Dissertations / Theses on the topic 'Reoxygenation'
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Tones, Michael Anthony. "Reoxygenation induced calcium uptake in the myocardium." Thesis, Imperial College London, 1985. http://hdl.handle.net/10044/1/37879.
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Cherif, Myriam. "Hypoxia-reoxygenation injury and stress related networks in the heart." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520611.
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Magagnin, Michaël Gaston Pietro. "Cellular adaptation to hypoxia and reoxygenation through gene specific mRNA translation." [Maastricht : Maastricht : Maastricht University] ; University Library, Universiteit Maastricht [host], 2008. http://arno.unimaas.nl/show.cgi?fid=12817.
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Teoh, Leok-Kheng Kristine. "Transforming growth factor-B1 and myocardial reperfusion/reoxygenation injury : in vitro studies." Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.498511.
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Kolamunne, Rajitha K. "Reactive oxygen and nitrogen species production in cardiomyoblasts during hypoxia and reoxygenation." Thesis, Aston University, 2010. http://publications.aston.ac.uk/10052/.
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Hypoxia is a stress condition in which tissues are deprived of an adequate O2 supply; this may trigger cell death with pathological consequences in cardiovascular or neurodegenerative disease. Reperfusion is the restoration of an oxygenated blood supply to hypoxic tissue and can cause more cell injury. The kinetics and consequences of reactive oxygen and nitrogen species (ROS/RNS) production in cardiomyoblasts are poorly understood. The present study describes the systematic characterization of the kinetics of ROS/RNS production and their roles in cell survival and associated protection during hypoxia and hypoxia/reperfusion. H9C2 cells showed a significant loss of viability under 2% O2 for 30min hypoxia and cell death; associated with an increase in protein oxidation. After 4h, apoptosis induction under 2% O2 and 10% O2 was dependent on the production of mitochondrial superoxide (O2-•) and nitric oxide (•NO), partly from nitric oxide synthase (NOS). Both apoptotic and necrotic cell death during 2% O2 for 4h could be rescued by the mitochondrial complex I inhibitor; rotenone and NOS inhibitor; L-NAME. Both L-NAME and the NOX (NADPH oxidase) inhibitor; apocynin reduced apoptosis under 10% O2 for 4h hypoxia. The mitochondrial uncoupler; FCCP significantly reduced cell death via a O2-• dependent mechanism during 2% O2, 30min hypoxia. During hypoxia (2% O2, 4h)/ reperfusion (21% O2, 2h), metabolic activity was significantly reduced with increased production of O2-• and •NO, during hypoxia but, partially restored during reperfusion. O2-• generation during hypoxia/reperfusion was mitochondrial and NOX- dependent, whereas •NO generation depended on both NOS and non-enzymatic sources. Inhibition of NOS worsened metabolic activity during reperfusion, but did not effect this during sustained hypoxia. Nrf2 activation during 2% O2, a sustained hypoxia and reperfusion was O2-•/•NO dependent. Inhibition of NF-?B activation aggravated metabolic activity during 2% O2, 4h hypoxia. In conclusion, mitochondrial O2-•, but, not ATP depletion is the major cause of apoptotic and necrotic cell death in cardiomyoblasts under 2% O2, 4h hypoxia, whereas apoptotic cell death under 10% O2, 4h, is due to NOS-dependent •NO. The management of ROS/RNS rather than ATP is required for improved survival during hypoxia. O2-• production from mitochondria and NOS is cardiotoxic during hypoxia/reperfusion. NF-?B activation during hypoxia and NOS activation during reperfusion is cardiomyoblast protective.
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Viret, Muriel. "Effect of hypoxia and reoxygenation on the lower respiratory compartment of the lung /." [S.l.] : [s.n.], 2009. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000288148.
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Evans, Emma Louise. "The effect of hypoxia and reoxygenation on STAT3 regulation in potential cardiomyocyte models." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/28293/.
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Cardiomyocyte apoptosis is an important contributory factor towards the progression of ischaemic heart disease. Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor has that been implicated in normal heart development and function. Most interestingly, STAT3 also appears to play a role in cardioprotection, including hypoxic preconditioning. In this thesis the levels and activities of ST A T3 were measured in response to hypoxic insult in primary rat cardiomyocytes (RCMs) and two cardiomyocyte cell lines (H9c2 and P19CL6 cells). P19CL6 cells were extremely sensitive to hypoxia-induced apoptosis whereas RCMs and H9c2 cells were highly resistant. Apoptosis in P19CL6 cells correlated with loss of STAT3 DNA binding, which was preceded by serine phosphorylation and followed by loss of tyrosine phosphorylation. Treatment with LIF partially protected P19CL6 cells from hypoxia-induced apoptosis, as did exogenous expression of STAT3 but not a redox-insensitive ST AT3 mutant (STAT3C3s ). Moreover, STAT3 expression rescued mitochondrial ATP production during hypoxia whereas the redox-insensitive mutant did not. These data indicate that the contribution of STAT3 to cardiomyocyte survival under hypoxic stress involves the maintenance of mitochondrial function by a redox-dependent mechanism. Understanding how STAT3 is regulated in cardiomyocytes will be important for the development of therapeutic approaches for ischaemic heart disease in the future.
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Hung, T. H. "In vitro hypoxia-reoxygenation as a model for placental oxidative stress in preeclampsia." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604788.
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Oxidative stress of the placenta is considered a key intermediary step in the pathogenesis of preeclampsia, but the cause for the stress remains unknown. Ischaemia-reperfusion injury, as a result of intermittent placental perfusion secondary to deficient trophoblast invasion of the endometrial arteries, is a possible mechanism. This thesis therefore tests whether hypoxia-reoxygenation (H/R) in vitro can induce placental oxidative stress, and cause increased apoptosis and production of tumour necrosis factor-α as seen in the preeclamptic placenta. The first aim was to examine the oxidative status of human placental tissues during periods of hypoxia and reoxygenation in vitro. Rapid generation of reactive oxygen species (ROS) was detected using a fluorescent marker when hypoxic villous samples were reoxygenated. The expression of oxidative stress markers including nitrotyrosine residues, 4-hydroxy-2-nonenal adducts, and inducible heat shock protein 72 was greatly increased in villous samples subjected to H/R compared to the controls maintained under constant hypoxia. Furthermore, preloading villous samples with ROS scavengers such as desferrioxamine and α-phenyl-N-tert-butylnitrone significantly reduced the levels of oxidative stress in H/R. Having demonstrated that in vitro H/R is capable of inducing oxidative stress in a reproducible and manipulable manner, investigations were next carried out to study the effects of resultant oxidative stress on apoptosis within the trophoblast. Compared to hypoxic and normoxic controls, there was a significant increase in the release of cytochrome c from mitochondria, activation of caspase , and cleavage of poly (ADP-ribose) polymerase in villous samples subjected to H/R. These events were associated with an increased number of syncytiotrophoblastic nuclei displaying apoptotic changes and increased lactate dehydrogenase release into the medium. The causal relationship between the generation of ROS and these apoptotic changes was revealed by the fact that pre-administration of desferrioxamine attenuated the insult.
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Arab, Amina. "Reoxygenation of hypoxic coronary smooth muscle cells amplifies growth-retarding effects of ionizing irradiation." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975997874.
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Huang, Ying [Verfasser]. "Effects of propofol on hypoxia/reoxygenation induced neuronal cell damage in vitro. / Ying Huang." Kiel : Universitätsbibliothek Kiel, 2013. http://d-nb.info/1037109392/34.
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Azarbayjani, Faranak. "Common mechanism for teratogenicity of antiepileptic drugs : Drug-induced embryonic arrhythmia and hypoxia-reoxygenation damage." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5065-2/.
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Lindblom, Emely. "Searching for the optimal radiotherapy treatment time, dose and fractionation - the role of hypoxia and reoxygenation : A modelling study." Licentiate thesis, Stockholms universitet, Fysikum, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-109348.
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The search for the optimal choice of treatment time, dose and fractionation regimen is one of the major challenges in radiation therapy. Several aspects of the radiation response of tumours and normal tissues give different indications of how the parameters defining a fractionation schedule should be altered relative to each other which often results in contradictory conclusions. For example, the increased sensitivity to fractionation in late-reacting as opposed to early-reacting tissues indicates that a large number of fractions is beneficial, while the issue of accelerated repopulation of tumour cells starting at about three weeks into a radiotherapy treatment would suggest as short overall treatment time as possible. Another tumour-to-normal tissue differential relevant to the sensitivity as well as the fractionation and overall treatment time is the issue of tumour hypoxia and reoxygenation. The tumour oxygenation is one of the most influential factors impacting on the outcome of many types of treatment modalities. Hypoxic cells are up to three times as resistant to radiation as well oxygenated cells, presenting a significant obstacle to overcome in radiotherapy as solid tumours often contain hypoxic areas as a result of their poorly functioning vasculature. Furthermore, the oxygenation is highly dynamic, with changes being observed both from fraction to fraction and over a time period of weeks as a result of fast and slow reoxygenation of acute and chronic hypoxia. With an increasing number of patients treated with hypofractionated stereotactic body radiotherapy (SBRT), the clinical implications of a substantially reduced number of fractions and hence also treatment time thus have to be evaluated with respect to the oxygenation status of the tumour. The perhaps most promising tool available for the type of study aiming at determining the optimal SBRT approach with respect to fractionation is radiobiological modelling. With clinically-derived tissue-specific radiobiological parameters and well-established survival models, in silico modelling offers a wide range of opportunities to test various hypotheses with respect to time, dose, fractionation and details of the tumour microenvironment. Any type of radiobiological modelling study intended to provide a realistic representation of a clinical tumour should therefore take into account details of both the spatial and temporal tumour oxygenation. This thesis, consisting of papers I-III and a summary, presents the results of three-dimensional radiobiological modelling of the response of tumours with heterogeneous oxygenation to various radiation qualities, fractionation schemes, oxygenation levels and dynamics using different survival models. The results of this work indicate that hypoxia and its dynamics play a major role in the outcome of both photon and carbon ion radiotherapy, and that neglecting the oxygenation status of tumours treated with SBRT may compromise the treatment outcome substantially. Continued to include clinical studies on the impact of hypoxia on the treatment outcome in lung cancer patients treated with SBRT, this project will hopefully advance the evolution towards routinely incorporating functional imaging of hypoxia into treatment planning. This is ultimately expected to result in increased levels of local control with more patients being cured from their cancer.
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Niklewski, Paul J. "Surrogates, In-Vitro, and Clinical Investigations into the Safety and Effectiveness of Anesthesia." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1383644949.
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Donnelly, John Leo. "The effects of hypoxia and reoxygenation on the fine structure of myocardial capillaries in relation to permeability." Thesis, Queen Mary, University of London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243907.
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Vohra, Hunaid Ahmed. "Apoptosis and necrosis in ischaemia/reoxygenation injury of the human myocardium : mechanism of protection by ischaemic preconditioning." Thesis, University of Leicester, 2005. http://hdl.handle.net/2381/29881.
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Gene ChipRTM microarrays were used to analyse mRNA isolated from right atrial appendages (n=3/group) subjected to SI/R, IPC and caspase-3 inhibition. The initial studies were carried out with specific ischaemia/reoxygenation time-points. Apoptosis was shown to be greater than necrosis after 90min simulated ischaemia (SI) and 8h reoxygenation (R) but necrosis was greater than apoptosis by 24hr R. Inhibition of caspase-8+9 by z.IETD.fmk+z.LEHD.fmk (70nM) significantly reduced apoptosis following 90min SI and 2hr R and inhibition of caspase-3 by z.DEVD.fmk (70nM) almost completely abolished apoptosis, both without effecting necrosis. I have also shown that ischaemic preconditioning (IPC) is more efficacious in reducing apoptosis than necrosis. IPC inhibits necrosis in the human myocardium by signal transduction pathways that involve mitoKATP channels, PKC and p38MAPK. However, apoptosis that is inhibited by activation of mitoKATP channels and PKC is p38MAPK-independent. The observed changes in gene expression may help to understand the pathophysiology of ischaemic/reoxygenation injury and the mechanism of cardioprotection. With the information obtained in this thesis we have gained more information on the role of apoptosis in ischaemia/reperfusion injury of the human myocardium and a greater understanding of the underlying mechanisms and the signal transduction of cardioprotection by IPC. It is hoped that this knowledge will contribute to the design of therapeutical strategies that may reduce myocardial ischaeia/reperfusion injury in man.
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Halurkar, Manasi Suchit. "Effect of Endothelial Progenitor Cell-derived Exosomes on High Glucose and Hypoxia/ Reoxygenation-induced Injury of Astrocytes." Wright State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1565806287371214.
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Yerrapragada, Sri Meghana. "The Protective Effects of miR-210 Modified Endothelial Progenitor Cells Released Exosomes in Hypoxia/Reoxygenation Injured Neurons." Wright State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=wright1629835915811575.
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Parker, Catriona Anne. "The response of tumour cells to hypoxia and reoxygenation : roles and interactions of p53 and NF#kappa#B." Thesis, University of Sheffield, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246997.
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OUDOT, FABIEN. "Production d'eicosanoides par les cellules du systeme cardio-vasculaire : modulation par les acides gras polyinsatures et l'hypoxie-reoxygenation." Paris 7, 1996. http://www.theses.fr/1996PA077109.
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Les maladies cardiovasculaires peuvent etre prevenues, et leur gravite peut etre reduite, par la consommation d'acides gras polyinsatures (agpi) de la famille n-3 (que l'on trouve entre autre dans le poisson). Les agpi alimentaires sont incorpores dans les membranes, et ils modifient un certain nombre de fonctions biologiques comme la synthese des eicosanoides. La modification de cette derniere serait un des mecanismes cles gouvernant l'action protectrice des agpi n-3. Les effets de l'hypoxie et de la reoxygenation (consequences de l'ischemie cardiaque) sur la synthese des eicosanoides sont mal connus. De meme, les effets de l'incorporation des agpi n-3 dans les membranes cardiaques sur cette synthese, en conditions normales, ainsi qu'en hypoxie-reoxygenation, sont mal connus. L'origine des eicosanoides cardiaques serait principalement l'endothelium vasculaire. Cependant, la production de ces molecules par les cardiomyocytes reste controversee. Dans ce travail, le rapport agpi n-6/n-3 de cardiomyocytes et de cellules endotheliales en culture, a ete modifie. La synthese des eicosanoides par ces cellules a ete caracterisee en normoxie, ainsi qu'en hypoxie-reoxygenation. Ce travail suggere une participation non-negligeable des cardiomyocytes dans la synthese des prostaglandines au cours de l'infarctus du myocarde. Cette synthese serait inhibee par les agpi n-3 principalement lors de la reoxygenation. Ce travail suggere egalement des differences de regulation de la synthese des prostaglandines par les agpi, entre les myocytes et les cellules endotheliales
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BLANC, MARIE-CELINE. "Etude des mecanismes impliques dans la survenue des lesions hepatiques d'hypoxie-reoxygenation : phenomenes de toxicite directe et indirecte." Paris 6, 1998. http://www.theses.fr/1998PA066652.
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Au cours de la transplantation hepatique et de l'hepatectomie partielle, le foie est soumis a des conditions d'ischemie et de reperfusion. Au niveau cellulaire, les lesions endotheliales sinusoidales hepatiques sont clairement identifiees comme etant les plus severes et precoces ; pourtant, les mecanismes biochimiques impliques restent mal connus. Au cours de ce travail, nous avons examine le role des voies biochimiques et des differents types cellulaires impliques. Au prealable, la mise au point d'un modele cellulaire d'etude des lesions d'hypoxie-reoxygenation (h-r) a ete realisee en soumettant les cellules, dans un caisson etanche, a une hypoxie (n 2 95%) de 120 minutes puis a une hyperoxie (o 2 95%) de 90 minutes. Les cellules endotheliales sinusoidales hepatiques (cesh) et les cellules de kupffer ont ete isolees du foie de rat par perfusion enzymatique puis elutriation centrifuge et les polynucleaires neutrophiles ont ete obtenus apres induction d'une pleuresie chez le rat. Nous avons montre, sur ce modele, une toxicite de l'hyperoxie sur les cesh, imputable aux effets deleteres de l'oxygene ainsi qu'une toxicite specifique de l'h-r. A l'inverse, les cesh semblent resister a l'hypoxie. Nous avons observe, une production par ces cellules, de radicaux libres oxygenes indirectement mise en evidence par l'existence d'une peroxydation lipidique. Ces mediateurs proviennent probablement de la voie de la xanthine oxydase et des dysfonctionnements respiratoires mitochondriaux. Nous avons egalement montre le role toxique, sur les cesh, des milieux de culture pre-conditionnes par des cellules de kupffer ou des polynucleaires neutrophiles. En conclusion, les lesions endotheliales sinusoidales secondaires a l'h-r sont determinees a la fois par des phenomenes directs tels que la production de radicaux libres oxygenes et par des phenomenes de cooperation cellulaire, responsables d'une toxicite indirecte, via la synthese de mediateurs solubles.
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Thompson, Brandon. "Hypoxia/Reoxygenation Stress Modulates Atorvastatin Transport at the Blood-Brain Barrier: A Role for Organic Anion Transporting Polypeptide." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/337292.
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Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events in neurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for treatment of acute ischemia/reperfusion injury, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can "rescue" salvageable brain tissue and/or protect BBB integrity during cerebral hypoxia and subsequent reoxygenation stress (H/R). One approach that may enable neural tissue rescue following H/R is CNS delivery of drugs with brain protective effects such as HMG-CoA reductase inhibitors (i.e., statins). Our present in vivo data demonstrates that atorvastatin, a commonly prescribed statin, attenuates poly (ADP-ribose) polymerase (PARP) cleavage in the brain following H/R, suggesting neuroprotective efficacy. However, atorvastatin use as a CNS therapeutic is limited by poor blood-brain barrier (BBB) penetration. Therefore, we examined regulation and functional expression of the known statin transporter Oatp1a4 at the BBB under H/R conditions. In rat brain microvessels H/R (6% O₂, 60 min followed by 21% O₂, 10 min) increased Oatp1a4 expression. Brain uptake of taurocholate (i.e., Oap1a4 probe substrate) and atorvastatin were reduced by Oatp inhibitors (i.e., estrone-3-sulfate, fexofenadine), suggesting involvement of Oatp1a4 in brain drug delivery. Pharmacological inhibition of TGF-β/ALK5 signaling with the selective inhibitor SB431542 increased Oatp1a4 functional expression, suggesting a role for TGF-β/ALK5 signaling in Oatp1a4 regulation. Taken together, our novel data show that targeting an endogenous BBB drug uptake transporter (i.e., Oatp1a4) may be a viable approach for optimizing CNS drug delivery for treatment of diseases with an H/R component.
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Khawaja, Kiran [Verfasser]. "Involvement of connexin 43 in ATP release from endothelial cells during reoxygenation : Role of PKA signaling pathway / Kiran Khawaja." Gießen : Universitätsbibliothek, 2011. http://d-nb.info/1063177596/34.
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Barua, Anupama. "The role of neuronal nitric oxide synthase (nNOS) in ischaemia/reoxygenation-induced injury and in protection of the mammalian myocardium." Thesis, University of Leicester, 2010. http://hdl.handle.net/2381/8754.
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Background: In physiological condition, NO is produced by two constitutive NOS isoform; eNOS and nNOS. Both isoforms have specific cellular locations and although the role of eNOS in myocardial ischaemic injury and in cardioprotection has been thoroughly addressed, but the role of nNOS remains unclear. Therefore, the aims of the thesis were to: (i) investigate the role of nNOS in ischaemia/reoxygenation-induced injury, (ii) determine whether its effect is species-dependent, (iii) elucidate the relationship of nNOS with mitoKATP channels and p38MAPK, two key components of IP and (iv) investigate whether modulation of the NO metabolism can overcome the unresponsiveness of the diabetic myocardium to IP. Methods and Results: Ventricular myocardial slices from rats and mice, nNOS knockout mice, and also from human right atrial slices were subjected to 90min ischaemia and 120min reoxygenation (37°C). Muscles were randomized to receive various treatments. Both the provision of exogenous NO and the inhibition of endogenous NO production significantly reduced tissue injury (creatine kinase release, cell necrosis and apoptosis), an effect that was species–independent. The protection seen with nNOS inhibition was as potent as that of IP, however, in nNOS-knocked out mice the cardioprotective effect of non-selective NOS (L-NAME) and selective nNOS inhibition (TRIM) and also that of IP was blocked while the benefit of exogenous NO remained intact. Additional studies revealed that the cardioprotection afforded by of exogenous NO and by inhibition of nNOS were unaffected by the mitoKATP channel blocker 5-HD although it was abrogated by p38MAPK blocker SB203580. Finally, in diabetic myocardium, IP did not decrease CK release neither reduced cell necrosis or apoptosis. In diabetic myocardium NO donor SNAP, inhibitor L-NAME and TRIM significantly reduced CK leakage, cell necrosis and apoptosis. Conclusions: nNOS plays a dual role in ischaemia/reoxygenation on that its presence is necessary to afford cardioprotection by IP but its inhibition reduces myocardial ischaemic injury. The role of nNOS is species-independent and exerted downstream of the mitoKATP channels and upstream of p38MAPK. Moreover, both the provision of exogenous NO and the suppression of endogenous NO production resulted in potent protection of diabetic human myocardium, overcoming the unresponsiveness of these tissues to IP.
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Alpuerto, Jasper Benedict Battad. "Physiological, Metabolic, and Transcriptional Analysis of Submergence Tolerance in Rice and Nitrogen Use Efficiency in Wheat." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/92003.
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Flooding is a major environmental stress that damages agricultural production worldwide. Using the key regulator of submergence tolerance in rice, SUB1A, as a model, we have advanced our understanding of how plants coordinate transcriptional, hormonal, and metabolic responses to submergence. However, the contribution of SUB1A to recovery from sublethal submergence is still unknown. This study revealed SUB1A's additional role in the recovery phase: promotion of a rapid return to normal metabolic status upon desubmergence through quick recovery of photosystem II photochemistry and carbon fixation. We also investigated how SUB1A differentially regulates adaptive responses in two functionally distinct leaves, growing and mature leaves, under submergence. This study revealed that rice plants promote rapid carbohydrate and nitrogen remobilization and transport in mature leaves, supporting quick elongation growth of growing leaves. In the presence of SUB1A, these metabolic processes were suppressed in mature leaves, resulting in the avoidance of energy starvation in the source tissues. In growing leaves, SUB1A enhanced the accumulation of abscisic acid, but repressed the level of ACC, a precursor of ethylene, contributing to the restriction of elongation growth and leaf senescence in the sink tissues.
Application of nitrogen fertilizers is a necessary step to maintain high grain yield in cereals, but plants absorb only 30-50% of supplied N. Wheat, one of the most widely grown crops in the world, requires a high level of nitrogen application to maintain grain yield and protein content. In
this study, we investigated how nitrogen input affects the accumulation of major N and C compounds and expression of genes associated with N and C metabolism in flag leaves of wheat. We used two genotypes with distinct nitrogen use efficiencies (NUE), VA08MAS-369 and VA07W-415. VA08MAS-369 displayed higher grain yield, stover biomass, and stover N content at low N, which results from greater N-uptake efficiency in this genotype. Consistently, high N-uptake efficiency was reflected by increased mRNA accumulation of nitrate transporters and their transcriptional regulator, NAC2, in flag leaves at the post-anthesis stage. Overall, this study advanced our knowledge of the important mechanisms in plant response to flooding and N limitation in these key staple cereals.PHD
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Bhogal, Ricky Harminder. "The role of oxidative stress and CD154-mediated reactive oxygen species in regulating hepatocyte cell death during hypoxia and hypoxia-reoxygenation." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/3857/.
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Hypoxia and hypoxia-reoxygenation (H-R) are pathogenic factors in many liver diseases and lead to hepatocyte death as a result of reactive oxygen species (ROS) accumulation. Activation of the Tumour Necrosis Factor-a (TNFa) super-family member CD40 by its cognate ligand CD 154 can induce hepatocyte apoptosis via induction of autocrine/paracrine F as Ligand/CD178 expression but the relationship between CD40 activation, ROS generation and hepatocyte cell death is poorly understood. Therefore, human hepatocytes were isolated from liver tissue and exposed to an in vitro model of hypoxia and H-R in the presence or absence of CD154 and/or various inhibitors. Hepatocyte ROS production, apoptosis, necrosis and autophagy were determined by a four-colour reporter flow cytometry assay. The in vivo regulation of liver injury by CD40 and CD 154 was determined using a murine model of partial liver ischaemia. Exposure of human hepatocytes to recombinant CD 154 or platelet-derived soluble CD 154 augmented ROS accumulation during H-R resulting in NADPH oxidase-dependent apoptosis and necrosis. The cyto-protectivc mechanism of autophagy limited apoptotic cell death during hypoxia and H-R. CD40 and CD 154 knockout mice but not wild type mice were protected from ischaemic liver injury. Hence, CD40:CD154 mediate hepatocytes cell death in vitro and in vivo during hypoxia and H-R.
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Ibbotson, Kathryn, Joshua Yell, and Patrick T. Ronaldson. "Nrf2 signaling increases expression of ATP-binding cassette subfamily C mRNA transcripts at the blood–brain barrier following hypoxia-reoxygenation stress." BIOMED CENTRAL LTD, 2017. http://hdl.handle.net/10150/623277.
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Background: Strategies to maintain BBB integrity in diseases with a hypoxia/reoxygenation (H/R) component involve preventing glutathione (GSH) loss from endothelial cells. GSH efflux transporters include multidrug resistance proteins (Mrps). Therefore, characterization of Mrp regulation at the BBB during H/R is required to advance these transporters as therapeutic targets. Our goal was to investigate, in vivo, regulation of Abcc1, Abcc2, and Abcc4 mRNA expression (i.e., genes encoding Mrp isoforms that transport GSH) by nuclear factor E2-related factor (Nrf2) using a well-established H/R model. Methods: Female Sprague-Dawley rats (200-250 g) were subjected to normoxia (Nx, 21% O-2, 60 min), hypoxia (Hx, 6% O-2, 60 min) or H/R (6% O-2, 60 min followed by 21% O-2, 10 min, 30 min, or 1 h) or were treated with the Nrf2 activator sulforaphane (25 mg/kg, i.p.) for 3 h. Abcc mRNA expression in brain microvessels was determined using quantitative real-time PCR. Nrf2 signaling activation was examined using an electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) respectively. Data were expressed as mean +/- SD and analyzed via ANOVA followed by the post hoc Bonferroni t test. Results: We observed increased microvascular expression of Abcc1, Abcc2, and Abcc4 mRNA following H/R treatment with reoxygenation times of 10 min, 30 min, and 1 h and in animals treated with sulforaphane. Using a biotinylated Nrf2 probe, we observed an upward band shift in brain microvessels isolated from H/R animals or animals administered sulforaphane. ChIP studies showed increased Nrf2 binding to antioxidant response elements on Abcc1, Abcc2, and Abcc4 promoters following H/R or sulforaphane treatment, suggesting a role for Nrf2 signaling in Abcc gene regulation. Conclusions: Our data show increased Abcc1, Abcc2, and Abcc4 mRNA expression at the BBB in response to H/R stress and that Abcc gene expression is regulated by Nrf2 signaling. Since these Mrp isoforms transport GSH, these results may point to endogenous transporters that can be targeted for BBB protection during H/R stress. Experiments are ongoing to examine functional implications of Nrf2-mediated increases in Abcc transcript expression. Such studies will determine utility of targeting Mrp isoforms for BBB protection in diseases with an H/R component.
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Gonçalves, Julio Cesar de Souza Inácio. "Avaliação de metodologias para a determinação indireta do coeficiente de reoxigenação superficial (K2)." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/18/18138/tde-26102017-155547/.
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O coeficiente de reoxigenação superficial (K2) é o parâmetro mais importante dos modelos matemáticos usados para simular a qualidade da água em rios. Ele quantifica indiretamente a capacidade de um corpo dágua recuperar-se, em termos de concentração de oxigênio dissolvido, após receber cargas poluidoras. Técnicas de previsão foram criadas para estimar o valor desse coeficiente, mas obtiveram sucesso apenas parcial; algumas são imprecisas e outras são dispendiosas. Esse trabalho traz contribuições teóricas e experimentais acerca de metodologias para a determinação indireta do coeficiente de reoxigenação superficial. Os estudos foram realizados em um tanque hidrodinâmico agitado por jatos e planejados de forma a avaliar a existência de correlações entre o fenômeno de reoxigenação superficial e os fenômenos físicos associados às novas metodologias de previsão do K2 propostas nesse trabalho. O resfriamento de um sólido metálico, o decaimento da concentração de sólidos totais dissolvidos (STD) em esferas perfuradas com minibrocas de 0,4 e 0,5 mm de diâmetro e a variação da componente vertical da velocidade junto à superfície livre foram os fenômenos físicos investigados. Modelos matemáticos foram produzidos através de análises de regressão linear entre os parâmetros K2 e o coeficiente de transferência térmica (Kt), associado ao resfriamento do sólido metálico; K2 vs. H (profundidade da água no tanque) e o coeficiente de transferência de massa por convecção (hm), associado ao decaimento de STD; e K2 e a taxa de dissipação de energia cinética turbulenta por unidade de massa (ε), associada à intensidade turbulenta junto à superfície livre. Os resultados revelaram que há uma forte correlação entre o K2 e os parâmetros associados aos fenômenos físicos aqui investigados, com coeficientes de correlação acima de 0,9. A aplicabilidade dos modelos obtidos é restrita às condições hidrodinâmicas nas quais os ensaios foram realizados, uma vez que não há base teórica e nem experimental indicando que as relações entre os fenômenos sejam constantes e independentes da turbulência. Sugere-se que validações em campo, com desenvolvimento de métodos específicos, sejam um próximo passo em pesquisas futuras para que se possa atribuir utilidade definitiva às metodologias aqui estudadas.The surface reoxygenation coefficient (K2) is the most important parameter in the water quality mathematical modelling in streams. It indirectly measures the ability of a water mass recover quality after a release of wastewater. Predictive techniques have been produced for estimating K2, but they achieved only partial success; some are inaccurate and others are expensive. This work includes contributions from experimental and theoretical studies about methods for the indirect determination of the surface reoxygenation coefficient. Studies were carried out in a jet-agitated vessel and were planned to assess the correlations between surface reoxygenation and physical phenomena, which are related to the new methods for the prediction of K2. The cooling of a solid metal, total dissolved solids (TDS) concentration decay, vertical component velocity near the free surface were the physical phenomena investigated. Mathematical models have been produced using linear regression analysis between K2 and thermal transfer coefficient (Kt), associated with the solid metal cooling; K2 vs. H (depth of the water in the vessel) and mass transfer coefficient by convection (hm), associated with the TDS concentration decay; and K2 and turbulence kinetic energy dissipation rate (ε), associated with the vertical component velocity near the free surface. Results revealed that there is a strong correlation between K2 and the physical parameters here investigated, statistically confirmed by correlation coefficients above 0,9. The applicability of the approach used here is limited to hydrodynamic conditions in which the tests were performed, once there is no theoretical basis, or experimental, indicating that the relations between the physical parameters are constant and independent of the turbulence level. It is suggested that field tests with the development of specific methods are a next step for future research, rendering useful the methods studied here.
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Vanderlelie, Jessica, and n/a. "Placental Oxidative Stress in Preeclampsia." Griffith University. School of Medical Science, 2006. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20060918.161726.
Full textAbstract:
Affecting 6-8% of all pregnancies, preeclampsia is the leading cause of maternal morbidity in the western world and is charactensed by hypertension, proteinuria, edema and platelet aggregation. Despite its prevalence and severity, no comprehensive theory or single factor has been suggested to explain the pathophysiology of this multi system disorder of pregnancy, with the only therapies being bed rest, pharmacological symptom management and if necessary early delivery. Oxidative stress plays an important role in the pathophysiology of preeclampsia, resulting from defective trophoblast invasion, reductions in placental perfusion and placental hypoxia/reoxygenation. The inability of endogenous antioxidant systems up regulated in normal pregnancy, to control increased levels of oxidative stress, is suggested as a possible factor in the feed forward generation of reactive oxygen species and placental oxidative stress. That in turn may stimulate increased syncytiotrophoblast apoptosis, endothelial cell activation and the maternal hyper immune response characteristic of preeclampsia. Analysis of the research literature revealed that previous evaluations of placental oxidation and antioxidant enzyme activity in preeclampsia were by no means comprehensive, and exhibited significant inter-study variations. It was the aim of this thesis to clarify the placental oxidative state and the endogenous antioxidant activity of glutathione peroxidase, thioredoxin reductase, thioredoxin and superoxide dismutase in human placentae in an attempt to determine if variations in antioxidant function were due to changes in gene expression or protein oxidation. The findings reported in this thesis indicate the presence of increased levels of oxidative stress in the preeclamptic placenta, associated with significant reductions in antioxidant enzyme capacity. Quantitative real-time PCR analysis of placental samples revealed that deceases in antioxidant capacity in the placenta are more likely to be related to the significant oxidative burden within the tissue rather than reductions in gene expression. A number of animal models exist to investigate components of preeclampsia pathophysiology, however the ability of these models to mimic the oxidative and antioxidant features of preeclampsia remains unclear. The exposure of pregnant rats to N(G)-nitro-L-arginine methyl ester is a widely used model of endothelial cell dysfunction during preeclampsia. It was the aim of this thesis to determine the biochemical characteristics of this model in an attempt to assess its effectiveness in mimicking oxidative changes in the preeclamptic placenta. Although this model is capable of producing a syndiome in rats similar to the disorder in terms of physiology, this is not manifest in terms of placental biochemistry. The importance of selenium in the synthesis of selenobased antioxidants such as glutathione peroxidase and thioredoxin reductase is well documented. Increasing demand for selenium by the developing fetus may be linked to reductions in selenium status during pregnancy. Considering preeclampsia is associated with significant reductions in selenium status it may be hypothesised that reductions in antioxidant function may be linked to selenium inadequacy. The modulation of dietary selenium in pregnant rats was used to determine the importance of selenium during pregnancy and its effect on antioxidant function and placental oxidative stress. The results of this analysis revealed that selenium deficiency causes a pregnancy specific condition similar to preeclampsia. This condition was found to be associated with increased placental oxidative stress and significant reductions in the systemic activity of selenobased antioxidants that could be modified through selenium supplementation. In summary, data obtained in this thesis indicate that placental oxidative stress and reduced antioxidant enzyme activity play a significant role in the pathogenesis of preeclampsia. These studies support the hypothesis that antioxidant sufficiency is crucial in the maintenance of oxidative balance and that antioxidant dysfunction may result in damage to the placenta and the progression of the disease. These novel data further our understanding of the pathophysiology of preeclampsia and provide new insight into the pathogenesis of clinical complications exhibited in this condition, suggesting antioxidant therapy as a possible means for improving the health outcomes of both mother and baby.
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Abujamara, Laís Donini. "Efeitos da pré-exposição ao cobre sobre respostas bioquímicas da anêmona-do-mar Bunodosoma cangicum a hipóxiae reoxigenação." reponame:Repositório Institucional da FURG, 2012. http://repositorio.furg.br/handle/1/4039.
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Dissertação(mestrado) - Universidade Federal do Rio Grande, Programa de Pós–Graduação em Oceanografia Biológica, Instituto de Oceanografia, 2012.Submitted by Cristiane Gomides (cristiane_gomides@hotmail.com) on 2013-10-11T11:38:27Z No. of bitstreams: 1 Lais.pdf: 937026 bytes, checksum: 99723480330641cd5bc515f0c200b9f0 (MD5)
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Os organismos bentônicos intermareais enfrentam oscilações periódicas nos níveis de oxigênio na água associadas ao ciclo de marés. Durante o recuo da maré, eles ficam expostos ao ar e sujeitos a hipóxia, favorecendo uma redução nas espécies reativas de oxigênio (ERO) e nas defesas antioxidantes. Porém, na reoxigenação há um aumento acentuado na geração de ERO. Para minimizar os prejuízos desse processo, existem mecanismos antecipatórios, tal como o aumento das defesas antioxidantes durante a hipóxia. Por sua vez, o estresse causado por poluentes químicos, como o cobre, pode alterar o padrão destas respostas. Neste estudo foram avaliadas respostas de biomarcadores associados ao estresse oxidativo e metabolismo (capacidade antioxidante total contra radicais peroxil - ACAP, atividade da superóxido dismutase - SOD, concentração de glutationa reduzida - GSH, peroxidação lipídica - LPO e concentração de ATP) na anêmona Bunodosoma cangicum pré-exposta (96 h) ao cobre (6,1 ± 2.7 μg.L-1) e submetida a hipóxia (6 h a 0.5 mgO2.L-1) seguida da reoxigenação (6 h a 7.5 mg O2.L-1). Nas anêmonas controle não foram observadas variações na ACAP, GSH, LPO e ATP. Entretanto, a atividade da SOD aumentou durante a hipóxia. Nas anêmonas pré-expostas ao cobre, a ACAP foi reduzida na hipóxia e reoxigenação. A atividade da SOD não se alterou e a concentração de GSH aumentou no início do experimento, na hipóxia e na reoxigenação. A concentração de ATP diminuiu na reoxigenação, porém a LPO não se alterou em todas as condições experimentais. Estes resultados indicam a existência de mecanismos antecipatórios para prevenção dos efeitos negativos da reoxigenação em B. cangicum e que a exposição ao cobre em concentração ambientalmente relevante afeta negativamente estes mecanismos.
Intertidal benthic organisms are subjected to changes in oxygen availability during the tidal cycle. A hypoxic condition may occur during air exposure, thus favoring a decreased level of oxygen reactive species (ROS) and antioxidant defenses. However, during re-oxygenation a ROS overproduction may occur. Anticipatory mechanisms such as a buildup of antioxidant defenses under hypoxia could be present to avoid a possible oxidative damage occurring during these processes. In turn, chemical stress induced pollutants such as copper may affect the response of these mechanisms. In the present study, the response of biomarkers associated with oxidative stress and energy (total antioxidant capacity against peroxyl radicals - ACAP, superoxide dismutase activity - SOD, lipid peroxidation - LPO, reduced glutathione - GSH, and ATP concentration) were evaluated in the sea anemone Bunadosoma cangicum pre-exposed (96 h) to copper (6.1 ± 2.7 μg.L-1) and submitted to hypoxia (6 h at 5 mg O2.L-1) followed by re-oxygenation (6 h at 7.5 mg O2.L-1). In sea anemones kept under control conditions, ACAP, GSH concentration, LPO and ATP concentration did not change over the experimental time. However, SOD activity was increased under hypoxia. In sea anemones pre-exposed to copper, ACAP was reduced under hypoxia and re-oxygenation. GSH concentration was increased during hypoxia and reoxygenation, while ATP concentration was reduced during re-oxygenation. These findings indicate that B. cangicum shows anticipatory mechanisms to avoid the oxidative stress during re-oxygenation and that pre-exposure to an environmentally relevant concentration of copper affects these mechanisms.
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Vanderlelie, Jessica. "Placental Oxidative Stress in Preeclampsia." Thesis, Griffith University, 2006. http://hdl.handle.net/10072/365679.
Full textAbstract:
Affecting 6-8% of all pregnancies, preeclampsia is the leading cause of maternal morbidity in the western world and is charactensed by hypertension, proteinuria, edema and platelet aggregation. Despite its prevalence and severity, no comprehensive theory or single factor has been suggested to explain the pathophysiology of this multi system disorder of pregnancy, with the only therapies being bed rest, pharmacological symptom management and if necessary early delivery. Oxidative stress plays an important role in the pathophysiology of preeclampsia, resulting from defective trophoblast invasion, reductions in placental perfusion and placental hypoxia/reoxygenation. The inability of endogenous antioxidant systems up regulated in normal pregnancy, to control increased levels of oxidative stress, is suggested as a possible factor in the feed forward generation of reactive oxygen species and placental oxidative stress. That in turn may stimulate increased syncytiotrophoblast apoptosis, endothelial cell activation and the maternal hyper immune response characteristic of preeclampsia. Analysis of the research literature revealed that previous evaluations of placental oxidation and antioxidant enzyme activity in preeclampsia were by no means comprehensive, and exhibited significant inter-study variations. It was the aim of this thesis to clarify the placental oxidative state and the endogenous antioxidant activity of glutathione peroxidase, thioredoxin reductase, thioredoxin and superoxide dismutase in human placentae in an attempt to determine if variations in antioxidant function were due to changes in gene expression or protein oxidation. The findings reported in this thesis indicate the presence of increased levels of oxidative stress in the preeclamptic placenta, associated with significant reductions in antioxidant enzyme capacity. Quantitative real-time PCR analysis of placental samples revealed that deceases in antioxidant capacity in the placenta are more likely to be related to the significant oxidative burden within the tissue rather than reductions in gene expression. A number of animal models exist to investigate components of preeclampsia pathophysiology, however the ability of these models to mimic the oxidative and antioxidant features of preeclampsia remains unclear. The exposure of pregnant rats to N(G)-nitro-L-arginine methyl ester is a widely used model of endothelial cell dysfunction during preeclampsia. It was the aim of this thesis to determine the biochemical characteristics of this model in an attempt to assess its effectiveness in mimicking oxidative changes in the preeclamptic placenta. Although this model is capable of producing a syndiome in rats similar to the disorder in terms of physiology, this is not manifest in terms of placental biochemistry. The importance of selenium in the synthesis of selenobased antioxidants such as glutathione peroxidase and thioredoxin reductase is well documented. Increasing demand for selenium by the developing fetus may be linked to reductions in selenium status during pregnancy. Considering preeclampsia is associated with significant reductions in selenium status it may be hypothesised that reductions in antioxidant function may be linked to selenium inadequacy. The modulation of dietaty selenium in pregnant rats was used to determine the importance of selenium during pregnancy and its effect on antioxidant function and placental oxidative stress. The results of this analysis revealed that selenium deficiency causes a pregnancy specific condition similar to preeclampsia. This condition was found to be associated with increased placental oxidative stress and significant reductions in the systemic activity of selenobased antioxidants that could be modified through selenium supplementation. In summary, data obtained in this thesis indicate that placental oxidative stress and reduced antioxidant enzyme activity play a significant role in the pathogenesis of preeclampsia. These studies support the hypothesis that antioxidant sufficiency is crucial in the maintenance of oxidative balance and that antioxidant dysfunction may result in damage to the placenta and the progression of the disease. These novel data further our understanding of the pathophysiology of preeclampsia and provide new insight into the pathogenesis of clinical complications exhibited in this condition, suggesting antioxidant therapy as a possible means for improving the health outcomes of both mother and baby.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
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Caligtan, Marc J. "Ischemic Preconditioning Protects Adult Rat Cardiomyocytes Against Necrosis but not Apoptosis, via Activation of PKG." VCU Scholars Compass, 2005. http://scholarscompass.vcu.edu/etd/1442.
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The role of cyclic guanosine monophosphate (cGMP) dependent protein kinase (PKG) in necrotic and apoptotic pathways of many cell types is well established; however its role in the ischemic preconditioning (IPC) of cardiomyocytes is not clearly defined. In the current study, we assessed the hypothesis that PKG protects against cell death following ischemidreperfusion injury in myocytes subjected to IPC. Freshly isolated adult rat ventricular myocytes were subjected to IPC by incubating in ischemic buffer for 30 minutes (min) followed by incubation in normal medium for 30 min. Prolonged simulated ischemia (SI) was created by incubating myocytes in the ischemic buffer for 90 min and reoxygenation (RO) for 120 min in the normal medium. Necrosis was determined by trypan blue exclusion and apoptosis was assessed by TUNEL assay. IPC reduced necrosis as shown by significant decrease in trypan blue positive cells as compared to virgin non-preconditioned myocytes subjected to SI and RO alone (p<.01). Similarly, the number of TUNEL positive myocytes following SI and 18 hrs of RO were significantly reduced in the IPC group. Treatment with PKG inhibitor, KT5832 (2pM) completely abolished the protection against necrosis by IPC. However, KT5832 failed to abolish the protective affect of IPC against apoptosis. Furthermore, myocytes infected with an adenoviral construct of PKG-la (1 x 1 o4 particles/cell) significantly reduced the number of trypan blue and TUNEL positive cells. These results suggest that the PKG signaling pathway plays an essential role in the preconditioning of myocytes against necrosis following SI / RO injury. Furthermore, while the overexpression of PKG protects myocytes against necrosis, as well as apoptosis, IPC may not induce a sufficient level of PKG during 18 hours of RO to induce protection against apoptosis.
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Matsubayashi, Keiko. "Contribution of cytochrome P450 3A pathway to bromocriptine metabolism and effects of ferrous iron and hypoxia-reoxygenation on its elimination in the perfused rat liver." Kyoto University, 1997. http://hdl.handle.net/2433/202219.
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Kanji, Hussein D. "Differential roles for sarcK¦A¦T¦P and mitoK¦A¦T¦P channels in hypoxia and reoxygenation injury, a study of cell viability and ion channel pharmacology." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ64965.pdf.
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Costa, Daniel Jadyr Leite. "Estudo da influência de macro-rugosidades do leito de um canal hidráulico sobre o coeficiente de reoxigenação superficial." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/18/18138/tde-11052011-085142/.
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O parâmetro que determina o processo de transferência de oxigênio através da interface ar-água em escoamentos com superficie livre é o coeficiente de reaeração superficial, \'K IND.2\'. Existe um grande número de equações na literatura científica que realizam a previsão do coeficiente de reaeração, no entanto, a maioria dessas equações considera apenas algumas características hidráulicas do corpo de água como a velocidade e a profundidade, e ainda, como em sua maioria são de natureza empírica, acabam sendo adequadas para corpos de água específicos. Além destes dois parâmetros (velocidade e profundidade do escoamento), existem outros doze que são considerados importantes para estudos de reoxigenação em águas superficiais. É neste contexto que o objetivo deste trabalho foi estudar em condições de laboratório a influência da rugosidade do leito de um canal sobre o coeficiente de reaeração superficial. Além da rugosidade, foram variadas as condições de velocidade média do escoamento e profundidade da lâmina de água. A variação da rugosidade foi realizada através da implementação de obstáculos com geometria conhecida, dispostos transversalmente ao escoamento, e denominados como macro-rugosidades. Os resultados demonstraram evidências de que o coeficiente de reaeração superficial é controlado de forma significativa pela rugosidade do leito do canal. Foram desenvolvidos dois modelos matemáticos de natureza semi-empírica para a previsão do \'K IND.2\', os quais incorporam variáveis hidrodinâmicas e geométricas consideradas relevantes para o processo de transferência de massa na interface ar-água.The parameter that determines the process of oxygen transfer through the air-water interface in flows with free surface is the superficial reaeration coefficient, \'K IND.2\'. There are a large quantity of equations in the cientific literature that perform the prevision of the reaeration coefficient; however, most of them consider only some of the hydraulic characteristics of water body; for example, the velocity and the depth. Most of these equations have empirical origin and are adequate just for a specific water body. In addition to these two parameters (velocity and depth of flow), there are another twelve important parameters in reoxygenation studies in superficial waters. In this context, the aim of this work was to study the influence of bed roughness of a channel on the superficial reaeration coefficient, under laboratory conditions. Besides the roughness, the conditions of mean velocity of the flow and depth of water were varied. The variation of roughness was done with implementation of obstacles with known geometry, arranged transversely to the flow direction, and called macro-roughness. The results have shown evidences that the surface reaeration coefficient is controlled significantly by the roughness of the channel bed. Two mathematical models of semi-empirical origin for the \'K IND.2\' prevision were developed, which incorporate hydrodynamic and geometric variables considered relevant in the process of mass transfer in air-water interface.
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Silveira, Alexandre. "Influência da umidade atmosférica sobre o mecanismo de transferência de gases através da interface água-atmosfera." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/18/18138/tde-29082016-091551/.
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O trabalho apresenta uma investigação sobre a influência da umidade atmosférica no processo de absorção de oxigênio atmosférico por corpo de água através de sua superfície líquida livre. Os experimentos realizados em laboratório consistem na reoxigenação de uma massa de água, contida em um tanque cilíndrico, submetida à agitação mecânica. A atmosfera que reabastece de oxigênio a massa líquida é controlada e os ensaios são conduzidos com vários níveis de umidade do ar, o que provoca diferentes taxas de evaporação. Simultaneamente, determinam-se os coeficientes de reoxigenação, K2 (h-1), em cada experimento. Investiga-se neste trabalho a correlação entre esses dois parâmetros. O processo de reoxigenação é analisado inicialmente com o uso de metodologia clássica baseada em modelos matemáticos tradicionais (possivelmente inadequados). Propõe-se neste trabalho, um modelo original para essa mesma análise.The influence of the atmospheric humidity on the process of absorption of oxygen by a water body through its free surface is presented herein. Laboratory experiments were run for the reoxygenation of a water mass kept in a cylindrical vessel under mechanical agitation. The quality of the atmospheric air transferring oxygen to water is controlled and the tests are run with several levels of air humidity, what renders different rates of evaporation. The corresponding coefficients of reaeration K2 (h-1) are determined for each experiment. The correlation between these two latter parameters is investigated. The process of reoxygenation is analyzed initially using a classical methodology based on traditional mathematical models (possibly inadequate). An original model for the same analysis is proposed in this work.
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Wagner, Kay-Dietrich. "Effekte von Hypoxie und Reoxygenierung auf die kontraktile Funktion von Vorhoftrabekeln und Rattenpapillarmuskeln - Möglichkeiten der Protektion." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 1998. http://dx.doi.org/10.18452/14401.
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Die vorliegende Untersuchung sollte die kontraktile Funktion von humanen Vorhoftrabekeln und linksventrikulären Papillarmuskeln der Ratte während Hypoxie / Reoxygenierung als Hauptkomponenten von Ischämie / Reperfusion charakterisieren. Weitere Merkmale der Ischämie wurden durch erhöhte extrazelluläre K+-Konzentration und Azidose simuliert. Einblicke in die zelluläre Ca2+-Regulation ergaben sich aus Aktionspotential-(AP)-messungen, der SR- Ca2+-ATPase-Aktivität und Kraft-Intervall- Beziehungen. Die Rolle des Energiestoffwechsels und der endogenen antioxidativen Kapazität für die kontraktile Funktion von infarktbedingt hypertrophiertem Rattenmyokard während Hypoxie / Reoxygenierung ist durch Messung der Kreatinkinase-(CK)-Aktivität, ihrer Isoenzymverteilung und der Aktivitäten von Superoxiddismutase (SOD) und Glutathionperoxidase (GSH-Px) charakterisiert worden. Der Einsatz der Radikalfänger Histidin und Butylhydroxytoluen während Hypoxie und schneller Reoxygenierung an Rattenpapillarmuskeln sollte zur Protektion gegen den toxischen Effekt unterschiedlicher reaktiver Sauerstoffspezies dienen. In den durchgeführten Experimenten zeigte sich eine geringere Empfindlichkeit des humanen Vorhofmyokards gegenüber reduzierter O2-Versorgung und Reoxygenierung als im Rattenmyokard. Die während simulierter Ischämie im humanen Myokard auftretende Azidose hat einen günstigen Effekt auf die Wiederherstellung der isometrischen Kontraktionskraft nach Reoxygenierung, was jedoch mit einer gestörten Regulation der kontraktilen Funktion verbunden ist. Hypertrophiertes Myokard in der chronischen Phase nach Infarkt zeigt eine verminderte Empfindlichkeit gegenüber Hypoxie / Reoxygenierung, was auf adaptive Veränderungen im Energiestoffwechsel (erhöhte CK-MB und CK-BB Isoenzyme mit kleinerem Km-Wert für Kreatinphosphat), in der endogenen antioxidativen Kapazität (Erhöhung der Aktivitäten von SOD und GSH-Px um 40% bzw. 50%) und in der Regulation der kontraktilen Funktion (verminderte SR Ca2+-ATPase-Aktivität und Isomyosinverschiebung von V1 nach V3) zurückgeführt werden kann. Eine bessere Erholung der kontraktilen Funktion nach Reoxygenierung kann durch schnellen pO2- Wiederanstieg erreicht werden. Der Einsatz von Pharmaka mit verschiedenen Angriffspunkten im Radikalstoffwechsel und besonders deren Kombination während Hypoxie / Reoxygenierung ermöglicht zusätzlich eine verbesserte Kardioprotektion.This study characterizes the contractile function of human atrial trabeculae and rat left ventricular papillary muscles during hypoxia / reoxygenation as the major components of ischemia / reperfusion. Further characteristics of ischemia were simulated by increased extracellular K+ concentration and acidosis during hypoxia. Insights into the cellular Ca2+ regulation were obtained from action potential recordings, from measurements of sarcoplasmic reticulum (SR) Ca2+ transport, and from force-interval relations. We examined changes in SR calcium transport, creatine kinase (CK) system, the antioxidant enzymes glutathionperoxidase (GSH-Px) and superoxiddismutase (SOD) 6 wks. after infarction (MI) due to coronary ligation in rats. Phenotypic modifications vs. sham operation (SHAM) were related to the contractile response of hypertrophied papillary muscle to hypoxia / reoxygenation. The oxygen radical scavengers histidine and butylhydroxytoluene were applied during hypoxia and rapid reoxygenation to protect the myocardium against oxygen radical damage. Generally, human atrial trabeculae were less sensitive to reduced oxygen supply and reoxygenation when compared to rat papillary muscles. In human atrial trabeculae, isometric peak force development recovered better after simulated ischemia than after hypoxia but the regulation of contractile function was clearly disturbed. In rat papillary muscles, rapid reoxygenation caused a better recovery of contractile function after hypoxia. Application of the oxygen radical scavengers histidine, butylhydroxytoluene, and especially their combination during hypoxia / reoxygenation had additional cardioprotective effects. In MI vs. SHAM we observed under aerobic control conditions: decreses in isometric contraction and relaxation rate, a reduced Vmax-equivalent of sarcomeric shortening, a faster twitch-to- twitch decay of post-rest potentiation (PRC) which correlated closely to the decrease in SR Ca2+ uptake (-25%), a decrease in CK activity (-20%), reduced CK-MI and CK-MM, increased CK-MB and CK-BB, and enhanced activities of SOD (+40%) and GSH-Px (+50%). During hypoxia, an initial increase in peak force (PF) was followed by a slower PF decline in MI vs. SHAM. During reoxygenation, rates of contraction and relaxation recovered better in MI. In SHAM but not MI, twitch-to-twitch decay of PRC was accelerated after reoxygenation vs. aerobic control. The results suggest that adaptive changes in SR Ca2+ handling, CK isoenzymes, and antioxidant enzymes may contribute to higher resistance against reduced O2 supply and reoxygenation in hypertrophy due to MI.
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Chen, Hongjiang. "Studies on Cell Injury Induced by Hypoxia-Reoxygenation and Oxidized Low Density Lipoprotein : With Special Reference to the Protectiove Effect of Mixed Tocopherols, Omega-3 Fatty Acids and Transforming Growth Factor-beta1." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3769.
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Bravo, Daniela Manzoli [UNIFESP]. "Avaliação das cinéticas do consumo de oxigênio e da reoxigenação muscular esquelética na recuperação do exercício de alta intensidade em pacientes com miopatia mitocondrial: implicações sobre os mecanismos de intolerância ao exercício." Universidade Federal de São Paulo (UNIFESP), 2011. http://repositorio.unifesp.br/handle/11600/9055.
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Previous issue date: 2011-03-31Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Introdução: Os pacientes com Miopatia Mitocondrial (MM) e Oftalmoplegia Externa Progressiva (OEP) apresentam disfunção na cadeia respiratória com incapacidade de aumentar a extração de oxigênio muscular e sintetizar ATP aerobicamente, levando à intolerância ao esforço e lentificação da cinética do O2. Quando a extração de oxigênio é comprometida, na tentativa de se manter o consumo de oxigênio muscular, uma hipótese é que estes pacientes poderiam aumentar compensatoriamente a oferta de oxigênio, apresentando, assim, uma resposta hipercinética cardiovascular e ventilatória. Por outro lado, alguns indícios de menor oferta de oxigênio foram encontrados em pacientes com MM, como um menor fluxo sanguíneo muscular no antebraço e uma maior capacidade de produção de ATP após a suplementação de oxigênio. A cinética do O2 na fase de recuperação (REC) nos fornece, assim, subsídios quanto ao pagamento do débito de oxigênio tecidual e ao reabastecimento do estoque de oxigênio sanguíneo após o exercício. Ao nosso conhecimento, a cinética do O2 REC nunca foi avaliada nos pacientes com MM, assim como a integração desta variável com as respostas não-invasivas cardiovasculares e de extração de oxigênio muscular. Objetivo: contrastar as dinâmicas da oferta e da utilização de oxigênio na recuperação do exercício em pacientes com MM; e identificar os principais mecanismos fisiopatológicos da intolerância ao esforço nestes indivíduos. Métodos: Foram avaliadas em 12 pacientes com MM e 12 controles saudáveis, as cinéticas de recuperação: (i) do O2 pulmonar, (ii) da variação na concentração da deoxiemoglobina ([HHb], mensurada pela espectroscopia de raios quasi infravermelhos - NIRS) no vasto lateral, (iii) do débito cardíaco (DC) por bioimpedância transtorácica, após um teste de carga constante de alta intensidade (70% da carga máxima atingida em teste incremental prévio) até o limite da tolerância em cicloergômetro. Resultados: Foram observadas cinéticas mais lentas de reoxigenação da [HHb], ([HHb] = 43,7 ± 21,2 vs 27,5 ± 6,7) e do O2 ( O2 = 58,1 ± 25,1 vs 38,8 ± 7,6) nos pacientes com MM em relação aos controles, respectivamente. Estas respostas foram associadas a uma cinética de DC mais rápida em relação ao O2, nos pacientes comparados aos controles (T½DC * 1,44 / O2 = 1,3 ± 0,4 vs 1,7 ± 0,6). Conclusão: Os pacientes com MM na forma OEP apresentam, na recuperação do exercício de alta intensidade, um pagamento elevado do débito de oxigênio contraído no exercício e reoxigenação mais lenta da [HHb]. Estas respostas, associadas à cinética mais rápida do DC em relação ao O2 são indícios de que possa haver um déficit no transporte de oxigênio microvascular, além do comprometimento mitocondrial característico desta doença.
Background: Mitochondrial Myopathy patients (MM) and Progressive External Ophthalmoplegia (PEO) present with respiratory chain dysfunction and inability to increase muscle oxygen extraction and aerobic ATP synthesis, leading to exercise intolerance and slower O2 kinetics. When oxygen extraction is impaired, in an attempt to maintain muscle oxygen uptake, these patients could increase oxygen delivery, thus exhibiting a hyperkinetic cardiovascular and ventilatory response. On the other hand, some evidence of oxygen delivery impairment was found in MM patients, such as a decrease in muscle blood flow in the forearm and a greater capacity for ATP production after oxygen supplementation. Recovery O2 kinetics provides information on tissue oxygen debt repayment and oxygen blood store replenishment after exercise. To our knowledge, recovery O2 kinetics has never been evaluated in MM patients, as well as its integration with the non-invasive cardiovascular and muscle reoxygenation responses. Objective: to contrast oxygen delivery and utilization dynamics on exercise recovery of MM patients and to identify the main pathophysiologic mechanisms of exercise intolerance in these subjects. Methods: Were evaluated in 12 MM patients and 12 healthy controls, the recovery kinetics of: (i) O2 (ii) deoxyhemoglobin variation ([HHb], measured by near-infrared spectroscopy - NIRS) in vastus lateralis, (iii) cardiac output (CO) by transthoracic bioimpedance, after a high-intensity constant work rate test (70% of maximal workload in a previous incremental test) to the limit of tolerance in a cycle ergometer. Results: We detected slower kinetics for [HHb] ([HHb] = 43.7 ± 21.2 vs. 27.5 ± 6.7) and for O2 ( O2 = 58.1 ± 25.1 vs. 38.8 ± 7.6) in MM patients compared to controls, respectively. Additionally, these responses were associated with a faster recovery CO kinetics in relation to O2 kinetics in MM patients compared to controls (T½DC*1,44 / O2 = 1,3 ± 0,4 vs. 1,7 ± 0,6). Conclusion: Patients with MM and PEO present with a higher oxygen debt and slower reoxygenation kinetics in the recovery of a high-intensity exercise test. Those responses were associated with a faster CO recovery in relation to O2 kinetics, indicating a microvascular oxygen transport deficit, besides the characteristic mitochondrial impairment observed in these patients.
TEDE
BV UNIFESP: Teses e dissertações
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Maia, Guilherme Del Nero. "Análise dos parâmetros cinéticos no fenômeno da reoxigenação e desoxigenação da água." Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/18/18138/tde-17102016-154830/.
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A reoxigenação de água residuária é tratada na literatura técnica de maneira análoga à reoxigenação na água limpa; os efeitos do consumo de oxigênio pela população bacteriana ativa são quantificados pela introdução dos parâmetros alfa e beta. Alfa corrige o coeficiente volumétrico de transferência de massa do oxigênio e beta corrige a concentração de saturação do oxigênio dissolvido na água. Com o presente estudo pretende-se tornar explícitos os parâmetros cinéticos envolvidos no processo, de modo a fornecer base conceitual para um melhor entendimento do fenômeno. A pesquisa é feita a partir de trabalho experimental, seguido de modelagem matemática conceitual. No entanto, no lugar dos microrganismos como sumidouro de oxigênio dissolvido foi utilizado o borbulhamento sub-superficial de gás nitrogênio, em processo de stripping. Um processo físico, portanto, substitui o processo bioquímico no papel de retirar o oxigênio dissolvido no seio líquido. O modelo matemático proposto ajustou-se bem aos dados experimentais, sendo que a sua validação pôde ser obtida através das análises estatísticas realizadas.The reoxygenation in wastewater is seen in the technical literature in an analogous way as the reoxygenation of clean water. The effects of the oxygen consumed by active bacteria population are quantified with the introduction of the parameters alpha and beta. Alpha corrects for the volumetric mass transfer coefficient and beta corrects for the dissolved oxygen saturation concentration. The present research intends to make explicit the kinetic of the process, in order to supply conceptual support to a better understanding of the phenomenon. The research is done through experimental work, followed by conceptual, mathematical modeling. Stripping with nitrogen is used as an oxygen sink instead of microorganisms. Thus, a physical process replaces the biochemical process. The proposed mathematical model fitted well to the experimental data, and its validation could be obtained through the statistical analyses done.
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Aubert, Vivien. "Lésions d'ischémie-reperfusion rénale en transplantation : modélisation par agents des effets de l’oxygénation sur la dynamique cellulaire-tissulaire de l'inflammation et de la fibrose." Thesis, Poitiers, 2015. http://www.theses.fr/2015POIT1405/document.
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En préservation-transplantation rénale, l’ischémie-reperfusion (IR) induit inflammation, fibrose, dysfonction et perte du greffon. Les événements d’IR sont de mieux en mieux identifiés, mais leurs complexité limite prédiction et thérapeutique. A partir d’une analyse bibliographique détaillée, nous proposons un modèle par agents de la réponse rénale aux lésions d’IR au niveau cellulaire/tissulaire, réalisé avec l'outil de modélisation NetLogo.Dans un premier temps, nous développons un modèle dynamique de l’oxygénation du cortex rénal, avec apport et diffusion de l’oxygène (O2), et consommation dépendant de la filtration. Nous adaptons ce modèle à l’état stationnaire pour l’O2, puis nous couplons les niveaux de PO2 à l'état énergétique (ATP) des cellules épithéliales et endothéliales (avec voies aérobie et anaérobie). Le statut de viabilité cellulaire est lié au niveau d'ATP, aboutissant à une représentation semi-phénoménologique de la réparation/survie vs apoptose/nécrose. Enfin, nous explorons le destin cellulaire et tissulaire lors d’IR simulées, avec l’ajout progressif d’éléments clefs de l’inflammation (invasion tissulaire par leucocytes, signaux lésionnels, phagocytose) et de la fibrose (fibroblastes, collagène). L’évolution du modèle vers la résolution de l’inflammation/régénération du tissu ou vers la fibrose tissulaire est observée selon les conditions imposées (durée/intensité, ischémie vs hypoxémie).Cette construction constitue le premier modèle des effets de l’oxygénation sur la dynamique cellulaire-tissulaire de l’inflammation-fibrose rénale en réponse à l’IR. A terme, elle permettra d'aborder clinique et thérapeutique de la conservation-transplantation rénaleIn renal preservation-transplantation, ischemia-reperfusion (IR) causes graft inflammation and fibrosis, dysfunction and loss. Events involved in IR injury grow identified, but their intricacy hampers prediction and therapeutics. Based on a detailed bibliographical analysis, we propose an Agent-Based Model of renal response to IR injury at cell and tissue levels, created with the modeling tool NetLogo.First, we develop and validate a dynamic model of the oxygenation of the renal cortex, featuring blood perfusion, oxygen diffusion, and oxygen consumption (driven by sodium filtered load and transport). We then adapt this model to oxygen steady-state, and PO2 level is coupled to energetic status (ATP) in epithelial and endothelial cells (aerobic and anaerobic pathways). Cell viability is coupled to ATP level, leading to a semi-phenomenological representation of repair/survival versus apoptosis/necrosis. Finally, we explore (and verify) cell and tissue fate during simulated IR sequences, with the gradual addition of key elements of inflammation (leukocytes infiltration, injury signals, phagocytosis) and fibrosis (fibroblasts, collagen). Model evolution toward the resolution of inflammation/tissue regeneration or toward tissue fibrosis is observed along imposed conditions (duration/intensity, ischemia vs hypoxemia). Results are compared to experiments from our laboratory.This construction is the first model of the effects of oxygenation on cell-tissue dynamics during renal inflammation-fibrosis response to IR. Ultimately, it will allow to address clinical and therapeutic aspects of renal transplantation and conservation
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Jan, Budour H. 1984. "The Role of Kindlin-2 in the progression of renal fibrosis." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/543848.
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Chronic kidney disease (CKD) is usually characterized by histological lesions of glomerulosclerosis and tubulointerstitial fibrosis (TIF). The progressive TIF is mediated by multiple mediators such as growth factors, metabolic toxins and stress molecules. One of the key mediators of this process is TGF-1 that induces cellular responses in a wide variety of cell types. In renal tubular cells TGF-1 activation requires the binding of Kindlin-2 to the TGF-1 receptor.
The expression of Kindlin-2 was assessed in three different situations and correlated with the progression of the renal fibrotic process.
After 48 hours, 7 days and 45 days of ischemic lesion, mouse cortical tissue expressed Kindlin-2 in similar level through the progression of the fibrotic process.
In human biopsies presenting histological characteristic of acute tubular necrosis (ATN), Kindlin-2 was also increased and showed high expression in tubules. Smooth muscle cells from arteries showed decreased expression as compared to the biopsies without ATN characteristics.
Kindlin-2 is demonstrated to be activated in a very early time after injury and will likely to keep the progression of the fibrotic lesion of the kidneyLa enfermedad renal crónica (ERC) se caracteriza habitualmente por lesiones histológicas relacionadas con la glomeruloesclerosis y la fibrosis tubulointersticial (FTI). La progresión de la FTI se induce por múltiples mecanismos moleculares como factores de transcripción, toxinas metabólicas y moléculas de estrés. Uno de los mediadores clave en esta progresión es TGF-1 que induce respuestas en gran variedad de tipos celulares. En las células tubulares renales, la activación del TGF-1 requiere la unión de Kindlin-2 al receptor de TGF-1. La expresión de Kindlin-2 se testó en tres condiciones de lesión distintas y se encontró su correlación con la progresión del proceso fibrótico renal. Después de 48 horas, 7 días y 45 días tras una lesión isquémica, el tejido renal de ratón expresó Kindlin-2 de una forma similar durante la evolución del proceso fibrótico. En las biopsias humanas con características compatibles con la necrosis tubular aguda (NTA), Kindlin-2 se detectó en varias zonas del tejido renal. Se describió una alta expresión en túbulos y en células de músculo liso de las arterias se encontró disminuido. Este perfil fue opuesto en las biopsias sin características histológicas de NTA. Kindlin-2 está activado en los procesos más inmediatos en la lesión y se mantiene a lo largo de la progresión, asumiendo un papel necesario en este proceso.
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Assaly, Rana. "Protection du myocarde ischémique et pore géant mitochondrial : applications pharmacologiques." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00734466.
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La maladie coronaire d'origine ischémique reste l'une des principales causes de mortalité dans le monde industrialisé. Le traitement de l'ischémie aiguë du myocarde est cependant entré dans une nouvelle ère où la mortalité peut être diminuée de moitié en utilisant des procédures qui permettent un retour rapide du débit sanguin dans la zone ischémique du myocarde, c'est-à-dire la revascularisation. Toutefois, cette reperfusion entraîne par elle-même des complications appelées lésions de la reperfusion qui ont été décrites pour la première fois par Jennings et al., en 1960. Par conséquent, le développement de stratégies cardioprotectrices associées à la reperfusion constitue un besoin majeur en clinique afin d'améliorer la fonction myocardique, de diminuer l'incidence des arythmies, de retarder l'apparition de la mort cardiomyocytaire et de limiter la taille de l'infarctus du myocarde lors de l'ischémie/reperfusion (I/R). La découverte de deux formes principales de mécanismes cardioprotecteurs endogènes, qui consistent en la réalisation de brefs cycles d'I/R appliqués avant l'ischémie (pré-conditionnement ischémique) ou après une longue période d'ischémie au début de la reperfusion (post-conditionnement ischémique), a encouragé la recherche de nouveaux moyens pharmacologiques capables de protéger le myocarde ischémié/reperfusé et a développé nos connaissances sur les bases moléculaires des lésions et de la survie cellulaire au cours des processus d'I/R.L'étude des mécanismes responsables de l'induction de la mort cellulaire a permis de mettre en évidence le rôle prépondérant joué par la mitochondrie et l'augmentation de la perméabilité de ses membranes, induite notamment par la formation/ouverture d'un pore au niveau des points de contacts entre les membranes mitochondriales ; ce pore a été appelé " pore de transition de la perméabilité mitochondriale " (mPTP). L'inhibition de l'ouverture de ce pore apparaît comme une stratégie privilégiée pour protéger le myocarde.De nombreuses études ont montré que les espèces réactives d'oxygène (EROs) jouent un rôle majeur dans les lésions de l'I/R et dans l'ouverture du mPTP. En revanche, il existe peu d'informations claires sur le seuil et la période de production (ischémie et/ou reperfusion) des EROs qui conduisent à l'ouverture du mPTP.Par conséquent, nous avons mis au point un modèle cellulaire d'hypoxie/réoxygénation (H/R) afin d'établir une relation causale entre la production d'EROs, l'ouverture du mPTP et la mort cellulaire tout en explorant le rôle de différents types d'EROs.Ce modèle d'H/R développé sur des cardiomyocytes de rats adultes fraîchement isolés nous a permis de mesurer en temps réel et simultanément la production des EROs, l'ouverture du mPTP et la mort cellulaire. Nous avons montré que la production des EROs débute pendant la période d'hypoxie et que cette production est directement liée à l'augmentation du temps d'hypoxie. Cette production d'EROs à l'hypoxie, plus particulièrement de radicaux hydroxyles et de peroxyde d'hydrogène, a été directement relié, et ceci pour la première fois, à l'ouverture du mPTP et à la mort cellulaire lors de l'H/R.Nous avons utilisé ce modèle pour étudier le mécanisme d'action de deux stratégies pharmacologiques cardioprotectrices, un nouveau ligand de la protéine translocatrice mitochondriale (TSPO), le TRO 40303, et l'activation de la voie RISK (Reperfusion Injury Salvage Kinase) par la morphine. Nous avons ainsi montré que (1) les propriétés cardioprotectrices du TRO40303 sont associées à une inhibition de l'ouverture du mPTP, ce qui n'avait pas pu être démontré au moyen d'expériences réalisées ex vivo et (2) l'activation de la voie RISK par la morphine, qui aboutit à une limitation de la taille d'infarctus associée à une amélioration des fonctions respiratoires mitochondriales, entraîne également une inhibition de l'ouverture du mPTP et un retard de la mort cellulaire des cardiomyocytes isolés soumis à une H/R.La suite logique de ce travail sera de rechercher si l'inhibition du stress oxydant peut constituer un mécanisme commun aux deux stratégies pharmacologiques cardioprotectrices que nous avons décrites en utilisant notre modèle d'H/R. Pour cela, il serait possible d'étendre notre modèle à des animaux génétiquement modifiés pour appréhender plus précisément les phénomènes impliqués dans cette activité antioxydante.A plus long terme, il sera nécessaire d'approfondir nos connaissances sur la production d'EROs pendant l'I/R en recherchant plus spécifiquement l'origine de cette production, notamment le rôle joué par la mitochondrie et l'effet d'autres espèces réactives dans le but de cibler le traitement et de développer de nouvelles stratégies cardioprotectrices.
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Pomper, Jörn K. "Interaktion zwischen Sauerstoffspannung und epileptiformer Aktivität und deren Einfluss auf Zellschäden in juvenilen organotypischen hippokampalen Schnittkulturen der Ratte." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2006. http://dx.doi.org/10.18452/15416.
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In der Pathogenese der Temporallappenepilepsie wird kindlichen hippokampalen Schädigungen eine wesentliche Rolle zugeschrieben. Epileptische Krämpfe und perinatale Asphyxie sind zwei häufige Ursachen dieser Schädigungen. Anhaltende epileptiforme Aktivität im Niedrig-Mg2+-Modell als einer experimentellen Form epileptischer Krämpfe führt in organotypischen hippokampalen Schnittkulturen (OHSK) der Ratte, die als Ersatzsystem des kindlichen Hippokampus verwendet werden, zu Zellschäden. Während dieser Untersuchungen ergab sich der Verdacht auf eine zusätzlich schädigende Wirkung erhöhter Sauerstoffspannungen. In meiner ersten Versuchsreihe konnte ich nachweisen, dass erhöhte Sauerstoffspannungen (60 %, 95 %) verglichen mit 20%-Sauerstoffspannung zu reversiblen und irreversiblen Zellschäden in OHSK führen. Die Zellschäden wurden über Veränderungen reizinduzierter Feldpotentiale, d.h. Abnahme der Amplitude, Zunahme der Latenz und Zunahme des Doppelpulsindex, sowie über die Propidium Jodid (PJ)-Fluoreszenzintensität bestimmt. In der zweiten Versuchsreihe konnte gezeigt werden, dass erhöhte Sauerstoffspannungen auch nach einer Hypoxie im Sinne einer hyperoxischen Reoxygenierung verglichen mit normoxischer Reoxygenierung vermehrt Zellschäden in OHSK zur Folge haben. In der dritten Versuchsreihe konnte ich ausschließen, dass erhöhte Sauerstoffspannungen eine notwendige Bedingung für Zellschäden infolge anhaltender epileptiformer Aktivität sind. Um die zellschädigende Rolle von Spreading Depressions (SDs), die während epileptiformer Aktivität auftreten, zu bestimmen, wurde in der vierten Versuchsreihe eine Methode etabliert, SD-ähnliche Ereignisse isoliert und zuverlässig in normoxischen OHSK auszulösen. Auf diese Weise wiederholt ausgelöste SD-ähnliche Ereignisse führten zu Zellschäden, bestimmt über die Veränderung elektrophysiologischer Eigenschaften von SD-ähnlichen Ereignissen, Abnahme der Feldpotentialamplitude und PJ-Fluoreszenzintensität.Hippocampal damage during infancy is thought to play an important role in the pathogenesis of temporal lobe epilepsy. Epileptic seizures and perinatal asphyxia are two frequent causes of these damages. Sustained epileptiform activity induced in the low Mg2+-model of epileptic seizures leads to cell damage in organotypic hippocampal slice cultures (OHSC) of the rat, which are used as a surrogate for the infantile hippocampus. During a previous study utilising this model the suspicion arose that increased oxygen tension could have an additional damaging effect. My first series of experiments proved that increased oxygen tension (60 %, 95 %) lead to reversible and irreversible cell damage in OHSC compared to 20%-oxygen tension. Cell damage was determined by alterations of evoked field potentials, i.e. decrement of amplitude, increment of latency and paired pulse index, as well as by propidium iodide fluorescence. The second series of experiments showed that increased oxygen tension applied after an hypoxic period (hyperoxic reoxygenation) result in augmented cell damage compared to normoxic reoxygenation. With the third series of experiments it could be excluded that increased oxygen tension is an essential condition for the occurrence of cell damage due to sustained epileptiform activity. In order to elucidate the damaging role of spreading depressions (SD), which emerge during epileptiform activity, a method was established in the fourth series of experiments that allowed the reliable induction of SD-like events in normoxic OHSC. Repetitive SD-like events induced by this method led to cell damage, assessed by alterations of electrophysiological characteristics of SD-like events, decrement of evoked field potential amplitude and propidium iodide fluorescence.
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Le, Pape Sylvain. "Rôle de la réponse au mauvais repliement protéique dans l'endothélium vasculaire au cours de l'hypoxie-réoxygénation." Thesis, Poitiers, 2014. http://www.theses.fr/2014POIT1411.
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L'ischémie-reperfusion (IR) est un syndrome associant un arrêt de la perfusion sanguine suivie de son rétablissement au sein d'un organe. L'IR est rencontrée dans de nombreuses pathologies telles que le syndrome coronarien aigu, la chirurgie vasculaire mais également durant la transplantation d'organes solides au moment de la préservation de l'organe. L'ischémie entraîne de nombreux désordres métaboliques générant un stress cellulaire parmi lequel deux organelles sont particulièrement touchées : la mitochondrie et le réticulum endoplasmique (RE). Notre projet de recherche visait à comprendre l'impact du stress du RE et de sa réponse, appelée Unfolded Protein Response (UPR), au cours de l'IR. Nous avons étudié la cinétique d'activation et le rôle de chacune des voies de l'UPR – IRE1α–XBP1, PERK-eIF2α-ATF4 et ATF6 – dans la survie des cellules endothéliales artérielles humaines soumises à différentes durées d'IR.Nous avons observé une activation successive des voies PERK-eIF2α-ATF4, ATF6 et IRE1α-XBP1 en fonction de la durée de l'ischémie froide. À l'aide de méthodes bioinformatiques, d'agents pharmacologiques et de techniques d'extinction génique post-transcriptionnelle (siRNA) nous avons observé que la voie ATF6 était délétère, que la voie PERK-eIF2α-ATF4 était protectrice lorsqu'elle était maintenue activée durant l'ischémie et que la voie IRE1α-XBP1 avait un rôle dual.Par extrapolation à la clinique, nos résultats indiquent que l'UPR est une voie d'intérêt thérapeutique pour optimiser la survie des greffons ainsi que la qualité de vie des patients et que ses médiateurs pourraient permettre d'estimer la qualité du greffon lors de la transplantationIschemia-reperfusion injury (IRI) is a syndrome combining the cessation of blood flow followed by its reestablishment in the organ. IRI is encountered in various pathologies including acute coronary syndrome, vascular surgery but also solid organ transplantation at the time of organ preservation. Ischemia induces numerous metabolic disorders resulting in cellular stress among which the mitochondria and the endoplasmic reticulum (ER) are the most injured organelles.Our research project aimed at understanding the impact of ER stress and its response, the Unfolded Protein Response (UPR), during IRI. We investigated the activation kinetics and the specific role of each UPR pathway – IRE1α–XBP1, PERK-eIF2α-ATF4 and ATF6 – on the survival of human arterial endothelial cells subjected to different durations of IR. We observed a successive activation of PERK-eIF2α-ATF4, ATF6 and IRE1α-XBP1 pathways proportionally to the duration of cold ischemia. We employed bioinformatics methods, pharmacological agents and post-transcriptional gene silencing techniques (siRNA) and we observed that ATF6 pathway was detrimental, that PERK-eIF2α-ATF4 was protective only when pharmacologically over-activated, and that IRE1α-XBP1 pathway has a dual role.By extrapolating these to the clinics, our results support the UPR as a therapeutic target to improve graft survival and the quality of life of the transplanted patients but also they indicate a possible use of UPR mediators as biomarkers of organ quality during transplantation
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Bensaid, Samir. "Mise en place de contre-mesures pour limiter la perte protéique de cellules musculaires squelettiques consécutive à l’hypoxie cellulaire." Thesis, Lille 2, 2019. http://www.theses.fr/2019LIL2S021.
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Introduction et : ’exposition chronique à une hypoxie (diminution du taux d’oxygène) sévère engendre des effets délétères sur le système musculaire, entrainant des conséquences néfastes sur la masse musculaire squelettique. L'hypoxie provoque un déséquilibre de l'homéostasie protéique (balance entre anabolisme et catabolisme), en diminuant la synthèse des protéines (principalement régulée par la voie PI3K-Akt-mTOR) tout en augmentant la dégradation des protéines (principalement par autophagie et dégradation protéasomique). En revanche, les stimulations mécaniques (activité physique) et la supplémentation nutritionnelle, en particulier les acides aminés essentiel branché (BCAA), induisent l'activation de la voie mTOR tout en inhibant les voies cataboliques du muscles squelettiques chez l'homme, l’animal et cellules musculaires misent en culture. Sur un modèle in vitro de cellule musculaire squelettique, nous avons essayé de déterminer si la combinaison de la stimulation mécanique, la supplémentation nutritionnelle et une période de réoxygénation post-stimulation pourrait inverser les effets délétères de l'hypoxie sur l'homéostasie protéique.Protocole expérimentalPour vérifier notre hypothèse, nous avons utilisé un modèle de cellule musculaire squelettique en culture (C2C12). Après quatre jours de différenciation les myotubes C2C12 ont été placés dans une chambre hypoxique à 4% de O2 pendant 24h. Á la suite de cette période d’hypoxie, un programme de stimulation électrique a été appliquée aux cellules musculaires en utilisant un générateur d'impulsions électriques. Á la fin de la stimulation électrique, les myotubes ont tout d'abord été supplémentés avec des acides aminés essentiel branché (BCAA: mélange de leucine, d'isoleucine et de valine ajoutés à un milieu de culture), puis placés pendant 2 heures dans un environnement de normoxie (21% O2) (correspondant à la période de réoxygénation).RésultatsAprès 24 heures d'hypoxie, l'analyse morphologique des myotubes montre une diminution significative de leur diamètre, traduisant l'activation des voies de dégradation des protéines aux dépens des voies de synthèse des protéines. Appliqué séparément, chaque traitement a peu d’effet sur la voie mTOR et la morphologie des myotubes. Alors que, la combinaison de la stimulation électrique, de la supplémentation en BCAA et de la réoxygénation conduit à une augmentation de la phosphorylation de protéines clés impliquées dans la voie de synthèse des protéines (Akt, mTOR, p70S6K, GSK-3β), reflétant ainsi leur état d'activation. De plus, l'analyse morphologique montre une augmentation significative du diamètre du myotube et de l'indice de fusion (reflétant l'état de différenciation), signe de la présence d'une hypertrophie musculaire.ConclusionNos résultats suggèrent que la voie mTOR (l’une des voies principales de l’anabolisme) répond à une combinaison de stimulation électrique, de supplémentation en nutriments et de réoxygénation par phosphorylation de régulateurs clés de la synthèse des protéines, pouvant ainsi inverser la perte de protéines induite par l'hypoxieBackground and aims : Chronic exposure to severe hypoxia has deleterious effects on the muscular system, in particular on skeletal muscle mass. Hypoxia leads to imbalance of protein homeostasis, decreasing protein synthesis (mainly regulated through PI3K-Akt-mTOR pathway) while increasing protein degradation (mainly through autophagy and proteasomal degradation). In contrast, mechanical stimuli and nutrients, particularly the branched-chain amino acids (BCAA), induce activation of the mTOR pathway in human and rat skeletal muscle as well as and in cultured muscle cells, and decrease protein catabolism. In a model of skeletal muscle cell culture, we attempt to determine whether the combination of mechanical stimulation, nutritional supplementation and reoxygenation could reverse the deleterious effects of hypoxia on protein homeostasis.Experimental methodsWe induced a hypoxic stress on skeletal muscle murine cells differentiated into myotubes C2C12: four days after differentiation, the C2C12 myotubes were placed into a hypoxic chamber at 4% O2 for 24h. Electrical stimulation was applied to the cells using a pulse generator to provide electric pulses. Following the ES treatment, myotubes were firstly supplemented with branched-chain amino acids (BCAA: mixture of leucine, isoleucine and valine added to culture media) while placed to normoxia during 2 hours (corresponding so to a reoxygenation protocol).ResultsAfter 24 hours of hypoxia, the morphological analysis of myotubes shows a significant decrease in their diameter, translating the activation of protein degradation pathways at the expense of protein synthesis pathways. When applied separately, each treatment has little effect on the mTOR pathway and morphology of myotubes. However, the combination of electrical stimulation, supplementation BCAA and reoxygenation lead to an increase of the phosphorylation of key proteins involved in protein synthesis pathway (Akt and p70S6 kinase), thus reflecting their activation state. In addition, morphological analysis shows a significant increase in myotube diameter and fusion index (reflecting the state of differentiation), a sign of the presence of muscle hypertrophy.ConclusionOur preliminary results suggested that mTOR pathway responds to a combination of electrostimulation, nutrient supplementation and reoxygenation by phosphorylation of key regulators of protein synthesis, and could reverse the protein loss induced by hypoxia
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Feliu, Catherine. "Implication des récepteurs P1 et P2 dans la protection des cellules endothéliales au cours de l’hypoxie-reoxygenation Complementary Role of P2 and adenosine receptors in ATP induced-anti-apoptotic effects against hypoxic injury of HUVECs Current knowledge on the role of P2Y receptors in cardioprotection against ischemia-reperfusion Intra-extracellular quantification of nucleotides and adenosine using UHPLCHRMS: improvement of robustness by the use of ascorbic acid in mobile phase Description of the novel cytoprotective action pathways of ticagrelor against hypoxic lesions at the endothelium." Thesis, Reims, 2019. http://www.theses.fr/2019REIMM202.
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Au cours de l’ischémie cardiaque, la lésion est initiée au niveau de l’endothélium, et progresse aux cardiomyocytes environnants. La signalisation purinergique joue un rôle important au cours d’épisodes l’ischémie/reperfusion (I/R). De multiples travaux ont portés sur l’étude des mécanismes de protection des nucléotides et nucléosides, sans pour autant étudier leurs rôles spécifiques sur l’endothélium. Dans ce travail, nous mettons en évidence une augmentation des concentrations extracellulaires en ATP et adénosine provenant de l’endothélium soumis à une hypoxie. Au niveau endothélial, nous mettons en évidence un effet protecteur de l’ATP extracellulaire ainsi qu’un rôle complémentaire des récepteurs P2 et P1. Les récepteurs P2 impliquent les voies de signalisation PI3K, ERK1/2, le canal mKATP et mettent également en jeu la NOS. La protection médiée par les récepteurs P1 implique les voies MEK/ERK1/2, PKA et NOS. Dans un second temps, nous rapportons un nouveau mécanisme cytoprotecteur du ticagrelor, indépendant des éléments figurés du sang et de son effet antiagrégant plaquettaire. Ce mécanisme est initié par l’augmentation de la biodisponibilité de l’adénosine extracellulaire qui déclenche les effets protecteurs via ses récepteurs A3 et A2A. Ceci peut expliquer, en partie, les effets cardioprotecteurs du ticagrelor décrit chez l’homme. L’ensemble de nos données conforte le rôle protecteur de l’ATP et de l’adénosine vis-à-vis de l’hypoxie au niveau endothélial et suggèrent un rôle bénéfique de ces médiateurs dans diverses ischémies notamment cardiaque, rénale ou cérébraleDuring cardiac ischemia, the lesion is triggered in the endothelium and progresses to the surrounding cardiomyocytes. Purinergic signalling plays an important role during ischemia/reperfusion (I/R) events. Many studies have been carried out to study the mechanisms of protection of nucleotides and nucleosides, without studying their specific roles on the endothelium. In this work, we report an increase in extracellular concentrations of ATP and adenosine from the endothelium exposed to hypoxia. We report a protective effect of extracellular ATP and a complementary role of the P2 and P1 receptors. P2 receptors protective effects involve the PI3K, ERK1/2, mKATP channel signalling and also involve NOS. The protection mediated by the P1 receptors involves the MEK/ERK1/2, PKA and NOS. In a second step, we describe a new cytoprotective mechanism of ticagrelor, independent of the blood element and its antiplatelet anti-aggregating effect. This mechanism is initiated by the increased of extracellular adenosine bioavailability, which triggers protective effects via its A3 and A2A receptors. This may explain, in part, the reported cardioprotective effects of the ticagrelor in clinical studies. Together, our data support the protective role of ATP and adenosine against deleterious effects ofendothelium hypoxia and suggest a beneficial role for these mediators in different ischemia, including cardiac, renal or cerebral ischemia
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Lai, Mei-Hsiu, and 賴美秀. "Hypoxia and Reoxygenation Induced Arrhythmogenesis on Pulmonary Vein and Atrium." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/53403595875130821697.
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碩士國防醫學院
生理學研究所
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Introduction Atrial fibrillation (AF) is the most important clinical arrhythmia which induces cardiac dysfunction and increase mortality and morbidity. Ischemia -reperfusion injury is a common condition after heart transplantation. Studies on hypoxia/reoxygenation-induced AF is associated with significant morbidities. Pulmonary veins (PVs) were known to be important sources of ectopic beats with the initiation of paroxysmal atrial fibrillation and the foci of ectopic atrial tachycardia. Aim The purpose of this study is to examine the effects of hypoxia and reoxygenation in the electrophysiological characteristics of pulmonary vein (PV), left atrium (LA) and right atrium (RA) and to investigate the role of ATP sensitive potassium channel (KATP) and oxidative stress in the genesis of ischemia/reperfusion induced atrial fibrillation. Methods and Methods Conventional microelectrodes were used to record action potential (AP) and a transducer to record contractile force after superfusion of hypoxia (95% N2+5% CO2) and reoxygenation (97% O2+3% CO2) application in isolated right superior PV, LA and RA tissue samples obtained from rabbits. Acute exposed to glibenclamide 100μM (a K+ATP channel blockers) or pinacidil 30μM (a K+ATP channel openers) in the presence of hypoxia on PV and LA. Acute exposed to N-mercaptopropionyl-glycine 5mM (N-MPG, free radical •OH scavenger) and chloramphenicol 300μM (CA, an antibiotics) in the presence of reoxygenation on PV. Results (1) Hypoxia decreased the PV spontaneous rates from 1.75±0.14 Hz to 0.83±0.11 Hz and after reoxygenation PV spontaneous rates was recovered but not to control level. Hypoxia and reoxygenation easily induced early afterdepolarizations (EAD)、delayed afterdepolarizations (DAD) and burst firings in PV. (2) Hypoxia shortened APD90 in PV and LA. After reoxygenation on PV, APD90 was recovered but not in LA. In addition, hypoxia and reoxygenation had no significant effects on APD90 in RA. However hypoxia caused to decrease in contractile force in both LA and RA, and recovered partially after reoxygenation. (3) Hypoxia-induced pacemaker activity decreasing was eliminated by exposure to glibenclamide (100μM) on PV. In addition, pinacidil (30μM) administration could significantly decrease spontaneous rates. Simultaneous exposure to both glibenclamide (100μM) and hypoxia abolished the reduction in APD90 of hypoxia alone on PV and LA. (4) N-MPG (5mM) administration in the presence of reoxygenation on PV could decrease incidence of burst firing induced by reoxygenation. (5) Pre-treatment with chloramphenicol (300μM) in the presence of reoxygenation, spontaneous rates was significantly recovered and decreased incidence of burst firing induced by reoxygenation. (6) Pre-treatment with chloramphenicol (300μM) in the presence of reoxygenation compared with reoxygenation alone, ROS was significantly decreased. Conclusions The present experiments show that hypoxia and reoxygenation significantly increases PV arrhythmogenesis mainly through an generation of ROS. Hypoxia /reoxygenation-induced arrhythmia were suppressed by the administration of chloramphenicol through an inhibition of ROS. In addition, K+ATP channel played a role of protection. It could protect against Hypoxia-induced arrhythmia.
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Shin, Eyun-Jung. "Leptin protects rat cardiomyocytes from H2O2-and hypoxia/reoxygenation-induced Apoptosis /." 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR51626.
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Thesis (M.Sc.)--York University, 2008. Graduate Programme in Biology.Typescript. Includes bibliographical references (leaves 77-94). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR51626
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Dixon, Ian M. C. "Altered sarcolemmal Na+-C2+ exchange in hearts subjected to hypoxia-reoxygenation." 1987. http://hdl.handle.net/1993/24437.
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Fang, Chih-Wen, and 方治文. "Biological effects of reoxygenation on hypoxia-treated clear cell renal cell carcinoma." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/72645935398026289024.
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