate at the same rate, an essential property to eliminate inherent eigenvalue stiffness. This session discusses a synthesis of the thermochemical nonequilibrium flux-splitting developed by Grossman and Cinnella and the characteristic wave preconditioning of Van Leer into a powerful tool for implicitly solving two and three-dimensional flows with generalized finite-rate chemistry. For finite-rate chemistry, the state vector of unknowns is variable in length. Therefore, the preconditioning matrix extended to generalized finite-rate chemistry must accommodate a flexible system of moving waves. Fortunately, no new kind of wave appears in the system. The only existing waves are entropy and vorticity waves, which move with the fluid, and acoustic waves, which propagate in Mach number dependent 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.

  18. Sensory preconditioning in newborn rabbits: from common to distinct odor memories.

    PubMed

    Coureaud, Grard; Tourat, Audrey; Ferreira, Guillaume

    2013-09-01

    This study evaluated whether olfactory preconditioning is functional in newborn rabbits and based on joined or independent memory of odorants. First, after exposure to odorants A+B, the conditioning of A led to high responsiveness to odorant B. Second, responsiveness to B persisted after amnesia of A. Third, preconditioning was also functional with two overlapping pairs of odorants (A+B and B+C) and amnesia of one odorant did not affect memory of the others. Thus, incidental pairing of odorants allows reinforcement of one odorant to implicitly reinforce the others, the bond then vanishes, and the memory of each element becomes independent. PMID:23950192

  19. Preconditioning electromyographic data for an upper extremity model using neural networks

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

    A back propagation neural network has been employed to precondition the electromyographic signal (EMG) that drives a computational model of the human upper extremity. This model is used to determine the complex relationship between EMG and muscle activation, and generates an optimal muscle activation scheme that simulates the actual activation. While the experimental and model predicted results of the ballistic muscle movement are very similar, the activation function between the start and the finish is not. This neural network preconditions the signal in an attempt to more closely model the actual activation function over the entire course of the muscle movement.

  20. Sensory Stimulation as a Precondition for the Learning of a Language Task by Fourth and Sixth Grade Children.

    ERIC Educational Resources Information Center

    March, Lester William

    This study was designed to explore learning behavior of children following four specific preconditioning experiences: sensory deprivation, sensory bombardment, routine worksheet exercises, and a sensory awareness game. The study occurred in three parts: preconditioning of the subjects, teaching of a language skill, and performance of a task

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

    PubMed Central

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

    2015-01-01

    Hypoxic preconditioning was shown to improve the therapeutic efficacy of bone marrow-derived multipotent mesenchymal stromal cells (MSCs) upon transplantation in ischemic tissue. Given the interest in clinical applications of umbilical cord blood-derived MSCs, we developed a specific hypoxic preconditioning protocol and investigated its anti-apoptotic and pro-angiogenic effects on cord blood MSCs undergoing simulated ischemia in vitro by subjecting them to hypoxia and nutrient deprivation with or without preceding hypoxic preconditioning. Cell number, metabolic activity, surface marker expression, chromosomal stability, apoptosis (caspases-3/7 activity) and necrosis were determined, and phosphorylation, mRNA expression and protein secretion of selected apoptosis and angiogenesis-regulating factors were quantified. Then, human umbilical vein endothelial cells (HUVEC) were subjected to simulated ischemia in co-culture with hypoxically preconditioned or naïve cord blood MSCs, and HUVEC proliferation was measured. Migration, proliferation and nitric oxide production of HUVECs were determined in presence of cord blood MSC-conditioned medium. Cord blood MSCs proved least sensitive to simulated ischemia when they were preconditioned for 24 h, while their basic behavior, immunophenotype and karyotype in culture remained unchanged. Here, “post-ischemic” cell number and metabolic activity were enhanced and caspase-3/7 activity and lactate dehydrogenase release were reduced as compared to non-preconditioned cells. Phosphorylation of AKT and BAD, mRNA expression of BCL-XL, BAG1 and VEGF, and VEGF protein secretion were higher in preconditioned cells. Hypoxically preconditioned cord blood MSCs enhanced HUVEC proliferation and migration, while nitric oxide production remained unchanged. We conclude that hypoxic preconditioning protects cord blood MSCs by activation of anti-apoptotic signaling mechanisms and enhances their angiogenic potential. Hence, hypoxic preconditioning might be a translationally relevant strategy to increase the tolerance of cord blood MSCs to ischemia and improve their therapeutic efficacy in clinical applications. PMID:26380983

  2. Research on the Changes to the Lipid/Polymer Membrane Used in the Acidic Bitterness Sensor Caused by Preconditioning

    PubMed Central

    Harada, Yuhei; Noda, Junpei; Yatabe, Rui; Ikezaki, Hidekazu; Toko, Kiyoshi

    2016-01-01

    A taste sensor that uses lipid/polymer membranes can evaluate aftertastes felt by humans using Change in membrane Potential caused by Adsorption (CPA) measurements. The sensor membrane for evaluating bitterness, which is caused by acidic bitter substances such as iso-alpha acid contained in beer, needs an immersion process in monosodium glutamate (MSG) solution, called “MSG preconditioning”. However, what happens to the lipid/polymer membrane during MSG preconditioning is not clear. Therefore, we carried out three experiments to investigate the changes in the lipid/polymer membrane caused by the MSG preconditioning, i.e., measurements of the taste sensor, measurements of the amount of the bitterness substance adsorbed onto the membrane and measurements of the contact angle of the membrane surface. The CPA values increased as the preconditioning process progressed, and became stable after 3 d of preconditioning. The response potentials to the reference solution showed the same tendency of the CPA value change during the preconditioning period. The contact angle of the lipid/polymer membrane surface decreased after 7 d of MSG preconditioning; in short, the surface of the lipid/polymer membrane became hydrophilic during MSG preconditioning. The amount of adsorbed iso-alpha acid was increased until 5 d preconditioning, and then it decreased. In this study, we revealed that the CPA values increased with the progress of MSG preconditioning in spite of the decrease of the amount of iso-alpha acid adsorbed onto the lipid/polymer membrane, and it was indicated that the CPA values increase because the sensor sensitivity was improved by the MSG preconditioning. PMID:26891299

  3. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... § 86.085-2 or § 86.1803-01 as applicable, two Highway Fuel Economy Driving Schedules, found in 40 CFR... 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete... to prevent entry of water or other contaminants into the fuel tank. During storage in the test...

  4. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... § 86.085-2 or § 86.1803-01 as applicable, two Highway Fuel Economy Driving Schedules, found in 40 CFR... 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete... to prevent entry of water or other contaminants into the fuel tank. During storage in the test...

  5. 40 CFR 86.132-96 - Vehicle preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... § 86.085-2 or § 86.1803-01 as applicable, two Highway Fuel Economy Driving Schedules, found in 40 CFR... 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete... to prevent entry of water or other contaminants into the fuel tank. During storage in the test...

  6. Progress Toward a Stabilization and Preconditioning Protocol for Polycrystalline Thin-Film Photovoltaic Modules

    SciTech Connect

    del Cueto, J. A.; Deline, C. A.; Rummel, S. R.; Anderberg, A.

    2010-08-01

    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. This study examines the metastable performance changes in these PV modules with the goal of establishing standard preconditioning or stabilization exposure procedures to mitigate measured variations prior to current-voltage (IV) measurements.

  7. An anisotropic preconditioning for the Wilson fermion matrix on the lattice

    SciTech Connect

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

    2010-01-01

    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.

  8. Professors' and Trainees' Perceptions of Educational Quality as Related to Preconditions of Deep Learning in "Musikdidaktik"

    ERIC Educational Resources Information Center

    Ferm, Cecilia; Johansen, Geir

    2008-01-01

    Interview-based case studies, involving two institutions, four professors and 11 music teacher trainees were conducted in order to investigate the preconditions for deep learning in the subject of higher music education called "musikdidaktik". Analysis was based on the "didaktiktriangle" which is a theoretical model that

  9. Preconditioned iterative methods for nonselfadjoint or indefinite elliptic boundary value problems

    SciTech Connect

    Bramble, J.H.; Pasciak, J.E.

    1984-01-01

    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 to iteration procedures whose iterative convergence rates are independent of the number of unknowns in the solution.

  10. Preconditioned pseudo-compressibility methods for incompressible Navier-Stokes equations

    NASA Astrophysics Data System (ADS)

    Qian, Zhansen; Zhang, Jingbai; Li, Chunxuan

    2010-11-01

    This paper investigates the pseudo-compressibility method for the incompressible Navier-Stokes equations and the preconditioning technique for accelerating the time marching for stiff hyperbolic equations, and derives and presents the eigenvalues and eigenvectors of the Jacobian matrix of the preconditioned pseudo-compressible Navier-Stokes equations in generally cur-vilinear coordinates. Based on the finite difference discretization the cored for efficiently solving incompressible flows numerically is established. The reliability of the procedures is demonstrated by the application to the inviscid flow past a circular cylinder, the laminar flow over a flat plate, and steady low Reynolds number viscous incompressible flows past a circular cylinder. It is found that the solutions to the present algorithm are in good agreement with the exact solutions or experimental data. The effects of the pseudo-compressibility factor and the parameter brought by preconditioning in convergence characteristics of the solution are investigated systematically. The results show that the upwind Roes scheme is superior to the second order central scheme, that the convergence rate of the pseudo-compressibility method can be effectively improved by preconditioning and that the self-adaptive pseudo-compressibility factor can modify the numerical convergence rate significantly compared to the constant form, without doing artificial tuning depending on the specific flow conditions. Further validation is also performed by numerical simulations of unsteady low Reynolds number viscous incompressible flows past a circular cylinder. The results are also found in good agreement with the existing numerical results or experimental data.

  11. 40 CFR 85.2219 - Idle test with loaded preconditioning-EPA 91.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Idle test with loaded preconditioning-EPA 91. 85.2219 Section 85.2219 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Performance Warranty Short Tests § 85.2219 Idle test with loaded preconditioning—EPA 91. (a)...

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

    PubMed

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

    2007-06-01

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

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

    PubMed Central

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

    2013-01-01

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

  14. An M-step preconditioned conjugate gradient method for parallel computation

    NASA Technical Reports Server (NTRS)

    Adams, L.

    1983-01-01

    This paper describes a preconditioned conjugate gradient method that can be effectively implemented on both vector machines and parallel arrays to solve sparse symmetric and positive definite systems of linear equations. The implementation on the CYBER 203/205 and on the Finite Element Machine is discussed and results obtained using the method on these machines are given.

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

    ERIC Educational Resources Information Center

    Preler, Anna-Lena; Knen, Tanja; Hasselhorn, Marcus; Krajewski, Kristin

    2014-01-01

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

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

    PubMed

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

    2013-10-22

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

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

    SciTech Connect

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

    2010-12-01

    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.

  18. 40 CFR 1065.590 - PM sampling media (e.g., filters) preconditioning and tare weighing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false PM sampling media (e.g., filters) preconditioning and tare weighing. 1065.590 Section 1065.590 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.590...

  19. 40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Vehicle and canister preconditioning; refueling test. 86.153-98 Section 86.153-98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and...

  20. 40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Vehicle and canister preconditioning; refueling test. 86.153-98 Section 86.153-98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and...

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

    PubMed Central

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

    2014-01-01

    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?. PMID:24667295

  2. 40 CFR 92.125 - Pre-test procedures and preconditioning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Pre-test procedures and preconditioning. 92.125 Section 92.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.125 Pre-test procedures and...

  3. Using Chebyshev polynomials and approximate inverse triangular factorizations for preconditioning the conjugate gradient method

    NASA Astrophysics Data System (ADS)

    Kaporin, I. E.

    2012-02-01

    In order to precondition a sparse symmetric positive definite matrix, its approximate inverse is examined, which is represented as the product of two sparse mutually adjoint triangular matrices. In this way, the solution of the corresponding system of linear algebraic equations (SLAE) by applying the preconditioned conjugate gradient method (CGM) is reduced to performing only elementary vector operations and calculating sparse matrix-vector products. A method for constructing the above preconditioner is described and analyzed. The triangular factor has a fixed sparsity pattern and is optimal in the sense that the preconditioned matrix has a minimum K-condition number. The use of polynomial preconditioning based on Chebyshev polynomials makes it possible to considerably reduce the amount of scalar product operations (at the cost of an insignificant increase in the total number of arithmetic operations). The possibility of an efficient massively parallel implementation of the resulting method for solving SLAEs is discussed. For a sequential version of this method, the results obtained by solving 56 test problems from the Florida sparse matrix collection (which are large-scale and ill-conditioned) are presented. These results show that the method is highly reliable and has low computational costs.

  4. Professors' and Trainees' Perceptions of Educational Quality as Related to Preconditions of Deep Learning in "Musikdidaktik"

    ERIC Educational Resources Information Center

    Ferm, Cecilia; Johansen, Geir

    2008-01-01

    Interview-based case studies, involving two institutions, four professors and 11 music teacher trainees were conducted in order to investigate the preconditions for deep learning in the subject of higher music education called "musikdidaktik". Analysis was based on the "didaktiktriangle" which is a theoretical model that…

  5. A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2

    PubMed Central

    Lee, Sang Gil; Lee, Chan Gyu; Wu, Hong Min; Oh, Choong Sik; Chung, So Won; Kim, Sang Geon

    2015-01-01

    An understanding of the effects of hypergravity on energy homeostasis is necessary in managing proper physiological countermeasures for aerospace missions. This study investigated whether a single or multiple load(s) of mice to hypergravity has an effect on molecules associated with energy metabolism. In the liver, AMPKα level and its signaling were repressed 6 h after a load to +9 Gz hypergravity for 1 h, and then gradually returned toward normal. AMPKα level was restored after 3 loads to +9 Gz, suggestive of preconditioning adaptation. In cDNA microarray analyses, 221 genes were differentially expressed by +9 Gz, and the down-regulated genes included Nrf2 targets. Nrf2 gene knockout abrogated the recovery of AMPKα elicited by 3 loads to +9 Gz, indicating that Nrf2 plays a role in the adaptive increase of AMPKα. In addition, +9 Gz stress decreased STAT3, FOXO1/3 and CREB levels, which was attenuated during the resting time. Similarly, apoptotic markers were enhanced in the liver, indicating that the liver may be vulnerable to hypergravity stress. Preconditioning loads prevented hepatocyte apoptosis. Overall, a load of mice to +9 Gz hypergravity causes AMPKα repression with liver injury, which may be overcome by multiple loads to hypergravity as mediated by Nrf2. PMID:26493041

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

    PubMed

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

    2000-02-01

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

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

    PubMed Central

    Leal, Antonio Jos Gonalves; Tannuri, Ana Cristina Aoun; Belon, Alessandro Rodrigo; Guimares, Raimundo Renato Nunes; Coelho, Maria Ceclia Mendona; de Oliveira Gonalves, Josiane; Serafini, Suellen; de Melo, Evandro Sobroza; Tannuri, Uenis

    2015-01-01

    OBJECTIVE: In most cases of pediatric liver transplantation, the clinical scenario of large-for-size transplants can lead to hepatic dysfunction and a decreased blood supply to the liver graft. The objective of the present experimental investigation was to evaluate the effects of ischemic preconditioning on this clinical entity. METHODS: Eighteen pigs were divided into three groups and underwent liver transplantation: a control group, in which the weights of the donors were similar to those of the recipients, a large-for-size group, and a large-for-size + ischemic preconditioning group. Blood samples were collected from the recipients to evaluate the pH and the sodium, potassium, aspartate aminotransferase and alanine aminotransferase levels. In addition, hepatic tissue was sampled from the recipients for histological evaluation, immunohistochemical analyses to detect hepatocyte apoptosis and proliferation and molecular analyses to evaluate the gene expression of Bax (pro-apoptotic), Bcl-XL (anti-apoptotic), c-Fos and c-Jun (immediate-early genes), ischemia-reperfusion-related inflammatory cytokines (IL-1, TNF-alpha and IL-6, which is also a stimulator of hepatocyte regeneration), intracellular adhesion molecule, endothelial nitric oxide synthase (a mediator of the protective effect of ischemic preconditioning) and TGF-beta (a pro-fibrogenic cytokine). RESULTS: All animals developed acidosis. At 1 hour and 3 hours after reperfusion, the animals in the large-for-size and large-for-size + ischemic preconditioning groups had decreased serum levels of Na and increased serum levels of K and aspartate aminotransferase compared with the control group. The molecular analysis revealed higher expression of the Bax, TNF-alpha, I-CAM and TGF-beta genes in the large-for-size group compared with the control and large-for-size + ischemic preconditioning groups. Ischemic preconditioning was responsible for an increase in c-Fos, IL-1, IL-6 and e-NOS gene expression. CONCLUSION: Ischemia-reperfusion injury in this model of large-for-size liver transplantation could be partially attenuated by ischemic preconditioning. PMID:25789522

  8. Anesthetic Preconditioning Inhibits Isoflurane-Mediated Apoptosis in the Developing Rat Brain

    PubMed Central

    Peng, Jun; Drobish, Julie K.; Liang, Ge; Wu, Zhen; Liu, Chunxia; Joseph, Donald J.; Abdou, Hossam; Eckenhoff, Maryellen F.; Wei, Huafeng

    2014-01-01

    Background We hypothesized that preconditioning with a short exposure to isoflurane (ISO) would reduce neurodegeneration induced by prolonged exposure to ISO in neonatal rats, as previously shown in neuronal cell culture. Methods We randomly divided 7-day-old Sprague-Dawley rats into 3 groups: control, 1.5% ISO, and preconditioning (PC) + 1.5% ISO. The control group was exposed to carrier gas (30% oxygen balanced in nitrogen) for 30 min and then carrier gas again for 6 h the following day. The 1.5% ISO group was exposed to carrier gas for 30 min and then 1.5% ISO for 6 h the following day. The PC + 1.5% ISO group was preconditioned with a 30 min 1.5% ISO exposure and then exposed to 1.5% ISO for 6 h the following day. Blood and brain samples were collected 2 h after the exposures for determination of neurodegenerative biomarkers, including caspase-3, S100?, caspase-12, and an autophagy biomarker Beclin-1. Results Prolonged exposure to ISO significantly increased cleaved caspase-3 expression in the cerebral cortex of 7-day old rats compared to the group preconditioned with ISO and the controls using Western blot assays. However, significant differences were not detected for other markers of neuronal injury. Conclusion The ISO-mediated increase in cleaved caspase-3 in the postnatal day 7 rat brain is ameliorated by preconditioning with a brief anesthetic exposure, and differences were not detected in other markers of neuronal injury. PMID:25099925

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

    PubMed

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

    1995-03-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-01-01

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

  12. Catestatin Increases the Expression of Anti-Apoptotic and Pro-Angiogenetic Factors in the Post-Ischemic Hypertrophied Heart of SHR

    PubMed Central

    Penna, Claudia; Pasqua, Teresa; Amelio, Daniela; Perrelli, Maria-Giulia; Angotti, Carmelina; Tullio, Francesca; Mahata, Sushil K.; Tota, Bruno; Pagliaro, Pasquale; Cerra, Maria C.; Angelone, Tommaso

    2014-01-01

    Background In the presence of comorbidities the effectiveness of many cardioprotective strategies is blunted. The goal of this study was to assess in a hypertensive rat model if the early reperfusion with anti-hypertensive and pro-angiogenic Chromogranin A-derived peptide, Catestatin (CST:hCgA352372; CST-Post), protects the heart via Reperfusion-Injury-Salvage-Kinases (RISK)-pathway activation, limiting infarct-size and apoptosis, and promoting angiogenetic factors (e.g., hypoxia inducible factor, HIF-1?, and endothelial nitric oxide synthase, eNOS, expression). Methods and Results The effects of CST-Post on infarct-size, apoptosis and pro-angiogenetic factors were studied in isolated hearts of spontaneously hypertensive rats (SHR), which underwent the following protocols: (a) 30-min ischemia and 120-min reperfusion (I/R); (b) 30-min ischemia and 20-min reperfusion (I/R-short), both with and without CST-Post (75 nM for 20-min at the beginning of reperfusion). In unprotected Wistar-Kyoto hearts, used as normal counterpart, infarct-size resulted smaller than in SHR. CST-Post reduced significantly infarct-size and improved post-ischemic cardiac function in both strains. After 20-min reperfusion, CST-Post induced S-nitrosylation of calcium channels and phosphorylation of RISK-pathway in WKY and SHR hearts. Yet specific inhibitors of the RISK pathway blocked the CST-Post protective effects against infarct in the 120-min reperfusion groups. Moreover, apoptosis (evaluated by TUNEL, ARC and cleaved caspase) was reduced by CST-Post. Importantly, CST-Post increased expression of pro-angiogenetic factors (i.e., HIF-1? and eNOS expression) after two-hour reperfusion. Conclusions CST-Post limits reperfusion damages and reverses the hypertension-induced increase of I/R susceptibility. Moreover, CST-Post triggers antiapoptotic and pro-angiogenetic factors suggesting that CST-Post can be used as an anti-maladaptive remodeling treatment. PMID:25099124

  13. Mesenchymal stem/stromal cells precondition lung monocytes/macrophages to produce tolerance against allo- and autoimmunity in the eye.

    PubMed

    Ko, Jung Hwa; Lee, Hyun Ju; Jeong, Hyun Jeong; Kim, Mee Kum; Wee, Won Ryang; Yoon, Sun-Ok; Choi, Hosoon; Prockop, Darwin J; Oh, Joo Youn

    2016-01-01

    Intravenously administered mesenchymal stem/stromal cells (MSCs) engraft only transiently in recipients, but confer long-term therapeutic benefits in patients with immune disorders. This suggests that MSCs induce immune tolerance by long-lasting effects on the recipient immune regulatory system. Here, we demonstrate that i.v. infusion of MSCs preconditioned lung monocytes/macrophages toward an immune regulatory phenotype in a TNF-?-stimulated gene/protein (TSG)-6-dependent manner. As a result, mice were protected against subsequent immune challenge in two models of allo- and autoimmune ocular inflammation: corneal allotransplantation and experimental autoimmune uveitis (EAU). The monocytes/macrophages primed by MSCs expressed high levels of MHC class II, B220, CD11b, and IL-10, and exhibited T-cell-suppressive activities independently of FoxP3(+) regulatory T cells. Adoptive transfer of MSC-induced B220(+)CD11b(+) monocytes/macrophages prevented corneal allograft rejection and EAU. Deletion of monocytes/macrophages abrogated the MSC-induced tolerance. However, MSCs with TSG-6 knockdown did not induce MHC II(+)B220(+)CD11b(+) cells, and failed to attenuate EAU. Therefore, the results demonstrate a mechanism of the MSC-mediated immune modulation through induction of innate immune tolerance that involves monocytes/macrophages. PMID:26699483

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

    PubMed

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

    2008-12-01

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

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

    SciTech Connect

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

    2014-02-01

    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 18 h or 1 h prior to an APAP overdose. Administration of allopurinol 18 h prior to APAP overdose resulted in an 88% reduction in liver injury (serum ALT) 6 h after APAP; however, 1 h 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 (2 h) however late JNK activation (6 h) 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) 18 h or 1 h 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 18 h 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. - Highlights: • 18 h allopurinol pretreatment protects against acetaminophen-induced liver injury. • 1 h allopurinol pretreatment does not protect from APAP-induced injury. • 18 h or 1 h oxypurinol pretreatment does not alter APAP-induced injury. • Inhibiting aldehyde oxidase eliminates protection from 18 h allopurinol pretreatment. • 18 h allopurinol induces metallothionein which protects the liver against APAP injury.

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

    SciTech Connect

    Bruss, D. E.; Morel, J. E.; Ragusa, J. C.

    2013-07-01

    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)

  17. Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice

    SciTech Connect

    Mirrione, M.M.; Mirrione, M.M.; Konomosa, D.K.; Ioradanis, G.; Dewey, S.L.; Agzzid, A.; Heppnerd, F.L.; Tsirka, St.E.

    2010-04-01

    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) preconditioning (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 preconditioning with LPS 24 h prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation.

  18. A Note on Substructuring Preconditioning for Nonconforming Finite Element Approximations of Second Order Elliptic Problems

    NASA Technical Reports Server (NTRS)

    Maliassov, Serguei

    1996-01-01

    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 preconditioned 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 preconditioned 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.

  19. Role of Al, Ti, and Zr in Gray Iron Preconditioning/Inoculation

    NASA Astrophysics Data System (ADS)

    Riposan, Iulian; Chisamera, Mihai; Stan, Stelian; Ecob, Chris; Wilkinson, David

    2009-02-01

    A research was done to investigate the effect of strong deoxidizing elements, such as Al, Zr, and Ti, in gray irons in laboratory experiments. The conclusions drawn were based mainly on thermal analysis, chill (carbides) sensitivity, graphite characteristics, and SEM analysis. Al and Zr have visible beneficial effects in preconditioning of gray irons, by favoring lower undercooling during solidification. Ti has an inconclusive role, with limited influence, but promotes undercooled graphite formation. Complex (Mn,X)S compounds, nucleated on the previously formed small oxide-based sites, were found as the major nucleation sites for graphite in gray irons, with specific distribution of Al, Ti, and Zr. Al,Zr-FeSi preconditioning of electrically melted and Sr-FeSi inoculated gray irons avoided type D graphite and carbides in 3 mm sections castings.

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

    NASA Astrophysics Data System (ADS)

    Schroeder, Isaac D.; Black, Bryan A.; Sydeman, William J.; Bograd, Steven J.; Hazen, Elliott L.; Santora, Jarrod A.; Wells, Brian K.

    2013-02-01

    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> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li class="active"><span>17</span></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_17 --> <div id="page_18" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="341"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014JCoPh.273..706B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014JCoPh.273..706B"><span id="translatedtitle">S2SA <span class="hlt">preconditioning</span> for the Sn equations with strictly nonnegative spatial discretization</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Bruss, Don E.; Morel, Jim E.; Ragusa, Jean C.</p> <p>2014-09-01</p> <p>Preconditioners based upon transport sweeps and diffusion-synthetic acceleration have been constructed and applied to the zeroth and first spatial moments of the 1-D Sn transport equation using a strictly nonnegative nonlinear spatial closure. Linear and nonlinear preconditioners have been derived and analyzed. The effectiveness of various combinations of these preconditioners are compared using the source iteration, matrix-free Picard Krylov, and nonlinear Krylov acceleration methods. In one dimension, <span class="hlt">preconditioning</span> with a linear S2SA diffusion equation is found to be essentially equivalent to using a nonlinear diffusion equation. The ability to use a linear diffusion equation has important implications for <span class="hlt">preconditioning</span> the Sn equations with a strictly nonnegative spatial discretization in multiple dimensions.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26463920','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26463920"><span id="translatedtitle">Role of Circulating Immune Cells in Stroke and <span class="hlt">Preconditioning</span>-Induced Protection.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gesuete, Raffaella; Stevens, Susan L; Stenzel-Poore, Mary P</p> <p>2016-01-01</p> <p>Stroke activates an inflammatory response that results in the infiltration of peripheral immune cells into the ischemic area, contributing to exacerbation of tissue damage. However, evidence indicates that inflammatory cell infiltration can also promote neuroprotection through regulatory immune cells that mitigate injury. These immune regulatory cells may also be important mediators of neuroprotection associated with <span class="hlt">preconditioning</span>, a phenomenon whereby small exposure to a potential harmful stimulus is able to induce protection against a subsequent ischemic event. The elucidation of mechanisms that allow these immune cells to confer neuroprotection is critical to developing new therapeutic strategies against acute stroke. In the present review, we discuss the dual role of peripheral immune cells in stroke-related brain injury and neuroprotection. Furthermore, we report new data from our laboratory that supports the important role of peripheral cells and their interaction with the brain endothelium for the establishment of the protective phenotype in <span class="hlt">preconditioning</span>. PMID:26463920</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/biblio/22233566','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/biblio/22233566"><span id="translatedtitle">On linearization and <span class="hlt">preconditioning</span> for radiation diffusion coupled to material thermal conduction equations</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Feng, Tao; Graduate School of China Academy Engineering Physics, Beijing 100083 ; An, Hengbin; Yu, Xijun; Li, Qin; Zhang, Rongpei</p> <p>2013-03-01</p> <p>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> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4768971','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4768971"><span id="translatedtitle">Hypoxic <span class="hlt">preconditioning</span> increases the protective effect of bone marrow mesenchymal stem cells on spinal cord ischemia/reperfusion injury</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>WANG, ZHILIN; FANG, BO; TAN, ZHIBIN; ZHANG, DONG; MA, HONG</p> <p>2016-01-01</p> <p>Transplantation of bone marrow mesenchymal stem cells (BMSCs) protect against spinal cord ischemia/reperfusion injury (SCIRI). However, a large number of transplanted BMSCs often undergo apoptosis, which severely affects the treatment outcome. Previous studies have demonstrated that hypoxic <span class="hlt">preconditioning</span> effectively increases the survival rate of BMSCs following transplantation, and increases their protective effect on injured tissues. However, there have been few reports regarding roles of hypoxic <span class="hlt">preconditioning</span> in SCIRI. The present study isolated rat BMSCs and separately transplanted hypoxia- and non-hypoxia-<span class="hlt">preconditioned</span> BMSCs into the spinal cord tissues of rats with SCIRI. The role of hypoxic <span class="hlt">preconditioning</span> in the promotion of the protective effect of BMSCs on SCIRI was investigated using neurological function scores, Evans blue staining, hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. In addition, reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression levels of hypoxia-inducible factor 1α (HIF-1α), and to investigate its possible underlying mechanism of action. The results indicated that hypoxic <span class="hlt">preconditioning</span> effectively increased the protective effects of BMSCs on neurological function, blood spinal cord barrier and tissue damage following SCIRI, and inhibited apoptosis. Furthermore, hypoxic <span class="hlt">preconditioned</span> BMSCs upregulated the expression of HIF-1α in spinal cord tissues. Therefore, hypoxic <span class="hlt">preconditioning</span> effectively increased the protective effect of BMSCs on SCIRI and may be associated with upregulation of the expression of HIF-1α. Hypoxic <span class="hlt">preconditioning</span> may serve as an effective means of increasing the protective effect of BMSCs on SCIRI. PMID:26783161</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4245882','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4245882"><span id="translatedtitle"><span class="hlt">Preconditioning</span> Human Mesenchymal Stem Cells with a Low Concentration of BMP2 Stimulates Proliferation and Osteogenic Differentiation In Vitro</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Baatrup, Anette; Foldager, Casper Bindzus; Bünger, Cody</p> <p>2014-01-01</p> <p>Abstract Clinical trials using bone morphogenetic protein-2 (BMP2) for bone reconstruction have shown promising results. However, the relatively high concentration needed to be effective raises concerns for efficacy and safety. The aim of this study was to investigate the osteogenic effect of an alternative treatment strategy in which human bone marrow–derived mesenchymal stem cells (hMSCs) are <span class="hlt">preconditioned</span> with low concentrations of BMP2 for a short time in vitro. hMSCs in suspension were stimulated for 15 min with 10 and 20 ng/mL of BMP2. After the BMP2 was removed, the cells were seeded and cultured in osteogenic medium. The effects of <span class="hlt">preconditioning</span> were analyzed with regard to proliferation and expression of osteogenic markers at both gene and protein level. The results were compared to those from cultures with continuous BMP2 stimulation. A significant increase in proliferation was seen with both <span class="hlt">precondition</span> and continuous stimulation with BMP2, with no difference between the treatments. <span class="hlt">Preconditioning</span> with BMP2 significantly increased gene expression of RUNX2, COLI, ALP, and OC, and protein levels of COLI and ALP. This was not found with continuous stimulation. The role of <span class="hlt">preconditioning</span> with BMP2 in osteogenesis was validated by findings of increased gene expression of SMAD1 and an increase in dual phosphorylation of ser 463 and ser 465 in the SMAD 1/5/8 pathway. We concluded that <span class="hlt">preconditioning</span> hMSCs with BMP2 stimulates osteogenesis: proliferation with matrix secretion and matrix maturation of hMSCs. This implies that <span class="hlt">preconditioning</span> with BMP2 might be more effective at inducing proliferation and osteogenic differentiation of hMSCs than continuous stimulation. <span class="hlt">Preconditioning</span> with BMP2 could benefit the clinical application of BMP2 since side effects from high-dose treatments could be avoided. PMID:25469313</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/biblio/5458149','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/biblio/5458149"><span id="translatedtitle"><span class="hlt">Preconditioning</span> technique for indefinite systems resulting from mixed approximations of elliptic problems</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Bramble, J.H.; Pasciak, J.E.</p> <p>1988-01-01</p> <p>This paper provides a <span class="hlt">preconditioned</span> iterative technique for the solution of saddle point problems. These problems typically arise in the numerical approximation of partial differential equations by Lagrange multiplier techniques and/or mixed methods. The saddle point problem is reformulated as a symmetric positive definite system, which is then solved by conjugate gradient iteration. Applications to the equations of elasticity and Stokes are discussed and the results of numerical experiments are given.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4443717','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4443717"><span id="translatedtitle">Novel Cellular Mechanisms for Neuroprotection in Ischemic <span class="hlt">Preconditioning</span>: A View from Inside Organelles</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Sisalli, Maria Jos; Annunziato, Lucio; Scorziello, Antonella</p> <p>2015-01-01</p> <p>Ischemic <span class="hlt">preconditioning</span> represents an important adaptation mechanism of CNS, which results in its increased tolerance to the lethal cerebral ischemia. The molecular mechanisms responsible for the induction and maintenance of ischemic tolerance in the brain are complex and not yet completely clarified. In the last 10?years, great attention has been devoted to unravel the intracellular pathways activated by <span class="hlt">preconditioning</span> and responsible for the establishing of the tolerant phenotype. Indeed, recent papers have been published supporting the hypothesis that mitochondria might act as master regulators of <span class="hlt">preconditioning</span>-triggered endogenous neuroprotection due to their ability to control cytosolic calcium homeostasis. More interestingly, the demonstration that functional alterations in the ability of mitochondria and endoplasmic reticulum (ER) managing calcium homeostasis during ischemia, opened a new line of research focused to the role played by mitochondria and ER cross-talk in the pathogenesis of cerebral ischemia in order to identify new molecular mechanisms involved in the ischemic tolerance. In line with these findings and considering that the expression of the three isoforms of the sodium calcium exchanger (NCX), NCX1, NCX2, and NCX3, mainly responsible for the regulation of Ca2+ homeostasis, was reduced during cerebral ischemia, it was investigated whether these proteins might play a role in neuroprotection induced by ischemic tolerance. In this review, evidence supporting the involvement of ER and mitochondria interaction within the <span class="hlt">preconditioning</span> paradigm will be provided. In particular, the key role played by NCXs in the regulation of Ca2+-homeostasis at the different subcellular compartments will be discussed as new molecular mechanism proposed for the establishing of ischemic tolerant phenotype. PMID:26074868</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25743572','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25743572"><span id="translatedtitle">Effect of zinc supplements in the attenuated cardioprotective effect of ischemic <span class="hlt">preconditioning</span> in hyperlipidemic rat heart.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep</p> <p>2015-06-01</p> <p>Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic <span class="hlt">preconditioning</span> (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic <span class="hlt">preconditioning</span> in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4cycles of ischemic <span class="hlt">preconditioning</span> (IPC), then 30min of ischemia followed by 120min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10?M) perfused during reperfusion for 120min, significantly abrogated the attenuated cardioprotective effect of ischemic <span class="hlt">preconditioning</span> in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10?M), perfused during reperfusion 2min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion. PMID:25743572</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26531833','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26531833"><span id="translatedtitle">Possible role of thromboxane A2 in remote hind limb <span class="hlt">preconditioning</span>-induced cardioprotection.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sharma, Roohani; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh</p> <p>2016-01-01</p> <p>Remote hind limb <span class="hlt">preconditioning</span> (RIPC) is a protective strategy in which short episodes of ischemia and reperfusion in a remote organ (hind limb) protects the target organ (heart) against sustained ischemic reperfusion injury. The present study was designed to investigate the possible role of thromboxane A2 in RIPC-induced cardioprotection in rats. Remote hind limb <span class="hlt">preconditioning</span> was performed by four episodes of 5 min of inflation and 5 min of deflation of pressure cuff. Occlusion of the hind limb with blood pressure cuff is most feasible, non-invasive, clinically relevant, and safe method for inducing RIPC. Isolated rat hearts were perfused on Langendorff apparatus and were subjected to global ischemia for 30 min followed by 120-min reperfusion. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in coronary effluent to assess the degree of myocardial injury. The extent of myocardial infarct size along with the functional parameters including left ventricular developed pressure (LVDP), dp/dtmax, and dp/dtmin were also measured. Ozagrel (thromboxane synthase inhibitor) and seratrodast (thromboxane A2 receptor antagonist) were employed as pharmacological modulators of thromboxane A2. Remote hind limb <span class="hlt">preconditioning</span> significantly attenuated ischemia/reperfusion-induced myocardial injury and produced cardioprotective effects. However, administration of ozagrel and seratrodast completely abolished the cardioprotective effects of RIPC suggesting the key role of thromboxane A2 in RIPC-induced cardioprotection. It may be concluded that brief episodes of <span class="hlt">preconditioning</span> ischemia and reperfusion activates the thromboxane synthase enzyme that produces thromboxane A2, which may elicit cardioprotection either involving humoral or neurogenic pathway. PMID:26531833</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/24526448','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/24526448"><span id="translatedtitle">Lrg participates in lipopolysaccharide <span class="hlt">preconditioning</span>-induced brain ischemia injury via TLR4 signaling pathway.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gong, Gu; Bai, Shurong; Wu, Wei; Hu, Ling; Liu, Yinghai; Niu, Jie; Dai, Xuemei; Yin, Liang; Wang, Xiaowu</p> <p>2014-09-01</p> <p>Lipopolysaccharide (LPS) <span class="hlt">preconditioning</span> is a powerful neuroprotective phenomenon by which an injurious stimulus renders the brain resistant to a subsequent damaging ischemic insult. The LPS response gene (Lrg) is a recently identified gene in human dental pulp cells treated with LPS. However, the role and mechanism of Lrg in brain ischemia injury have not yet been demonstrated. Here, we sought to determine whether Lrg participates in LPS <span class="hlt">preconditioning</span>-induced brain ischemia injury. The Lrg protein accumulates in brain tissue after middle cerebral artery occlusion (MCAO). Furthermore, knockdown of Lrg by small interfering RNA (siRNA) significantly increased the infarct size of brain injury. In addition, we investigated the mechanism of Lrg in brain ischemia injury. Lrg-siRNA could regulate inflammatory cytokine expression. Moreover, interleukin-1 receptor-associated kinase 1 (IRAK-1) and nuclear factor Kappa B (NF-?B) p65 protein levels were significantly increased by Lrg-siRNA in mice after MCAO. Conversely, interferon regulatory factor 3 (IRF3) protein level was decreased by Lrg-siRNA. Taken together, these results suggest that Lrg regulates the expression of inflammatory cytokines in LPS <span class="hlt">preconditioning</span>-induced brain ischemia injury via the toll-like receptor 4 (TLR4) signaling pathway. Lrg may therefore serve as a novel therapeutic target for brain ischemia injury. PMID:24526448</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2011LNCS.6538..150C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2011LNCS.6538..150C"><span id="translatedtitle"><span class="hlt">Precondition</span> Inference from Intermittent Assertions and Application to Contracts on Collections</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Cousot, Patrick; Cousot, Radhia; Logozzo, Francesco</p> <p></p> <p>Programmers often insert assertions in their code to be optionally checked at runtime, at least during the debugging phase. In the context of design by contracts, these assertions would better be given as a <span class="hlt">precondition</span> of the method/procedure which can detect that a caller has violated the procedure's contract in a way which definitely leads to an assertion violation (e.g., for separate static analysis). We define precisely and formally the contract inference problem from intermittent assertions inserted in the code by the programmer. Our definition excludes no good run even when a non-deterministic choice (e.g., an interactive input) could lead to a bad one (so this is not the weakest <span class="hlt">precondition</span>, nor its strengthening by abduction, since a terminating successful execution is not guaranteed). We then introduce new abstract interpretation-based methods to automatically infer both the static contract <span class="hlt">precondition</span> of a method/procedure and the code to check it at runtime on scalar and collection variables.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4612942','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4612942"><span id="translatedtitle">The protective effect of intraperitoneal medical ozone <span class="hlt">preconditioning</span> and treatment on hepatotoxicity induced by methotrexate</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Aslaner, Arif; Çakır, Tuğrul; Çelik, Betül; Doğan, Uğur; Akyüz, Cebrail; Baştürk, Ahmet; Polat, Cemal; Gündüz, Umut; Mayir, Burhan; Şehirli, Ahmet Özer</p> <p>2015-01-01</p> <p>The aim of this study is to determine the effects of medical ozone <span class="hlt">preconditioning</span> and treatment on the methotrexate acute induced hepatotoxicity in rats that has not reports elsewhere. Eighteen rats were randomly assigned into three equal groups; control, Mtx and Mtx with ozone. Hepatotoxicity was performed with a single dose of 20 mg/kg Mtx to group 2 and group 3 at the fifteenth day. The medical ozone <span class="hlt">preconditioning</span> was administered intraperitonealy in group 3 for fifteen days and more five days after inducing Mtx. The other rats of the group 1 and 2 received saline injection. At the twentyfirst day the blood and the liver tissue samples were obtained to measure the levels of liver enzymes ALT and AST, proinflamatory cytokines TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. And the histolopatological examination was evaluated for injury score. In our study Mtx administration caused a significant increase on the liver enzymes ALT and AST, the tissue MDA and MPO activity and significant decrease in the tissue GSH. Moreover the both pro-inflammatory cytokines were significantly increased in the Mtx group. Medical ozone <span class="hlt">preconditioning</span> and treatment reversed all these biochemical parameters and histopathological changes of the hepatotoxicity induced by Mtx. We conclude that medical ozone ameliorates Mtx induced hepatotoxicity in rats. PMID:26550257</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25419789','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25419789"><span id="translatedtitle">Voluntary Exercise <span class="hlt">Preconditioning</span> Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I; Stoica, Bogdan A</p> <p>2015-09-01</p> <p>Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (<span class="hlt">preconditioning</span>) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise <span class="hlt">preconditioning</span> (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise <span class="hlt">preconditioning</span> activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3-only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI. PMID:25419789</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26925416','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26925416"><span id="translatedtitle">Renal Ischemia/Reperfusion Injury in Diabetic Rats: The Role of Local Ischemic <span class="hlt">Preconditioning</span>.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ozbilgin, Sule; Ozkardesler, Sevda; Akan, Mert; Boztas, Nilay; Ozbilgin, Mucahit; Ergur, Bekir Ugur; Derici, Serhan; Guneli, Mehmet Ensari; Meseri, Reci</p> <p>2016-01-01</p> <p>Background. The aim of this study was to evaluate the effects of local ischemic <span class="hlt">preconditioning</span> using biochemical markers and histopathologically in the diabetic rat renal IR injury model. Methods. DM was induced using streptozotocin. Rats were divided into four groups: Group I, nondiabetic sham group (n = 7), Group II, diabetic sham group (n = 6), Group III, diabetic IR group (diabetic IR group, n = 6), and Group IV, diabetic IR + local ischemic <span class="hlt">preconditioning</span> group (diabetic IR + LIPC group, n = 6). Ischemic renal injury was induced by clamping the bilateral renal artery for 45 min. 4 h following ischemia, clearance protocols were applied to assess biochemical markers and histopathologically in rat kidneys. Results. The histomorphologic total cell injury scores of the nondiabetic sham group were significantly lower than diabetic sham, diabetic IR, and diabetic IR + LIPC groups. Diabetic IR group scores were not significantly different than the diabetic sham group. But diabetic IR + LIPC group scores were significantly higher than the diabetic sham and diabetic IR groups. Conclusion. Local ischemic <span class="hlt">preconditioning</span> does not reduce the risk of renal injury induced by ischemia/reperfusion in diabetic rat model. PMID:26925416</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2012AGUFM.A13A0213K','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2012AGUFM.A13A0213K"><span id="translatedtitle">Contribution of tropical cyclone for the <span class="hlt">preconditioning</span> of the Madden-Julian Oscillation during CINDY2011</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Kubota, H.; Yoneyama, K.; Hamada, J.</p> <p>2012-12-01</p> <p>During the international field experiment "Cooperative Indian Ocean experiment on intraseasonal variability in the Year 2011 (CINDY2011)", three Madden-Julian Oscillation (MJO) were generated over the Indian Ocean. In this study, the <span class="hlt">preconditioning</span> process of the third MJO is investigated. After the second active phase of MJO reached maritime continent in early December 2011, its eastward propagation became unclear. Different convections were activated over the maritime continent in mid-December and third MJO was generated in late December over the Indian Ocean. During the <span class="hlt">preconditioning</span> stage of the third MJO, westward propagating disturbances were observed from Sumatera Island to the central Indian Ocean and moistened the atmosphere. Convections over the Sumatera Island were activated from December 15th when the moist air mass reached from South China Sea. The origin of the moist air mass was tropical cyclone which was formed in South China Sea in December 10th. The high moisture associated with tropical cyclone activated the convection over Sumatera Island, promoted westward propagating disturbances, and acted a favorable environment for the <span class="hlt">preconditioning</span> of the MJO.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3839792','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3839792"><span id="translatedtitle">Acute bioenergetic intervention or pharmacological <span class="hlt">preconditioning</span> protects neuron against ischemic injury</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Liu, Shimin; Zhen, Gehua; Li, Rung-chi; Dor, Sylvain</p> <p>2013-01-01</p> <p>Although acute ischemic stroke has high mortality and morbidity rate but yet still has very limited treatment. In this study we have tested the concept of neuron protection by acute bioenergetic intervention or by pharmacological <span class="hlt">preconditioning</span> with natural antioxidants. Adenosine triphosphate (ATP), pentobarbital, and suramin were encapsulated in pH-sensitive liposomes and used as bioenergy stabilizer. We induced ATP depletion model by incubating cells with media added with ATP-depleting agents for 2 hours. Treatment with bioenergy stabilizer started 10-min post inducing of ATP-depletion. The acute treatment with bioenergy stabilizer significantly increased cell viability in neuro-2a cells. In searching for a pharmacological <span class="hlt">preconditioning</span> candidate for reducing ischemic injury, we tested cocoa-derived flavanols using bilateral common carotid artery occlusion (BCCAO). We pretreated mice with cocoa-derived flavanols (75 mg/kg) or water orally for 7 days and subjected mice for 12 minutes BCCAO. At 7 days post-ischemia, the number of surviving hippocampal CA1 neurons was significantly higher in the treated mice than in the water-treated controls. The protection from cocoa-derived flavanols was found associated with increased total antioxidant capacity in the brain. Our results indicate that for reducing acute ischemic injury bioenergetic intervention using advanced drug delivery tools is conceptually feasible, and for reducing reperfusion related secondary injury pharmacological <span class="hlt">preconditioning</span> may provide significant protection. PMID:24285991</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2013SPIE.9067E..1ZY','NASAADS'); return false;" href="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> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Yu, Qian; Li, Tong; Liu, JinZhuo; Zhang, Xuan; Yu, Yong</p> <p>2013-12-01</p> <p>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> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2002IJNAM..26..341L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2002IJNAM..26..341L"><span id="translatedtitle">Performance of Jacobi <span class="hlt">preconditioning</span> in Krylov subspace solution of finite element equations</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Lee, F.-H.; Phoon, K. K.; Lim, K. C.; Chan, S. H.</p> <p>2002-04-01</p> <p>This paper examines the performance of the Jacobi preconditioner when used with two Krylov subspace iterative methods. The number of iterations needed for convergence was shown to be different for drained, undrained and consolidation problems, even for similar condition number. The differences were due to differences in the eigenvalue distribution, which cannot be completely described by the condition number alone. For drained problems involving large stiffness ratios between different material zones, ill-conditioning is caused by these large stiffness ratios. Since Jacobi <span class="hlt">preconditioning</span> operates on degrees-of-freedom, it effectively homogenizes the different spatial sub-domains. The undrained problem, modelled as a nearly incompressible problem, is much more resistant to Jacobi <span class="hlt">preconditioning</span>, because its ill-conditioning arises from the large stiffness ratios between volumetric and distortional deformational modes, many of which involve the similar spatial domains or sub-domains. The consolidation problem has two sets of degrees-of-freedom, namely displacement and pore pressure. Some of the eigenvalues are displacement dominated whereas others are excess pore pressure dominated. Jacobi <span class="hlt">preconditioning</span> compresses the displacement-dominated eigenvalues in a similar manner as the drained problem, but pore-pressure-dominated eigenvalues are often over-scaled. Convergence can be accelerated if this over-scaling is recognized and corrected for.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4746276','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4746276"><span id="translatedtitle">Renal Ischemia/Reperfusion Injury in Diabetic Rats: The Role of Local Ischemic <span class="hlt">Preconditioning</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ozbilgin, Sule; Ozkardesler, Sevda; Akan, Mert; Boztas, Nilay; Ozbilgin, Mucahit; Ergur, Bekir Ugur; Derici, Serhan; Guneli, Mehmet Ensari; Meseri, Reci</p> <p>2016-01-01</p> <p>Background. The aim of this study was to evaluate the effects of local ischemic <span class="hlt">preconditioning</span> using biochemical markers and histopathologically in the diabetic rat renal IR injury model. Methods. DM was induced using streptozotocin. Rats were divided into four groups: Group I, nondiabetic sham group (n = 7), Group II, diabetic sham group (n = 6), Group III, diabetic IR group (diabetic IR group, n = 6), and Group IV, diabetic IR + local ischemic <span class="hlt">preconditioning</span> group (diabetic IR + LIPC group, n = 6). Ischemic renal injury was induced by clamping the bilateral renal artery for 45 min. 4 h following ischemia, clearance protocols were applied to assess biochemical markers and histopathologically in rat kidneys. Results. The histomorphologic total cell injury scores of the nondiabetic sham group were significantly lower than diabetic sham, diabetic IR, and diabetic IR + LIPC groups. Diabetic IR group scores were not significantly different than the diabetic sham group. But diabetic IR + LIPC group scores were significantly higher than the diabetic sham and diabetic IR groups. Conclusion. Local ischemic <span class="hlt">preconditioning</span> does not reduce the risk of renal injury induced by ischemia/reperfusion in diabetic rat model. PMID:26925416</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25712525','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25712525"><span id="translatedtitle">Zinc <span class="hlt">preconditioning</span> protects against neuronal apoptosis through the mitogen-activated protein kinase-mediated induction of heat shock protein 70.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lee, Jeong-Min; Lee, Jong-Min; Kim, Ki-Ryeong; Im, Hana; Kim, Yang-Hee</p> <p>2015-04-01</p> <p>During brain ischemic <span class="hlt">preconditioning</span> (PC), mild bursts of ischemia render neurons resistant to subsequent strong ischemic injuries. Previously, we reported that zinc plays a key role in PC-induced neuroprotection in vitro and in vivo. Zinc-triggered p75(NTR) induction transiently activates caspase-3, which cleaves poly(ADP-ribose) polymerase-1 (PARP-1). Subsequently, the PARP-1 over-activation-induced depletion of nicotinamide adenine dinucleotide (NAD(+))/adenosine triphosphate (ATP) after exposures to lethal doses of zinc or N-methyl-D-aspartate is significantly attenuated in cortical neuronal cultures. In the present study, zinc-mediated <span class="hlt">preconditioning</span> (Zn PC) reduced apoptotic neuronal death that was caused by N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), etoposide, or staurosporine in mouse cortical cells. We focused on heat shock protein 70 (HSP70) because NAD(+)/ATP depletion does not directly cause apoptosis, and HSP70 can inhibit the activation of caspase-9 or caspase-3 by <span class="hlt">preventing</span> apoptosome formation or cytochrome C release. Zn PC-mediated HSP70 induction was required for neuroprotection against neuronal apoptosis, and geldanamycin-induced HSP70 induction sufficiently blocked neuronal apoptotic cell death. Furthermore, Zn PC-mediated HSP70 induction was blocked by chemical inhibitors of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein kinase (MAPK) signaling, but not c-Jun N-terminal protein kinase. Similarly, neuroprotection by Zn PC against TPEN-induced apoptosis was almost completely reversed by the blockade of ERK or p38 MAPK signaling. Our findings suggest that the ERK- or p38 MAPK-mediated induction of HSP70 plays a key role in inhibiting caspase-3 activation during Zn PC. PMID:25712525</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_18 --> <div id="page_19" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="361"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4057195','PMC'); return false;" href="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> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Chen, Ying; Ying, Yi-Lin; Ma, Li; Song, Xiao-Qin; Wang, Lu; Chen, Er-Zhen; Mao, En-Qiang</p> <p>2014-01-01</p> <p>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. PMID:24927128</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4294405','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4294405"><span id="translatedtitle">Increased BDNF protein expression after ischemic or PKC epsilon <span class="hlt">preconditioning</span> promotes electrophysiologic changes that lead to neuroprotection</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Neumann, Jake T; Thompson, John W; Raval, Ami P; Cohan, Charles H; Koronowski, Kevin B; Perez-Pinzon, Miguel A</p> <p>2015-01-01</p> <p>Ischemic <span class="hlt">preconditioning</span> (IPC) via protein kinase C epsilon (PKC?) activation induces neuroprotection against lethal ischemia. Brain-derived neurotrophic factor (BDNF) is a pro-survival signaling molecule that modulates synaptic plasticity and neurogenesis. Interestingly, BDNF mRNA expression increases after IPC. In this study, we investigated whether IPC or pharmacological <span class="hlt">preconditioning</span> (PKC? activation) promoted BDNF-induced neuroprotection, if neuroprotection by IPC or PKC? activation altered neuronal excitability, and whether these changes were BDNF-mediated. We used both in vitro (hippocampal organotypic cultures and cortical neuronal-glial cocultures) and in vivo (acute hippocampal slices 48 hours after <span class="hlt">preconditioning</span>) models of IPC or PKC? activation. BDNF protein expression increased 24 to 48 hours after <span class="hlt">preconditioning</span>, where inhibition of the BDNF Trk receptors abolished neuroprotection against oxygen and glucose deprivation (OGD) in vitro. In addition, there was a significant decrease in neuronal firing frequency and increase in threshold potential 48 hours after <span class="hlt">preconditioning</span> in vivo, where this threshold modulation was dependent on BDNF activation of Trk receptors in excitatory cortical neurons. In addition, 48 hours after PKC? activation in vivo, the onset of anoxic depolarization during OGD was significantly delayed in hippocampal slices. Overall, these results suggest that after IPC or PKC? activation, there are BDNF-dependent electrophysiologic modifications that lead to neuroprotection. PMID:25370861</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4426742','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4426742"><span id="translatedtitle">CpG <span class="hlt">preconditioning</span> regulates miRNA expression that modulates genomic reprogramming associated with neuroprotection against ischemic injury</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Vartanian, Keri B; Mitchell, Hugh D; Stevens, Susan L; Conrad, Valerie K; McDermott, Jason E; Stenzel-Poore, Mary P</p> <p>2015-01-01</p> <p>Cytosine-phosphate-guanine (CpG) <span class="hlt">preconditioning</span> reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms underlying genomic reprogramming are incompletely understood. MicroRNAs (miRNAs) regulate gene expression; however, their role in modulating gene responses produced by CpG <span class="hlt">preconditioning</span> is unknown. We evaluated brain miRNA expression in response to CpG <span class="hlt">preconditioning</span> before and after stroke using microarray. Importantly, we have data from previous gene microarrays under the same conditions, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. CpG <span class="hlt">preconditioning</span> did not significantly alter miRNA expression before stroke, indicating that miRNA regulation is not critical for the initiation of <span class="hlt">preconditioning</span>-induced neuroprotection. However, after stroke, differentially regulated miRNAs between CpG- and saline-treated animals associated with the upregulation of several neuroprotective genes, implicating these miRNAs in genomic reprogramming that increases neuroprotection. Statistical analysis revealed that the miRNA targets were enriched in the gene population regulated in the setting of stroke, implying that miRNAs likely orchestrate this gene expression. These data suggest that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel neuroprotective processes that reduce damage. PMID:25388675</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4080061','PMC'); return false;" href="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> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Dharmani, Charan Kamal Kaur; Singh, Shamsher; Logani, Ajay; Shah, Naseem</p> <p>2014-01-01</p> <p>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 loading). Microleakage at occlusal and gingival margins was evaluated using methylene blue dye penetration method. Statistical analysis was done using Kruskal-wallis test and Mann-Whitney U test. Results: Microleakage at cementum margins was higher than at enamel margins in all the groups. <span class="hlt">Preconditioning</span> with AA resulted in increased micro leakage. Conclusion: AA as a <span class="hlt">preconditioning</span> agent was ineffective in producing superior tooth-restoration bonding. PMID:24995240</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26342941','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26342941"><span id="translatedtitle">Proteomic analysis of the hippocampus in nave and ischemic-<span class="hlt">preconditioned</span> rat.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Nakajima, Takayuki; Hata, Ryusuke; Kondo, Tomohiro; Takenaka, Shigeo</p> <p>2015-11-15</p> <p>The hippocampus exhibits regional differences in vulnerability to ischemia, wherein pyramidal cells in the CA1 region are vulnerable to ischemia while pyramidal cells in the CA3 region and granule cells in the dentate gyrus (DG) region are relatively ischemia resistant. However, pyramidal cells in the CA1 region reportedly exhibit ischemic tolerance following exposure to a brief non-lethal period of ischemia known as ischemic <span class="hlt">preconditioning</span>. In this study, we used proteomic analysis to examine the difference in protein expression between nave rat CA1 and CA3/DG regions, as well as the altered protein expression in the CA1 region after 3min of ischemic <span class="hlt">preconditioning</span>. Proteomic analysis identified ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), glutathione S-transferase ?5 (GST?5), glutamine synthetase (GS), and dynamin-1 as proteins with differential expression levels in nave CA1 and CA3/DG regions. The difference in expression levels of GST?5 and GS between these two regions was further confirmed by western blot. Our analysis also identified aconitase2, ?-tubulin, protein-l-isoaspartate O-methiltransferase (PIMT), and voltage-dependent anion channel 1 (VDCA1) as proteins with down-regulated expression levels in the CA1 region following 3min ischemic <span class="hlt">preconditioning</span>. The decrease in the expression of aconitase2 was also confirmed by western blot and immunohistochemical staining. The present results suggest that GST?5 and GS may be associated with ischemia-resistance in the CA3/DG region and that aconitase2 may play a part in the ischemic tolerance in the CA1 region. PMID:26342941</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/16407854','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/16407854"><span id="translatedtitle">CBF changes associated with focal ischemic <span class="hlt">preconditioning</span> in the spontaneously hypertensive rat.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhao, Liang; Nowak, Thaddeus S</p> <p>2006-09-01</p> <p>Experimental stroke models exhibit robust protection after prior <span class="hlt">preconditioning</span> (PC) insults. This study comprehensively examined cerebral blood flow (CBF) responses to permanent middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats <span class="hlt">preconditioned</span> by noninjurious transient focal ischemia, using [(14)C]iodoantipyrine autoradiography at varied occlusion intervals. <span class="hlt">Preconditioning</span> was produced by 10-min occlusion of the MCA and ipsilateral common carotid artery under halothane anesthesia. These vessels were permanently coagulated 24 h later in naïve, PC, and sham-operated rats. Infarct volumes were determined from hematoxylin-eosin-stained frozen sections after 1 or 3 days. Edema-corrected infarct volume was reduced from 127+/-21 in naïve rats to 101+/-31 and 52+/-28 mm(3) in sham and PC groups, respectively, at 1 day, with similar results at 3 days. All animals exhibited a consistent CBF threshold for infarction (approximately 30 mL/100 g/min). Tissue volumes below this threshold were identical in naïve and PC groups after 15-min occlusion. However, by 3 h the volume of ischemic cortex decreased in the PC group but remained unchanged in naïve rats, predicting final infarct volumes. Cerebral blood flow recovery was confirmed in brains of individual rats evaluated by repeated laser Doppler perfusion imaging during the same 3-h interval. Modest sham protection correlated with better-maintained global perfusion, detectable also in the contralateral cortex, apparently reflecting the PC effects of prior anesthesia. These results establish that timely reperfusion of penumbra, achieved by synergistic mechanisms, is a primary determinant of PC-induced protection in experimental stroke. PMID:16407854</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3994570','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3994570"><span id="translatedtitle">Females transplanted with ovaries subjected to hypoxic <span class="hlt">preconditioning</span> show impair of ovarian function</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2014-01-01</p> <p>Background Cryopreservation of the ovarian tissue has shown promising results. However, there remain controversial issues such as the short half-life of grafts. In this aspect, there are some evidences that <span class="hlt">preconditioning</span> the ovarian tissue before transplantation is beneficial. Objective To determine the effect of hypoxic <span class="hlt">preconditioning</span> in vitro on ovarian tissue prior to transplantation. Methods Eighteen female adult Wistar rats, were sorted into three experimental groups. Ovaries were maintained in DMEM low glucose serum free at 37°C with 5% CO2, at atmospheric oxigen concentration (normoxia) or 1% O2 (hypoxia) for 16 hours. Oxigen concentration was determined by injection of nitrogen in the incubator. Animals submitted to ovarian transplantation immediately after oophorectomy were the Control Group (C). After this, the ovaries were implanted in the retroperitoneum with nonabsorbable suture and animals evaluated for thirty days after transplantation. Beginning on postoperative (PO) day 11, a daily collection of vaginal smear was carried out. Analyses comprised morphological, morphometric (counting ovarian follicles and corpora lutea) and immunohistochemistry for cleaved caspase-3 (apoptosis). Results In normoxia and control groups all animals recovered their estrous cycles, while in the hypoxia group, two animals did not ovulate but, among those which did, resumption took longer than in the other groups (p < 0.05). The number of ovarian follicles and corpora lutea decreased significantly in the hypoxia group when compared to the other two groups (p < 0.001) and apoptosis was increased in the few ovarian follicles which remained viable (p < 0.001). Conclusion The hypoxic <span class="hlt">preconditioning</span> in vitro was not beneficial to the graft and worsened their viability, compromising its functionality or delaying the return of this. PMID:24655551</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19930005696','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19930005696"><span id="translatedtitle"><span class="hlt">Preconditioned</span> conjugate-gradient methods for low-speed flow calculations</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Ajmani, Kumud; Ng, Wing-Fai; Liou, Meng-Sing</p> <p>1993-01-01</p> <p>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 is 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. <span class="hlt">Preconditioning</span> techniques are used with the new solver to enhance the stability and 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 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 <span class="hlt">preconditioned</span> 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 <span class="hlt">preconditioned</span> solver, when compared with the LGSR solver.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4612991','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4612991"><span id="translatedtitle">Effects of sevoflurane <span class="hlt">preconditioning</span> on lung injury during one lung ventilation</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Feng, Hao; Wang, Gong-Ming; Qiao, Yong; Zhao, Xin; Liu, Dong-Yi; Ding, Yin-Lu; Liu, Zhong-Hao</p> <p>2015-01-01</p> <p>Background: To study the lung protective effects of heme oxygenase-1 (HO-1) expression and sevoflurane <span class="hlt">preconditioning</span> in patients with lobectomy. Methods: 30 patients receiving lobectomy were divided into two groups: propofol intravenous anesthesia group (Pro group) and sevoflurane <span class="hlt">preconditioning</span> group (Sev group). In Pro group, propofol was used for intravenous anesthetic. In Sev group, 1%-2% sevoflurane was used during anesthesia induction to one lung ventilation (OLV). Venous blood was taken before OLV (T1), at the end of OLV (T2) and at 30 min after lung ventilation (T3) to measure the concentration of serum malondialdehyde (MDA) in two groups. HO-1 protein and mRNA expression in resected lung tissue were measured with PT-PCR and Western blot technique. Oxygenation index was detected at 2 hours after operation. Results: HO-1 protein (2.88±0.23 ng/ml) and mRNA expression in Sev group were significantly higher compared to protein (1.89±0.12 ng/ml)and mRNA expression in Pro group (P<0.05). Difference was not found in MDA concentration at T1 compared to T2 (P>0.05), however, at T3, MDA concentration was higher in Pro group than that in Sev group (P<0.05). oxygenation index in Sev group was 380±67 mmHg, which was significantly different from that in Pro group (290±56 mmHg) (P<0.05). Conclusion: Sevoflurane <span class="hlt">preconditioning</span> can reduce oxidative stress injury induced by OLV and protect lung tissue by increasing HO-1 expression in lung tissue. PMID:26550306</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015JCoPh.303..295X','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015JCoPh.303..295X"><span id="translatedtitle">Effective matrix-free <span class="hlt">preconditioning</span> for the augmented immersed interface method</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Xia, Jianlin; Li, Zhilin; Ye, Xin</p> <p>2015-12-01</p> <p>We present effective and efficient matrix-free <span class="hlt">preconditioning</span> techniques for the augmented immersed interface method (AIIM). AIIM has been developed recently and is shown to be very effective for interface problems and problems on irregular domains. GMRES is often used to solve for the augmented variable(s) associated with a Schur complement A in AIIM that is defined along the interface or the irregular boundary. The efficiency of AIIM relies on how quickly the system for A can be solved. For some applications, there are substantial difficulties involved, such as the slow convergence of GMRES (particularly for free boundary and moving interface problems), and the inconvenience in finding a preconditioner (due to the situation that only the products of A and vectors are available). Here, we propose matrix-free structured <span class="hlt">preconditioning</span> techniques for AIIM via adaptive randomized sampling, using only the products of A and vectors to construct a hierarchically semiseparable matrix approximation to A. Several improvements over existing schemes are shown so as to enhance the efficiency and also avoid potential instability. The significance of the preconditioners includes: (1) they do not require the entries of A or the multiplication of AT with vectors; (2) constructing the preconditioners needs only O (log ? N) matrix-vector products and O (N) storage, where N is the size of A; (3) applying the preconditioners needs only O (N) flops; (4) they are very flexible and do not require any a priori knowledge of the structure of A. The preconditioners are observed to significantly accelerate the convergence of GMRES, with heuristical justifications of the effectiveness. Comprehensive tests on several important applications are provided, such as Navier-Stokes equations on irregular domains with traction boundary conditions, interface problems in incompressible flows, mixed boundary problems, and free boundary problems. The <span class="hlt">preconditioning</span> techniques are also useful for several other problems and methods.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4556686','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4556686"><span id="translatedtitle">Ischemic <span class="hlt">Preconditioning</span> Mediates Neuroprotection against Ischemia in Mouse Hippocampal CA1 Neurons by Inducing Autophagy</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zhang, Xuebin; Huang, Huiling; Wang, Jin; Wang, Yajing; Tong, Xiaoguang; Wang, Jinhuan; Wu, Jialing</p> <p>2015-01-01</p> <p>The hippocampal CA1 region is sensitive to hypoxic and ischemic injury but can be protected by ischemic <span class="hlt">preconditioning</span> (IPC). However, the mechanism through which IPC protects hippocampal CA1 neurons is still under investigation. Additionally, the role of autophagy in determining the fate of hippocampal neurons is unclear. Here, we examined whether IPC induced autophagy to alleviate hippocampal CA1 neuronal death in vitro and in vivo with oxygen glucose deprivation (OGD) and bilateral carotid artery occlusion (BCCAO) models. Survival of hippocampal neurons increased from 51.5% ± 6.3% in the non-IPC group (55 min of OGD) to 77.3% ± 7.9% in the IPC group (15 min of OGD, followed by 55 min of OGD 24 h later). The number of hippocampal CA1 layer neurons increased from 182 ± 26 cells/mm2 in the non-IPC group (20 min of BCCAO) to 278 ± 55 cells/mm2 in the IPC group (1 min × 3 BCCAO, followed by 20 min of BCCAO 24 h later). Akt phosphorylation and microtubule-associated protein light chain 3 (LC3)-II/LC3-I expression were increased in the <span class="hlt">preconditioning</span> group. Moreover, the protective effects of IPC were abolished only by inhibiting the activity of autophagy, but not by blocking the activation of Akt in vitro. Using in vivo experiments, we found that LC3 expression was upregulated, accompanied by an increase in neuronal survival in hippocampal CA1 neurons in the <span class="hlt">preconditioning</span> group. The neuroprotective effects of IPC on hippocampal CA1 neurons were completely inhibited by treatment with 3-MA. In contrast, hippocampal CA3 neurons did not show changes in autophagic activity or beneficial effects of IPC. These data suggested that IPC may attenuate ischemic injury in hippocampal CA1 neurons through induction of Akt-independent autophagy. PMID:26325184</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/8523449','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/8523449"><span id="translatedtitle">Transient inhibition of glucose uptake mimics ischemic <span class="hlt">preconditioning</span> by salvaging ischemic myocardium in the rabbit heart.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Goto, M; Tsuchida, A; Liu, Y; Cohen, M V; Downey, J M</p> <p>1995-09-01</p> <p>The aim of this study was to test whether transient inhibition of glucose uptake could <span class="hlt">precondition</span> the rabbit heart. Rabbit hearts experienced 30 min regional ischemia followed by either 120 min (isolated heart protocol) or 180 min (in situ protocol) reperfusion. Infarct size was determined by tetrazolium staining. In isolated heart experiments, 15 min perfusion with glucose-free Krebs buffer starting 30 min prior to ischemia significantly limited infarct size to 9.9 +/- 2.6% of the risk zone as compared with 29.4 +/- 1.7% infarction in controls. This protection could be blocked (30.8 +/- 3.4%) by polymyxin B (50 microM), a protein kinase C inhibitor, but not by 8-(p-sulfophenyl)theophylline, an adenosine receptor inhibitor, suggesting the mechanism was similar to that of ischemic <span class="hlt">preconditioning</span> but without involvement of adenosine receptors. Pyruvate and acetate inhibit glucose uptake without incurring a metabolic deficit. When 20 mM pyruvate or 1 mM acetate was added to the glucose-containing buffer for 15 min prior to ischemia, protection was evident (12.0 +/- 3.0% and 10.0 +/- 3.7% infarction, respectively). However, when acetate (1 mM) was present in the perfusate throughout the experiment, neither omission of glucose nor addition of pyruvate caused protection (26.1 +/- 2.2% and 28.9 +/- 4.7% infarction, respectively). Furthermore, when in situ hearts which preferably utilize lipid substrates were treated with pyruvate (2 g/kg i.v. 20 min before ischemia), infarct size was 40.3 +/- 3.0%, which did not differ from that in untreated hearts (38.6 +/- 3.2%). Hence transient inhibition of glucose uptake can <span class="hlt">precondition</span> the heart, but only if other substrates which are utilized in preference to glucose are absent. PMID:8523449</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4567080','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4567080"><span id="translatedtitle">Simultaneous optical flow and source estimation: Spacetime discretization and <span class="hlt">preconditioning</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Andreev, R.; Scherzer, O.; Zulehner, W.</p> <p>2015-01-01</p> <p>We consider the simultaneous estimation of an optical flow field and an illumination source term in a movie sequence. The particular optical flow equation is obtained by assuming that the image intensity is a conserved quantity up to possible sources and sinks which represent varying illumination. We formulate this problem as an energy minimization problem and propose a spacetime simultaneous discretization for the optimality system in saddle-point form. We investigate a <span class="hlt">preconditioning</span> strategy that renders the discrete system well-conditioned uniformly in the discretization resolution. Numerical experiments complement the theory. PMID:26435561</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/servlets/purl/962335','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/servlets/purl/962335"><span id="translatedtitle">Non-<span class="hlt">preconditioned</span> conjugate gradient on cell and FPCA-based hybrid supercomputer nodes</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Dubois, David H; Dubois, Andrew J; Boorman, Thomas M; Connor, Carolyn M</p> <p>2009-03-10</p> <p>This work presents a detailed implementation of a double precision, Non-<span class="hlt">Preconditioned</span>, Conjugate Gradient algorithm on a Roadrunner heterogeneous supercomputer node. These nodes utilize the Cell Broadband Engine Architecture{trademark} in conjunction with x86 Opteron{trademark} processors from AMD. We implement a common Conjugate Gradient algorithm, on a variety of systems, to compare and contrast performance. Implementation results are presented for the Roadrunner hybrid supercomputer, SRC Computers, Inc. MAPStation SRC-6 FPGA enhanced hybrid supercomputer, and AMD Opteron only. In all hybrid implementations wall clock time is measured, including all transfer overhead and compute timings.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19980000320','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19980000320"><span id="translatedtitle">Graph Embedding Techniques for Bounding Condition Numbers of Incomplete Factor <span class="hlt">Preconditioning</span></span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Guattery, Stephen</p> <p>1997-01-01</p> <p>We extend graph embedding techniques for bounding the spectral condition number of <span class="hlt">preconditioned</span> systems involving symmetric, irreducibly diagonally dominant M-matrices to systems where the preconditioner is not diagonally dominant. In particular, this allows us to bound the spectral condition number when the preconditioner is based on an incomplete factorization. We provide a review of previous techniques, describe our extension, and give examples both of a bound for a model problem, and of ways in which our techniques give intuitive way of looking at incomplete factor preconditioners.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009AGUFMDI22A..07M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009AGUFMDI22A..07M"><span id="translatedtitle">Efficient <span class="hlt">preconditioning</span> strategies for finite element discretisations of variable viscosity Stokes flow. (Invited)</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>May, D.</p> <p>2009-12-01</p> <p>Many geodynamic processes such as mantle convection, slab subduction and the deformation of the lithoshpere may be represented by the evolution of a very viscous, incompressible fluid - i.e. Stokes flow. For geodynamic applications, the flow equations are complicated through the introduction of a viscosity which may vary spatially. Such variations may arise due to simply having different material layers, or because the viscosity exhibits a very strong temperature dependence and or a stress/strain-rate dependence. It should be emphasized that in such applications, the ratio between the largest and smallest viscosity values in the problem domain may vary from O(10) to O(10^20). In terms of computation, the solution of the discrete Stokes flow problem is the most time consuming component of many geodynamic simulations. Combined with the ubiquitous nature of variable viscosity Stokes flow, numerous studies relevant to geodynamics have been conducted to develop efficient solution techniques for this problem. Whilst the ever increasing availability and affordability of high performance computers continues to motivate researchers in computational geodynamics to perform higher resolution numerical simulations, the efficiency of such codes crucially depends on solution methods adopted. To harness the full potential of these resources to solve the discrete Stokes flow problem, Krylov methods combined with multilevel preconditioners are advocated. Effective <span class="hlt">preconditioning</span> is the most important aspect of the approach. The main challenge is to devise preconditioners which i) yield convergence rates which are independent of the grid resolution and are independent of the structure of the viscosity field, ii) yield solution times which scale linearly with respect to the number of unknowns and iii) exhibit good overall parallel scalability on large distributed memory clusters. In this talk I will outline a number of scalable <span class="hlt">preconditioning</span> approaches that have successfully been used to solve variable viscosity Stokes flow. With a particular emphasis on finite element discretisations, several <span class="hlt">preconditioning</span> strategies will be described which are suitable for classical mixed finite elements and the polynomial pressure stabilised discretisations. The preconditioners discussed utilise approximate commutator methods and block component splittings. These preconditioners are composed from simpler sub-problems for which efficient, scalable and robust mutilevel methods exist - hence collectively the entire <span class="hlt">preconditioning</span> approach is optimal. A collection of idealised problems characterising the structure and magnitude of viscosity variations typical of geodynamic problems are used to demonstrate the effectiveness of the proposed preconditioners.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015CMMPh..55.2080V','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015CMMPh..55.2080V"><span id="translatedtitle"><span class="hlt">Preconditioning</span> of Navier-Stokes equations in the computation of free convective flows</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Volkov, K. N.; Emel'yanov, V. N.; Karpenko, A. G.</p> <p>2015-12-01</p> <p>Specific features of simulation of free convective flows of viscous compressible fluids based on the full Navier-Stokes equations are considered. The finite volume discretization of the Navier-Stokes equations in the case of low Mach numbers is discussed. To stabilize the numerical computations, <span class="hlt">preconditioning</span>, which is based on the use of physical variables, and the dual time stepping method, which introduces internal iterations on pseudotime, are employed. The capabilities of the proposed approach are demonstrated on the example of simulation of free convection in a gap between coaxial cylinders.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3697576','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3697576"><span id="translatedtitle"><span class="hlt">Preconditioning</span> with Cations Increases the Attachment of Anoxybacillus flavithermus and Geobacillus Species to Stainless Steel</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Flint, Steve; Palmer, Jon; Brooks, John; Lindsay, Denise</p> <p>2013-01-01</p> <p><span class="hlt">Preconditioning</span> of Anoxybacillus flavithermus E16 and Geobacillus sp. strain F75 with cations prior to attachment often significantly increased (P ≤ 0.05) the number of viable cells that attached to stainless steel (by up to 1.5 log CFU/cm2) compared with unconditioned bacteria. It is proposed that the transition of A. flavithermus and Geobacillus spp. from milk formulations to stainless steel product contact surfaces in milk powder manufacturing plants is mediated predominantly by bacterial physiological factors (e.g., surface-exposed adhesins) rather than the concentrations of cations in milk formulations surrounding bacteria. PMID:23645192</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/servlets/purl/956510','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/servlets/purl/956510"><span id="translatedtitle">Non-<span class="hlt">preconditioned</span> conjugate gradient on cell and FPGA based hybrid supercomputer nodes</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Dubois, David H; Dubois, Andrew J; Boorman, Thomas M; Connor, Carolyn M</p> <p>2009-01-01</p> <p>This work presents a detailed implementation of a double precision, non-<span class="hlt">preconditioned</span>, Conjugate Gradient algorithm on a Roadrunner heterogeneous supercomputer node. These nodes utilize the Cell Broadband Engine Architecture{sup TM} in conjunction with x86 Opteron{sup TM} processors from AMD. We implement a common Conjugate Gradient algorithm, on a variety of systems, to compare and contrast performance. Implementation results are presented for the Roadrunner hybrid supercomputer, SRC Computers, Inc. MAPStation SRC-6 FPGA enhanced hybrid supercomputer, and AMD Opteron only. In all hybrid implementations wall clock time is measured, including all transfer overhead and compute timings.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4625514','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4625514"><span id="translatedtitle">Cerebrospinal fluid from rats given hypoxic <span class="hlt">preconditioning</span> protects neurons from oxygen-glucose deprivation-induced injury</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zhang, Yan-bo; Guo, Zheng-dong; Li, Mei-yi; Li, Si-jie; Niu, Jing-zhong; Yang, Ming-feng; Ji, Xun-ming; Lv, Guo-wei</p> <p>2015-01-01</p> <p>Hypoxic <span class="hlt">preconditioning</span> activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic <span class="hlt">preconditioning</span> reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic <span class="hlt">preconditioning</span> protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats. PMID:26604909</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_19 --> <div id="page_20" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="381"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2270833','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2270833"><span id="translatedtitle">Analysis of the retinal gene expression profile after hypoxic <span class="hlt">preconditioning</span> identifies candidate genes for neuroprotection</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Thiersch, Markus; Raffelsberger, Wolfgang; Frigg, Rico; Samardzija, Marijana; Wenzel, Andreas; Poch, Olivier; Grimm, Christian</p> <p>2008-01-01</p> <p>Background Retinal degeneration is a main cause of blindness in humans. Neuroprotective therapies may be used to rescue retinal cells and preserve vision. Hypoxic <span class="hlt">preconditioning</span> 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 retina using microarrays and real-time PCR. Results Hypoxic exposure induced a marked alteration in the retinal transcriptome with significantly different expression levels of 431 genes immediately after hypoxic exposure. The normal expression profile was restored within 16 hours of reoxygenation. Among the differentially regulated genes, several candidates for neuroprotection were identified like metallothionein-1 and -2, the HIF-1 target gene adrenomedullin and the gene encoding the antioxidative and cytoprotective enzyme paraoxonase 1 which was previously not known to be a hypoxia responsive gene in the retina. The strongly upregulated cyclin dependent kinase inhibitor p21 was excluded from being essential for neuroprotection. Conclusion Our data suggest that neuroprotection after hypoxic <span class="hlt">preconditioning</span> is the result of the differential expression of a multitude of genes which may act in concert to protect visual cells against a toxic insult. PMID:18261226</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4404827','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4404827"><span id="translatedtitle">Role of MicroRNAs in innate neuroprotection mechanisms due to <span class="hlt">preconditioning</span> of the brain</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Jimenez-Mateos, Eva M.</p> <p>2015-01-01</p> <p>Insults to the brain that are sub-threshold for damage activate endogenous protective pathways, which can temporarily protect the brain against a subsequent harmful episode. This mechanism has been named as tolerance and its protective effects have been shown in experimental models of ischemia and epilepsy. The <span class="hlt">preconditioning</span>-stimulus can be a short period of ischemia or mild seizures induced by low doses of convulsant drugs. Gene-array profiling has shown that both ischemic and epileptic tolerance feature large-scale gene down-regulation but the mechanism are unknown. MicroRNAs are a class of small non-coding RNAs of ~2022 nucleotides length which regulate gene expression at a post-transcriptional level via mRNA degradation or inhibition of protein translation. MicroRNAs have been shown to be regulated after non-harmful and harmful stimuli in the brain and to contribute to neuroprotective mechanisms. This review focuses on the role of microRNAs in the development of tolerance following ischemic or epileptic <span class="hlt">preconditioning</span>. PMID:25954143</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4744640','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4744640"><span id="translatedtitle">Ameliorative Effect of Recombinant Human Erythropoietin and Ischemic <span class="hlt">Preconditioning</span> on Renal Ischemia Reperfusion Injury in Rats</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Elshiekh, Mohammed; Kadkhodaee, Mehri; Seifi, Behjat; Ranjbaran, Mina; Ahghari, Parisa</p> <p>2015-01-01</p> <p>Background: Ischemia-reperfusion (IR) injury is one of the most common causes of renal dysfunction. There is increasing evidence about the role of the reactive oxygen species (ROS) in these injuries and endogenous antioxidants seem to have an important role in decreasing the renal tissue injury. Objectives: The aim of this study was to compare the effect of recombinant human erythropoietin (EPO) and ischemic <span class="hlt">preconditioning</span> (IPC) on renal IR injury. Materials and Methods: Twenty four male Wistar rats were allocated into four experimental groups: sham-operated, IR, EPO + IR, and IPC + IR. Rats were underwent 50 minutes bilateral ischemia followed by 24 hours reperfusion. Erythropoietin (5000 IU/kg, i.p) was administered 30 minutes before onset of ischemia. Ischemic <span class="hlt">preconditioning</span> was performed by three cycles of 3 minutes ischemia followed by 3 minutes reperfusion. Plasma concentrations of urea and creatinine were measured. Kidney samples were taken for reactive oxidative species (ROS) measurement including superoxide dismutase (SOD) activity, glutathione (GSH) contents, and malondialdehyde (MDA) levels. Results: Compared to the sham group, IR led to renal dysfunction as evidenced by significantly higher plasma urea and creatinine. Treatment with EPO or IPC decreased urea, creatinine, and renal MDA levels and increased SOD activity and GSH contents in the kidney. Conclusions: Pretreatment with EPO and application of IPC significantly ameliorated the renal injury induced by bilateral renal IR. However, both treatments attenuated renal dysfunction and oxidative stress in kidney tissues. There were no significant differences between pretreatment with EPO or application of IPC. PMID:26866008</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3731649','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3731649"><span id="translatedtitle">Endoplasmic reticulum stress <span class="hlt">preconditioning</span> attenuates methylmercury-induced cellular damage by inducing favorable stress responses</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Usuki, Fusako; Fujimura, Masatake; Yamashita, Akio</p> <p>2013-01-01</p> <p>We demonstrate that methylmercury (MeHg)-susceptible cells <span class="hlt">preconditioned</span> with an inhibitor of endoplasmic reticulum (ER) Ca2+-ATPase, thapsigargin, showed resistance to MeHg cytotoxicity through favorable stress responses, which included phosphorylation of eukaryotic initiation factor 2 alpha (Eif2α), accumulation of activating transcription factor 4 (Atf4), upregulation of stress-related proteins, and activation of extracellular signal regulated kinase pathway. In addition, ER stress <span class="hlt">preconditioning</span> induced suppression of nonsense-mediated mRNA decay (NMD) mainly through the phospho-Eif2α-mediated general suppression of translation initiation and possible combined effects of decreased several NMD components expression. Atf4 accumulation was not mediated by NMD inhibition but translation inhibition of its upstream open reading frame (uORF) and translation facilitation of its protein-coding ORF by the phospho-Eif2α. These results suggested that ER stress plays an important role in MeHg cytotoxicity and that the modulation of ER stress has therapeutic potential to attenuate MeHg cytotoxicity, the underlying mechanism being the induction of integrated stress responses. PMID:23907635</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3990011','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3990011"><span id="translatedtitle">Remote ischemic <span class="hlt">preconditioning</span> to reduce contrast-induced nephropathy: study protocol for a randomized controlled trial</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2014-01-01</p> <p>Background Despite the increasing use of pre- and posthydration protocols and low-osmolar instead of high-osmolar iodine-containing contrast media, the incidence of contrast-induced nephropathy (CIN) is still significant. There is evidence that contrast media cause ischemia-reperfusion injury of the medulla. Remote ischemic <span class="hlt">preconditioning</span> (RIPC) is a non-invasive, safe, and low-cost method to reduce ischemia-reperfusion injury. Methods The RIPCIN study is a multicenter, single-blinded, randomized controlled trial in which 76 patients at risk of CIN will receive standard hydration combined with RIPC or hydration with sham <span class="hlt">preconditioning</span>. RIPC will be applied by four cycles of 5min ischemia and 5min reperfusion of the forearm by inflating a blood pressure cuff at 50mmHg above the actual systolic pressure. The primary outcome measure will be the change in serum creatinine from baseline to 48 to 72h after contrast administration. Discussion A recent pilot study reported that RIPC reduced the incidence of CIN after coronary angioplasty. The unusual high incidence of CIN in this study is of concern and limits its generalizability. Therefore, we propose a randomized controlled trial to study whether RIPC reduces contrast-induced kidney injury in patients at risk for CIN according to the Dutch guidelines. Trial registration Current Controlled Trials ISRCTN76496973 PMID:24721127</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26509376','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26509376"><span id="translatedtitle">Myths and Facts About the Effects of Ischemic <span class="hlt">Preconditioning</span> on Performance.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Marocolo, M; da Mota, G R; Simim, M A M; Appell Coriolano, H-J</p> <p>2016-02-01</p> <p>Although numerous studies have demonstrated the effect of ischemic <span class="hlt">preconditioning</span> (IPC) in clinical application, the effectiveness of this procedure on performance and physiological variables is still debatable. Therefore a systematic review was performed, including a meta-analysis and evaluation of the quality of the papers that addressed this scope. The electronic databases of the National Library of Medicine (PubMed), Google Scholar (using [advanced search], [all fields]) and other online journals were searched, for the following descriptors: a) "ischemic <span class="hlt">preconditioning</span>"; b) "blood flow" and "hyperemia"; c) "blood flow occlusion," combined with "exercise performance", "athletes", "exercise" and "performance". Relevant studies were included, if they conformed to strict pre-formulated criteria, excluding systematic review articles, meta-analyses and studies with only animals or non-healthy subjects. The 20 studies included had high quality scores (87%). The majority of the studies lacked statistical significance (P<0.05) for both performance and physiological variables when comparing IPC, placebo and control groups. Most studies showed that IPC has no significant influence on performance. The few studies with significant differences mainly described an improvement only in performance without altered physiological parameters. Therefore, the influence of IPC on performance is still unclear and physiologically highly debatable. PMID:26509376</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26254913','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26254913"><span id="translatedtitle">The Protective Effect of Remote Renal <span class="hlt">Preconditioning</span> Against Hippocampal Ischemia Reperfusion Injury: Role of KATP Channels.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mehrjerdi, Fatemeh Zare; Aboutaleb, Nahid; Pazoki-Toroudi, Hamidreza; Soleimani, Mansoureh; Ajami, Marjan; Khaksari, Mehdi; Safari, Fatemeh; Habibey, Rouhollah</p> <p>2015-12-01</p> <p>Remote ischemic <span class="hlt">preconditioning</span> (RIPC), which consists of several brief ischemia/reperfusion applied at the remote site of lethal ischemia reperfusion, can, through activating different mechanisms, increase the ability of the body's endogenous protection against prolonged ischemia/reperfusion. Recent studies have shown that RIPC has neuroprotective effects, but its mechanisms are not well elucidated. The present study aimed to determine whether activation of KATP channels in remote renal <span class="hlt">preconditioning</span> decreases hippocampus damage induced by global cerebral ischemia. RIPC was induced by ischemia of the left renal artery (IPC); 24h later, global cerebral ischemia reperfusion (IR) was induced by common carotid arteries occlusion. 5hydroxydecanoate (5HD) and glibenclamide (Gli) were injected before of IPC. The levels of malondialdehyde (MDA) and catalase (CAT) activity were assessed in hippocampus. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was assessed to detect apoptotic cells in hippocampus. RIPC inhibited apoptosis by decreasing positive TUNEL cells (P?<?0.05). KATP channels blocking with 5HD and Gli markedly increased apoptosis in hippocampal cells in RIPC group (P?<?0.001). RIPC decreased MDA level and increased CAT activity in ischemic hippocampus (P?<?0.01). Also, 5HD and Gli inhibited the effect of RIPC on MDA level and CAT activity (P?<?0.05). The present study shows that RIPC can effectively attenuate programmed cell death, increase activity of CAT, and reduce MDA levels. Blocking of KATP channels inhibited the protective effects of RIPC. PMID:26254913</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4637611','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4637611"><span id="translatedtitle">Platelet-derived microvesicles are involved in cardio-protective effects of remote <span class="hlt">preconditioning</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ma, Fang; Liu, Hengchao; Shen, Yong; Zhang, Yingjie; Pan, Shaojun</p> <p>2015-01-01</p> <p>The ischemia-protective mechanism of remote <span class="hlt">precondition</span> has been a mystery for a long time. Little was known about details of the inter-organ cardio-protective. Microvesicles, also known as microparticles (MPs), are small membrane-vesicles budding from the plasma membrane of cell. Recent studies have indicated MPs to be an important messenger in various biological processes. Our research mainly examined the hypothesis that remote ischemic conditioning can attenuate heart infarction in a rat after they were subjected to 30 min ischemia and 180 min reperfusion (I/R) by MPs. MPs were extracted from three groups of rat: 1) healthy rats, 2) healthy rats that underwent hindlimb ischemia-reperfusion <span class="hlt">preconditioning</span> (RIPC) immediately, 3) healthy rats that underwent RIPC in 6 hours. Isolated MPs were transfused into rats that had undergone I/R without RIPC. The transfusion of MPs from rats that underwent RIPC immediately resulted in an increase in platelet-derived MPs in blood and reduction in infarction size, confirmed by 2-3-5-triphenyltetrazolium chloride staining. We further observed the contractile function in hearts after they were subjected to different treatments. However, no significant difference was observed in transfusion of MPs from rats that underwent RIPC in 6 hours. RIPC induces an increase in MPs, and platelet-derived MPs may confer at least part of the remote protective effect against cardiac ischemic-reperfusion injury. PMID:26617796</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/servlets/purl/936450','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/servlets/purl/936450"><span id="translatedtitle">Overlapping Schwarz for Nonlinear Problems. An Element Agglomeration Nonlinear Additive Schwarz <span class="hlt">Preconditioned</span> Newton Method for Unstructured Finite Element Problems</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Cai, X C; Marcinkowski, L; Vassilevski, P S</p> <p>2005-02-10</p> <p>This paper extends previous results on nonlinear Schwarz <span class="hlt">preconditioning</span> ([4]) to unstructured finite element elliptic problems exploiting now nonlocal (but small) subspaces. The non-local finite element subspaces are associated with subdomains obtained from a non-overlapping element partitioning of the original set of elements and are coarse outside the prescribed element subdomain. The coarsening is based on a modification of the agglomeration based AMGe method proposed in [8]. Then, the algebraic construction from [9] of the corresponding non-linear finite element subproblems is applied to generate the subspace based nonlinear preconditioner. The overall nonlinearly <span class="hlt">preconditioned</span> problem is solved by an inexact Newton method. Numerical illustration is also provided.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4780766','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4780766"><span id="translatedtitle">Hormesis in Cholestatic Liver Disease; <span class="hlt">Preconditioning</span> with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Verhaag, Esther M.; Buist-Homan, Manon; Koehorst, Martijn; Groen, Albert K.; Moshage, Han; Faber, Klaas Nico</p> <p>2016-01-01</p> <p>Introduction Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis. Aim To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions. Methods HepG2.rNtcp cells were <span class="hlt">preconditioned</span> (24 h) with sub-apoptotic concentrations (0.1–50 μM) of various bile acids, the superoxide donor menadione, TNF-α or the Farsenoid X Receptor agonist GW4064, followed by a challenge with the apoptosis-inducing bile acid glycochenodeoxycholic acid (GCDCA; 200 μM for 4 h), menadione (50 μM, 6 h) or cytokine mixture (CM; 6 h). Levels of apoptotic and necrotic cell death, mRNA expression of the bile salt export pump (ABCB11) and bile acid sensors, as well as intracellular GCDCA levels were analyzed. Results <span class="hlt">Preconditioning</span> with the pro-apoptotic bile acids GCDCA, taurocholic acid, or the protective bile acids (tauro)ursodeoxycholic acid reduced GCDCA-induced caspase-3/7 activity in HepG2.rNtcp cells. Bile acid <span class="hlt">preconditioning</span> did not induce significant levels of necrosis in GCDCA-challenged HepG2.rNtcp cells. In contrast, <span class="hlt">preconditioning</span> with cholic acid, menadione or TNF-α potentiated GCDCA-induced apoptosis. GCDCA <span class="hlt">preconditioning</span> specifically reduced GCDCA-induced cell death and not CM- or menadione-induced apoptosis. The hormetic effect of GCDCA <span class="hlt">preconditioning</span> was concentration- and time-dependent. GCDCA-, CDCA- and GW4064- <span class="hlt">preconditioning</span> enhanced ABCB11 mRNA levels, but in contrast to the bile acids, GW4064 did not significantly reduce GCDCA-induced caspase-3/7 activity. The GCDCA challenge strongly increased intracellular levels of this bile acid, which was not lowered by GCDCA-<span class="hlt">preconditioning</span>. Conclusions Sub-toxic concentrations of bile acids in the range that occur under normal physiological conditions protect HepG2.rNtcp cells against GCDCA-induced apoptosis, which is independent of FXR-controlled changes in bile acid transport. PMID:26950211</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/biblio/22215952','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/biblio/22215952"><span id="translatedtitle">Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia <span class="hlt">preconditioning</span> with cobalt chloride</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju</p> <p>2012-11-01</p> <p>High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl{sub 2}), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia <span class="hlt">preconditioning</span> by CoCl{sub 2} supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl{sub 2} supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia <span class="hlt">preconditioning</span> by CoCl{sub 2} supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia <span class="hlt">preconditioning</span>. -- Highlights: ► We supplemented rats with CoCl{sub 2} for 15 days along with training. ► CoCl{sub 2} supplementation augmented endurance performance and aerobic respiration. ► It increased glucose uptake and metabolism in muscle. ► It enhanced mitochondrial biogenesis in red gastrocnemius muscle.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/22100641','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/22100641"><span id="translatedtitle">Age-related loss of cardiac <span class="hlt">preconditioning</span>: impact of protein kinase A.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Huhn, Ragnar; Weber, Nina C; Preckel, Benedikt; Schlack, Wolfgang; Bauer, Inge; Hollmann, Markus W; Heinen, André</p> <p>2012-01-01</p> <p>Helium induces <span class="hlt">preconditioning</span> (He-PC) by mitochondrial calcium-sensitive potassium (mK(Ca)) channel-activation, but this effect is lost in the aged myocardium. Both, the upstream signalling pathway of He-PC and the underlying mechanisms for an age-related loss of <span class="hlt">preconditioning</span> are unknown. A possible candidate as upstream regulator of mK(Ca) channels is protein kinase A (PKA). We investigated whether 1) regulation of PKA is involved in He-PC and 2) regulation of PKA is age-dependent. Young (2-3 months) and aged (22-24 months) Wistar rats were randomised to eight groups (each n=8). All animals underwent 25 min regional myocardial ischemia and 120 min reperfusion. Control (Con, Age Con) animals were not further treated. Young rats inhaled 70% helium for 3×5 min (He-PC). The PKA-blocker H-89 (10 μg/kg) was administered with and without helium (He-PC+H-89, H-89). Furthermore, we tested the effect of direct activation of mK(Ca) channels with NS1619. The adenylyl cyclase activator forskolin (For) was administered in young (300 μg/kg) and aged animals (300 and 1000 μg/kg). He-PC reduced infarct size from 60±4% (Con) to 37±10% (p<0.05). Infarct size reduction was completely abolished by H-89 (58±5%; p<0.05), but H-89 alone had no effect (57±2%). NS1619 reduced infarct size in the same concentration in both, young and aged rats (35±6%; p<0.05 vs. Con and 34±8%; p<0.05 vs. Age Con). Forskolin in a concentration of 300 μg/kg reduced infarct size in young (37±6%; p<0.05) but not in aged rats (48±13%; n.s.). In contrast, 1000 μg/kg Forskolin reduced infarct size also in aged rats (28±3%; p<0.05). He-PC is mediated by activation of PKA. Alterations in PKA regulation might be an underlying mechanism for the age-dependent loss of <span class="hlt">preconditioning</span>. PMID:22100641</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3846389','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3846389"><span id="translatedtitle">Molecular Imaging-Assisted Optimization of Hsp70 Expression during Laser-Induced Thermal <span class="hlt">Preconditioning</span> for Wound Repair Enhancement</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Wilmink, Gerald J.; Opalenik, Susan R.; Beckham, Joshua T.; Abraham, Alexander A.; Nanney, Lillian B.; Mahadevan-Jansen, Anita; Davidson, Jeffrey M.; Jansen, E. Duco</p> <p>2013-01-01</p> <p>Patients at risk for impaired healing may benefit from prophylactic measures aimed at improving wound repair. Several photonic devices claim to enhance repair by thermal and photochemical mechanisms. We hypothesized that laser-induced thermal <span class="hlt">preconditioning</span> would enhance surgical wound healing that was correlated with hsp70 expression. Using a pulsed diode laser (λ =1.85 μm, τp=2 ms, 50 Hz, H =7.64 mJcm−2), the skin of transgenic mice that contain an hsp70 promoter-driven luciferase was <span class="hlt">preconditioned</span> 12 hours before surgical incisions were made. Laser protocols were optimized in vitro and in vivo using temperature, blood flow, and hsp70-mediated bioluminescence measurements as benchmarks. Biomechanical properties and histological parameters of wound healing were evaluated for up to 14 days. Bioluminescent imaging studies indicated that an optimized laser protocol increased hsp70 expression by 10-fold. Under these conditions, laser-<span class="hlt">preconditioned</span> incisions were two times stronger than control wounds. Our data suggest that this molecular imaging approach provides a quantitative method for optimization of tissue <span class="hlt">preconditioning</span> and that mild laser-induced heat shock may be a useful therapeutic intervention prior to surgery. PMID:18580963</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2002PNAS...9913114M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2002PNAS...9913114M"><span id="translatedtitle">Cell transplantation after oxidative hepatic <span class="hlt">preconditioning</span> with radiation and ischemia-reperfusion leads to extensive liver repopulation</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Malhi, Harmeet; Gorla, Giridhar R.; Irani, Adil N.; Annamaneni, Pallavi; Gupta, Sanjeev</p> <p>2002-10-01</p> <p>The inability of transplanted cells to proliferate in the normal liver hampers cell therapy. We considered that oxidative hepatic DNA damage would impair the survival of native cells and promote proliferation in transplanted cells. Dipeptidyl peptidase-deficient F344 rats were <span class="hlt">preconditioned</span> with whole liver radiation and warm ischemia-reperfusion followed by intrasplenic transplantation of syngeneic F344 rat hepatocytes. The <span class="hlt">preconditioning</span> was well tolerated, although serum aminotransferase levels rose transiently and hepatic injury was observed histologically, along with decreased catalase activity and 8-hydroxy adducts of guanine, indicating oxidative DNA damage. Transplanted cells did not proliferate in the liver over 3 months in control animals and animals <span class="hlt">preconditioned</span> with ischemia-reperfusion alone. Animals treated with radiation alone showed some transplanted cell proliferation. In contrast, the liver of animals <span class="hlt">preconditioned</span> with radiation plus ischemia-reperfusion was replaced virtually completely over 3 months. Transplanted cells integrated in the liver parenchyma and liver architecture were preserved normally. These findings offer a paradigm for repopulating the liver with transplanted cells. Progressive loss of cells experiencing oxidative DNA damage after radiation and ischemia-reperfusion injury could be of significance for epithelial renewal in additional organs.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4227258','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4227258"><span id="translatedtitle">Exercise <span class="hlt">Preconditioning</span> Protects against Spinal Cord Injury in Rats by Upregulating Neuronal and Astroglial Heat Shock Protein 72</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Chang, Cheng-Kuei; Chou, Willy; Lin, Hung-Jung; Huang, Yi-Ching; Tang, Ling-Yu; Lin, Mao-Tsun; Chang, Ching-Ping</p> <p>2014-01-01</p> <p>The heat shock protein 72 (HSP 72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercised rats (given pre-SCI exercise) had significantly higher levels of neuronal and astroglial HSP 72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non-exercised rats. pSUPER plasmid expressing HSP 72 small interfering RNA (SiRNA-HSP 72) was injected into the injured spinal cords. In addition to reducing neuronal and astroglial HSP 72, the (SiRNA-HSP 72) significantly attenuated the beneficial effects of exercise <span class="hlt">preconditioning</span> in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise <span class="hlt">preconditioning</span> induces increased neuronal and astroglial levels of HSP 72 in the gray matter of normal spinal cord tissue, exercise <span class="hlt">preconditioning</span> promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP 72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP 72 in protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP 72-mediated exercise <span class="hlt">preconditioning</span> is a promising strategy for facilitating functional recovery from SCI. PMID:25334068</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1850722','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1850722"><span id="translatedtitle">Ischemic <span class="hlt">Preconditioning</span> Increases the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Serafn, Anna; Rosell-Catafau, Joan; Prats, Neus; Xaus, Carme; Gelp, Emilio; Peralta, Carmen</p> <p>2002-01-01</p> <p>Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether <span class="hlt">preconditioning</span>, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic <span class="hlt">preconditioning</span> reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of <span class="hlt">preconditioning</span>. Thus, ischemic <span class="hlt">preconditioning</span> could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation. PMID:12163383</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4451753','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4451753"><span id="translatedtitle">Limb Ischemic <span class="hlt">Preconditioning</span> Protects Endothelium from Oxidative Stress by Enhancing Nrf2 Translocation and Upregulating Expression of Antioxidases</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Chen, Min; Zhang, Mingsheng; Zhang, Xuanping; Li, Jie; Wang, Yan; Fan, Yanying; Shi, Ruizan</p> <p>2015-01-01</p> <p>Remote ischemic <span class="hlt">preconditioning</span> is often performed by limb ischemic <span class="hlt">preconditioning</span> (LIPC), which has been demonstrated to be beneficial to various cells, including endothelial cells. The mechanisms underlying the protection have not been well clarified. The present study was designed to observe the effects of sera derived from rats after LIPC on human umbilical vein endothelial cells (HUVECs) injured by hydrogen peroxide (H2O2) -induced oxidative stress and explore the involvement of redox state in the protection. Incubation with 1 mM H2O2 for 2 h induced a significant reduction in HUVECs viability with increased production of malondialdehyde (MDA) and reactive oxygen species (ROS). Preincubation with early <span class="hlt">preconditioning</span> serum (EPS) or delayed <span class="hlt">preconditioning</span> serum (DPS) derived from rats subjected to LIPC alleviated these changes. Both EPS and DPS increased the nuclear translocation of transcription factor nuclear factor E2-related factor 2 (Nrf2) and the expression of antioxidases. The protective effects of EPS and DPS were blocked neither by MEK/ERK inhibitors U0126 nor by PI3K/Akt inhibitors LY294002. In conclusion, the present study provides the evidence that LIPC protects the HUVECs from H2O2-induced injury by, at least partially, enhancement of Nrf2 translocation and upregulation of antioxidases via signaling pathways independent of MEK/ERK and PI3K/Akt. PMID:26029932</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4555667','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4555667"><span id="translatedtitle">Hydrogen sulfide <span class="hlt">preconditioning</span> protects against myocardial ischemia/reperfusion injury in rats through inhibition of endo/sarcoplasmic reticulum stress</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Li, Changyong; Hu, Min; Wang, Yuan; Lu, Huan; Deng, Jing; Yan, Xiaohong</p> <p>2015-01-01</p> <p>Ischemia reperfusion (I/R) injury is a major cause of myocardial damage. Hydrogen sulfide (H2S), a gaseous signal molecule, has drawn considerable attention for its role in various pathophysiological processes. Multiple lines of evidence reveal the protective effects of H2S in various models of cardiac injury, however, the exact mechanism underlying this protective effect of H2S against myocardial I/R injury is not fully understood. The present study was designed to investigate whether H2S <span class="hlt">preconditioning</span> attenuates myocardial I/R injury in rats and whether the observed protection is associated with reduced endo/sarcoplasmic reticulum (ER/SR) stress. We found that H2S <span class="hlt">preconditioning</span> significantly reduced myocardial infarct size, preserved left ventricular function, and inhibited I/R-induced cardiomyocyte apoptosis in vivo. Furthermore, H2S <span class="hlt">preconditioning</span> significantly attenuated I/R-induced ER/SR stress responses, including the increased expression of glucose-regulated protein 78, C/EBP homologous protein, and activate transcription factor in myocardium. Additionally, we demonstrate that H2S <span class="hlt">preconditioning</span> attenuates ER/SR stress and inhibits cardiomyocyte apoptosis in an in vitro model of hypoxia/reoxygenation in rat H9c2 cardiac myocytes. In conclusion, these results suggest that H2S-attenuated ER/SR stress plays an important role in its protective effects against I/R-induced myocardial injury. PMID:26339339</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=61821&keyword=thoracic+AND+surgery&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50&CFID=57512596&CFTOKEN=48887434','EPA-EIMS'); return false;" href="http://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=61821&keyword=thoracic+AND+surgery&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50&CFID=57512596&CFTOKEN=48887434"><span id="translatedtitle">TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC <span class="hlt">PRECONDITIONING</span></span></a></p> <p><a target="_blank" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p> <p></p> <p></p> <p>Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.<br><br>Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic <span class="hlt">Preconditioning</span><br><br>Craig...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26574485','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26574485"><span id="translatedtitle">A MultiCenter Pilot Randomized Controlled Trial of Remote Ischemic <span class="hlt">Preconditioning</span> in Major Vascular Surgery.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Healy, D A; Boyle, E; McCartan, D; Bourke, M; Medani, M; Ferguson, J; Yagoub, H; Bashar, K; O'Donnell, M; Newell, J; Canning, C; McMonagle, M; Dowdall, J; Cross, S; O'Daly, S; Manning, B; Fulton, G; Kavanagh, E G; Burke, P; Grace, P A; Moloney, M Clarke; Walsh, S R</p> <p>2015-11-01</p> <p>A pilot randomized controlled trial that evaluated the effect of remote ischemic <span class="hlt">preconditioning</span> (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed. PMID:26574485</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_20 --> <div id="page_21" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="401"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/biblio/6643317','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/biblio/6643317"><span id="translatedtitle">Lipid compositional changes during low-temperature <span class="hlt">pre-conditioning</span> against SO sub 2 in coleus</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Norman, H.A.; Krizek, D.T.; Mirecki, R.M. )</p> <p>1989-04-01</p> <p>Short periods of temperature <span class="hlt">preconditioning</span> at 13{degrees}C. were found to provide protection against SO{sub 2} injury in coleus. The present study was conducted to determine whether changes in lipid metabolism and membrane fluidity might contribute to this phytoprotection. After 5 days of hardening at 13{degrees}C, there were significant differences in polar lipid composition and free fatty acid (FA) levels between SO{sub 2}-sensitive cultivar Buckley Supreme and SO{sub 2}-insensitive Marty. Molecular species of chloroplast lipids in Marty contained increased levels of linolenic acid. Differences were also found in total FA pools. At 20{degrees}C, palmitic acid and stearic acid were the major components. After temperature hardening at 13{degrees}C, total FA levels decreased in Marty but increased in Buckley Supreme. These modifications in lipid composition suggest a possible mechanism for cultivar differences in response in SO{sub 2}.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014JCoPh.258..555C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014JCoPh.258..555C"><span id="translatedtitle">Fluid <span class="hlt">preconditioning</span> for Newton-Krylov-based, fully implicit, electrostatic particle-in-cell simulations</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Chen, G.; Chacón, L.; Leibs, C. A.; Knoll, D. A.; Taitano, W.</p> <p>2014-02-01</p> <p>A recent proof-of-principle study proposes an energy- and charge-conserving, nonlinearly implicit electrostatic particle-in-cell (PIC) algorithm in one dimension [9]. The algorithm in the reference employs an unpreconditioned Jacobian-free Newton-Krylov method, which ensures nonlinear convergence at every timestep (resolving the dynamical timescale of interest). Kinetic enslavement, which is one key component of the algorithm, not only enables fully implicit PIC as a practical approach, but also allows <span class="hlt">preconditioning</span> the kinetic solver with a fluid approximation. This study proposes such a preconditioner, in which the linearized moment equations are closed with moments computed from particles. Effective acceleration of the linear GMRES solve is demonstrated, on both uniform and non-uniform meshes. The algorithm performance is largely insensitive to the electron-ion mass ratio. Numerical experiments are performed on a 1D multi-scale ion acoustic wave test problem.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/1997PNAS...94.3235M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/1997PNAS...94.3235M"><span id="translatedtitle">Regular Alcohol Consumption Mimics Cardiac <span class="hlt">Preconditioning</span> by Protecting against Ischemia-Reperfusion Injury</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Miyamae, Masami; Diamond, Ivan; Weiner, Michael W.; Camacho, S. Albert; Figueredo, Vincent M.</p> <p>1997-04-01</p> <p>Epidemiologic studies indicate that long-term alcohol consumption decreases the incidence of coronary disease and may improve outcome after myocardial infarction. Attenuation of ischemia-reperfusion injury after myocardial infarction improves survival. This study investigates the possibility that alcohol consumption can improve survival after myocardial infarction by reducing ischemia-reperfusion injury. Hearts were isolated from guinea pigs after drinking ethanol for 3-12 weeks and subjected to global ischemia and reperfusion. Hearts from animals drinking ethanol showed improved functional recovery and decreased myocyte damage when compared with controls. Adenosine A1 receptor blockade abolished the protection provided by ethanol consumption. These findings indicate that long-term alcohol consumption reduces myocardial ischemia-reperfusion injury and that adenosine A1 receptors are required for this protective effect of ethanol. This cardioprotective effect of long-term alcohol consumption mimics <span class="hlt">preconditioning</span> and may, in part, account for the beneficial effect of moderate drinking on cardiac health.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19900005463','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19900005463"><span id="translatedtitle">Krylov methods <span class="hlt">preconditioned</span> with incompletely factored matrices on the CM-2</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Berryman, Harry; Saltz, Joel; Gropp, William; Mirchandaney, Ravi</p> <p>1989-01-01</p> <p>The performance is measured of the components of the key interative kernel of a <span class="hlt">preconditioned</span> Krylov space interative linear system solver. In some sense, these numbers can be regarded as best case timings for these kernels. Sweeps were timed over meshes, sparse triangular solves, and inner products on a large 3-D model problem over a cube shaped domain discretized with a seven point template. The performance of the CM-2 is highly dependent on the use of very specialized programs. These programs mapped a regular problem domain onto the processor topology in a careful manner and used the optimized local NEWS communications network. The rather dramatic deterioration in performance was documented when these ideal conditions no longer apply. A synthetic workload generator was developed to produce and solve a parameterized family of increasingly irregular problems.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/biblio/22230859','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/biblio/22230859"><span id="translatedtitle">Fluid <span class="hlt">preconditioning</span> for Newton–Krylov-based, fully implicit, electrostatic particle-in-cell simulations</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Chen, G.; Chacón, L.; Leibs, C.A.; Knoll, D.A.; Taitano, W.</p> <p>2014-02-01</p> <p>A recent proof-of-principle study proposes an energy- and charge-conserving, nonlinearly implicit electrostatic particle-in-cell (PIC) algorithm in one dimension [9]. The algorithm in the reference employs an unpreconditioned Jacobian-free Newton–Krylov method, which ensures nonlinear convergence at every timestep (resolving the dynamical timescale of interest). Kinetic enslavement, which is one key component of the algorithm, not only enables fully implicit PIC as a practical approach, but also allows <span class="hlt">preconditioning</span> the kinetic solver with a fluid approximation. This study proposes such a preconditioner, in which the linearized moment equations are closed with moments computed from particles. Effective acceleration of the linear GMRES solve is demonstrated, on both uniform and non-uniform meshes. The algorithm performance is largely insensitive to the electron–ion mass ratio. Numerical experiments are performed on a 1D multi-scale ion acoustic wave test problem.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015JChPh.142x4117S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015JChPh.142x4117S"><span id="translatedtitle">Efficient <span class="hlt">preconditioning</span> of the electronic structure problem in large scale ab initio molecular dynamics simulations</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Schiffmann, Florian; VandeVondele, Joost</p> <p>2015-06-01</p> <p>We present an improved <span class="hlt">preconditioning</span> scheme for electronic structure calculations based on the orbital transformation method. First, a preconditioner is developed which includes information from the full Kohn-Sham matrix but avoids computationally demanding diagonalisation steps in its construction. This reduces the computational cost of its construction, eliminating a bottleneck in large scale simulations, while maintaining rapid convergence. In addition, a modified form of Hotelling's iterative inversion is introduced to replace the exact inversion of the preconditioner matrix. This method is highly effective during molecular dynamics (MD), as the solution obtained in earlier MD steps is a suitable initial guess. Filtering small elements during sparse matrix multiplication leads to linear scaling inversion, while retaining robustness, already for relatively small systems. For system sizes ranging from a few hundred to a few thousand atoms, which are typical for many practical applications, the improvements to the algorithm lead to a 2-5 fold speedup per MD step.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014AGUFM.A34B..06A','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014AGUFM.A34B..06A"><span id="translatedtitle">Identification of Dynamic Processes Responsible for <span class="hlt">Preconditioning</span> the Atmosphere for Severe Convective Outbreaks in Midlatitudes</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Agard, J. V.; Emanuel, K.</p> <p>2014-12-01</p> <p>Budgets of the tendency of convective available potential energy (CAPE) are calculated using reanalysis data in case studies of several North American severe weather outbreaks from the years 2012 and 2013. These budgets separate the tendency of CAPE into terms arising from diabatic heating of the subcloud boundary layer, radiative cooling of the free troposphere, and advection of air in the free troposphere relative to the motion of a parcel to be lifted. It is found that in most cases, the CAPE tendency budget is dominated by the term representing diabatic heating of the subcloud layer, which establishes high CAPE values in advance of thunderstorm development. This result suggests the relative importance of surface entropy fluxes in supporting midlatitude severe local storms through atmospheric <span class="hlt">preconditioning</span> (CAPE buildup). By extension, this result warrants further investigation into the roles of environmental land surface properties as controls on the climatology of midlatitude severe convecton, as such properties play important roles in modulating surface entropy fluxes.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26133420','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26133420"><span id="translatedtitle">Efficient <span class="hlt">preconditioning</span> of the electronic structure problem in large scale ab initio molecular dynamics simulations.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Schiffmann, Florian; VandeVondele, Joost</p> <p>2015-06-28</p> <p>We present an improved <span class="hlt">preconditioning</span> scheme for electronic structure calculations based on the orbital transformation method. First, a preconditioner is developed which includes information from the full Kohn-Sham matrix but avoids computationally demanding diagonalisation steps in its construction. This reduces the computational cost of its construction, eliminating a bottleneck in large scale simulations, while maintaining rapid convergence. In addition, a modified form of Hotelling's iterative inversion is introduced to replace the exact inversion of the preconditioner matrix. This method is highly effective during molecular dynamics (MD), as the solution obtained in earlier MD steps is a suitable initial guess. Filtering small elements during sparse matrix multiplication leads to linear scaling inversion, while retaining robustness, already for relatively small systems. For system sizes ranging from a few hundred to a few thousand atoms, which are typical for many practical applications, the improvements to the algorithm lead to a 2-5 fold speedup per MD step. PMID:26133420</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/servlets/purl/1107797','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/servlets/purl/1107797"><span id="translatedtitle">Matrix multiplication operations with data <span class="hlt">pre-conditioning</span> in a high performance computing architecture</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Eichenberger, Alexandre E; Gschwind, Michael K; Gunnels, John A</p> <p>2013-11-05</p> <p>Mechanisms for performing matrix multiplication operations with data <span class="hlt">pre-conditioning</span> in a high performance computing architecture are provided. A vector load operation is performed to load a first vector operand of the matrix multiplication operation to a first target vector register. A load and splat operation is performed to load an element of a second vector operand and replicating the element to each of a plurality of elements of a second target vector register. A multiply add operation is performed on elements of the first target vector register and elements of the second target vector register to generate a partial product of the matrix multiplication operation. The partial product of the matrix multiplication operation is accumulated with other partial products of the matrix multiplication operation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/biblio/5398699','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/biblio/5398699"><span id="translatedtitle">Comparison of nested factorization, constrained pressure residual, and incomplete factorization <span class="hlt">preconditionings</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Behie, A.</p> <p>1985-02-01</p> <p>Two recently developed methods for the solution of the sparse block-banded linear equation sets generated by fully implicit reservoir simulators are investigated. Nested factorization is a new approach to forming an incomplete factorization of the linear system. Comparisons are made of the nested factorization approach and the incomplete LU factorization (ILU) approach. Tests are done on both model problems and on problems generated by reservoir simulators. The nested factorization was no better than the best ILU method on both types of problems in most cases. In some cases it was considerably worse. Constrained pressure residual <span class="hlt">preconditioning</span> (CPR) is a variant of the COMBINATIVE method. These two methods are compared on problems generated by black oil and steam simulators. CPR gives small improvements in convergence rates in some cases.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26857397','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26857397"><span id="translatedtitle"><span class="hlt">Preconditioning</span> of Nonlinear Mixed Effects Models for Stabilisation of Variance-Covariance Matrix Computations.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Aoki, Yasunori; Nordgren, Rikard; Hooker, Andrew C</p> <p>2016-03-01</p> <p>As the importance of pharmacometric analysis increases, more and more complex mathematical models are introduced and computational error resulting from computational instability starts to become a bottleneck in the analysis. We propose a <span class="hlt">preconditioning</span> method for non-linear mixed effects models used in pharmacometric analyses to stabilise the computation of the variance-covariance matrix. Roughly speaking, the method reparameterises the model with a linear combination of the original model parameters so that the Hessian matrix of the likelihood of the reparameterised model becomes close to an identity matrix. This approach will reduce the influence of computational error, for example rounding error, to the final computational result. We present numerical experiments demonstrating that the stabilisation of the computation using the proposed method can recover failed variance-covariance matrix computations, and reveal non-identifiability of the model parameters. PMID:26857397</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25993394','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25993394"><span id="translatedtitle">Quantification of neurovascular protection following repetitive hypoxic <span class="hlt">preconditioning</span> and transient middle cerebral artery occlusion in mice.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Poinsatte, Katherine; Selvaraj, Uma Maheswari; Ortega, Sterling B; Plautz, Erik J; Kong, Xiangmei; Gidday, Jeffrey M; Stowe, Ann M</p> <p>2015-01-01</p> <p>Experimental animal models of stroke are invaluable tools for understanding stroke pathology and developing more effective treatment strategies. A 2 week protocol for repetitive hypoxic <span class="hlt">preconditioning</span> (RHP) induces long-term protection against central nervous system (CNS) injury in a mouse model of focal ischemic stroke. RHP consists of 9 stochastic exposures to hypoxia that vary in both duration (2 or 4 hr) and intensity (8% and 11% O2). RHP reduces infarct volumes, blood-brain barrier (BBB) disruption, and the post-stroke inflammatory response for weeks following the last exposure to hypoxia, suggesting a long-term induction of an endogenous CNS-protective phenotype. The methodology for the dual quantification of infarct volume and BBB disruption is effective in assessing neurovascular protection in mice with RHP or other putative neuroprotectants. Adult male Swiss Webster mice were <span class="hlt">preconditioned</span> by RHP or duration-equivalent exposures to 21% O2 (i.e. room air). A 60 min transient middle cerebral artery occlusion (tMCAo) was induced 2 weeks following the last hypoxic exposure. Both the occlusion and reperfusion were confirmed by transcranial laser Doppler flowmetry. Twenty-two hr after reperfusion, Evans Blue (EB) was intravenously administered through a tail vein injection. 2 hr later, animals were sacrificed by isoflurane overdose and brain sections were stained with 2,3,5- triphenyltetrazolium chloride (TTC). Infarcts volumes were then quantified. Next, EB was extracted from the tissue over 48 hr to determine BBB disruption after tMCAo. In summary, RHP is a simple protocol that can be replicated, with minimal cost, to induce long-term endogenous neurovascular protection from stroke injury in mice, with the translational potential for other CNS-based and systemic pro-inflammatory disease states. PMID:25993394</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3928919','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3928919"><span id="translatedtitle"><span class="hlt">Preconditioning</span> somatothermal stimulation on Qimen (LR14) reduces hepatic ischemia/reperfusion injury in rats</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2014-01-01</p> <p>Background In human beings or animals, ischemia/reperfusion (I/R) injury of the liver may occur in many clinical conditions, such as circulating shock, liver transplantation and surgery and several other pathological conditions. I/R injury has a complex pathophysiology resulting from a number of contributing factors. Therefore, it is difficult to achieve effective treatment or protection by individually targeting the mediators. This study aimed at studying the effects of local somatothermal stimulation <span class="hlt">preconditioning</span> on the right Qimen (LR14) on hepatic I/R injury in rats. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups. The rats were <span class="hlt">preconditioned</span> with thermal tolerance study, which included one dose of local somatothermal stimulation (LSTS) on right Qimen (LR14) at an interval of 12h, followed by hepatic ischemia for 60min and then reperfusion for 60min. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been used to assess the liver functions, and liver tissues were taken for the measurements such as malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxidase dismutase (SOD), and myeloperoxidase (MPO). Results The results show that the plasma ALT and AST activities were higher in the I/R group than in the control group. In addition, the plasma ALT and AST activities decreased in the groups that received LSTS. The hepatic SOD levels reduced significantly by I/R injury. Moreover, the hepatic MPO activity significantly increased by I/R injury while it decreased in the groups given LSTS. Conclusions Our findings show that LSTS provides a protective effects on the liver from the I/R injury. Therefore, LSTS might offer an easy and inexpensive intervention for patients who have suffered from I/R of the liver especially in the process of hepatotomy and hepatic transplantation. PMID:24417801</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/15530650','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/15530650"><span id="translatedtitle">Neuroprotective gene expression profiles in ischemic cortical cultures <span class="hlt">preconditioned</span> with IGF-1 or bFGF.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yoshida, Erin; Atkinson, Trevor G; Chakravarthy, Balu</p> <p>2004-11-24</p> <p>The mechanisms underlying growth factor <span class="hlt">preconditioning</span> of neurons are only partially elucidated, and no studies have been conducted in this area using a gene profiling approach. We used cDNA microarrays to compare the transcriptional profiles of cells <span class="hlt">preconditioned</span> either with insulin-like growth factor I (IGF-1) or basic fibroblast growth factor (bFGF), to identify differentially regulated genes that may function in growth factor signaling, response to oxygen-glucose deprivation (OGD), and most importantly, cell survival. Primary rat cortical cultures were treated with bFGF or IGF-1 for 2, 24, or 24 h followed by OGD for 90 min, and compared with cells that were subject to OGD without growth factor pretreatment. Although the majority of surveyed genes were unchanged in all experimental treatments, 175 genes (10% of the cDNAs on the chip) were found to be differentially regulated in at least one of the treatment conditions. Hierarchical clustering of these 175 genes was used to identify four expression clusters: IGF-1 regulated, bFGF regulated, OGD regulated, and putative neuroprotective genes. Further analysis using realtime RT-PCR confirmed that we had identified genes that are regulated by single growth factors, as well as several more that are co-regulated by both IGF-1 and bFGF. These genes can influence neuronal survival by affecting diverse pathways such as growth factor signal transduction (CD44, DTR, DUSP6, EPS8, IGFBP3), DNA repair and transcription (FOXJ1), metabolic homeostasis (RASA1, SHMT2), cytoskeletal stability (MSN, MAPT) and cholesterol biosynthesis (FDFT1, FDPS). PMID:15530650</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3033420','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3033420"><span id="translatedtitle">Environmental and Genetic <span class="hlt">Preconditioning</span> for Long-Term Anoxia Responses Requires AMPK in Caenorhabditis elegans</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>LaRue, Bobby L.; Padilla, Pamela A.</p> <p>2011-01-01</p> <p>Background <span class="hlt">Preconditioning</span> environments or therapeutics, to suppress the cellular damage associated with severe oxygen deprivation, is of interest to our understanding of diseases associated with oxygen deprivation. Wildtype C. elegans exposed to anoxia enter into a state of suspended animation in which energy-requiring processes reversibly arrest. C. elegans at all developmental stages survive 24-hours of anoxia exposure however, the ability of adult hermaphrodites to survive three days of anoxia significantly decreases. Mutations in the insulin-like signaling receptor (daf-2) and LIN-12/Notch (glp-1) lead to an enhanced long-term anoxia survival phenotype. Methodology/Principal Findings In this study we show that the combined growth environment of 25C and a diet of HT115 E. coli will <span class="hlt">precondition</span> adult hermaphrodites to survive long-term anoxia; many of these survivors have normal movement after anoxia treatment. Animals fed the drug metformin, which induces a dietary-restriction like state in animals and activates AMPK in mammalian cell culture, have a higher survival rate when exposed to long-term anoxia. Mutations in genes encoding components of AMPK (aak-2, aakb-1, aakb-2, aakg-2) suppress the environmentally and genetically induced long-term anoxia survival phenotype. We further determine that there is a correlation between the animals that survive long-term anoxia and increased levels of carminic acid staining, which is a fluorescent dye that incorporates in with carbohydrates such as glycogen. Conclusions/Significance We conclude that small changes in growth conditions such as increased temperature and food source can influence the physiology of the animal thus affecting the responses to stress such as anoxia. Furthermore, this supports the idea that metformin should be further investigated as a therapeutic tool for treatment of oxygen-deprived tissues. Finally, the capacity for an animal to survive long bouts of severe oxygen deprivation is likely dependent on specific subunits of the heterotrimeric protein AMPK and energy stores such as carbohydrates. PMID:21304820</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4780774','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4780774"><span id="translatedtitle">Sulforaphane <span class="hlt">Preconditioning</span> Sensitizes Human Colon Cancer Cells towards the Bioreductive Anticancer Prodrug PR-104A</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Erzinger, Melanie M.; Bovet, Cédric; Hecht, Katrin M.; Senger, Sabine; Winiker, Pascale; Sobotzki, Nadine; Cristea, Simona; Beerenwinkel, Niko; Shay, Jerry W.; Marra, Giancarlo; Wollscheid, Bernd; Sturla, Shana J.</p> <p>2016-01-01</p> <p>The chemoprotective properties of sulforaphane (SF), derived from cruciferous vegetables, are widely acknowledged to arise from its potent induction of xenobiotic-metabolizing and antioxidant enzymes. However, much less is known about the impact of SF on the efficacy of cancer therapy through the modulation of drug-metabolizing enzymes. To identify proteins modulated by a low concentration of SF, we treated HT29 colon cancer cells with 2.5 μM SF. Protein abundance changes were detected by stable isotope labeling of amino acids in cell culture. Among 18 proteins found to be significantly up-regulated, aldo-keto reductase 1C3 (AKR1C3), bioactivating the DNA cross-linking prodrug PR-104A, was further characterized. <span class="hlt">Preconditioning</span> HT29 cells with SF reduced the EC50 of PR-104A 3.6-fold. The increase in PR-104A cytotoxicity was linked to AKR1C3 abundance and activity, both induced by SF in a dose-dependent manner. This effect was reproducible in a second colon cancer cell line, SW620, but not in other colon cancer cell lines where AKR1C3 abundance and activity were absent or barely detectable and could not be induced by SF. Interestingly, SF had no significant influence on PR-104A cytotoxicity in non-cancerous, immortalized human colonic epithelial cell lines expressing either low or high levels of AKR1C3. In conclusion, the enhanced response of PR-104A after <span class="hlt">preconditioning</span> with SF was apparent only in cancer cells provided that AKR1C3 is expressed, while its expression in non-cancerous cells did not elicit such a response. Therefore, a subset of cancers may be susceptible to combined food-derived component and prodrug treatments with no harm to normal tissues. PMID:26950072</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2075274','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2075274"><span id="translatedtitle">Hypoxic <span class="hlt">preconditioning</span> attenuates lipopolysaccharide-induced oxidative stress in rat kidneys</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Yang, Chih-Ching; Ma, Ming-Chieh; Chien, Chiang-Ting; Wu, Ming-Shiou; Sun, Wan-Kuan; Chen, Chau-Fong</p> <p>2007-01-01</p> <p>Chronic hypoxic (CH) <span class="hlt">preconditioning</span> reduces superoxide-induced renal dysfunction via the upregulation of superoxide dismutase (SOD) activity and contents. Endotoxaemia reduces renal antioxidant status. We hypothesize that CH <span class="hlt">preconditioning</span> might protect the kidney from subsequent endotoxaemia-induced oxidative injury. Endotoxaemia was induced by intraperitoneal injection of lipopolysaccharide (LPS; 4 mg kg?1) in rats kept at sea level (SL) and rats with CH in an altitude chamber (5500 m for 15 h day?1) for 4 weeks. LPS enhanced xanthine oxidase (XO) and gp91phox (catalytic subunit of NADPH oxidase) expression associated with burst amount of superoxide production from the SL kidney surface and renal venous blood detected by lucigenin-enhanced chemiluminescence. LPS induced a morphologic-independent renal dysfunction in baseline and acute saline loading stages and increased renal IL-1? protein and urinary protein concentration in the SL rats. After 4 weeks of induction, CH significantly increased Cu/ZnSOD, MnSOD and catalase expression (16 17, 128 35 and 48 21, respectively) in renal cortex, and depressed renal cortex XO (44 16%) and renal cortex (20 9%) and medulla (28 11%) gp91phox when compared with SL rats. The combined effect of enhanced antioxidant proteins and depressed oxidative proteins significantly reduced LPS-enhanced superoxide production, renal XO and gp91phox expression, renal IL-1? production, and urinary protein level. CH also ameliorated LPS-induced renal dysfunction in the baseline and acute saline loading periods. We conclude that CH treatment enhances the intrarenal antioxidant/oxidative protein ratio to overcome endotoxaemia-induced reactive oxygen species formation and inflammatory cytokine release. PMID:17317755</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4476636','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4476636"><span id="translatedtitle"><span class="hlt">Preconditioning</span> of skeletal myoblast-based engineered tissue constructs enables functional coupling to myocardium in vivo</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Treskes, Philipp; Neef, Klaus; Srinivasan, Sureshkumar Perumal; Halbach, Marcel; Stamm, Christof; Cowan, Douglas; Scherner, Maximilian; Madershahian, Navid; Wittwer, Thorsten; Hescheler, Jrgen; Wahlers, Thorsten; Choi, Yeong-Hoon</p> <p>2015-01-01</p> <p>Objective Skeletal myoblasts fuse to form functional syncytial myotubes as an integral part of the skeletal muscle. During this differentiation process, expression of proteins for mechanical and electrical integration is seized, which is a major drawback for the application of skeletal myoblasts in cardiac regenerative cell therapy, because global heart function depends on intercellular communication. Methods Mechanically <span class="hlt">preconditioned</span> engineered tissue constructs containing neonatal mouse skeletal myoblasts were transplanted epicardially. A Y-chromosomal specific polymerase chain reaction (PCR) was undertaken up to 10 weeks after transplantation to confirm the presence of grafted cells. Histologic and electrophysiologic analyses were carried out 1 week after transplantation. Results Cells within the grafted construct expressed connexin 43 at the interface to the host myocardium, indicating electrical coupling, confirmed by sharp electrode recordings. Analyses of the maximum stimulation frequency (5.65 0.37 Hz), conduction velocity (0.087 0.011 m/s) and sensitivity for pharmacologic conduction block (0.736 0.080 mM 1-heptanol) revealed effective electrophysiologic coupling between graft and host cells, although significantly less robust than in native myocardial tissue (maximum stimulation frequency, 11.616 0.238 Hz, P<.001; conduction velocity, 0.300 0.057 m/s, P<.01; conduction block, 1.983 0.077 mM 1-heptanol, P<.001). Conclusions Although untreated skeletal myoblasts cannot couple to cardiomyocytes, we confirm that mechanical <span class="hlt">preconditioning</span> enables transplanted skeletal myoblasts to functionally interact with cardio-myocytes in vivo and, thus, reinvigorate the concept of skeletal myoblast-based cardiac cell therapy. PMID:25439779</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25693898','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25693898"><span id="translatedtitle">Effect of a prior bout of <span class="hlt">preconditioning</span> exercise on muscle damage from downhill walking.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Maeo, Sumiaki; Ochi, Yusuke; Yamamoto, Masayoshi; Kanehisa, Hiroaki; Nosaka, Kazunori</p> <p>2015-03-01</p> <p>This study investigated whether reduced-duration downhill walking (DW) would confer a protective effect against muscle damage induced by a subsequent bout of longer duration DW performed 1 week or 4 weeks later. Healthy young adults were allocated to a control or one of the <span class="hlt">preconditioning</span> exercise (PRE-1wk or PRE-4wk) groups (10 men and 4 women per group). PRE-1wk and PRE-4wk groups performed 20-min DW (-28% slope, 5 km/h, 10% body mass added to a backpack) 1 week and 4 weeks before 40-min DW, respectively, and the control group performed 40-min DW only. Maximal voluntary contraction (MVC) knee extension torque, plasma creatine kinase (CK) activity, and muscle soreness (100-mm visual analog scale) were measured before, immediately after, and 24, 48, and 72 h after DW, and the changes in these variables were compared among groups. The control group showed symptoms of muscle damage (e.g., prolonged decrease in MVC: -14% 10% at 48 h post-DW) after 40-min DW. Changes in all variables after 40-min DW of PRE-1wk and PRE-4wk groups were 54%-61% smaller (P < 0.05) than the control group, without significant differences between PRE-1wk and PRE-4wk groups for MVC and plasma CK activity. Importantly, changes after the <span class="hlt">preconditioning</span> exercise (20-min DW) were 67%-69% smaller (P < 0.05) than those after the 40-min DW of the control group. These findings suggest that 20-min DW resulting in minor muscle damage conferred a protective effect against subsequent 40-min DW, and its effect could last for more than 4 weeks. PMID:25693898</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25785553','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25785553"><span id="translatedtitle"><span class="hlt">Preconditioning</span> of model biocarriers by soluble pollutants: a QCM-D study.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Huang, Hui; Ding, Li-li; Ren, Hong-qiang; Geng, Jin-ju; Xu, Ke; Zhang, Yan</p> <p>2015-04-01</p> <p><span class="hlt">Preconditioning</span> of a biocarrier surface is the first step in triggering biofilm formation in attached-growth bioreactors. However, the quantification and control of this step as influenced by solution conditions and biocarrier properties have been rarely explored. In this paper, deposition behaviors of soluble pollutants on the model biocarriers polystyrene (PS) and polyamide (PA) were performed using a quartz crystal microbalance with dissipation monitoring (QCM-D). Three types of wastewater from municipal and industrial wastewater treatment plants and 12 synthetic wastewaters with different configurations of model macromolecules (bovine serum albumin and sodium alginate) and ionic compositions (Na(+) and Ca(2+)) were prepared. Results showed that high organic contents (protein and humic acid) in real wastewater increased deposition compared to the impact of ions on the two types of carriers. For synthetic wastewater, an interesting phenomenon was observed in that the presence of Ca(2+) can transform a thin and rigid adlayer into a denser and viscoelastic one on the surface of PS with low organic contents, yet a viscoelastic adlayer can directly form on PS and an increase in the ionic strength hinders deposition in the presence of high organic contents. The deposition of solutes on PA produces a thicker and viscoelastic adlayer that is strengthened an elevated concentration of organic materials. Additionally, a weakening effect of Ca(2+) on deposition was revealed under high ionic strength. This is the first demonstration of control strategies for <span class="hlt">preconditioning</span> hydrophilic and hydrophobic biocarriers under different water quality conditions and has important implications for the design of a start-up process for biofilm formation in attached-growth bioreactors. PMID:25785553</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_21 --> <div id="page_22" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="421"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4120131','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4120131"><span id="translatedtitle">Cardiac <span class="hlt">preconditioning</span> with sphingosine-1-phosphate requires activation of signal transducer and activator of transcription-3</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kelly-Laubscher, Roisin F; King, Jonathan C; Hacking, Damian; Somers, Sarin; Hastie, Samantha; Stewart, Tessa; Imamdin, Aqeela; Maarman, Gerald; Pedretti, Sarah; Lecour, Sandrine</p> <p>2014-01-01</p> <p>Summary Aims Sphingosine-1-phosphate (S1P) is a cardioprotective agent. Signal transducer and activator of transcription 3 (STAT-3) is a key mediator of many cardioprotective agents. We aimed to explore whether STAT-3 is a key mediator in S1P-induced <span class="hlt">preconditioning</span>. Methods Langendorff-perfused hearts from Wistar rats and wild-type or cardiomyocyte-specific STAT-3 knockout mice were pre-treated with S1P (10 nmol/l), with or without the STAT-3 pathway inhibitor AG490, before an ischaemiareperfusion insult. Triphenyltetrazolium chloride and Evans blue staining were used for the determination of infarct size. Western blot analysis was carried out on the S1P pre-treated hearts for detection of cytosolic, nuclear and mitochondrial phosphorylated and total STAT-3 proteins. Results Pre-treatment with S1P decreased the infarct size in isolated rat (5 3% vs control 26 8%, p < 0.01) and wild-type mouse hearts (13 1% vs control 33 3%, p < 0.05). This protective effect was abolished in the rat hearts pre-treated with AG490 (30 10%, p = ns vs control) and in the hearts from STAT-3 knockout mice (35 4% vs control 30 3%, p = ns). Levels of phosphorylated STAT-3 were significantly increased in both the nuclear (p < 0.05 vs control) and mitochondrial (p < 0.05 vs control) fractions in the S1P pre-treated hearts, but remained unchanged in the cytosolic fraction (p = ns vs control). Conclusion These novel results demonstrate that pharmacological <span class="hlt">preconditioning</span> with S1P in the isolated heart is mediated by activation of mitochondrial and nuclear STAT-3, therefore suggesting that S1P may be a novel therapeutic target to modulate mitochondrial and nuclear function in cardiovascular disease in order to protect the heart against ischaemiareperfusion. PMID:25000441</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4769182','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4769182"><span id="translatedtitle">Identifying the Source of a Humoral Factor of Remote (<span class="hlt">Pre)Conditioning</span> Cardioprotection</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Mastitskaya, Svetlana; Basalay, Marina; Hosford, Patrick S.; Ramage, Andrew G.; Gourine, Andrey; Gourine, Alexander V.</p> <p>2016-01-01</p> <p>Signalling pathways underlying the phenomenon of remote ischaemic <span class="hlt">preconditioning</span> (RPc) cardioprotection are not completely understood. The existing evidence agrees that intact sensory innervation of the remote tissue/organ is required for the release into the systemic circulation of <span class="hlt">preconditioning</span> factor(s) capable of protecting a transplanted or isolated heart. However, the source and molecular identities of these factors remain unknown. Since the efficacy of RPc cardioprotection is critically dependent upon vagal activity and muscarinic mechanisms, we hypothesized that the humoral RPc factor is produced by the internal organ(s), which receive rich parasympathetic innervation. In a rat model of myocardial ischaemia/reperfusion injury we determined the efficacy of limb RPc in establishing cardioprotection after denervation of various visceral organs by sectioning celiac, hepatic, anterior and posterior gastric branches of the vagus nerve. Electrical stimulation was applied to individually sectioned branches to determine whether enhanced vagal input to a particular target area is sufficient to establish cardioprotection. It was found that RPc cardioprotection is abolished in conditions of either total subdiaphragmatic vagotomy, gastric vagotomy or sectioning of the posterior gastric branch. The efficacy of RPc cardioprotection was preserved when hepatic, celiac or anterior gastric vagal branches were cut. In the absence of remote ischaemia/reperfusion, electrical stimulation of the posterior gastric branch reduced infarct size, mimicking the effect of RPc. These data suggest that the circulating factor (or factors) of RPc are produced and released into the systemic circulation by the visceral organ(s) innervated by the posterior gastric branch of the vagus nerve. PMID:26918777</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2697672','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2697672"><span id="translatedtitle">Accelerated inactivation of cardiac L-type calcium channels triggered by anaesthetic-induced <span class="hlt">preconditioning</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Tampo, A; Hogan, CS; Sedlic, F; Bosnjak, ZJ; Kwok, WM</p> <p>2009-01-01</p> <p>Background and purpose: Cardioprotection against ischaemia by anaesthetic-induced <span class="hlt">preconditioning</span> (APC) is well established. However, the mechanism underlying Ca2+ overload attenuation by APC is unknown. The effects of APC by isoflurane on the cardiac L-type Ca channel were investigated. Experimental approach: In a model of in vivo APC, Wistar rats were exposed to isoflurane (1.4%), delivered via a vaporizer in an enclosure, prior to thoracotomy. The Dahl S rats were similarly <span class="hlt">preconditioned</span> to determine strain-dependent effects. Whole-cell patch clamp using cardiac ventricular myocytes was used to determine the L-type Ca2+ current (ICa,L) characteristics and calmodulin (CaM) levels were determined by Western blot analysis. Cytosolic Ca2+ levels were monitored using fluo-4-AM. Action potential (AP) simulations examined the effects of APC. Key results: In Wistar rats, APC significantly accelerated ICa,L inactivation kinetics. This was abolished when external Ca2+ was replaced with Ba2+, suggesting that Ca2+-dependent inactivation of ICa,L was modulated by APC. Expression levels of CaM, a determinant of ICa,L inactivation, were not affected. Attenuation of cytosolic Ca2+ accumulation following oxidative stress was observed in the APC group. Simulations showed that the accelerated inactivation of ICa,L resulted in a shortening of the AP duration. The Dahl S rat strain was resistant to APC and changes in ICa,L inactivation were not observed in cardiomyocytes prepared from these rats. Conclusions and implications: APC triggered persistent changes in the inactivation of cardiac L-type Ca channels. This can potentially lead to a reduction in Ca2+ influx and attenuation of Ca2+ overload during ischaemia/reperfusion. PMID:19154423</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/24891774','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/24891774"><span id="translatedtitle">Effect of leptin and apelin <span class="hlt">preconditioning</span> on hepatic ischemia reperfusion injury in rats.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sagiroglu, Tamer; Aksoy, Mustafa Burak; Sagiroglu, Gonul; Tozkir, Hilmi; Oguz, Serhat; Yalta, Tulin; Yagci, Mehmet A; Sezer, Atakan</p> <p>2014-04-01</p> <p>Leptin and apelin are important adipocytokines involved in a variety of endocrine and paracrine functions. The aim of this study was to evaluate the effect of exogenous leptin and apelin <span class="hlt">preconditioning</span> on hepatic ischemia reperfusion (I/R) injury in rats. Forty mice were assigned to four groups (n?=?10): sham-operated control (sham), I/R injury, I/R + leptin (I/R + L), and I/R + apelin (I/R + A). Leptin 100?g/kg/day and apelin 2?g/kg/day were delivered intraperitoneally starting 3days prior to surgical procedure in I/R?+?L and I/R?+?A groups, respectively. All I/R groups underwent 45min of warm ischemia, followed by 30min of reperfusion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver malondialdehyde (MDA) and glutathione (GSH), and liver histopathology were compared between groups. MDA was elevated in I/R, but stayed similar in I/R + L and I/R + A compared to sham. I/R + A had significantly lower MDA compared to I/R. GSH levels did not differ significantly between the groups. ALT and AST were elevated in all I/R groups, but significant reduction was observed in I/R + L and I/R + A compared to I/R. Liver histopathology was mostly mild in I/R + L and I/R + A, in contrast to severe injury observed in the I/R group. Leptin and apelin <span class="hlt">preconditioning</span> significantly reduced hepatic I/R injury in rats. PMID:24891774</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2007SPIE.6427E..05N','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2007SPIE.6427E..05N"><span id="translatedtitle">Tumor cell hyperresistance to photodynamic killing arising from nitric oxide <span class="hlt">preconditioning</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Niziolek-Kierecka, Magdalena; Korytowski, Witold; Girotti, Albert W.</p> <p>2007-02-01</p> <p>Relatively little is known about how nitric oxide (NO) generated by tumor vascular cells or tumor cells themselves might affect the outcome of photodynamic therapy (PDT). Using a breast tumor epithelial line (COH-BR1) metabolically sensitized with protoporphyrin IX (PpIX) by pre-treating with 5-aminolevulinic acid (ALA), we have recently shown that NO from chemical donors can elicit both an immediate (NO-now) and delayed (NO-then) hyperresistance to photokilling. Cell death was mainly apoptotic when PpIX was confined to mitochondria, but mainly necrotic when it was allowed to diffuse to the cell periphery. We found that NO-now operates primarily by scavenging lipid-derived free radicals, whereas NO-then "<span class="hlt">preconditions</span>" cells by some other mechanism. In addressing this, we have used a biologically relevant NO donor/tumor target model, viz. RAW 264.7 macrophages grown on microporous membrane inserts and COH-BR1 cells grown in culture plate wells. The RAW cells were activated with lipopolysaccharide, and 15 h later (when NO output was ~ 2 μM/h) placed over the tumor cells for 20 h, after which the latter were ALA-treated and then irradiated. Prior exposure to activated RAW macrophages reduced tumor cell photokilling by >50 %. This effect was completely lost when the RAW cells were pre-treated with the nitric oxide synthase inhibitor L-NAME, confirming that NO was involved in the hyperresistance. Results from other experiments suggest that heme oxygenase-1 and ferritin play a role in the <span class="hlt">preconditioning</span> effect described. These studies provide new insights into how NO might modulate PDT efficacy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/23562311','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/23562311"><span id="translatedtitle">A <span class="hlt">preconditioning</span> regimen with a PKC? activator improves islet graft function in a mouse transplant model.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hamilton, Diana; Rugg, Caitlin; Davis, Nicolynn; Kvezereli, Manana; Tafti, Bashir Akhavan; Busque, Stephan; Fontaine, Magali</p> <p>2014-01-01</p> <p>Transplantation of islets isolated from deceased donor pancreata is an attractive method of ?-cell replacement therapy for patients with type 1 diabetes (T1D). However, the loss of islet cell viability and function during the peritransplant period is a limiting factor to long-term islet engraftment. Activation of the isoenzyme PKC? may improve islet survival and function. The current study assesses the effects of PKC? activation on islet graft function in a syngeneic streptozotocin-induced diabetic mouse model. Islets were isolated from wild-type BALB/c mice <span class="hlt">preconditioned</span> with either a PKC? activator (??RACK) or a TAT carrier control peptide. Islets were further treated with the same agents during isolation, purification, and incubation prior to transplantation. Two hundred seventy-five islet equivalents were transplanted under the kidney capsule of streptozotocin-induced diabetic BALB/c mice. Islet function was assessed by measurement of blood glucose levels every 3 days for 42 days after transplant and through an intraperitoneal glucose tolerance test (IPGTT). The time for return to euglycemia in mice transplanted with islets treated with ??RACK was improved at 14 6 days versus 21 6 days with TAT-treated islets. The IPGTT showed a 50% reduction in the area under the curve associated with an improved insulin response in mice transplanted with ??RACK-treated islets compared to TAT-treated islets. A <span class="hlt">preconditioning</span> regimen using PKC? agonist before pancreatic recovery and during islet isolation improves islet graft function and resistance to high glucose stress after transplantation. PMID:23562311</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2012InvPr..28e5015C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2012InvPr..28e5015C"><span id="translatedtitle">Left and right <span class="hlt">preconditioning</span> for electrical impedance tomography with structural information</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Calvetti, Daniela; McGivney, Debra; Somersalo, Erkki</p> <p>2012-05-01</p> <p>A common problem in computational inverse problems is to find an efficient way of solving linear or nonlinear least-squares problems. For large-scale problems, iterative solvers are the method of choice for solving the associated linear systems, and for nonlinear problems, an additional effective local linearization method is required. In this paper, we discuss an efficient <span class="hlt">preconditioning</span> scheme for Krylov subspace methods, based on the Bayesian analysis of the inverse problem. The model problem to which we apply this methodology is electrical impedance tomography (EIT) augmented with prior information coming from a complementary modality, such as x-ray imaging. The particular geometry considered here models the x-ray-guided EIT for breast imaging. The interest in applying EIT concurrently with x-ray breast imaging arises from the experimental observation that the impedivity spectra of certain types of malignant and benign tissues differ significantly from each other, thus offering a possibility of diagnosis without more invasive tissue sampling. After setting up the EIT inverse problem within a Bayesian framework, we present an inner and outer iteration scheme for computing a maximum a posteriori estimate. The prior covariance provides a right preconditioner and the modeling error covariance provides a left preconditioner for the iterative method used to solve the linear least-squares problem at each outer iteration of the optimization problem. Moreover, the stopping criterion for the inner iterations is coupled with the progress of the solution of the outer iteration. Besides the <span class="hlt">preconditioning</span> scheme, the computational efficiency relies on a very efficient method to compute the Jacobian, obtained by carefully organizing the forward computation. Computed examples illustrate the robustness and computational efficiency of the proposed algorithm.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/19191501','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/19191501"><span id="translatedtitle">Combined effects of scaffold stiffening and mechanical <span class="hlt">preconditioning</span> cycles on construct biomechanics, gene expression, and tendon repair biomechanics.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Nirmalanandhan, Victor Sanjit; Juncosa-Melvin, Natalia; Shearn, Jason T; Boivin, Gregory P; Galloway, Marc T; Gooch, Cynthia; Bradica, Gino; Butler, David L</p> <p>2009-08-01</p> <p>Our group has previously reported that in vitro mechanical stimulation of tissue-engineered tendon constructs significantly increases both construct stiffness and the biomechanical properties of the repair tissue after surgery. When optimized using response surface methodology, our results indicate that a mechanical stimulus with three components (2.4% strain, 3000 cycles/day, and one cycle repetition) produced the highest in vitro linear stiffness. Such positive correlations between construct and repair stiffness after surgery suggest that enhancing structural stiffness before surgery could not only accelerate repair stiffness but also <span class="hlt">prevent</span> premature failures in culture due to poor mechanical integrity. In this study, we examined the combined effects of scaffold crosslinking and subsequent mechanical stimulation on construct mechanics and biology. Autologous tissue-engineered constructs were created by seeding mesenchymal stem cells (MSCs) from 15 New Zealand white rabbits on type I collagen sponges that had undergone additional dehydrothermal crosslinking (termed ADHT in this manuscript). Both constructs from each rabbit were mechanically stimulated for 8h/day for 12 consecutive days with half receiving 100 cycles/day and the other half receiving 3000 cycles/day. These paired MSC-collagen autologous constructs were then implanted in bilateral full-thickness, full-length defects in the central third of rabbit patellar tendons. Increasing the number of in vitro cycles/day delivered to the ADHT constructs in culture produced no differences in stiffness or gene expression and no changes in biomechanical properties or histology 12 weeks after surgery. Compared to MSC-based repairs from a previous study that received no additional treatment in culture, ADHT crosslinking of the scaffolds actually lowered the 12-week repair stiffness. Thus, while ADHT crosslinking may initially stiffen a construct in culture, this specific treatment also appears to mask any benefits of stimulation among repairs postsurgery. Our findings emphasize the importance of properly <span class="hlt">preconditioning</span> a scaffold to better control/modulate MSC differentiation in vitro and to further enhance repair outcome in vivo. PMID:19191501</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2792106','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2792106"><span id="translatedtitle">Combined Effects of Scaffold Stiffening and Mechanical <span class="hlt">Preconditioning</span> Cycles on Construct Biomechanics, Gene Expression, and Tendon Repair Biomechanics</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Juncosa-Melvin, Natalia; Shearn, Jason T.; Boivin, Gregory P.; Galloway, Marc T.; Gooch, Cynthia; Bradica, Gino; Butler, David L.</p> <p>2009-01-01</p> <p>Our group has previously reported that in vitro mechanical stimulation of tissue-engineered tendon constructs significantly increases both construct stiffness and the biomechanical properties of the repair tissue after surgery. When optimized using response surface methodology, our results indicate that a mechanical stimulus with three components (2.4% strain, 3000?cycles/day, and one cycle repetition) produced the highest in vitro linear stiffness. Such positive correlations between construct and repair stiffness after surgery suggest that enhancing structural stiffness before surgery could not only accelerate repair stiffness but also <span class="hlt">prevent</span> premature failures in culture due to poor mechanical integrity. In this study, we examined the combined effects of scaffold crosslinking and subsequent mechanical stimulation on construct mechanics and biology. Autologous tissue-engineered constructs were created by seeding mesenchymal stem cells (MSCs) from 15 New Zealand white rabbits on type I collagen sponges that had undergone additional dehydrothermal crosslinking (termed ADHT in this manuscript). Both constructs from each rabbit were mechanically stimulated for 8?h/day for 12 consecutive days with half receiving 100?cycles/day and the other half receiving 3000?cycles/day. These paired MSCcollagen autologous constructs were then implanted in bilateral full-thickness, full-length defects in the central third of rabbit patellar tendons. Increasing the number of in vitro cycles/day delivered to the ADHT constructs in culture produced no differences in stiffness or gene expression and no changes in biomechanical properties or histology 12 weeks after surgery. Compared to MSC-based repairs from a previous study that received no additional treatment in culture, ADHT crosslinking of the scaffolds actually lowered the 12-week repair stiffness. Thus, while ADHT crosslinking may initially stiffen a construct in culture, this specific treatment also appears to mask any benefits of stimulation among repairs postsurgery. Our findings emphasize the importance of properly <span class="hlt">preconditioning</span> a scaffold to better control/modulate MSC differentiation in vitro and to further enhance repair outcome in vivo. PMID:19191501</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/20855438','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/20855438"><span id="translatedtitle">Fatigue <span class="hlt">preconditioning</span> increases fatigue resistance in mouse flexor digitorum brevis muscles with non-functioning K(ATP) channels.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Boudreault, Louise; Cifelli, Carlo; Bourassa, Franois; Scott, Kyle; Renaud, Jean-Marc</p> <p>2010-11-15</p> <p>The objective of this study was to determine how an initial fatigue bout (FAT1 at 37C) affects free myoplasmic Ca(2+) concentration and force ([Ca(2+)](i)/force) during a subsequent fatigue bout (FAT2) in mouse flexor digitorum brevis (FDB). During FAT1, both tetanic [Ca(2+)](i)/force decreased; however, they decreased to significantly lower levels when FAT1 was carried out in the presence of glibenclamide, a sarcolemmal K(ATP) (sK(ATP)) channel blocker. Glibenclamide also elicited greater increases in unstimulated [Ca(2+)](i)/force, which occurred when fibres failed to fully relax between contractions during FAT1. Finally, glibenclamide impaired force recovery after FAT1. The decreases in tetanic [Ca(2+)](i)/force and increases in unstimulated [Ca(2+)](i)/force were slower during FAT2 elicited 60 min after FAT1. Under control conditions, the effects were small with very few significant differences. In the presence of glibenclamide, on the other hand, the differences between FAT1 and FAT2 were very large. Unexpectedly, the differences in unstimulated and tetanic [Ca(2+)](i)/force between control and glibenclamide conditions observed during FAT1 were no longer observed during FAT2. The lack of differences was not related to a failure of glibenclamide to block K(ATP) channels during FAT2 because the effects of FAT1 on FAT2 were also observed using Kir6.2(-/-) mouse FDB, which lack sK(ATP) channel activity. The differences in [Ca(2+)](i)/force between FAT1 and FAT2 could be observed with FAT1 duration of just 30 s and a FAT1-FAT2 interval of at least 30 min. A modulation of factors involved in ischaemic <span class="hlt">pre-conditioning</span>, i.e. A1-adenosine receptors, sK(ATP) and mitochondrial K(ATP) (mK(ATP)) channels, PKC and reactive oxygen species, during FAT1 had no effect on FAT2 fatigue kinetics. It is concluded that a preceding fatigue bout triggers an acute physiological process that <span class="hlt">prevents</span> the contractile dysfunction induced by non-functioning K(ATP) channels. PMID:20855438</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://transplantliving.org/after-the-transplant/staying-healthy/preventing-rejection/','NIH-MEDLINEPLUS'); return false;" href="http://transplantliving.org/after-the-transplant/staying-healthy/preventing-rejection/"><span id="translatedtitle"><span class="hlt">Preventing</span> Rejection</span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>... Staying Healthy Post-Transplant Tests <span class="hlt">Preventing</span> Rejection Infections & Immunity Health Concerns Diet & Exercise Recovery Resources Support Services ... These drugs also allow you to maintain enough immunity to <span class="hlt">prevent</span> overwhelming infection. Many of the medications ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=73619&keyword=grant+AND+funding&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50&CFID=55787603&CFTOKEN=40973995','EPA-EIMS'); return false;" href="http://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=73619&keyword=grant+AND+funding&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50&CFID=55787603&CFTOKEN=40973995"><span id="translatedtitle">POLLUTION <span class="hlt">PREVENTION</span></span></a></p> <p><a target="_blank" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p> <p></p> <p></p> <p>The GLNPO pollution <span class="hlt">prevention</span> grant assistance program in the Great Lakes basin has evolved over the years from funding general pollution <span class="hlt">prevention</span> technical assistance to supporting activities to reduce persistent toxic substances of concern, with a special emphasis on mercury...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25979673','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25979673"><span id="translatedtitle">Sevoflurane <span class="hlt">preconditioning</span> improving cerebral focal ischemia-reperfusion damage in a rat model via PI3K/Akt signaling pathway.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhang, Yan; Tian, Shou-Yuan; Li, Yan-Wei; Zhang, Ling; Yu, Jian-Bo; Li, Jing; Chen, Yi-Yang; Wang, Ya-Xin; Liang, Yu; Zhang, Xiu-Shan; Wang, Wen-Sheng; Liu, Hai-Gen</p> <p>2015-09-10</p> <p>In this study, we aimed to assess the neuroprotective effect of sevoflurane <span class="hlt">preconditioning</span> in a cerebral focal ischemia-reperfusion rat model. Sixty Sprague Dawley rats were divided into six groups: sham operated group, cerebral focal ischemia-reperfusion (CIR) group, CIR+sevoflurane <span class="hlt">preconditioning</span> (SP) (2%) group, CIR+sevoflurane <span class="hlt">preconditioning</span> (2.5%) group, CIR+sevoflurane <span class="hlt">preconditioning</span> (3%) group, and CIR+sevoflurane <span class="hlt">preconditioning</span> (3.5%) group. All subjects were euthanized 2days post-surgery and their hippocampus tissues were removed. Tissue malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were measured and hippocampus tissue samples were examined histopathologically. Results showed that significant difference in antioxidant, immunity indexes, and apoptosis-related protein expression was detected in hippocampus tissue between sham-operated control and CIR groups. Sevoflurane <span class="hlt">preconditioning</span> significantly dose-dependently reduced MDA, IL-1?, IL-6, IL-10 and TNF-? levels and enhanced antioxidant enzyme activities in hippocampus tissue of CIR+SP groups compared to CIR group. In addition, sevoflurane <span class="hlt">preconditioning</span> significantly dose-dependently upregulated PI3K, p-Akt and Bcl-2 levels and downregulated caspase-3 and Bax levels in hippocampus tissue of CIR+SP groups compared to CIR group. It can be concluded that sevoflurane <span class="hlt">preconditioning</span> demonstrates a strong and ameliorative effect on cerebral I/R damage in rats. The neuroprotective mechanisms of sevoflurane <span class="hlt">preconditioning</span> are associated with its properties of anti-apoptosis and anti-oxidation as well as regulation of PI3K and p-Akt signal activation. PMID:25979673</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26313243','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26313243"><span id="translatedtitle">Hypoxic <span class="hlt">preconditioning</span> promotes the translocation of protein kinase C ? binding with caveolin-3 at cell membrane not mitochondrial in rat heart.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yu, Hongmei; Yang, Zhaogang; Pan, Su; Yang, Yudan; Tian, Jiayi; Wang, Luowei; Sun, Wei</p> <p>2015-11-17</p> <p>Protein kinase C has been shown to play a central role in the cardioprotection of ischemic <span class="hlt">preconditioning</span>. However, the mechanism underlying PKC-mediated cardioprotection is not completely understood. Given that caveolae are critical for PKC signaling, we sought to determine whether hypoxic <span class="hlt">preconditioning</span> promotes translocation and association of PKC isoforms with caveolin-3. A cellular model of hypoxic <span class="hlt">preconditioning</span> from adult rat cardiac myocytes (ARCM) or H9c2 cells was employed to examine PKC isoforms by molecular, biochemical and cellular imaging analysis. Hypoxia was induced by incubating the cells in an airtight chamber in which O2 was replaced by N2 with glucose-free Tyrode's solution. Cells were subjected to hypoxic <span class="hlt">preconditioning</span> with 10 minutes of hypoxia followed by 30 minutes of reoxygenation. Western blot data indicated that the band intensity for PKC?, PKC? or PKC?, but not PKC? and PKC? was enhanced significantly by hypoxic <span class="hlt">preconditioning</span> from the caveolin-enriched plasma membrane interactions. Immunoprecipitation experiments from the caveolin-enriched membrane fractions of ARCM showed that the level of PKC?, PKC? and PKC? in the anti-caveolin-3 immunoprecipitates was also increased by hypoxic <span class="hlt">preconditioning</span>. Further, our FRET analysis in H9c2 cells suggested that there is a minimum FRET signal for caveolin-3 and PKC? along cell peripherals, but hypoxic <span class="hlt">preconditioning</span> enhanced the FRET signal, indicating a potential interaction between caveolin-3 and PKC?. And also treatment of the cells with hypoxic <span class="hlt">preconditioning</span> led to a smaller amount of translocation of PKC? to the mitochondria than that to the membrane. We demonstrate that hypoxic <span class="hlt">preconditioning</span> promotes rapid association of PKC?, PKC? and PKC? with the caveolin-enriched plasma membrane microdomain of cardiac myocytes, and PKC? via direct molecular interaction with caveolin-3. This regulatory mechanism may play an important role in cardioprotection. PMID:26313243</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://files.eric.ed.gov/fulltext/ED440346.pdf','ERIC'); return false;" href="http://files.eric.ed.gov/fulltext/ED440346.pdf"><span id="translatedtitle"><span class="hlt">Preventing</span> Addiction.</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Moore, Susan Fordney</p> <p></p> <p>The purpose of this paper is to provide the beginning counselor with an overview of <span class="hlt">prevention</span> concepts. <span class="hlt">Prevention</span> is a relatively new emphasis in community efforts to stem the rising costs of substance abuse and other high-risk behaviors. The paper discusses agent, host, and environmental <span class="hlt">prevention</span> models and how they relate to causal theories</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4625520','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4625520"><span id="translatedtitle">Optimal concentration and time window for proliferation and differentiation of neural stem cells from embryonic cerebral cortex: 5% oxygen <span class="hlt">preconditioning</span> for 72 hours</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Yuan, Li-li; Guan, Ying-jun; Ma, Deng-dian; Du, Hong-mei</p> <p>2015-01-01</p> <p>Hypoxia promotes proliferation and differentiation of neural stem cells from embryonic day 12 rat brain tissue, but the concentration and time of hypoxic <span class="hlt">preconditioning</span> are controversial. To address this, we cultured neural stem cells isolated from embryonic day 14 rat cerebral cortex in 5% and 10% oxygen in vitro. MTT assay, neurosphere number, and immunofluorescent staining found that 5% or 10% oxygen <span class="hlt">preconditioning</span> for 72 hours improved neural stem cell viability and proliferation. With prolonged hypoxic duration (120 hours), the proportion of apoptotic cells increased. Thus, 5% oxygen <span class="hlt">preconditioning</span> for 72 hours promotes neural stem cell proliferation and neuronal differentiation. Our findings indicate that the optimal concentration and duration of hypoxic <span class="hlt">preconditioning</span> for promoting proliferation and differentiation of neural stem cells from the cerebral cortex are 5% oxygen for 72 hours. PMID:26604915</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2002AGUFMOS11D0252M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2002AGUFMOS11D0252M"><span id="translatedtitle">Effect of salinity barrier layer in the <span class="hlt">preconditioning</span> and onset of El Nino</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Maes, C.; Picaut, J.; Belamari, S.</p> <p>2002-12-01</p> <p>Specific salinity stratification of the western Pacific warm pool known as the barrier layer has been proposed to be important in the coupling between sea surface temperature (SST) and winds leading to El Nino-Southern Oscillation. Thick barrier layer maintains surface waters warmer than 28C (the threshold for organized atmospheric convection) by reducing the entrainment cooling from below the ocean mixed layer. This mechanism allows an accumulation of heat in the upper ocean layers prior to El Nino. It also confines the forcing of westerly wind burst (WWB), the most accepted process as a trigger of El Nino, in a shallow mixed layer thus increasing the eastward displacement of the eastern edge of the warm pool. The importance of salinity barrier layer in the <span class="hlt">preconditioning</span> phase characterized by high ocean heat content and in the onset phase characterized by high WWB activity is investigated using a general circulation coupled model of the tropical Pacific. coupled to a general circulation model. The Meteo-France/ARPEGE global atmospheric model coupled to the LODYC/OPA ocean model is able to reproduce self-sustained El Nino events together with WWBs. The methodology consists of removing the stratification effect of salinity in the vertical mixing parameterization. This cutoff is restricted to the western side of the equatorial band (4N-4S) where SST is larger than 28C. By removing the barrier layer, the main effect is to reduce the ocean heat content in the <span class="hlt">preconditioning</span> period and to modify the ocean dynamics in response to WWBs in the onset period. Considering three El Nino events of different intensities, hindcasts show that interactions between the ocean and the atmosphere over the warm pool do not amplify and each El Nino is weakened or even aborted. A detailed analysis confirms that the physics of the warm pool such as vertical diffusion and horizontal advection is essential to set up the favorable conditions for the development of El Nino. For each event, a 5 additional members ensemble confirms that salinity stratification play a crucial and significant role during these initial phases of El Nino and that it should be considered in coupled models in order to improve El Nino forecasts.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014JCoPh.276..508S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014JCoPh.276..508S"><span id="translatedtitle">Nonlinear <span class="hlt">preconditioning</span> for efficient and accurate interface capturing in simulation of multicomponent compressible flows</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Shukla, Ratnesh K.</p> <p>2014-11-01</p> <p>Single fluid schemes that rely on an interface function for phase identification in multicomponent compressible flows are widely used to study hydrodynamic flow phenomena in several diverse applications. Simulations based on standard numerical implementation of these schemes suffer from an artificial increase in the width of the interface function owing to the numerical dissipation introduced by an upwind discretization of the governing equations. In addition, monotonicity requirements which ensure that the sharp interface function remains bounded at all times necessitate use of low-order accurate discretization strategies. This results in a significant reduction in accuracy along with a loss of intricate flow features. In this paper we develop a nonlinear transformation based interface capturing method which achieves superior accuracy without compromising the simplicity, computational efficiency and robustness of the original flow solver. A nonlinear map from the signed distance function to the sigmoid type interface function is used to effectively couple a standard single fluid shock and interface capturing scheme with a high-order accurate constrained level set reinitialization method in a way that allows for oscillation-free transport of the sharp material interface. Imposition of a maximum principle, which ensures that the multidimensional <span class="hlt">preconditioned</span> interface capturing method does not produce new maxima or minima even in the extreme events of interface merger or breakup, allows for an explicit determination of the interface thickness in terms of the grid spacing. A narrow band method is formulated in order to localize computations pertinent to the <span class="hlt">preconditioned</span> interface capturing method. Numerical tests in one dimension reveal a significant improvement in accuracy and convergence; in stark contrast to the conventional scheme, the proposed method retains its accuracy and convergence characteristics in a shifted reference frame. Results from the test cases in two dimensions show that the nonlinear transformation based interface capturing method outperforms both the conventional method and an interface capturing method without nonlinear transformation in resolving intricate flow features such as sheet jetting in the shock-induced cavity collapse. The ability of the proposed method in accounting for the gravitational and surface tension forces besides compressibility is demonstrated through a model fully three-dimensional problem concerning droplet splash and formation of a crownlike feature.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016RScI...87bB129U','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016RScI...87bB129U"><span id="translatedtitle"><span class="hlt">Pre-conditioning</span> procedure suitable for internal-RF-antenna of J-PARC RF-driven H- ion source</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Ueno, A.; Ohkoshi, K.; Ikegami, K.; Takagi, A.; Asano, H.; Oguri, H.</p> <p>2016-02-01</p> <p>The Japan Proton Accelerator Research Complex (J-PARC) cesiated RF-driven H- ion source has been successfully operated for about 1 yr. By the world brightest level beam, the J-PARC design beam power of 1 MW was successfully demonstrated. Although no internal-RF-antenna failure, except for the once caused by an excess cesium due to a misoperation, occurred in the operation, many antennas failed in <span class="hlt">pre-conditionings</span> for the first hundred days. The antenna failure rate was drastically decreased by using an antenna with coating thicker than a standard value and the <span class="hlt">pre-conditioning</span> procedure repeating 15 min 25 kW RF-power operation and impurity-gas evacuation a few times, before the full power (50 kW) operation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26932011','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26932011"><span id="translatedtitle"><span class="hlt">Pre-conditioning</span> procedure suitable for internal-RF-antenna of J-PARC RF-driven H(-) ion source.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ueno, A; Ohkoshi, K; Ikegami, K; Takagi, A; Asano, H; Oguri, H</p> <p>2016-02-01</p> <p>The Japan Proton Accelerator Research Complex (J-PARC) cesiated RF-driven H(-) ion source has been successfully operated for about 1 yr. By the world brightest level beam, the J-PARC design beam power of 1 MW was successfully demonstrated. Although no internal-RF-antenna failure, except for the once caused by an excess cesium due to a misoperation, occurred in the operation, many antennas failed in <span class="hlt">pre-conditionings</span> for the first hundred days. The antenna failure rate was drastically decreased by using an antenna with coating thicker than a standard value and the <span class="hlt">pre-conditioning</span> procedure repeating 15 min 25 kW RF-power operation and impurity-gas evacuation a few times, before the full power (50 kW) operation. PMID:26932011</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_22 --> <div id="page_23" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="441"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25562631','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25562631"><span id="translatedtitle"><span class="hlt">Preconditioning</span> effect of (S)-3,5-dihydroxyphenylglycine on ischemic injury in middle cerebral artery occluded Sprague-Dawley rats.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Nik Ramli, Nik Nasihah; Omar, Nursyazwani; Husin, Andrean; Ismail, Zalina; Siran, Rosfaiizah</p> <p>2015-02-19</p> <p>Glutamate receptors are the integral cellular components associated with excitotoxicity mechanism induced by the ischemic cascade events. Therefore the glutamate receptors have become the major molecular targets of neuroprotective agents in stroke researches. Recent studies have demonstrated that a Group I metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) <span class="hlt">preconditioning</span> elicits neuroprotection in the hippocampal slice cultures exposed to toxic level of N-methyl-d-aspartate (NMDA). We further investigated the <span class="hlt">preconditioning</span> effects of (S)-3,5-DHPG on acute ischemic stroke rats. One 10 or 100?M of (S)-3,5-DHPG was administered intrathecally to Sprague-Dawley adult male rats, 2h prior to induction of acute ischemic stroke by middle cerebral artery occlusion (MCAO). After 24h, neurological deficits were evaluated by modified stroke severity scores and grid-walking test. All rats were sacrificed and infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining. The serum level of neuron-specific enolase (NSE) of each rat was analyzed by enzyme-linked immunosorbent assay (ELISA). One and 10?M of (S)-3,5-DHPG <span class="hlt">preconditioning</span> in the stroke rats showed significant improvements in motor impairment (P<0.01), reduction in the infarct volume (P<0.01) and reduction in the NSE serum level (P<0.01) compared to the control stroke rats. We conclude that 1 and 10?M (S)-3,5-DHPG <span class="hlt">preconditioning</span> induced protective effects against acute ischemic insult in vivo. PMID:25562631</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4532361','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4532361"><span id="translatedtitle">Extracellular Adenosine Formation by Ecto-5-Nucleotidase (CD73) Is No Essential Trigger for Early Phase Ischemic <span class="hlt">Preconditioning</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2015-01-01</p> <p>Background Adenosine is a powerful trigger for ischemic <span class="hlt">preconditioning</span> (IPC). Myocardial ischemia induces intracellular and extracellular ATP degradation to adenosine, which then activates adenosine receptors and elicits cardioprotection. Conventionally extracellular adenosine formation by ecto-5-nucleotidase (CD73) during ischemia was thought to be negligible compared to the massive intracellular production, but controversial reports in the past demand further evaluation. In this study we evaluated the relevance of ecto-5-nucleotidase (CD73) for infarct size reduction by ischemic <span class="hlt">preconditioning</span> in in vitro and in vivo mouse models of myocardial infarction, comparing CD73-/- and wild type (WT) mice. Methods and Results 3x5 minutes of IPC induced equal cardioprotection in isolated saline perfused hearts of wild type (WT) and CD73-/- mice, reducing control infarct sizes after 20 minutes of ischemia and 90 minutes of reperfusion from 46 6.3% (WT) and 56.1 7.6% (CD73-/-) to 26.8 4.7% (WT) and 25.6 4.7% (CD73-/-). Coronary venous adenosine levels measured after IPC stimuli by high-pressure liquid chromatography showed no differences between WT and CD73-/- hearts. Pharmacological <span class="hlt">preconditioning</span> of WT hearts with adenosine, given at the measured venous concentration, was evenly cardioprotective as conventional IPC. In vivo, 4x5 minutes of IPC reduced control infarct sizes of 45.3 8.9% (WT) and 40.5 8% (CD73-/-) to 26.3 8% (WT) and 22.6 6.6% (CD73-/-) respectively, eliciting again equal cardioprotection. The extent of IPC-induced cardioprotection in male and female mice was identical. Conclusion The infarct size limiting effects of IPC in the mouse heart in vitro and in vivo are not significantly affected by genetic inactivation of CD73. The ecto-5-nucleotidase derived extracellular formation of adenosine does not contribute substantially to adenosines well known cardioprotective effect in early phase ischemic <span class="hlt">preconditioning</span>. PMID:26261991</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26808606','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26808606"><span id="translatedtitle">The neuroprotective effects of <span class="hlt">preconditioning</span> exercise on brain damage and neurotrophic factors after focal brain ischemia in rats.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Otsuka, Shotaro; Sakakima, Harutoshi; Sumizono, Megumi; Takada, Seiya; Terashi, Takuto; Yoshida, Yoshihiro</p> <p>2016-04-15</p> <p><span class="hlt">Preconditioning</span> exercise can exert neuroprotective effects after stroke. However, the mechanism underlying these neuroprotective effects by <span class="hlt">preconditioning</span> exercise remains unclear. We investigated the neuroprotective effects of <span class="hlt">preconditioning</span> exercise on brain damage and the expression levels of the midkine (MK) and brain-derived neurotrophic factor (BDNF) after brain ischemia. Animals were assigned to one of 4 groups: exercise and ischemia (Ex), no exercise and ischemia (No-Ex), exercise and no ischemia (Ex-only), and no exercise and intact (Control). Rats ran on a treadmill for 30min once a day at a speed of 25m/min for 5days a week for 3 weeks. After the exercise program, stroke was induced by a 60min left middle cerebral artery occlusion using an intraluminal filament. The infarct volume, motor function, neurological deficits, and the cellular expressions levels of MK, BDNF, GFAP, PECAM-1, caspase 3, and nitrotyrosine (NT) were evaluated 48h after the induction of ischemia. The infarct volume, neurological deficits and motor function in the Ex group were significantly improved compared to that of the No-Ex group. The expression levels of MK, BDNF, GFAP, and PECAM-1 were enhanced in the Ex group compared to the expression levels in the No-Ex group after brain ischemia, while the expression levels of activated caspase 3 and NT were reduced in the area surrounding the necrotic lesion. Our findings suggest that <span class="hlt">preconditioning</span> exercise reduced the infract volume and ameliorated motor function, enhanced expression levels of MK and BDNF, increased astrocyte proliferation, increased angiogenesis, and reduced neuronal apoptosis and oxidative stress. PMID:26808606</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/22955056','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/22955056"><span id="translatedtitle">Reactive oxygen species are not a required trigger for exercise-induced late <span class="hlt">preconditioning</span> in the rat heart.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Taylor, Ryan P; Starnes, Joseph W</p> <p>2012-11-01</p> <p>Reactive oxygen species (ROS) have been reported to play a primary role in triggering the cardioprotective adaptations by some <span class="hlt">preconditioning</span> procedures, but whether they are required for exercise-induced <span class="hlt">preconditioning</span> is unclear. Thus in this study we used the free radical scavenger N-(2-mercaptopropionyl)glycine (MPG) to test the hypothesis that ROS is the trigger for exercise-induced <span class="hlt">preconditioning</span> of the heart against ischemia-reperfusion injury. Male F344 rats were assigned to four groups: sedentary (SED, n = 7), SED/MPG (100 mg/kg ip daily for 2 days, n = 12), exercised on a treadmill for 2 days at 20 m/min, 6 grade, for 60 min (RUN, n = 7), and RUN/MPG with 100 mg/kg MPG injected 15 min before exercise (n = 10). Preliminary experiments verified that MPG administration maintained myocardial redox status during the exercise bout. Twenty-four hours postexercise or MPG treatment isolated perfused working hearts were subjected to global ischemia for 22.5 min followed by reperfusion for 30 min. Recovery of myocardial external work (percentage of preischemic systolic pressure times cardiac output) for SED (50.4 4.5) and SED/RUN (54.7 6.6) was similar and improved in both exercise groups (P < 0.05) to 77.9 3.0 in RUN and 76.7 4.5 in RUN/MPG. A 2 2 ANOVA also revealed that exercise decreased lactate dehydrogenase release from the heart during reperfusion (marker of cell damage) without MPG effects or interactions. Expression of the cytoprotective protein inducible heat shock protein 70 increased by similar amounts in the left ventricles of RUN and RUN/MPG compared with sedentary groups (P < 0.05). We conclude that ROS are not a necessary trigger for exercise-induced <span class="hlt">preconditioning</span> in rats. PMID:22955056</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4637547','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4637547"><span id="translatedtitle">Cardiac sodium/calcium exchanger <span class="hlt">preconditioning</span> promotes anti-arrhythmic and cardioprotective effects through mitochondrial calcium-activated potassium channel</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zhang, Jian-Ying; Cheng, Kang; Lai, Dong; Kong, Ling-Heng; Shen, Min; Yi, Fu; Liu, Bing; Wu, Feng; Zhou, Jing-Jun</p> <p>2015-01-01</p> <p>Background: Reverse-mode of the Na+/Ca2+ exchanger (NCX) stimulation provides cardioprotective effects for the ischemic/reperfused heart during ischemic <span class="hlt">preconditioning</span> (IP). This study was designed to test the hypothesis that pretreatment with an inhibitor of cardiac delayed-rectifying K+ channel (IKr), E4031, increases reverse-mode of NCX activity, and triggers <span class="hlt">preconditioning</span> against infarct size (IS) and arrhythmias caused by ischemia/reperfusion injury through mitoKCa channels. Materials and methods: In the isolated perfused rat heart, myocardial ischemia/reperfusion injury was created by occlusion of the left anterior descending coronary artery for 30 min followed by 120 min reperfusion. Two cycles of coronary occlusion for 5 min and reperfusion were performed, or pretreatment with E4031 or sevoflurane (Sevo) before the 30 min occlusion with the reversed-mode of NCX inhibitor (KB-R7943) or not. Results: E4031 or Sevo <span class="hlt">preconditioning</span> not only markedly decreased IS but also reduced arrhythmias, which was significantly blunted by KB-R7943. Furthermore, these effects of E4031 <span class="hlt">preconditioning</span> on IS and arrhythmias were abolished by inhibition of the mitoKCa channels. Similarly, pretreatment with NS1619, an opener of the mitoKCa channels, for 10 min before occlusion reduced both the infarct size and arrhythmias caused by ischemia/reperfusion. However, these effects werent affected by blockade of the NCX with KB-R7943. Conclusion: Taken together, these preliminary results conclude that pretreatment with E4031 reduces infarct size and produces anti-arrhythmic effect via stimulating the reverse-mode NCX, and that the mitoKCa channels mediate the protective effects. PMID:26617732</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/biblio/5136165','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/biblio/5136165"><span id="translatedtitle">Successive overrelaxation, multigrid, and <span class="hlt">preconditioned</span> conjugate gradients algorithms for solving a diffusion problem on a vector computer</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Gary, J.; Mccormick, S.; Sweet, R.</p> <p>1983-11-01</p> <p>The authors discuss the treatment of three numerical algorithms: successive overrelaxation, multigrid and conjugate gradients <span class="hlt">preconditioned</span> by a fast poisson solver for solving large but mildly behaved diffusion problems on a vector computer with memory-to-memory architecture. The problem is a symmetric nonnegative definite matrix equation arising from a cell-centered finite difference approximation of a 3-d diffusion equation with full Neumann boundary conditions. 9 references.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25146899','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25146899"><span id="translatedtitle">Intermittent hypoxia <span class="hlt">preconditioning</span>-induced epileptic tolerance by upregulation of monocarboxylate transporter 4 expression in rat hippocampal astrocytes.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gao, Chen; Wang, Chao; Liu, Bei; Wu, Hao; Yang, Qianli; Jin, Jungong; Li, Huanfa; Dong, Shan; Gao, Guodong; Zhang, Hua</p> <p>2014-11-01</p> <p>Noxious stimuli applied at doses close to but below the threshold of cell injury induce adaptive responses that provide a defense against additional stress. Epileptic <span class="hlt">preconditioning</span> protects neurons against status epilepticus and ischemia; however, it is not known if the converse is true. During hypoxia/ischemia (H/I), lactate released from astrocytes is taken up by neurons and is stored for energy, a process mediated by monocarboxylate transporter 4 (MCT4) in astroglia. The present study investigated whether H/I <span class="hlt">preconditioning</span> can provide protection to neurons against epilepsy through upregulation of MCT4 expression in astrocytes in vitro and in vivo. An oxygen/glucose deprivation protocol was used in primary astrocyte cultures, while rats were subjected to an intermittent hypoxia <span class="hlt">preconditioning</span> (IHP) paradigm followed by lithium-pilocarpine-induced epilepsy as well as lactate transportation inhibitor injection, with a subsequent evaluation of protein expression as well as behavior. H/I induced an upregulation of MCT4 expression, while an IHP time course of 5 days provided the greatest protection against epileptic seizures, which was most apparent by 3 days after IHP. However, lactate transport function disturbances can block the protective effect induced by IHP. These findings provide a potential basis for the clinical treatment of epilepsy. PMID:25146899</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/23981244','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/23981244"><span id="translatedtitle">Bradykinin <span class="hlt">preconditioning</span> affects the number of degenerated neurons and the level of antioxidant enzymes in spinal cord ischemia in rabbits.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mechrov, Eva; Danielisov, Viera; Domorkov, Iveta; Dankov, Marianna; Stebnick, Milan; Mi?kov, Helena; Burda, Jozef</p> <p>2014-01-01</p> <p>Bradykinin <span class="hlt">preconditioning</span> has been used for acquisition of tolerance after spinal cord ischemia. Rabbits were <span class="hlt">preconditioned</span> intraperitoneally with bradykinin 48 h prior to 20 min of abdominal aorta ligation followed by 24 and 48 h of reperfusion. The activities of SOD and catalase were measured and Fluoro Jade B (FJB)-positive degenerated neurons were evaluated. The outcomes of Tarlov scoring system used to assess neurological functions showed significant improvement in bradykinin groups compared to the ischemic group. The number of FJB-positive degenerated neurons was decreased in ventral horns of both bradykinin groups. Significantly decreased activities of total SOD and mitochondrial Mn-SOD were also detected in both bradykinin groups versus ischemic group while CuZn-SOD and catalase activities were significantly decreased only in the bradykinin group after 24h of reperfusion versus ischemic group. These findings suggest that one of the possibilities of the neuroprotective effect of delayed bradykinin <span class="hlt">preconditioning</span> against spinal cord ischemic injury could be realized by mitochondrial protection and decreased synthesis of Mn-SOD as well as by promotion of neuronal survival. PMID:23981244</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.healthychildren.org/English/safety-prevention/all-around/Pages/Poison-Prevention.aspx','NIH-MEDLINEPLUS'); return false;" href="https://www.healthychildren.org/English/safety-prevention/all-around/Pages/Poison-Prevention.aspx"><span id="translatedtitle">Poison <span class="hlt">Prevention</span></span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>... <span class="hlt">Prevention</span> Listen Espaol Text Size Email Print Share Poison <span class="hlt">Prevention</span> Page Content Article Body Post the Poison Help number 1-800-222-1222 on the ... or empty container of a toxic substance, call Poison Help immediately. More than a million American children ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://eric.ed.gov/?q=preventive+AND+maintenance&pg=6&id=ED196158','ERIC'); return false;" href="http://eric.ed.gov/?q=preventive+AND+maintenance&pg=6&id=ED196158"><span id="translatedtitle"><span class="hlt">Preventative</span> Maintenance.</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Migliorino, James</p> <p></p> <p>Boards of education must be convinced that spending money up front for <span class="hlt">preventive</span> maintenance will, in the long run, save districts' tax dollars. A good program of <span class="hlt">preventive</span> maintenance can minimize disruption of service; reduce repair costs, energy consumption, and overtime; improve labor productivity and system equipment reliability; handle…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26218309','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26218309"><span id="translatedtitle">Ischemic <span class="hlt">Preconditioning</span> and Exercise Performance: A Systematic Review and Meta-Analysis.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Salvador, Amadeo F; De Aguiar, Rafael A; Lisboa, Felipe D; Pereira, Kayo L; Cruz, Rogrio S; Caputo, Fabrizio</p> <p>2016-01-01</p> <p>Although the amount of evidence demonstrating the beneficial effects of ischemic <span class="hlt">preconditioning</span> (IPC) on exercise performance is increasing, conclusions about its efficacy cannot yet be drawn. Therefore, the purposes of this review were to determine the effect of IPC on exercise performance and identify the effects of different IPC procedures, exercise types, and subject characteristics on exercise performance. The analysis comprised 19 relevant studies from 2000 to 2015, 15 of which were included in the meta-analyses. Effect sizes (ES) were calculated as the standardized mean difference. Overall, IPC had a small beneficial effect on exercise performance (ES = 0.43; 90% confidence interval [CI], 0.28 to 0.51). The largest ES were found for aerobic (ES = 0.51; 90% CI, 0.35 to 0.67) and anaerobic (ES = 0.23; 90% CI, -0.12 to 0.58) exercise. In contrast, an unclear effect was observed in power and sprint performance (ES = 0.16; 90% CI, -0.20 to 0.52). In conclusion, IPC can effectively enhance aerobic and anaerobic exercise performance. PMID:26218309</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/23450811','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/23450811"><span id="translatedtitle">Neural correlates of sensory <span class="hlt">preconditioning</span>: a preliminary fMRI investigation.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yu, Tao; Lang, Simone; Birbaumer, Niels; Kotchoubey, Boris</p> <p>2014-04-01</p> <p>Sensory <span class="hlt">preconditioning</span> (SPC; also known as behaviorally silent learning) consists of a combination of two neutral stimuli, none of which elicits an unconditional response. After one of them is later paired with an unconditional stimulus (US), the other neutral stimulus also yields a conditional response although it has never been paired with the US. In this study, an event-related functional magnetic resonance imaging (fMRI) paradigm was used to specify brain regions involved in SPC. The results demonstrated that SPC was associated with significant changes in activity of several regions, notably, the left amygdala, the left hippocampus, the bilateral thalamus, the bilateral medial globus pallidus, the bilateral cerebellum, the bilateral premotor cortex, and the bilateral middle frontal gyrus. This is a first effort to use fMRI to examine the effects of SPC on brain activation. Our data suggest that there is a distributed network of structures involved in SPC including both cortical and subcortical regions, therefore add to our understanding of the neural mechanisms underlying the ability to associative learning. PMID:23450811</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/17697262','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/17697262"><span id="translatedtitle">Ischemic <span class="hlt">pre-conditioning</span> in deceased donor liver transplantation: a prospective randomized clinical trial.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Amador, A; Grande, L; Mart, J; Deulofeu, R; Miquel, R; Sol, A; Rodriguez-Laiz, G; Ferrer, J; Fondevila, C; Charco, R; Fuster, J; Hotter, G; Garca-Valdecasas, J C</p> <p>2007-09-01</p> <p>To assess the immediate and long-term effects of ischemic <span class="hlt">preconditioning</span> (IPC) in deceased donor. liver transplantation (LT), we designed a prospective, randomized controlled trial involving 60 donors: control group (CTL, n = 30) or study group (IPC, n = 30). IPC was induced by 10-min hiliar clamping immediately before recovery of organs. Clinical data and blood and liver samples were obtained in the donor and in the recipient for measurements. IPC significantly improved biochemical markers of liver cell function such as uric acid, hyaluronic acid and Hypoxia-Induced Factor-1 alpha (HIF-1 alpha) levels. Moreover, the degree of apoptosis was significantly lower in the IPC group. On clinical basis, IPC significantly improved the serum aspartate aminotransferase (AST) levels and reduced the need for reoperation in the postoperative period. Moreover, the incidence of primary nonfunction (PNF) was lower in the IPC group, but did not achieve statistical significance. We conclude that 10-min IPC protects against I/R injury in deceased donor LT. PMID:17697262</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/23750305','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/23750305"><span id="translatedtitle">Using hormetic strategies to improve ischemic <span class="hlt">preconditioning</span> and postconditioning against stroke.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhao, Heng; Joo, Sungpil; Xie, Weiying; Ji, Xunming</p> <p>2013-01-01</p> <p>Both ischemic <span class="hlt">preconditioning</span> (IPreC) and ischemic postconditioning (IPostC) trigger endogenous neuroprotective mechanisms in cerebral ischemia. IPreC is defined as a brief ischemia that protects against a subsequent severe ischemia, while IPostC refers to a series of brief cerebral blood vessel occlusions performed at reperfusion following an ischemic event. Hormesis describes a biphasic dose-response relationship in toxicology, where a low dose of toxicant stimulates and a high dose inhibits biological responses. In general, any minor stress will stimulate a biological system to generate an adaptive response; in most cases, if not all, such an adaptive response to a minor stress is beneficial to the biological system. Proponents of hormesis suggest that this effect is independent of any models, either in vivo or in vitro, from animal, plant, fungi, yeast, to bacteria, by any measurement of end points, survival ratio or time, growth, tissue repair, life span, cognition, learning and memory. In this review, we examine whether IPreC and IPostC are actually sub-forms of hormesis and whether quantitative hormetic strategies can be used to study IPreC and IPostC. By integrating the concepts of IPreC and IPostC with hormesis, we aim to broaden the avenues leading to clinical translation of IPreC and IPostC in stroke treatment. PMID:23750305</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4338382','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4338382"><span id="translatedtitle">Impact of Ischemic <span class="hlt">Preconditioning</span> on Outcome in Clinical Liver Surgery: A Systematic Review</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Chu, Michael J. J.; Vather, Ryash; Hickey, Anthony J. R.; Phillips, Anthony R. J.; Bartlett, Adam S. J. R.</p> <p>2015-01-01</p> <p>Background. Ischemia-reperfusion injury is a major cause of post-liver-surgery complications. Ischemic <span class="hlt">preconditioning</span> (IPC) has been demonstrated to protect against ischemia-reperfusion injury. Clinical studies have examined IPC in liver surgery but with conflicting results. This systematic review aimed to evaluate the effects of IPC on outcome in clinical liver surgery. Methods. An electronic search of OVID Medline and Embase databases was performed to identify studies that reported outcomes in patients undergoing liver surgery subjected to IPC. Basic descriptive statistics were used to summarise data from individual clinical studies. Results. 1093 articles were identified, of which 24 met the inclusion criteria. Seven topics were selected and analysed by subgroup. There were 10 studies in cadaveric liver transplantation, 2 in living-related liver transplantation, and 12 in liver resection. IPC decreases hepatocellular damage in liver surgery as determined by transaminases but does not translate to any significant clinical benefit in orthotopic liver transplant or liver resection. Conclusions. Available clinical evidence does not support routine use of IPC in liver surgery as it does not offer any apparent benefit in perioperative outcome. Further clinical studies will need to be carried out to determine the subset of patients that will benefit from IPC. PMID:25756045</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4458764','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4458764"><span id="translatedtitle">Low G <span class="hlt">preconditioning</span> reduces liver injury induced by high +Gz exposure in rats</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Shi, Bin; Feng, Zhi-Qiang; Li, Wen-Bing; Zhang, Hong-Yi</p> <p>2015-01-01</p> <p>AIM: To investigate the effect of repeated lower +Gz exposure on liver injury induced by high +Gz exposure in rats. METHODS: Sixty male Wister rats were randomly divided into a blank control group, a low G <span class="hlt">preconditioning</span> group (LG) (exposed to +4 Gz/5 min per day for 3 d before +10 Gz/5 min exposure), and a +10 Gz/5 min group (10G) (n = 20 in each group). Blood specimens and liver tissue were harvested at 0 h and 6 h after +10 Gz/5 min exposure. Liver function was analyzed by measuring serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and liver injury was further assessed by histopathological observation. Malondialdehyde (MDA), superoxide dismutase (SOD) and Na+-K+-ATPase were determined in hepatic tissue. RESULTS: The group LG had lower ALT, AST, and MDA values at 0 h after exposure than those in group 10G. SOD values and Na+-K+-ATPase activity in the LG group were higher than in group 10G 0 h post-exposure. Hepatocyte injury was significantly less in group LG than in group 10G on histopathological evaluation. CONCLUSION: It is suggested that repeated low +Gz exposure shows a protective effect on liver injury induced by high +Gz exposure in rats. PMID:26074692</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/24462544','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/24462544"><span id="translatedtitle">Spinal neuronal NOS activation mediates intrathecal fentanyl <span class="hlt">preconditioning</span> induced remote cardioprotection in rats.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lu, Yao; Hu, Jun; Zhang, Ye; Dong, Chunshan</p> <p>2014-03-01</p> <p>Fentanyl has been widely used in anesthesia and analgesia, especially for cardiovascular surgeries. The aim of the study was to evaluate whether remote intrathecal fentanyl <span class="hlt">preconditioning</span> (RFPC) provides cardioprotection and the role of spinal nitric oxide synthase (NOS) system in this effect. Fentanyl (0.3?g/kg) was administered intrathecally during RFPC by 3 cycles of 5-minute infusions interspersed with 5-minute infusion free periods. A non-specific nitric oxide synthase (NOS) inhibitor NG-nitro l-arginine methyl ester (l-NAME, 30nmol) and a selective nNOS inhibitor 7-nitroindazole (7-NI, 100nmol) were administered intrathecally 10min before RFPC, and were used to evaluate the involvement of the NOS system of the spinal cord. RFPC group markedly reduced the infarct size compared with control. However, the cardioprotection of RFPC could be abolished by pretreatment with l-NAME and 7-NI. RFPC merely increased the expression of nNOS and did not affect iNOS and eNOS expression. l-NAME reversed nNOS expression up-regulation induced by RFPC treatment. The present study demonstrated that RFPC effectively induced cardioprotection through activating the nNOS in the spinal cord. PMID:24462544</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25697105','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25697105"><span id="translatedtitle">PBT2 inhibits glutamate-induced excitotoxicity in neurons through metal-mediated <span class="hlt">preconditioning</span>.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Johanssen, Timothy; Suphantarida, Nuttawat; Donnelly, Paul S; Liu, Xiang M; Petrou, Steven; Hill, Andrew F; Barnham, Kevin J</p> <p>2015-09-01</p> <p>Excitotoxicity is the pathological process by which neuronal death occurs as a result of excessive stimulation of receptors at the excitatory synapse such as the NMDA receptor (NMDAR). Excitotoxicity has been implicated in the acute neurological damage from ischemia and traumatic brain injury and in the chronic neurodegeneration in Alzheimer's disease (AD) and Huntington's disease (HD). As a result NMDAR antagonists have become an attractive therapeutic strategy for the potential treatment of multiple neurodegenerative diseases. However NMDAR signaling is dichotomous in nature, with excessive increases in neuronal intracellular calcium through excessive NMDAR activity being lethal but moderate increases to intracellular calcium levels during normal synaptic function providing neuroprotection. Subsequently indiscriminant inhibition of this receptor is best avoided as was concluded from previous clinical trials of NMDAR antagonists. We show that the metal chaperone, PBT2, currently in clinical trials for HD, is able to protect against glutamate-induced excitotoxicity mediated through NMDARs. This was achieved by PBT2 inducing Zn(2+)-dependent increases in intracellular Ca(2+) levels resulting in <span class="hlt">preconditioning</span> of neurons and inhibition of Ca(2+)-induced neurotoxic signaling cascade involving calpain-activated cleavage of calcineurin. Our study demonstrates that modulating intracellular Ca(2+) levels by a zinc ionophore is a valid therapeutic strategy to protect against the effects of excitotoxicity thought to underlie both acute and chronic neurodegenerative diseases. PMID:25697105</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/scitech/biblio/22415473','SCIGOV-STC'); return false;" href="http://www.osti.gov/scitech/biblio/22415473"><span id="translatedtitle">Electrophilic surface sites as <span class="hlt">precondition</span> for the chemisorption of pyrrole on GaAs(001) surfaces</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciTech Connect</a></p> <p>Bruhn, Thomas; Fimland, Bjørn-Ove; Vogt, Patrick</p> <p>2015-03-14</p> <p>We report how the presence of electrophilic surface sites influences the adsorption mechanism of pyrrole on GaAs(001) surfaces. For this purpose, we have investigated the adsorption behavior of pyrrole on different GaAs(001) reconstructions with different stoichiometries and thus different surface chemistries. The interfaces were characterized by x-ray photoelectron spectroscopy, scanning tunneling microscopy, and by reflectance anisotropy spectroscopy in a spectral range between 1.5 and 5 eV. On the As-rich c(4 × 4) reconstruction that exhibits only nucleophilic surface sites, pyrrole was found to physisorb on the surface without any significant modification of the structural and electronic properties of the surface. On the Ga-rich GaAs(001)-(4 × 2)/(6 × 6) reconstructions which exhibit nucleophilic as well as electrophilic surface sites, pyrrole was found to form stable covalent bonds mainly to the electrophilic (charge deficient) Ga atoms of the surface. These results clearly demonstrate that the existence of electrophilic surface sites is a crucial <span class="hlt">precondition</span> for the chemisorption of pyrrole on GaAs(001) surfaces.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/19665135','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/19665135"><span id="translatedtitle">Mechanical response of periodontal ligament: effects of specimen geometry, <span class="hlt">preconditioning</span> cycles and time lapse.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bergomi, Marzio; Anselm Wiskott, H W; Botsis, John; Shibata, Tatsuya; Belser, Urs C</p> <p>2009-10-16</p> <p>This study was conducted as part of research line addressing the mechanical response of periodontal ligament (PDL) to tensile-compressive sinusoidal loading. The aim of the present project was to determine the effect of three potential sources of variability: (1) specimen geometry, (2) tissue <span class="hlt">preconditioning</span> and (3) tissue structural degradation over time. For the three conditions, selected mechanical parameters were evaluated and compared. (1) Standard flat specimens (obtained by sequentially slicing portions of bone, PDL and dentin using a precision band saw) and new cylindrical specimens (extracted with a diamond-coated trephine drill) were obtained from bovine mandibular first molars and subjected to a sinusoidal load profile. (2) Specimens were loaded with up to 2000 cycles. (3) Specimens were immersed in saline and tested after 0, 30 and 60 min. From the data generated, the following was concluded: (1) specimen geometry and preparation technique do not influence the mechanical response of the PDL; (2) the mechanical response stabilizes after approximately 1000 cycles; and (3) no major structural degradation occurs when PDL is immersed in saline for a time lapse up to 60 min. PMID:19665135</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_23 --> <div id="page_24" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="461"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2002CompM..30...12C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2002CompM..30...12C"><span id="translatedtitle">Enhancing the performance of the FETI method with <span class="hlt">preconditioning</span> techniques implemented on clusters of networked computers</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Charmpis, D. C.; Papadrakakis, M.</p> <p></p> <p>The FETI domain decomposition method for solving large-scale problems in computational structural mechanics involves the solution of an interface problem, which is handled by a <span class="hlt">Preconditioned</span> Conjugate Projected Gradient (PCPG) algorithm. Two preconditioners are widely used to accelerate the convergence of the iterative PCPG algorithm: the optimal Dirichlet preconditioner and the economical lumped preconditioner. The Dirichlet preconditioner is computationally more efficient than the lumped preconditioner for ill-conditioned problems, but needs additional storage for the stiffness matrices of the subdomains' internal degrees of freedom (d.o.f.). In this study a new set of PCPG preconditioners is presented by providing approximate expressions to the inverse iteration matrix of the PCPG algorithm. The resulting approximate Dirichlet preconditioners are obtained by using instead of the whole stiffness matrix of the internal d.o.f. in each subdomain the following alternatives: a diagonal scaling matrix, a SSOR type matrix or an incomplete Cholesky factorization matrix. The computational behavior and performance of the proposed PCPG preconditioners is evaluated using an implementation of the FETI method on a cluster of ethernet-networked PCs running the message passing software PVM. It is demonstrated that the FETI method equipped with the approximate Dirichlet preconditioners leads for a number of large-scale problems to faster and less storage demanding overall solutions than with either Dirichlet or lumped preconditioner.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015JaJAP..54hKG08S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015JaJAP..54hKG08S"><span id="translatedtitle">Acceleration of potential-induced degradation by salt-mist <span class="hlt">preconditioning</span> in crystalline silicon photovoltaic modules</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Suzuki, Soh; Nishiyama, Naoki; Yoshino, Seiji; Ujiro, Takumi; Watanabe, Shin; Doi, Takuya; Masuda, Atsushi; Tanahashi, Tadanori</p> <p>2015-08-01</p> <p>We examined the sequential effects of salt-mist stress followed by high-system-voltage stress on the power loss of crystalline silicon photovoltaic (PV) modules to determine whether a crucial failure as potential-induced degradation (PID) is accelerated by material-property changes caused by the long-term effects of a less harmful stress such as salt-mist spraying. Degradation profiles confirmed in this study show that PID is accelerated by certain types of salt-mist <span class="hlt">preconditioning</span>. For the acceleration of PID, the contribution of sodium ions liberated from the front glass of the PV module seems to be excluded. Therefore, we consider that the sodium ions penetrating into the PV modules from the ambient environment may also cause degradation according to the proposed mechanisms of PID, as the sodium ions existing in the front glass cause PID. Furthermore, this type of degradation may indicate the wear-out phenomenon after a long-term exposure in the field (especially near the coast).</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015InvPr..31l5005C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015InvPr..31l5005C"><span id="translatedtitle">A hierarchical KrylovBayes iterative inverse solver for MEG with physiological <span class="hlt">preconditioning</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Calvetti, D.; Pascarella, A.; Pitolli, F.; Somersalo, E.; Vantaggi, B.</p> <p>2015-12-01</p> <p>The inverse problem of MEG aims at estimating electromagnetic cerebral activity from measurements of the magnetic fields outside the head. After formulating the problem within the Bayesian framework, a hierarchical conditionally Gaussian prior model is introduced, including a physiologically inspired prior model that takes into account the preferred directions of the source currents. The hyperparameter vector consists of prior variances of the dipole moments, assumed to follow a non-conjugate gamma distribution with variable scaling and shape parameters. A point estimate of both dipole moments and their variances can be computed using an iterative alternating sequential updating algorithm, which is shown to be globally convergent. The numerical solution is based on computing an approximation of the dipole moments using a Krylov subspace iterative linear solver equipped with statistically inspired <span class="hlt">preconditioning</span> and a suitable termination rule. The shape parameters of the model are shown to control the focality, and furthermore, using an empirical Bayes argument, it is shown that the scaling parameters can be naturally adjusted to provide a statistically well justified depth sensitivity scaling. The validity of this interpretation is verified through computed numerical examples. Also, a computed example showing the applicability of the algorithm to analyze realistic time series data is presented.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://ntrs.nasa.gov/search.jsp?R=20020051027&hterms=newton+law&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D50%26Ntt%3Dnewton%2527s%2Blaw','NASA-TRS'); return false;" href="http://ntrs.nasa.gov/search.jsp?R=20020051027&hterms=newton+law&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D50%26Ntt%3Dnewton%2527s%2Blaw"><span id="translatedtitle">Discretization and <span class="hlt">Preconditioning</span> Algorithms for the Euler and Navier-Stokes Equations on Unstructured Meshes</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Barth, Timothy J.; Kutler, Paul (Technical Monitor)</p> <p>1998-01-01</p> <p>Several stabilized demoralization procedures for conservation law equations on triangulated domains will be considered. Specifically, numerical schemes based on upwind finite volume, fluctuation splitting, Galerkin least-squares, and space discontinuous Galerkin demoralization will be considered in detail. A standard energy analysis for several of these methods will be given via entropy symmetrization. Next, we will present some relatively new theoretical results concerning congruence relationships for left or right symmetrized equations. These results suggest new variants of existing FV, DG, GLS, and FS methods which are computationally more efficient while retaining the pleasant theoretical properties achieved by entropy symmetrization. In addition, the task of Jacobean linearization of these schemes for use in Newton's method is greatly simplified owing to exploitation of exact symmetries which exist in the system. The FV, FS and DG schemes also permit discrete maximum principle analysis and enforcement which greatly adds to the robustness of the methods. Discrete maximum principle theory will be presented for general finite volume approximations on unstructured meshes. Next, we consider embedding these nonlinear space discretizations into exact and inexact Newton solvers which are <span class="hlt">preconditioned</span> using a nonoverlapping (Schur complement) domain decomposition technique. Elements of nonoverlapping domain decomposition for elliptic problems will be reviewed followed by the present extension to hyperbolic and elliptic-hyperbolic problems. Other issues of practical relevance such the meshing of geometries, code implementation, turbulence modeling, global convergence, etc, will. be addressed as needed.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://ntrs.nasa.gov/search.jsp?R=20020048259&hterms=newton+law&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Dnewton%2527s%2Blaw','NASA-TRS'); return false;" href="http://ntrs.nasa.gov/search.jsp?R=20020048259&hterms=newton+law&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Dnewton%2527s%2Blaw"><span id="translatedtitle">Discretization and <span class="hlt">Preconditioning</span> Algorithms for the Euler and Navier-Stokes Equations on Unstructured Meshes</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Barth, Timothy; Chancellor, Marisa K. (Technical Monitor)</p> <p>1997-01-01</p> <p>Several stabilized discretization procedures for conservation law equations on triangulated domains will be considered. Specifically, numerical schemes based on upwind finite volume, fluctuation splitting, Galerkin least-squares, and space discontinuous Galerkin discretization will be considered in detail. A standard energy analysis for several of these methods will be given via entropy symmetrization. Next, we will present some relatively new theoretical results concerning congruence relationships for left or right symmetrized equations. These results suggest new variants of existing FV, DG, GLS and FS methods which are computationally more efficient while retaining the pleasant theoretical properties achieved by entropy symmetrization. In addition, the task of Jacobian linearization of these schemes for use in Newton's method is greatly simplified owing to exploitation of exact symmetries which exist in the system. These variants have been implemented in the "ELF" library for which example calculations will be shown. The FV, FS and DG schemes also permit discrete maximum principle analysis and enforcement which greatly adds to the robustness of the methods. Some prevalent limiting strategies will be reviewed. Next, we consider embedding these nonlinear space discretizations into exact and inexact Newton solvers which are <span class="hlt">preconditioned</span> using a nonoverlapping (Schur complement) domain decomposition technique. Elements of nonoverlapping domain decomposition for elliptic problems will be reviewed followed by the present extension to hyperbolic and elliptic-hyperbolic problems. Other issues of practical relevance such the meshing of geometries, code implementation, turbulence modeling, global convergence, etc. will be addressed as needed.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26168294','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26168294"><span id="translatedtitle"><span class="hlt">Preconditioning</span> allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rosen, Chava; Shezen, Elias; Aronovich, Anna; Klionsky, Yael Zlotnikov; Yaakov, Yasmin; Assayag, Miri; Biton, Inbal Eti; Tal, Orna; Shakhar, Guy; Ben-Hur, Herzel; Shneider, David; Vaknin, Zvi; Sadan, Oscar; Evron, Shmuel; Freud, Enrique; Shoseyov, David; Wilschanski, Michael; Berkman, Neville; Fibbe, Willem E; Hagin, David; Hillel-Karniel, Carmit; Krentsis, Irit Milman; Bachar-Lustig, Esther; Reisner, Yair</p> <p>2015-08-01</p> <p>Repair of injured lungs represents a longstanding therapeutic challenge. We show that human and mouse embryonic lung tissue from the canalicular stage of development (20-22 weeks of gestation for humans, and embryonic day 15-16 (E15-E16) for mouse) are enriched with progenitors residing in distinct niches. On the basis of the marked analogy to progenitor niches in bone marrow (BM), we attempted strategies similar to BM transplantation, employing sublethal radiation to vacate lung progenitor niches and to reduce stem cell competition. Intravenous infusion of a single cell suspension of canalicular lung tissue from GFP-marked mice or human fetal donors into naphthalene-injured and irradiated syngeneic or SCID mice, respectively, induced marked long-term lung chimerism. Donor type structures or 'patches' contained epithelial, mesenchymal and endothelial cells. Transplantation of differentially labeled E16 mouse lung cells indicated that these patches were probably of clonal origin from the donor. Recipients of the single cell suspension transplant exhibited marked improvement in lung compliance and tissue damping reflecting the energy dissipation in the lung tissues. Our study provides proof of concept for lung reconstitution by canalicular-stage human lung cells after <span class="hlt">preconditioning</span> of the pulmonary niche. PMID:26168294</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4466405','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4466405"><span id="translatedtitle">Mitochondrial Dihydrolipoamide Dehydrogenase Is Upregulated in Response to Intermittent Hypoxic <span class="hlt">Preconditioning</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Li, Rongrong; Luo, Xiaoting; Wu, Jinzi; Thangthaeng, Nopporn; Jung, Marianna E.; Jing, Siqun; Li, Linya; Ellis, Dorette Z.; Liu, Li; Ding, Zhengnian; Forster, Michael J.; Yan, Liang-Jun</p> <p>2015-01-01</p> <p>Intermittent hypoxia <span class="hlt">preconditioning</span> (IHP) has been shown to protect neurons against ischemic stroke injury. Studying how proteins respond to IHP may identify targets that can help fight stroke. The objective of the present study was to investigate whether mitochondrial dihydrolipoamide dehydrogenase (DLDH) would respond to IHP and if so, whether such a response could be linked to neuroprotection in ischemic stroke injury. To do this, we subjected male rats to IHP for 20 days and measured the content and activity of DLDH as well as the three ?-keto acid dehydrogenase complexes that contain DLDH. We also measured mitochondrial electron transport chain enzyme activities. Results show that DLDH content was indeed upregulated by IHP and this upregulation did not alter the activities of the three ?-keto acid dehydrogenase complexes. Results also show that the activities of the five mitochondrial complexes (I-V) were not altered either by IHP. To investigate whether IHP-induced DLDH upregulation is linked to neuroprotection against ischemic stroke injury, we subjected both DLDH deficient mouse and DLDH transgenic mouse to stroke surgery followed by measurement of brain infarction volume. Results indicate that while mouse deficient in DLDH had exacerbated brain injury after stroke, mouse overexpressing human DLDH also showed increased brain injury after stroke. Therefore, the physiological significance of IHP-induced DLDH upregulation remains to be further investigated. PMID:26078703</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26058479','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26058479"><span id="translatedtitle">Are the Beneficial Effects of Ischemic <span class="hlt">Preconditioning</span> on Performance Partly a Placebo Effect?</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Marocolo, M; da Mota, G R; Pelegrini, V; Appell Coriolano, H J</p> <p>2015-09-01</p> <p>The acute effect of ischemic <span class="hlt">preconditioning</span> (IPC) on the maximal performance in the 100-m freestyle event was studied in recreational swimmers. 15 swimmers (21.03.2?years) participated in a random crossover model on 3 different days (control [CON], IPC or SHAM), separated by 3-5 days. IPC consisted of 4 cycles of 5-min occlusion (220?mmHg)/5-min reperfusion in each arm, and the SHAM protocol was similar to IPC but with only 20?mmHg during the occlusion phase. The subjects were informed that both maneuvers (IPC and SHAM) would improve their performance. After IPC, CON or SHAM, the volunteers performed a maximal 100-m time trial. IPC improved performance (p=0.036) compared to CON. SHAM performance was only better than CON (p=0.059) as a tendency but did not differ from IPC performance. The individual response of the subjects to the different maneuvers was very heterogeneous. We conclude that IPC may improve performance in recreational swimmers, but this improvement could mainly be a placebo effect. PMID:26058479</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19940032140','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19940032140"><span id="translatedtitle"><span class="hlt">Preconditioned</span> implicit solvers for the Navier-Stokes equations on distributed-memory machines</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Ajmani, Kumud; Liou, Meng-Sing; Dyson, Rodger W.</p> <p>1994-01-01</p> <p>The GMRES method is parallelized, and combined with local <span class="hlt">preconditioning</span> 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 solver is designed to preserve the convergence rate of the equivalent 'serial' solver. A static domain-decomposition is used to partition the computational domain amongst the available processing nodes of the parallel machine. The SPMD (Single-Program Multiple-Data) programming model is combined with message-passing tools to develop the parallel code on a 32-node Intel Hypercube and a 512-node Intel Delta machine. The implicit parallel solver is validated for internal and external flow problems, and is found to compare identically with flow solutions obtained on a Cray Y-MP/8. A peak computational speed of 2300 MFlops/sec has been achieved on 512 nodes of the Intel Delta machine,k for a problem size of 1024 K equations (256 K grid points).</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015MSSP...50..249W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015MSSP...50..249W"><span id="translatedtitle">A <span class="hlt">preconditioned</span> conjugate gradient method for computing eigenvector derivatives with distinct and repeated eigenvalues</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Wu, Baisheng; Yang, Shitong; Li, Zhengguang; Zheng, Shaopeng</p> <p>2015-01-01</p> <p>A <span class="hlt">preconditioned</span> conjugate gradient method is proposed for computing eigenvector derivatives with distinct and repeated eigenvalues in the real symmetric eigensystems. In view of singular character of the coefficient matrices of the governing equations for particular solutions of eigenvector derivatives, a modified governing equation for the complementary part of the computed modal contribution excluding those of the repeated modes is introduced, and its coefficient matrix is symmetric and positive definite. The existing factored (shifted) stiffness matrix from an iterative eigensolution such as Lanczos or Subspace Iteration is then utilized as preconditioner. High accurate approximations to particular solutions of eigenvector derivatives can be provided with a few iterations. The present method can deal with both cases of simple and repeated eigenvalues in a unified manner, and can be integrated into a coupled eigensolver/derivative software module. It is especially suitable for the large sparse matrices that arise in industrial-size finite element models. Finally, two numerical examples are used to demonstrate the superior efficiency and fast convergence of the present method.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4725407','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4725407"><span id="translatedtitle">The Impact of Remote Ischemic <span class="hlt">Pre-Conditioning</span> on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography and Angioplasty: A Double-Blind Randomized Clinical Trial</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Gholoobi, Arash; Sajjadi, Seyyed Masoud; Shabestari, Mahmoud Mohammadzadeh; Eshraghi, Ali; Shamloo, Alireza Sepehri</p> <p>2015-01-01</p> <p>Background and objective Contrast-induced nephropathy (CIN) is an acute major complication following intravascular administration of iodinated contrast agents; however, the best approach for <span class="hlt">preventing</span> CIN is not clear. Remote ischemic <span class="hlt">pre-conditioning</span> (RIPC) is a new, non-pharmacological method that has been considered for the <span class="hlt">prevention</span> of CIN following coronary angiography. This study assessed the effects of RIPC with four brief episodes of upper limb ischemia and reperfusion in the <span class="hlt">prevention</span> of contrast-induced nephropathy (CIN) after coronary angiography and/or angioplasty. Methods In this double-blind randomized clinical trial, we enrolled 51 patients with chronic stable angina and non-ST elevation acute coronary syndrome (NSTE.ACS), and they underwent coronary angiography and/or angioplasty. Standard fluid therapy with normal saline was prescribed for all patients before and after the procedure. The patients were divided into two groups, i.e., a study group of patients who had undergone RIPC intervention and a control group of patients who had not undergone RIPC. One hour before the procedure, a sphygmomanometer cuff was placed around one arm and inflated up to 50 mmHg above the systolic pressure for five minutes; then, the cuff was deflated for another five minutes, and this cycle was repeated four times. The patients’ serum creatinine levels were measured at baseline and 48 hours after the procedure, and the incidence of CIN was calculated. Results Twenty-one males and 30 females were studied in two groups, i.e., an RIPC intervention group (n = 25) and a control group (n = 26) that were homogenous considering baseline characteristics. No significant difference was observed in the mean level of serum creatinine between the two groups at a post-intervention time of 48 hours (RICP: 1.74 ± 0.70 mg/dL vs. Control: 1.75 ± 0.87 mg/dL; P = 0.64). However, a lower incidence rate of CIN was observed 48 hours after the administration of the contrast medium in the RIPC group, but it was not statistically significant (RIPC: 23.1% vs. Control: 12.0%; P = 0.30). Conclusion It seems that adequate fluid therapy is still the most effective strategy for <span class="hlt">preventing</span> CIN and that RIPC might have additional protective effects in very high risk patients, such as those with severe renal insufficiency and heart failure. PMID:26816582</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3138826','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3138826"><span id="translatedtitle">Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and <span class="hlt">prevent</span> onset of diabetes in NOD mice</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Asari, Sadaki; Itakura, Shin; Rawson, Jeffrey; Ito, Taihei; Todorov, Ivan; Nair, Indu; Shintaku, Jonathan; Liu, Chih-Pin; Kandeel, Fouad; Mullen, Yoko</p> <p>2011-01-01</p> <p>Objectives Allogeneic mesenchymal stem cells (MSCs) and bone marrow cells (BMCs) were co-transplanted in NOD mice following none myeloablative <span class="hlt">preconditioning</span> and the development of chimerism, insulitis, diabetes, and graft versus host disease (GVHD) were monitored. Methods Eight-weeks-old female NOD mice were injected intravenously with 2×107 BMCs and 5×105 MSCs from C57BL/6 mice following treatment with 2 intraperitoneal injections of anti-CD3 antibody (days −7 and −4), and 3Gy total body irradiation (day −1). Thereafter, blood glucose and chimerism were monitored on peripheral blood samples. Results Stable mixed chimerism (3->90% of donor phenotype) was induced in 63.2% of BMCs-MSCs-(n=19) and 45.0% of BMCs alone recipients (n=20, p=0.256). Insulitis was <span class="hlt">prevented</span> and euglycemia persisted for >18 weeks in 89.5% of BMCs-MSCs recipients including those with <3% chimerism and 55% of BM alone recipients (p<0.05). In controls, 9.1% of mice receiving <span class="hlt">preconditioning</span> treatment alone (n=11) and 16.7% of <span class="hlt">preconditioned</span> mice receiving only MSCs (n=12) were non-diabetic. GVHD was not detected in all mice. Conclusion Co-injection of MSCs and BMCs increased the success rate in inducing chimerism and <span class="hlt">preventing</span> insulitis and overt diabetes with no incidence of GVHD. Results also indicated that even micro-chimerism with <3% donor cells is sufficient for blocking autoimmunity. PMID:21562444</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2978987','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2978987"><span id="translatedtitle">The epidemiology of bovine respiratory disease: What is the evidence for <span class="hlt">preventive</span> measures?</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Taylor, Jared D.; Fulton, Robert W.; Lehenbauer, Terry W.; Step, Douglas L.; Confer, Anthony W.</p> <p>2010-01-01</p> <p>Bovine respiratory disease (BRD) is the most common and costly disease of beef cattle in North America. Despite extensive research, industry practices are often more informed by dogma than by fact. Frequently advocated interventions, including vaccination, various processing procedures, and nutritional manipulation, have limited impact on morbidity and mortality. Evidence for use of oral antimicrobials, either in feed or water, appears to be equivocal. In contrast, <span class="hlt">preconditioning</span> and metaphylaxis have significant scientific evidence of efficacy, with weaning prior to sale potentially being the most important component of <span class="hlt">preconditioning</span>. The inability to reach more definitive conclusions in <span class="hlt">preventing</span> BRD may be attributable to difficulties in investigating the disease. Study challenges include potential for extensive confounding, tremendous variability, the multi-factorial nature of the disease, and inadequate methods for diagnosis. PMID:21358927</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.nlm.nih.gov/medlineplus/ency/patientinstructions/000052.htm','NIH-MEDLINEPLUS'); return false;" href="https://www.nlm.nih.gov/medlineplus/ency/patientinstructions/000052.htm"><span id="translatedtitle"><span class="hlt">Preventing</span> falls</span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, Rowe BH. Interventions for <span class="hlt">preventing</span> falls in older people living in the community. Cochrane Database of Systematic Reviews 2009, Issue ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.rorc.research.va.gov/rescue/independent-living/preventing-falls.cfm','NIH-MEDLINEPLUS'); return false;" href="http://www.rorc.research.va.gov/rescue/independent-living/preventing-falls.cfm"><span id="translatedtitle"><span class="hlt">Preventing</span> Falls</span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>... of falling. Exercises that improve balance, such as tai chi, are helpful. Your local health or senior center ... to <span class="hlt">prevent</span> falls. Do balance exercises, such as tai chi. These types of exercises can lower the chances ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.nlm.nih.gov/medlineplus/magazine/issues/fall06/articles/fall06pg12.html','NIH-MEDLINEPLUS'); return false;" href="https://www.nlm.nih.gov/medlineplus/magazine/issues/fall06/articles/fall06pg12.html"><span id="translatedtitle"><span class="hlt">Preventing</span> Diabetes</span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>... of this page please turn Javascript on. <span class="hlt">Preventing</span> Diabetes Past Issues / Fall 2006 Table of Contents The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) suggests these ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.niaid.nih.gov/topics/tuberculosis/understanding/Pages/prevention.aspx','NIH-MEDLINEPLUS'); return false;" href="http://www.niaid.nih.gov/topics/tuberculosis/understanding/Pages/prevention.aspx"><span id="translatedtitle">Tuberculosis <span class="hlt">Prevention</span></span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>... Skip Content Marketing Share this: Main Content Area Tuberculosis (TB) <span class="hlt">Prevention</span> TB is an airborne disease and ... patients. Many people who are infected with Mycobacterium tuberculosis ( Mtb ) do not get sick or spread the ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.cdc.gov/Features/Shingles/','NIH-MEDLINEPLUS'); return false;" href="http://www.cdc.gov/Features/Shingles/"><span id="translatedtitle"><span class="hlt">Prevent</span> Shingles</span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>... will develop chickenpox, not shingles. Disease of the Week App "Want to know more about shingles? Download CDC's mobile app now . See "Disease of the Week," highlighting disease facts and <span class="hlt">prevention</span> tips. Find "Shingles" ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.cdc.gov/dengue/prevention/','NIH-MEDLINEPLUS'); return false;" href="http://www.cdc.gov/dengue/prevention/"><span id="translatedtitle">Dengue <span class="hlt">Prevention</span></span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>... Outbreak Notices <span class="hlt">Prevention</span> If You Think You Have Dengue Epidemiology Continental U.S. Entomology/Ecology Mosquito Life-Cycle Mosquito Aquatic Habitats Dengue & Climate Clinical/Laboratory Guidance Clinical Guidance Laboratory Guidance ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://go4life.nia.nih.gov/sites/default/files/PreventingFalls.pdf','NIH-MEDLINEPLUS'); return false;" href="https://go4life.nia.nih.gov/sites/default/files/PreventingFalls.pdf"><span id="translatedtitle"><span class="hlt">Preventing</span> Falls</span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>... Stay physically active. Regular exercise makes you stronger. Weight-bearing activities, such as walking or climbing stairs, may slow bone loss from osteoporosis. Lower-body strength exercises and balance exercises can help you <span class="hlt">prevent</span> falls and avoid ...</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_24 --> <div id="page_25" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="481"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.nlm.nih.gov/medlineplus/magazine/issues/fall06/articles/fall06pg21.html','NIH-MEDLINEPLUS'); return false;" href="https://www.nlm.nih.gov/medlineplus/magazine/issues/fall06/articles/fall06pg21.html"><span id="translatedtitle"><span class="hlt">Preventing</span> Influenza</span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePLUS</a></p> <p></p> <p></p> <p>... Navigation Bar Home Current Issue Past Issues <span class="hlt">Preventing</span> Influenza Past Issues / Fall 2006 Table of Contents For ... page please turn Javascript on. Photo: PhotoDisc Because flu viruses spread in respiratory droplets distributed by coughing ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4766973','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4766973"><span id="translatedtitle"><span class="hlt">Preconditioning</span> Human Cardiac Stem Cells with an HO-1 Inducer Exerts Beneficial Effects After Cell Transplantation in the Infarcted Murine Heart</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Cai, Chuanxi; Guo, Yiru; Teng, Lei; Nong, Yibing; Tan, Min; Book, Michael J.; Zhu, Xiaoping; Wang, Xiao-Liang; Du, Junjie; Wu, Wen-Jian; Xie, Wei; Hong, Kyung U.; Li, Qianhong; Bolli, Roberto</p> <p>2016-01-01</p> <p>The regenerative potential of c-kit+ cardiac stem cells (CSCs) is severely limited by the poor survival of cells after transplantation in the infarcted heart. We have previously demonstrated that <span class="hlt">preconditioning</span> human CSCs (hCSCs) with the heme oxygenase-1 inducer, cobalt protoporphyrin (CoPP), has significant cytoprotective effects in vitro. Here, we examined whether <span class="hlt">preconditioning</span> hCSCs with CoPP enhances CSC survival and improves cardiac function after transplantation in a model of myocardial infarction induced by a 45-minute coronary occlusion and 35-day reperfusion in immunodeficient mice. At 30 minutes of reperfusion, CoPP-<span class="hlt">preconditioned</span> hCSCsGFP+, hCSCsGFP+, or medium were injected into the border zone. Quantitative analysis with real-time qPCR for the expression of the human-specific gene HLA revealed that the number of survived hCSCs was significantly greater in the <span class="hlt">preconditioned</span>-hCSC group at 24 hours and 7 and 35 days compared with the hCSC group. Coimmunostaining of tissue sections for both green fluorescent protein (GFP) and human nuclear antigen further confirmed greater hCSC numbers at 35 days in the <span class="hlt">preconditioned</span>-hCSC group. At 35 days, compared with the hCSC group, the <span class="hlt">preconditioned</span>-hCSC group exhibited increased positive and negative left ventricular (LV) dP/dt, end-systolic elastance, and anterior wall/apical strain rate (although ejection fraction was similar), reduced LV remodeling, and increased proliferation of transplanted cells and of cells apparently committed to cardiac lineage. In conclusion, CoPP-<span class="hlt">preconditioning</span> of hCSCs enhances their survival and/or proliferation, promotes greater proliferation of cells expressing cardiac markers, and results in greater improvement in LV remodeling and in indices of cardiac function after infarction. PMID:26299779</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4668996','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4668996"><span id="translatedtitle">Penehyclidine Hydrochloride <span class="hlt">Preconditioning</span> Provides Cardioprotection in a Rat Model of Myocardial Ischemia/Reperfusion Injury</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Lin, Duomao; Ma, Jun; Xue, Yanyan; Wang, Zhaoqi</p> <p>2015-01-01</p> <p>To investigate the impacts and related mechanisms of penehyclidine hydrochloride (PHC) on ischemia/reperfusion (I/R)-induced myocardial injury. A rat model of myocardial I/R injury was established by the ligation of left anterior descending coronary artery for 30 min followed by 3 h perfusion. Before I/R, the rats were pretreated with or without PHC. Cardiac function was measured by echocardiography. The activities/levels of myocardial enzymes, oxidants and antioxidant enzymes were detected. Evans blue/TTC double staining was performed to assess infarct size. Cardiomyocyte apoptosis was evaluated by TUNEL assay. The release of inflammatory cytokines and inflammatory mediators was detected by ELISA. Western blot was performed to analyze the expression of COX-2, IκB, p-IκB and NF-κB. Meanwhile, the rats were given a single injection of H-PHC before I/R. The effects of PHC on myocardial infarct and cardiac function were investigated after 7 days post-reperfusion. We found that PHC remarkably improved cardiac function, alleviated myocardial injury by decreasing myocardial enzyme levels and attenuated oxidative stress in a dose-dependent manner. Additionally, PHC <span class="hlt">preconditioning</span> significantly reduced infarct size and the apoptotic rate of cardiomyocytes. Administration of PHC significantly decreased serum TNF-α, IL-1β, IL-6 and PGE2 levels and myocardium COX-2 level. Meanwhile, the expression levels of p-IκB and NF-κB were downregulated, while IκB expression was upregulated. H-PHC also exerted long-term cardioprotection in a rat model of I/R injury by decreasing infarct size and improving cardiac function. These results suggest that PHC can efficiently protect the rats against I/R-induced myocardial injury. PMID:26632817</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19910017785','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19910017785"><span id="translatedtitle">A nonrecursive order N <span class="hlt">preconditioned</span> conjugate gradient: Range space formulation of MDOF dynamics</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Kurdila, Andrew J.</p> <p>1990-01-01</p> <p>While excellent progress has been made in deriving algorithms that are efficient for certain combinations of system topologies and concurrent multiprocessing hardware, several issues must be resolved to incorporate transient simulation in the control design process for large space structures. Specifically, strategies must be developed that are applicable to systems with numerous degrees of freedom. In addition, the algorithms must have a growth potential in that they must also be amenable to implementation on forthcoming parallel system architectures. For mechanical system simulation, this fact implies that algorithms are required that induce parallelism on a fine scale, suitable for the emerging class of highly parallel processors; and transient simulation methods must be automatically load balancing for a wider collection of system topologies and hardware configurations. These problems are addressed by employing a combination range space/<span class="hlt">preconditioned</span> conjugate gradient formulation of multi-degree-of-freedom dynamics. The method described has several advantages. In a sequential computing environment, the method has the features that: by employing regular ordering of the system connectivity graph, an extremely efficient preconditioner can be derived from the 'range space metric', as opposed to the system coefficient matrix; because of the effectiveness of the preconditioner, preliminary studies indicate that the method can achieve performance rates that depend linearly upon the number of substructures, hence the title 'Order N'; and the method is non-assembling. Furthermore, the approach is promising as a potential parallel processing algorithm in that the method exhibits a fine parallel granularity suitable for a wide collection of combinations of physical system topologies/computer architectures; and the method is easily load balanced among processors, and does not rely upon system topology to induce parallelism.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4198105','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4198105"><span id="translatedtitle">Exploring the Human Plasma Proteome for Humoral Mediators of Remote Ischemic <span class="hlt">Preconditioning</span> - A Word of Caution</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Helgeland, Erik; Breivik, Lars Ertesvg; Vaudel, Marc; Svendsen, yvind Sverre; Garberg, Hilde; Nordrehaug, Jan Erik; Berven, Frode Steingrimsen; Jonassen, Anne Kristine</p> <p>2014-01-01</p> <p>Despite major advances in early revascularization techniques, cardiovascular diseases are still the leading cause of death worldwide, and myocardial infarctions contribute heavily to this. Over the past decades, it has become apparent that reperfusion of blood to a previously ischemic area of the heart causes damage in and of itself, and that this ischemia reperfusion induced injury can be reduced by up to 50% by mechanical manipulation of the blood flow to the heart. The recent discovery of remote ischemic <span class="hlt">preconditioning</span> (RIPC) provides a non-invasive approach of inducing this cardioprotection at a distance. Finding its endogenous mediators and their operative mode is an important step toward increasing the ischemic tolerance. The release of humoral factor(s) upon RIPC was recently demonstrated and several candidate proteins were published as possible mediators of the cardioprotection. Before clinical applicability, these potential biomarkers and their efficiency must be validated, a task made challenging by the large heterogeneity in reported data and results. Here, in an attempt to reproduce and provide more experimental data on these mediators, we conducted an unbiased in-depth analysis of the human plasma proteome before and after RIPC. From the 68 protein markers reported in the literature, only 28 could be mapped to manually reviewed (Swiss-Prot) protein sequences. 23 of them were monitored in our untargeted experiment. However, their significant regulation could not be reproducibly estimated. In fact, among the 394 plasma proteins we accurately quantified, no significant regulation could be confidently and reproducibly assessed. This indicates that it is difficult to both monitor and reproduce published data from experiments exploring for RIPC induced plasma proteomic regulations, and suggests that further work should be directed towards small humoral factors. To simplify this task, we made our proteomic dataset available via ProteomeXchange, where scientists can mine for novel potential targets. PMID:25333471</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3779266','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3779266"><span id="translatedtitle">Direct reconstruction of cardiac PET kinetic parametric images using a <span class="hlt">preconditioned</span> conjugate gradient approach</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Rakvongthai, Yothin; Ouyang, Jinsong; Guerin, Bastien; Li, Quanzheng; Alpert, Nathaniel M.; El Fakhri, Georges</p> <p>2013-01-01</p> <p>Purpose: Our research goal is to develop an algorithm to reconstruct cardiac positron emission tomography (PET) kinetic parametric images directly from sinograms and compare its performance with the conventional indirect approach. Methods: Time activity curves of a NCAT phantom were computed according to a one-tissue compartmental kinetic model with realistic kinetic parameters. The sinograms at each time frame were simulated using the activity distribution for the time frame. The authors reconstructed the parametric images directly from the sinograms by optimizing a cost function, which included the Poisson log-likelihood and a spatial regularization terms, using the <span class="hlt">preconditioned</span> conjugate gradient (PCG) algorithm with the proposed preconditioner. The proposed preconditioner is a diagonal matrix whose diagonal entries are the ratio of the parameter and the sensitivity of the radioactivity associated with parameter. The authors compared the reconstructed parametric images using the direct approach with those reconstructed using the conventional indirect approach. Results: At the same bias, the direct approach yielded significant relative reduction in standard deviation by 12%29% and 32%70% for 50 106 and 10 106 detected coincidences counts, respectively. Also, the PCG method effectively reached a constant value after only 10 iterations (with numerical convergence achieved after 4050 iterations), while more than 500 iterations were needed for CG. Conclusions: The authors have developed a novel approach based on the PCG algorithm to directly reconstruct cardiac PET parametric images from sinograms, and yield better estimation of kinetic parameters than the conventional indirect approach, i.e., curve fitting of reconstructed images. The PCG method increases the convergence rate of reconstruction significantly as compared to the conventional CG method. PMID:24089922</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4366737','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4366737"><span id="translatedtitle">Role of morphine <span class="hlt">preconditioning</span> and nitric oxide following brain ischemia reperfusion injury in mice</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Arabian, Maedeh; Aboutaleb, Nahid; Soleimani, Mansoureh; Mehrjerdi, Fatemeh Zare; Ajami, Marjan; Pazoki-Toroudi, Hamidreza</p> <p>2015-01-01</p> <p>Objective(s): Morphine dependence (MD) potently protects heart against ischemia reperfusion (IR) injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical <span class="hlt">preconditioning</span>. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Materials and Methods: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day) of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg) or L-NAME (20 mg/kg) 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining) performed 72 hr after ischemia. Results: MD improved post ischemia memory performance (P<0.01) and neuronal survival (P<0.001) and decreased apoptosis (P<0.05) in region I of hippocampus (CA1 region) in mouse. Treatment with naloxone or L-NAME abolished all MD aforementioned effects. Conclusion: Results of the present study suggested that opioid receptors activation in the early hr post ischemia is crucial for MD-induced hippocampus tolerance against IR injury. Opioid receptor-dependent balance of NO production was another key factor in MD-induced protection. Further studies are required to determine the effect of MD on opioid receptor changes after ischemia and its correlation with MD-induced protection. PMID:25810871</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3871481','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3871481"><span id="translatedtitle">Effects of hyperbaric oxygen <span class="hlt">preconditioning</span> on cardiac stress markers after simulated diving</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Jrgensen, Arve; Foster, Philip P; Brubakk, Alf O; Eftedal, Ingrid</p> <p>2013-01-01</p> <p>Hyperbaric oxygen <span class="hlt">preconditioning</span> (HBO-PC) can protect the heart from injury during subsequent ischemia. The presence of high loads of venous gas emboli (VGE) induced by a rapid ambient pressure reduction on ascent from diving may cause ischemia and acute heart failure. The aim of this study was to investigate the effect of diving-induced VGE formation on cardiac stress marker levels and the cardioprotective effect of HBO-PC. To induce high loads of VGE, 63 female SpragueDawley rats were subjected to a rapid ambient pressure reduction from a simulated saturation dive (50 min at 709 kPa) in a pressure chamber. VGE loads were measured for 60 min in anesthetized animals by the use of ultrasonography. The animals were divided into five groups. Three groups were exposed to either diving or to HBO-PC (100% oxygen, 38 min at 303 kPa) with a 45 or 180 min interval between HBO-PC and diving. Two additional groups were used as baseline controls for the measurements; one group was exposed to equal handling except for HBO-PC and diving, and the other group was completely unexposed. Diving caused high loads of VGE, as well as elevated levels of the cardiac stress markers, cardiac troponin T (cTnT), natriuretic peptide precursor B (Nppb), and ?B-crystallin, in blood and cardiac tissue. There were strong positive correlations between VGE loads and stress marker levels after diving, and HBO-PC appeared to have a cardioprotective effect, as indicated by the lower levels of stress marker expression after diving-induced VGE formation. PMID:24400168</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4616436','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4616436"><span id="translatedtitle">Role of Trimetazidine in Ischemic <span class="hlt">Preconditioning</span> in Patients With Symptomatic Coronary Artery Disease</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Costa, Leandro M.A.; Rezende, Paulo C.; Garcia, Rosa M.R.; Uchida, Augusto H.; Seguro, Luis Fernando B.C.; Scudeler, Thiago L.; Bocchi, Edimar A.; Krieger, Jose E.; Hueb, Whady; Ramires, Jos Antonio F.; Filho, Roberto Kalil</p> <p>2015-01-01</p> <p>Abstract Ischemic <span class="hlt">preconditioning</span> (IP) is a powerful cardioprotective cellular mechanism that has been related to the warm-up phenomenon or walk-through angina, and has been documented through the use of sequential exercise tests (ETs). It is known that several drugs, for example, cromokalim, pinacidil, adenosine, and nicorandil, can interfere with the cellular pathways of IP. The purpose of this article is to report the effect of the anti-ischemic agent trimetazidine (TMZ) on IP in symptomatic coronary artery disease (CAD) patients. We conducted a prospective study evaluating IP by the analysis of ischemic parameters in 2 sequential ETs. In phase I, without TMZ, patients underwent ET1 and ET2 with a 30-minute interval between them. In phase II, after 1 week of TMZ 35?mg twice daily, all patients underwent 2 consecutive ETs (ET3 and ET4). IP was considered present when the time to 1.0-mm segment ST on electrocardiogram deviation (T-1.0?mm) and rate pressure product (RPP) were greater in the second of 2 tests. The improvement in T-1.0?mm and RPP were compared in the 2 phases: without TMZ and after 1-week TMZ to assess the action of such drug in myocardial protective mechanisms. ETs were analyzed by 2 independent cardiologists. From 135 CAD patients screened, 96 met inclusion criteria and 62 completed the study protocol. Forty patients manifested IP by demonstrating an improvement in T-1.0?mm in ET2 compared with ET1, without the use of any drugs (phase I). In phase II, after 1-week TMZ, 26 patients (65%) did not show any incremental result in ischemic parameters in ET4 compared with ET3. Furthermore, of these patients, 8 (20%) had IP blockage. In this study, TMZ did not add any benefit to IP in patients with stable symptomatic CAD. PMID:26287407</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3470827','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3470827"><span id="translatedtitle">Ischemic <span class="hlt">Preconditioning</span> Preserves Mitochondrial Membrane Potential and Limits Reactive Oxygen Species Production</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Quarrie, Ricardo; Lee, Daniel S.; Steinbaugh, Gregory; Cramer, Brandon; Erdahl, Warren; Pfeiffer, Douglas R.; Zweier, Jay L.; Crestanello, Juan A.</p> <p>2012-01-01</p> <p>Background Mitochondrial superoxide radical (O2?) production increases after cardiac ischemia-reperfusion (IR). Ischemic <span class="hlt">preconditioning</span> (IPC) preserves mitochondrial function and attenuates O2? production, but the mechanism is unknown. Mitochondrial membrane potential (m??) is known to affect O2? production; mitochondrial depolarization decreases O2? formation. We examined the relationship between O2? production and m?? during IR and IPC. Materials/Methods Rat hearts were subjected to Control or IPC. Mitochondria were isolated at end-equilibration (End EQ), end-ischemia (End I) and end-reperfusion (End RP). m?? was measured using a tetraphenylphosphonium electrode. Mitochondrial O2? production was measured by electron paramagnetic resonance (EPR) using DMPO spin trap. Cytochrome c levels were measured using high pressure liquid chromatography. Results IPC preserved m?? at End I (?1565 vs. ?1316 mV, p<0.001) and End RP (?1682 vs. ?1552 mV, p<0.05). At End RP, IPC attenuated O2? production (2527221 vs. 3523250 AU/mg protein, p<0.05). IPC preserved cytochrome c levels (35114 vs. 26916 picomoles/mg protein, p<0.05) at End RP, and decreased mitochondrial cristae disruption (104 vs. 337%, p<0.05) and amorphous density formation (184 vs. 281%, p<0.05). Conclusion We conclude that IPC preserves m??, possibly by limiting disruption of mitochondrial inner membrane. IPC also decreases mitochondrial O2? production and preserves mitochondrial ultrastructure after IR. While it was previously held that slight decreases in m?? decrease O2? production, our results indicate that preservation of m?? is associated with decreased O2? and preservation of cardiac function in IPC. These findings indicate that the mechanism of IPC may not involve m?? depolarization, but rather preservation of mitochondrial electrochemical potential. PMID:22763215</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/19269108','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/19269108"><span id="translatedtitle">Hypothermic <span class="hlt">preconditioning</span> of donor organs prior to harvesting and ischaemia using ice-cold intravenous fluids.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kämäräinen, Antti; Virkkunen, Ilkka; Tenhunen, Jyrki</p> <p>2009-07-01</p> <p>To promote organ transplantation and viability, hypothermia has been applied as a protective agent for decades. Current management of organ preservation includes hypothermia as a component of static storage. In rare cases, hypothermic perfusion is initiated in the donor organs prior to harvesting but this requires invasive perfusion techniques. Therefore, hypothermic organ protection is currently achieved only after organ retrieval and onset of ischaemic injury cascades. The relevant mechanisms of cellular and organ damage involve ischaemia-reperfusion injury and apoptosis. In this hypothesis, we propose the possibility of inducing hypothermic protective effects prior to organ harvesting using infusion of ice-cold (+4 degrees C) intravenous fluid in the organ donor. This method of cooling to mild hypothermia (32-34 degrees C) has been found feasible in e.g. cardiac arrest victims and already during the ischaemic insult. We hypothesize that cooling with ice-cold fluid preceding organ harvesting would downregulate organ metabolism and oxygen consumption resulting in improved tolerance to ischaemia. Furthermore, according to existing evidence, mild hypothermia possesses anti-apoptotic effects and suppresses reperfusion associated inflammatory response. Finally, diabetes insipidus is often observed in the brain dead donor. Subsequent hypovolemia is conveniently treated with additional infusion of cold intravenous fluid. We offer this hypothesis as a simple method of improving donor organ viability via improved tolerance to ischaemia and reperfusion injury. This method of hypothermic <span class="hlt">preconditioning</span> seems safe, inexpensive and easily applicable in virtually every institution treating organ donors. The feasibility and effects of this hypothesis could be further evaluated in comparison to current treatment protocols in laboratory settings including evaluation of organ preservation. PMID:19269108</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26739396','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26739396"><span id="translatedtitle">Effect of Remote Ischemic <span class="hlt">Preconditioning</span> on Platelet Activation Induced by Coronary Procedures.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lanza, Gaetano Antonio; Stazi, Alessandra; Villano, Angelo; Torrini, Flavia; Milo, Maria; Laurito, Marianna; Flego, Davide; Aurigemma, Cristina; Liuzzo, Giovanna; Crea, Filippo</p> <p>2016-02-01</p> <p>In this study, we aim to assess whether remote ischemic <span class="hlt">preconditioning</span> (RIPC) reduces platelet activation during coronary angiography (CA) and/or percutaneous coronary interventions. We studied 30 patients who underwent CA because of a suspect of stable angina. Patients were randomized to RIPC (3 short episodes of forearm ischemia) or sham RIPC (controls) before the procedure. Blood samples were collected at baseline, at the end of the procedure, and 24 hours later. Monocyte-platelet aggregate (MPA) formation and platelet CD41 in the MPA gate and CD41 and CD62 expression in the platelet gate were assessed by flow cytometry, in the absence and in the presence of adenosine diphosphate (ADP) stimulation. A significant increase in platelet activation occurred during the invasive procedure in controls, which persisted at 24 hours. However, compared with controls, RIPC group showed no or a lower increase in platelet variables, including MPA formation (p <0.0001) and CD41 (p = 0.002) in the MPA gate and CD41 (p <0.0001) and CD62 (p = 0.002) in the platelet gate. ADP increased platelet activation at baseline, but did not further increase platelet reactivity during the invasive procedure in either groups. Percutaneous coronary interventions, performed in 10 patients (6 in the RIPC group and 4 in controls), did not have any further significant effect on platelet activation and reactivity compared with CA alone. In conclusion, RIPC reduces platelet activation occurring during CA. In contrast, no effects were observed on platelet response to ADP stimulation, probably related to the administration of an ADP antagonist in all patients. PMID:26739396</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4717082','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4717082"><span id="translatedtitle">Protective effect of nitric oxide induced by ischemic <span class="hlt">preconditioning</span> on reperfusion injury of rat liver graft</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Gong, Jian-Ping; Tu, Bing; Wang, Wei; Peng, Yong; Li, Shou-Bai; Yan, Lu-Nan</p> <p>2004-01-01</p> <p>AIM: Ischemic <span class="hlt">preconditioning</span> (IP) is a brief ischemic episode, which confers a state of protection against the subsequent long-term ischemia-reperfusion injuries. However, little is known regarding the use of IP before the sustained cold storage and liver transplantation. The present study was designed to evaluate the protective effect of IP on the long-term preservation of liver graft and the prolonged anhepatic-phase injury. METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation. All livers underwent 10 min of ischemia followed by 10 min of reperfusion before harvest. Rat liver transplantation was performed with the portal vein clamped for 25 min. Tolerance of transplanted liver to the reperfusion injury and liver damage were investigated. The changes in adenosine concentration in hepatic tissue and those of nitric oxide (NO) and tumor necrosis factor (TNF) in serum were also assessed. RESULTS: Recipients with IP significantly improved their one-week survival rate and liver function, they had increased levels of circulating NO and hepatic adenosine, and a reduced level of serum TNF, as compared to controls. Histological changes indicating hepatic injuries appeared improved in the IP group compared with those in control group. The protective effect of IP was also obtained by administration of adenosine, while blockage of the NO pathway using N?-nitro-L-arginine methyl ester abolished the protective effect of IP. CONCLUSION: IP appears to have a protective effect on the long-term preservation of liver graft and the prolonged anhepatic-phase injuries. NO may be involved in this process. PMID:14695772</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25694588','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25694588"><span id="translatedtitle">Ischaemic <span class="hlt">preconditioning</span> preferentially increases protein S-nitrosylation in subsarcolemmal mitochondria.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sun, Junhui; Nguyen, Tiffany; Aponte, Angel M; Menazza, Sara; Kohr, Mark J; Roth, David M; Patel, Hemal H; Murphy, Elizabeth; Steenbergen, Charles</p> <p>2015-05-01</p> <p>Nitric oxide (NO) and protein S-nitrosylation (SNO) have been shown to play important roles in ischaemic <span class="hlt">preconditioning</span> (IPC)-induced acute cardioprotection. The majority of proteins that show increased SNO following IPC are localized to the mitochondria, and our recent studies suggest that caveolae transduce acute NO/SNO cardioprotective signalling in IPC hearts. Due to the close association between subsarcolemmal mitochondria (SSM) and the sarcolemma/caveolae, we tested the hypothesis that SSM, rather than the interfibrillar mitochondria (IFM), are major targets for NO/SNO signalling derived from caveolae-associated eNOS. Following either control perfusion or IPC, SSM and IFM were isolated from Langendorff perfused mouse hearts, and SNO was analysed using a modified biotin switch method with fluorescent maleimide fluors. In perfusion control hearts, the SNO content was higher in SSM compared with IFM (1.33 0.19, ratio of SNO content Perf-SSM vs. Perf-IFM), and following IPC SNO content significantly increased preferentially in SSM, but not in IFM (1.72 0.17 and 1.07 0.04, ratio of SNO content IPC-SSM vs. Perf-IFM, and IPC-IFM vs. Perf-IFM, respectively). Consistent with these findings, eNOS, caveolin-3, and connexin-43 were detected in SSM, but not in IFM, and IPC resulted in a further significant increase in eNOS/caveolin-3 levels in SSM. Interestingly, we did not observe an IPC-induced increase in SNO or eNOS/caveolin-3 in SSM isolated from caveolin-3(-/-) mouse hearts, which could not be protected with IPC. In conclusion, these results suggest that SSM may be the preferential target of sarcolemmal signalling-derived post-translational protein modification (caveolae-derived eNOS/NO/SNO), thus providing an important role in IPC-induced cardioprotection. PMID:25694588</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3110820','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3110820"><span id="translatedtitle"><span class="hlt">Preconditioning</span> Involves Selective Mitophagy Mediated by Parkin and p62/SQSTM1</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ratliff, Eric P.; Hernandez, Genaro; Lee, Pamela; Gottlieb, Roberta A.</p> <p>2011-01-01</p> <p>Autophagy-dependent mitochondrial turnover in response to cellular stress is necessary for maintaining cellular homeostasis. However, the mechanisms that govern the selective targeting of damaged mitochondria are poorly understood. Parkin, an E3 ubiquitin ligase, has been shown to be essential for the selective clearance of damaged mitochondria. Parkin is expressed in the heart, yet its function has not been investigated in the context of cardioprotection. We previously reported that autophagy is required for cardioprotection by ischemic <span class="hlt">preconditioning</span> (IPC). In the present study, we used simulated ischemia (sI) in vitro and IPC of hearts to investigate the role of Parkin in mediating cardioprotection ex vivo and in vivo. In HL-1 cells, sI induced Parkin translocation to mitochondria and mitochondrial elimination. IPC induced Parkin translocation to mitochondria in Langendorff-perfused rat hearts and in vivo in mice subjected to regional IPC. Mitochondrial depolarization with an uncoupling agent similarly induced Parkin translocation to mitochondria in cells and Langendorff-perfused rat hearts. Mitochondrial loss was blunted in Atg5-deficient cells, revealing the requirement for autophagy in mitochondrial elimination. Consistent with previous reports indicating a role for p62/SQSTM1 in mitophagy, we found that depletion of p62 attenuated mitophagy and exacerbated cell death in HL-1 cardiomyocytes subjected to sI. While wild type mice showed p62 translocation to mitochondria and an increase in ubiquitination, Parkin knockout mice exhibited attenuated IPC-induced p62 translocation to the mitochondria. Importantly, ablation of Parkin in mice abolished the cardioprotective effects of IPC. These results reveal for the first time the crucial role of Parkin and mitophagy in cardioprotection. PMID:21687634</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/23376195','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/23376195"><span id="translatedtitle">Hypoxic <span class="hlt">preconditioning</span> increases triiodothyronine (T3) level in the developing rat brain.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Minato, Kenji; Tomimatsu, Takuji; Mimura, Kazuya; Jugder, Otgonbaatar; Kakigano, Aiko; Kanayama, Tomoko; Fujita, Satoko; Taniguchi, Yukiko; Kanagawa, Takeshi; Endo, Masayuki; Kimura, Tadashi</p> <p>2013-03-21</p> <p>Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the major causes of neurodegeneration and mortality in the neonatal period. Although hypoxic <span class="hlt">preconditioning</span> (HPC) provided strong neuroprotection against HIE in an animal model, the mechanism underlying this effect is not fully understood especially in the immature brain. Here, we investigated whether thyroid hormones (THs), especially triiodothyronine (T3), which are essential during normal brain development, contribute to the neuroprotective mechanisms of HPC by using an established model of HPC in neonatal rats. HPC treatment (8% O2 for 2.5h at 37°C) was performed in immature rats at postnatal day 6 (P6). Subsequently, we investigated the levels of THs, TH receptors (TRs) and type 2 and 3 deiodinase (D2 and D3) mRNA, and glutamate transporter 1 (GLT1) at 24h after HPC treatment, and myelin basic protein (MBP) at 6, 12 and 24h after HPC treatment. The HIE procedure was performed at 24h after HPC, and the neuroprotective effect of HPC was assessed via microtubule-associated protein 2 (MAP2) and MBP immunohistochemical staining at 14 days after HIE (P21). HPC treatment afforded marked neuroprotection at 14 days after HIE. The local level of T3 was upregulated 24h after HPC treatment in the developing rat brain, probably via the upregulation of D2. In addition, the expression of MBP and GLT1, which are the downstream protein of T3, were significantly increased 24h after HPC treatment. The present study indicates that thyroid hormones and their associated molecules may be involved in neuroprotective mechanisms of HPC during the developmental period. PMID:23376195</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/26359484','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/26359484"><span id="translatedtitle">Effects of ischemic <span class="hlt">preconditioning</span> on maximal constant-load cycling performance.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cruz, Rogrio Santos de Oliveira; de Aguiar, Rafael Alves; Turnes, Tiago; Pereira, Kayo Leonardo; Caputo, Fabrizio</p> <p>2015-11-01</p> <p>This study investigated the effects of ischemic <span class="hlt">preconditioning</span> (IPC) on the ratings of perceived exertion (RPE), surface electromyography, and pulmonary oxygen uptake (V?o2) onset kinetics during cycling until exhaustion at the peak power output attained during an incremental test. A group of 12 recreationally trained cyclists volunteered for this study. After determination of peak power output during an incremental test, they were randomly subjected on different days to a performance protocol preceded by intermittent bilateral cuff pressure inflation to 220 mmHg (IPC) or 20 mmHg (control). To increase data reliability, the performance visits were replicated, also in a random manner. There was an 8.0% improvement in performance after IPC (control: 303 s, IPC 327 s, factor SDs of /1.13, P = 0.01). This change was followed by a 2.9% increase in peak V?o2 (control: 3.95 l/min, IPC: 4.06 l/min, factor SDs of /1.15, P = 0.04), owing to a higher amplitude of the slow component of the V?o2 kinetics (control: 0.45 l/min, IPC: 0.63 l/min, factor SDs of /2.21, P = 0.05). There was also an attenuation in the rate of increase in RPE (P = 0.01) and a progressive increase in the myoelectrical activity of the vastus lateralis muscle (P = 0.04). Furthermore, the changes in peak V?o2 (r = 0.73, P = 0.007) and the amplitude of the slow component (r = 0.79, P = 0.002) largely correlated with performance improvement. These findings provide a link between improved aerobic metabolism and enhanced severe-intensity cycling performance after IPC. Furthermore, the delayed exhaustion after IPC under lower RPE and higher skeletal muscle activation suggest they have a role on the ergogenic effects of IPC on endurance performance. PMID:26359484</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ncbi.nlm.nih.gov/pubmed/25972164','PUBMED'); return false;" href="http://www.ncbi.nlm.nih.gov/pubmed/25972164"><span id="translatedtitle">Sp3/REST/HDAC1/HDAC2 Complex Represses and Sp1/HIF-1/p300 Complex Activates ncx1 Gene Transcription, in Brain Ischemia and in Ischemic Brain <span class="hlt">Preconditioning</span>, by Epigenetic Mechanism.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Formisano, Luigi; Guida, Natascia; Valsecchi, Valeria; Cantile, Maria; Cuomo, Ornella; Vinciguerra, Antonio; Laudati, Giusy; Pignataro, Giuseppe; Sirabella, Rossana; Di Renzo, Gianfranco; Annunziato, Lucio</p> <p>2015-05-13</p> <p>The Na(+)-Ca(2+) exchanger 1 (NCX1) is reduced in stroke by the RE1-silencing transcription factor (REST), whereas it is increased in ischemic brain <span class="hlt">preconditioning</span> (PC) by hypoxia-inducible factor 1 (HIF-1). Because ncx1 brain promoter (ncx1-Br) has five putative consensus sequences, named Sp1A-E, for the specificity protein (Sp) family of transcription factors (Sp1-4), we investigated the role of this family in regulating ncx1 transcription in rat cortical neurons. Here we found that Sp1 is a transcriptional activator, whereas Sp3 is a transcriptional repressor of ncx1, and that both bind ncx1-Br in a sequence-specific manner, modulating ncx1 transcription through the Sp1 sites C-E. Furthermore, by transient middle cerebral artery occlusion (tMCAO) in rats, the transcriptional repressors Sp3 and REST colocalized with the two histone-deacetylases (HDACs) HDAC1 and HDAC2 on the ncx1-Br, with a consequent hypoacetylation. Contrarily, in PC+tMCAO the transcriptional activators Sp1 and HIF-1 colocalized with histone acetyltransferase p300 on ncx1-Br with a consequent hyperacetylation. In addition, in neurons silenced with siRNA of NCX1 and subjected to oxygen and glucose deprivation (OGD) (3 h) plus reoxygenation (RX) (24 h), the neuroprotection of Class I HDAC inhibitor MS-275 was counteracted, whereas in neurons overexpressing NCX1 and subjected to ischemic <span class="hlt">preconditioning</span> (PC+OGD/RX), the neurotoxic effect of p300 inhibitor C646 was <span class="hlt">prevented</span>. Collectively, these results demonstrate that NCX1 expression is regulated by the Sp3/REST/HDAC1/HDAC2 complex in tMCAO and by the Sp1/HIF-1/p300 complex in PC+tMCAO and that epigenetic intervention, by modulating the acetylation of ncx1-Br, may be a strategy for the development of innovative therapeutic intervention in stroke. PMID:25972164</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4369266','PMC'); return false;" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4369266"><span id="translatedtitle">The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by <span class="hlt">preconditioning</span>, postconditioning and remote conditioning</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Andreadou, Ioanna; Iliodromitis, Efstathios K; Rassaf, Tienush; Schulz, Rainer; Papapetropoulos, Andreas; Ferdinandy, Péter</p> <p>2015-01-01</p> <p>Ischaemic heart disease is one of the leading causes of morbidity and mortality worldwide. The development of cardioprotective therapeutic agents remains a partly unmet need and a challenge for both medicine and industry, with significant financial and social implications. Protection of the myocardium can be achieved by mechanical vascular occlusions such as <span class="hlt">preconditioning</span> (PC), when brief episodes of ischaemia/reperfusion (I/R) are experienced prior to ischaemia; postconditioning (PostC), when the brief episodes are experienced at the immediate onset of reperfusion; and remote conditioning (RC), when the brief episodes are experienced in another vascular territory. The elucidation of the sig