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Sample records for swine heart mitochondrial

  1. Effect of rosiglitazone on cardiac electrophysiology, infarct size and mitochondrial function in ischaemia and reperfusion of swine and rat heart.

    Science.gov (United States)

    Palee, Siripong; Weerateerangkul, Punate; Surinkeaw, Sirirat; Chattipakorn, Siriporn; Chattipakorn, Nipon

    2011-08-01

    Rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, has been used to treat type 2 diabetes. Despite debates regarding its cardioprotection, the effects of rosiglitazone on cardiac electrophysiology are still unclear. This study determined the effect of rosiglitazone on ventricular fibrillation (VF) incidence, VF threshold (VFT), defibrillation threshold (DFT) and mitochondrial function during ischaemia and reperfusion. Twenty-six pigs were used. In each pig, either rosiglitazone (1 mg kg(-1)) or normal saline solution was administered intravenously for 60 min. Then, the left anterior descending coronary artery was ligated for 60 min and released to promote reperfusion for 120 min. The cardiac electrophysiological parameters were determined at the beginning of the study and during the ischaemia and reperfusion periods. The heart was removed, and the area at risk and infarct size in each heart were determined. Cardiac mitochondria were isolated for determination of mitochondrial function. Rosiglitazone did not improve the DFT and VFT during the ischaemia-reperfusion period. In the rosiglitazone group, the VF incidence was increased (58 versus 10%) and the time to the first occurrence of VF was decreased (3 ± 2 versus 19 ± 1 min) in comparison to the vehicle group (P < 0.05). However, the infarct size related to the area at risk in the rosiglitazone group was significantly decreased (P < 0.05). In the cardiac mitochondria, rosiglitazone did not alter the level of production of reactive oxygen species and could not prevent mitochondrial membrane potential changes. Rosiglitazone increased the propensity for VF, and could neither increase defibrillation efficacy nor improve cardiac mitochondrial function.

  2. Mitochondrial Metabolism in Aging Heart

    OpenAIRE

    Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

    2016-01-01

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III a...

  3. Mitochondrial Metabolism in Aging Heart.

    Science.gov (United States)

    Lesnefsky, Edward J; Chen, Qun; Hoppel, Charles L

    2016-05-13

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area, there is ≈50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. © 2016 American Heart Association, Inc.

  4. Mitochondrial Metabolism in Aging Heart

    Science.gov (United States)

    Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

    2016-01-01

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

  5. The Role of Mitochondrial Oxidation in Endotoxin-Induced Liver-Dependent Swine Pulmonary Edema

    Science.gov (United States)

    Siore, Amsel M.; Parker, Richard E.; Cuppels, Chris; Thorn, Natalie; Hansen, Jason M.; Stecenko, Arlene A.; Brigham, Kenneth L.

    2012-01-01

    We reported previously studies in an in situ perfused swine preparation demonstrating that endotoxemia induced lung injury required the presence of the liver and that the response was accompanied by oxidative stress. To determine whether lung and liver mitochondrial oxidative stress was important to the response, we compared the effects of equimolar amounts of two antioxidants, n-acetylcysteine, which does not replenish mitochondrial glutathione, and procysteine which does, on endotoxemia induced lung injury in the swine preparation. In a swine perfused liver-lung preparation, we measured physiologic, biochemical and cellular responses of liver and lung to endotoxemia with and without the drugs. Endotoxemia caused oxidation of the mitochondria-specific protein, thioredoxin-2, in both the lungs and the liver. Procysteine reduced thioredoxin-2 oxidation, attenuated hemodynamic, gas exchange, hepatocellular dysfunction, and cytokine responses and prevented lung edema. n-acetylcysteine had more modest effects and did not prevent lung edema. Conclusions: We conclude that mitochondrial oxidation may be critical to the pathogenesis of endotoxemia-induced liver-dependent lung injury and that choices of antioxidant therapy for such conditions must consider the desired subcellular target in order to be optimally effective. PMID:22925572

  6. Pandora's Box: mitochondrial defects in ischaemic heart disease and stroke.

    Science.gov (United States)

    Andalib, Sasan; Divani, Afshin A; Michel, Tanja M; Høilund-Carlsen, Poul F; Vafaee, Manouchehr S; Gjedde, Albert

    2017-04-05

    Ischaemic heart disease and stroke are vascular events with serious health consequences worldwide. Recent genetic and epigenetic techniques have revealed many genetic determinants of these vascular events and simplified the approaches to research focused on ischaemic heart disease and stroke. The pathogenetic mechanisms of ischaemic heart disease and stroke are complex, with mitochondrial involvement (partially or entirely) recently gaining substantial support. Not only can mitochondrial reactive oxygen species give rise to ischaemic heart disease and stroke by production of oxidised low-density lipoprotein and induction of apoptosis, but the impact on pericytes contributes directly to the pathogenesis. Over the past two decades, publications implicate the causative role of nuclear genes in the development of ischaemic heart disease and stroke, in contrast to the potential role of mitochondrial DNA (mtDNA) in the pathophysiology of the disorders, which is much less understood, although recent studies do demonstrate that the involvement of mitochondria and mtDNA in the development of ischaemic heart disease and stroke is likely to be larger than originally thought, with the novel discovery of links among mitochondria, mtDNA and vascular events. Here we explore the molecular events and mtDNA alterations in relation to the role of mitochondria in ischaemic heart disease and stroke.

  7. Impaired mitochondrial function in chronically ischemic human heart

    DEFF Research Database (Denmark)

    Stride, Nis Ottesen; Larsen, Steen; Hey-Mogensen, Martin

    2013-01-01

    Chronic ischemic heart disease is associated with myocardial hypoperfusion. The resulting hypoxia potentially inflicts damage upon the mitochondria, leading to a compromised energetic state. Furthermore, ischemic damage may cause excessive production of reactive oxygen species (ROS), producing...... mitochondrial damage, hereby reinforcing a vicious circle. Ischemic preconditioning has been proven protective in acute ischemia, but the subject of chronic ischemic preconditioning has not been explored in humans. We hypothesized that mitochondrial respiratory capacity would be diminished in chronic ischemic...... regions of human myocardium but that these mitochondria would be more resistant to ex vivo ischemia and, second, that ROS generation would be higher in ischemic myocardium. The aim of this study was to test mitochondrial respiratory capacity during hyperoxia and hypoxia, to investigate ROS production...

  8. Mitochondrial energetics and calcium coupling in the heart.

    Science.gov (United States)

    Kohlhaas, Michael; Nickel, Alexander G; Maack, Christoph

    2017-06-15

    Contraction and relaxation of the heart consume large amounts of energy that need to be replenished by oxidative phosphorylation in mitochondria, and matching energy supply to demand involves the complimentary control of respiration through ADP and Ca 2+ . In heart failure, an imbalance between ADP and Ca 2+ leads to oxidation of mitochondrial pyridine nucleotides, where NADH oxidation may limit ATP production and contractile function, while NADPH oxidation can induce oxidative stress with consecutive maladaptive remodelling. Understanding the complex mechanisms that disturb this finely tuned equilibrium may aid the development of drugs that could ameliorate the progression of heart failure beyond the classical neuroendocrine inhibition. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  9. Quercetin Affects Erythropoiesis and Heart Mitochondrial Function in Mice

    Directory of Open Access Journals (Sweden)

    Lina M. Ruiz

    2015-01-01

    Full Text Available Quercetin, a dietary flavonoid used as a food supplement, showed powerful antioxidant effects in different cellular models. However, recent in vitro and in vivo studies in mammals have suggested a prooxidant effect of quercetin and described an interaction with mitochondria causing an increase in O2∙- production, a decrease in ATP levels, and impairment of respiratory chain in liver tissue. Therefore, because of its dual actions, we studied the effect of quercetin in vivo to analyze heart mitochondrial function and erythropoiesis. Mice were injected with 50 mg/kg of quercetin for 15 days. Treatment with quercetin decreased body weight, serum insulin, and ceruloplasmin levels as compared with untreated mice. Along with an impaired antioxidant capacity in plasma, quercetin-treated mice showed a significant delay on erythropoiesis progression. Heart mitochondrial function was also impaired displaying more protein oxidation and less activity for IV, respectively, than no-treated mice. In addition, a significant reduction in the protein expression levels of Mitofusin 2 and Voltage-Dependent Anion Carrier was observed. All these results suggest that quercetin affects erythropoiesis and mitochondrial function and then its potential use as a dietary supplement should be reexamined.

  10. Propofol Compared to Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

    Energy Technology Data Exchange (ETDEWEB)

    Kajimoto, Masaki; Atkinson, D. B.; Ledee, Dolena R.; Kayser, Ernst-Bernhard; Morgan, Phil G.; Sedensky, Margaret M.; Isern, Nancy G.; Des Rosiers, Christine; Portman, Michael A.

    2014-01-08

    Anesthetics used in infants and children are implicated in development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in an immature swine model anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon labeled glucose and leucine in the common carotid artery in order to assess citric acid cycle (CAC) metabolism in the parietal cortex. The anesthetics produced similar systemic hemodynamics and cerebral oxygen saturation by near-infrared-spectroscopy. Compared to isoflurane, propofol depleted ATP and glycogen stores. Propofol also decreased pools of the CAC intermediates, citrate and α-ketoglutarate, while markedly increasing succinate along with decreasing mitochondrial complex II activity. Propofol also inhibited acetyl-CoA entry into the CAC through pyruvate dehydrogenase, while promoting glycolytic flux with marked accumulation of lactate. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype which resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations which typically accompany propofol infusion syndrome. These metabolic abnormalities may play a role in neurotoxity observed with propofol in the vulnerable immature brain.

  11. Undiminished mitochondrial function during stunning in rabbit heart at 28 degrees C

    NARCIS (Netherlands)

    Zuurbier, C. J.; van Beek, J. H.

    1997-01-01

    To investigate effect of brief ischemia on mitochondrial function in intact myocardium, rather than in isolated mitochondria. The mitochondrial response was characterized by the mean response time (tmito) of cardiac mitochondrial O2 consumption to steps in heart rate. Isolated isovolumic rabbit

  12. Normal Values for Heart Electrophysiology Parameters of Healthy Swine Determined on Electrophysiology Study.

    Science.gov (United States)

    Noszczyk-Nowak, Agnieszka; Cepiel, Alicja; Janiszewski, Adrian; Pasławski, Robert; Gajek, Jacek; Pasławska, Urszula; Nicpoń, Józef

    2016-01-01

    Swine are a well-recognized animal model for human cardiovascular diseases. Despite the widespread use of porcine model in experimental electrophysiology, still no reference values for intracardiac electrical activity and conduction parameters determined during an invasive electrophysiology study (EPS) have been developed in this species thus far. The aim of the study was to develop a set of normal values for intracardiac electrical activity and conduction parameters determined during an invasive EPS of swine. The study included 36 healthy domestic swine (24-40 kg body weight). EPS was performed under a general anesthesia with midazolam, propofol and isoflurane. The reference values for intracardiac electrical activity and conduction parameters were calculated as arithmetic means ± 2 standard deviations. The reference values were determined for AH, HV and PA intervals, interatrial conduction time at its own and imposed rhythm, sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), anterograde and retrograde Wenckebach points, atrial, atrioventricular node and ventricular refractory periods. No significant correlations were found between body weight and heart rate of the examined pigs and their electrophysiological parameters. The hereby presented reference values can be helpful in comparing the results of various studies, as well as in more accurately estimating the values of electrophysiological parameters that can be expected in a given experiment.

  13. Development of isolated swine "working heart model" with parabiotic circulation

    OpenAIRE

    Silveira, LD; Petrucci, O; do Carmo, MR; de Oliveira, PPM; Vilarinho, KAD; Vieira, RW; Braile, DM

    2008-01-01

    OBJETIVO: Desenvolver modelo de coração isolado de suíno "working heart" sob suporte por circulação parabiótica e verificar se o mesmo é estável e se possibilitou de forma efetiva a mensuração dos dados propostos. MÉTODOS: O modelo foi padronizado durante preparação para estudo de associação de agente à solução cardioplégica. Foram realizados 18 experimentos com um animal suporte e um animal doador em cada. O coração do animal doador foi perfundido como coração isolado pelo animal suporte em ...

  14. Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

    International Nuclear Information System (INIS)

    Montaigne, David; Marechal, Xavier; Baccouch, Riadh; Modine, Thomas; Preau, Sebastien; Zannis, Konstantinos; Marchetti, Philippe; Lancel, Steve; Neviere, Remi

    2010-01-01

    The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 μM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt max of 105 ± 8 mN/s in control hearts vs. 49 ± 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 ± 0.2 in control hearts vs. 2.2 ± 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 ± 1 μM cytochrome c/min/mg in control hearts vs. 14 ± 3 μM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.

  15. Abnormal Mitochondrial L-Arginine Transport Contributes to the Pathogenesis of Heart Failure and Rexoygenation Injury

    Science.gov (United States)

    Byrne, Melissa; Joshi, Mandar; Horlock, Duncan; Lam, Nicholas T.; Gregorevic, Paul; McGee, Sean L.; Kaye, David M.

    2014-01-01

    Background Impaired mitochondrial function is fundamental feature of heart failure (HF) and myocardial ischemia. In addition to the effects of heightened oxidative stress, altered nitric oxide (NO) metabolism, generated by a mitochondrial NO synthase, has also been proposed to impact upon mitochondrial function. However, the mechanism responsible for arginine transport into mitochondria and the effect of HF on such a process is unknown. We therefore aimed to characterize mitochondrial L-arginine transport and to investigate the hypothesis that impaired mitochondrial L-arginine transport plays a key role in the pathogenesis of heart failure and myocardial injury. Methods and Results In mitochondria isolated from failing hearts (sheep rapid pacing model and mouse Mst1 transgenic model) we demonstrated a marked reduction in L-arginine uptake (pL-arginine transporter, CAT-1 (pL-arginine transport in modulating cardiac stress responses was examined in cardiomyocytes with mitochondrial specific overexpression of CAT-1 (mtCAT1) exposed to hypoxia-reoxygenation stress. mtCAT1 cardiomyocytes had significantly improved mitochondrial membrane potential, respiration and ATP turnover together with significantly decreased reactive oxygen species production and cell death following mitochondrial stress. Conclusion These data provide new insights into the role of L-arginine transport in mitochondrial biology and cardiovascular disease. Augmentation of mitochondrial L-arginine availability may be a novel therapeutic strategy for myocardial disorders involving mitochondrial stress such as heart failure and reperfusion injury. PMID:25111602

  16. Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure.

    Science.gov (United States)

    Nickel, Alexander G; von Hardenberg, Albrecht; Hohl, Mathias; Löffler, Joachim R; Kohlhaas, Michael; Becker, Janne; Reil, Jan-Christian; Kazakov, Andrey; Bonnekoh, Julia; Stadelmaier, Moritz; Puhl, Sarah-Lena; Wagner, Michael; Bogeski, Ivan; Cortassa, Sonia; Kappl, Reinhard; Pasieka, Bastian; Lafontaine, Michael; Lancaster, C Roy D; Blacker, Thomas S; Hall, Andrew R; Duchen, Michael R; Kästner, Lars; Lipp, Peter; Zeller, Tanja; Müller, Christian; Knopp, Andreas; Laufs, Ulrich; Böhm, Michael; Hoth, Markus; Maack, Christoph

    2015-09-01

    Mitochondrial reactive oxygen species (ROS) play a central role in most aging-related diseases. ROS are produced at the respiratory chain that demands NADH for electron transport and are eliminated by enzymes that require NADPH. The nicotinamide nucleotide transhydrogenase (Nnt) is considered a key antioxidative enzyme based on its ability to regenerate NADPH from NADH. Here, we show that pathological metabolic demand reverses the direction of the Nnt, consuming NADPH to support NADH and ATP production, but at the cost of NADPH-linked antioxidative capacity. In heart, reverse-mode Nnt is the dominant source for ROS during pressure overload. Due to a mutation of the Nnt gene, the inbred mouse strain C57BL/6J is protected from oxidative stress, heart failure, and death, making its use in cardiovascular research problematic. Targeting Nnt-mediated ROS with the tetrapeptide SS-31 rescued mortality in pressure overload-induced heart failure and could therefore have therapeutic potential in patients with this syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Longitudinal Hemodynamic Measurements in Swine Heart Failure Using a Fully Implantable Telemetry System

    Science.gov (United States)

    Choy, Jenny S.; Zhang, Zhen-Du; Pitsillides, Koullis; Sosa, Margo; Kassab, Ghassan S.

    2014-01-01

    Chronic monitoring of heart rate, blood pressure, and flow in conscious free-roaming large animals can offer considerable opportunity to understand the progression of cardiovascular diseases and can test new diagnostics and therapeutics. The objective of this study was to demonstrate the feasibility of chronic, simultaneous measurement of several hemodynamic parameters (left ventricular pressure, systemic pressure, blood flow velocity, and heart rate) using a totally implantable multichannel telemetry system in swine heart failure models. Two solid-state blood pressure sensors were inserted in the left ventricle and the descending aorta for pressure measurements. Two Doppler probes were placed around the left anterior descending (LAD) and the brachiocephalic arteries for blood flow velocity measurements. Electrocardiographic (ECG) electrodes were attached to the surface of the left ventricle to monitor heart rate. The telemeter body was implanted in the right side of the abdomen under the skin for approximately 4 to 6 weeks. The animals were subjected to various heart failure models, including volume overload (A-V fistula, n = 3), pressure overload (aortic banding, n = 2) and dilated cardiomyopathy (pacing-induced tachycardia, n = 3). Longitudinal changes in hemodynamics were monitored during the progression of the disease. In the pacing-induced tachycardia animals, the systemic blood pressure progressively decreased within the first 2 weeks and returned to baseline levels thereafter. In the aortic banding animals, the pressure progressively increased during the development of the disease. The pressure in the A-V fistula animals only showed a small increase during the first week and remained stable thereafter. The results demonstrated the ability of this telemetry system of long-term, simultaneous monitoring of blood flow, pressure and heart rate in heart failure models, which may offer significant utility for understanding cardiovascular disease

  18. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    DEFF Research Database (Denmark)

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard

    2013-01-01

    of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...

  19. Intracellular Renin Inhibits Mitochondrial Permeability Transition Pore via Activated Mitochondrial Extracellular Signal-Regulated Kinase (ERK) 1/2 during Ischemia in Diabetic Hearts.

    Science.gov (United States)

    Satoh, Terumori; Saotome, Masao; Katoh, Hideki; Nonaka, Daishi; Hasan, Prottoy; Hayashi, Hideharu; Maekawa, Yuichiro

    2017-12-25

    Although beneficial effects of non-secreting intracellular renin (ns-renin) against ischemia have been reported, the precise mechanism remains unclear. In this study, we investigated the roles of ns-renin and mitochondrial extracellular signal-related kinase (ERK) 1/2 on mitochondrial permeability transition pore (mPTP) opening during ischemia in diabetes mellitus (DM) hearts. When isolated hearts from Wistar rats (non-DM hearts) and Goto-Kakizaki rats (DM hearts) were subjected to ischemia for 70 min by left anterior descending coronary artery ligation, DM hearts exhibited higher left ventricular (LV) developed pressure and lower LV end-diastolic pressure than non-DM hearts, suggesting ischemic resistance. In addition, DM hearts showed increased intracellular renin (int-renin, including secreting and non-secreting renin) in the ischemic area, and a direct renin inhibitor (DRI; aliskiren) attenuated ischemic resistance in DM hearts. ERK1/2 was significantly phosphorylated after ischemia in both whole cell and mitochondrial fractions in DM hearts. In isolated mitochondria from DM hearts, rat recombinant renin (r-renin) significantly phosphorylated mitochondrial ERK1/2, and hyperpolarized mitochondrial membrane potential (ΔΨ m ) in a U0126 (an inhibitor of mitogen-activated protein kinases/ERK kinases)-sensitive manner. R-renin also attenuated atractyloside (Atr, an mPTP opener)-induced ΔΨ m depolarization and Atr-induced mitochondrial swelling in an U0126-sensitive manner in isolated mitochondria from DM hearts. Furthermore, U0126 attenuated ischemic resistance in DM hearts, whereas it did not alter the hemodynamics in non-DM hearts. Our results suggest that the increased int-renin during ischemia may inhibit mPTP opening through activation of mitochondrial ERK1/2, which may be involved in ischemic resistance in DM hearts.

  20. Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial Fission.

    Science.gov (United States)

    Tsushima, Kensuke; Bugger, Heiko; Wende, Adam R; Soto, Jamie; Jenson, Gregory A; Tor, Austin R; McGlauflin, Rose; Kenny, Helena C; Zhang, Yuan; Souvenir, Rhonda; Hu, Xiao X; Sloan, Crystal L; Pereira, Renata O; Lira, Vitor A; Spitzer, Kenneth W; Sharp, Terry L; Shoghi, Kooresh I; Sparagna, Genevieve C; Rog-Zielinska, Eva A; Kohl, Peter; Khalimonchuk, Oleh; Schaffer, Jean E; Abel, E Dale

    2018-01-05

    Cardiac lipotoxicity, characterized by increased uptake, oxidation, and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes mellitus. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood. To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo. Using a transgenic mouse model of cardiac lipotoxicity overexpressing ACSL1 (long-chain acyl-CoA synthetase 1) in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation in isolated mitochondria. Mitochondrial morphological changes and elevated ROS generation are also observed in palmitate-treated neonatal rat ventricular cardiomyocytes. Palmitate exposure to neonatal rat ventricular cardiomyocytes initially activates mitochondrial respiration, coupled with increased mitochondrial polarization and ATP synthesis. However, long-term exposure to palmitate (>8 hours) enhances ROS generation, which is accompanied by loss of the mitochondrial reticulum and a pattern suggesting increased mitochondrial fission. Mechanistically, lipid-induced changes in mitochondrial redox status increased mitochondrial fission by increased ubiquitination of AKAP121 (A-kinase anchor protein 121) leading to reduced phosphorylation of DRP1 (dynamin-related protein 1) at Ser637 and altered proteolytic processing of OPA1 (optic atrophy 1). Scavenging mitochondrial ROS restored mitochondrial morphology in vivo and in vitro. Our results reveal a molecular mechanism by which lipid overload-induced mitochondrial ROS generation causes mitochondrial dysfunction by inducing post-translational modifications of mitochondrial proteins that regulate mitochondrial dynamics. These findings provide a

  1. Regulation of mitochondrial contact sites in neonatal, juvenile and diabetic hearts

    Czech Academy of Sciences Publication Activity Database

    Ziegelhöffer-Mihalovičová, B.; Ziegelhöffer, A.; Ravingerová, T.; Kolář, František; Jacob, W.; Tribulová, N.

    2002-01-01

    Roč. 236, 1-2 (2002), s. 37-44 ISSN 0300-8177 Grant - others:VEGA(SK) 2/7157/21; VEGA(SK) 2/6094/21; VEGA(SK) 2/7155/21 Institutional research plan: CEZ:AV0Z5011922 Keywords : mitochondrial creatine phosphokinase * mitochondrial contact sites * diabetic heart Subject RIV: ED - Physiology Impact factor: 1.548, year: 2002

  2. Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis.

    Science.gov (United States)

    Melenovsky, Vojtech; Petrak, Jiri; Mracek, Tomas; Benes, Jan; Borlaug, Barry A; Nuskova, Hana; Pluhacek, Tomas; Spatenka, Jaroslav; Kovalcikova, Jana; Drahota, Zdenek; Kautzner, Josef; Pirk, Jan; Houstek, Josef

    2017-04-01

    Iron replacement improves clinical status in iron-deficient patients with heart failure (HF), but the pathophysiology is poorly understood. Iron is essential not only for erythropoiesis, but also for cellular bioenergetics. The impact of myocardial iron deficiency (MID) on mitochondrial function, measured directly in the failing human heart, is unknown. Left ventricular samples were obtained from 91 consecutive HF patients undergoing transplantation and 38 HF-free organ donors (controls). Total myocardial iron content, mitochondrial respiration, citric acid cycle and respiratory chain enzyme activities, respiratory chain components (complex I-V), and protein content of reactive oxygen species (ROS)-protective enzymes were measured in tissue homogenates to quantify mitochondrial function. Myocardial iron content was lower in HF compared with controls (156 ± 41 vs. 200 ± 38 µg·g -1 dry weight, P Heart Failure © 2016 European Society of Cardiology.

  3. Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine.

    Science.gov (United States)

    Sommer, Wiebke; Buechler, Gwen; Jansson, Katharina; Avsar, Murat; Knöfel, Ann-Kathrin; Salman, Jawad; Hoeffler, Klaus; Siemeni, Thierry; Gottlieb, Jens; Karstens, Johann H; Jonigk, Danny; Reising, Ansgar; Haverich, Axel; Strüber, Martin; Warnecke, Gregor

    2017-04-01

    Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism. © 2017 Steunstichting ESOT.

  4. POSSIBLE ROLE OF MITOCHONDRIAL GENOME MUTATIONS IN CORONARY HEART DISEASE

    Directory of Open Access Journals (Sweden)

    L. A. Egorova

    2014-07-01

    Full Text Available Mitochondria are not only the major producers of adenosine triphosphate, but also an endogenous source of reactive oxygen species. Mitochondrialdysfunction plays a key role in the trigger and progression of atherosclerotic lesion. Impaired function in the mitochondria due to their elevated level of oxidized oxygen species, the accumulation of mitochondrial DNA damages, and the exhaustion of respiratory chains induces dysfunction and apoptosis in the endothelial cells; activation of matrix metalloproteinases; growth of vascular smooth muscle cells and their migration into the intima; expression of adhesion molecules, and oxidation of low-density lipoproteins. Mitochondrial dysfunction may be an important unifying mechanism that accounts for the atherogenic effect of major cardiovascular risk factors. Small clinical pilot studies have shown an association of different mitochondrial genome mutations with atherosclerotic lesion in the artery. Taking into account the available data on the possible role of mitochondria in atherogenesis, novel drugs are now being designed to affect mitochondrial function.

  5. POSSIBLE ROLE OF MITOCHONDRIAL GENOME MUTATIONS IN CORONARY HEART DISEASE

    Directory of Open Access Journals (Sweden)

    L. A. Egorova

    2013-01-01

    Full Text Available Mitochondria are not only the major producers of adenosine triphosphate, but also an endogenous source of reactive oxygen species. Mitochondrialdysfunction plays a key role in the trigger and progression of atherosclerotic lesion. Impaired function in the mitochondria due to their elevated level of oxidized oxygen species, the accumulation of mitochondrial DNA damages, and the exhaustion of respiratory chains induces dysfunction and apoptosis in the endothelial cells; activation of matrix metalloproteinases; growth of vascular smooth muscle cells and their migration into the intima; expression of adhesion molecules, and oxidation of low-density lipoproteins. Mitochondrial dysfunction may be an important unifying mechanism that accounts for the atherogenic effect of major cardiovascular risk factors. Small clinical pilot studies have shown an association of different mitochondrial genome mutations with atherosclerotic lesion in the artery. Taking into account the available data on the possible role of mitochondria in atherogenesis, novel drugs are now being designed to affect mitochondrial function.

  6. High fat fed heart failure animals have enhanced mitochondrial function and acyl-coa dehydrogenase activities

    Science.gov (United States)

    We have previously shown that administration of high fat in heart failure (HF) increased mitochondrial respiration and did not alter left ventricular (LV) function. PPARalpha is a nuclear transcription factor that activates expression of genes involved in fatty acid uptake and utilization. We hypoth...

  7. Decreased mitochondrial oxidative phosphorylation capacity in the human heart with left ventricular systolic dysfunction

    DEFF Research Database (Denmark)

    Stride, Nis; Larsen, Steen; Hey-Mogensen, Martin

    2013-01-01

    Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could...

  8. Right ventricular metabolism during venoarterial extracorporeal membrane oxygenation in immature swine heart in vivo.

    Science.gov (United States)

    Kajimoto, Masaki; Ledee, Dolena R; Isern, Nancy G; Portman, Michael A

    2017-04-01

    Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides hemodynamic rescue for patients encountering right or left ventricular (RV or LV) decompensation, particularly after surgery for congenital heart defects. ECMO, supported metabolically by parenteral nutrition, provides reductions in myocardial work and energy demand and, therefore, enhances functional recovery. The RV must often assume systemic ventricular pressures and function on weaning from VA-ECMO. However the substrate utilization responses of the RV to VA-ECMO or stimulation are unknown. We determined RV and LV substrate utilization response to VA-ECMO in immature swine heart. Mixed-breed male Yorkshire pigs (33-49 days old) underwent normal pressure volume loading (control, n = 5) or were unloaded by VA-ECMO (ECMO, n = 10) for 8 h. Five pigs with ECMO received intravenous thyroid hormone [triiodothyronine (T 3 )] to alter substrate utilization. Carbon 13 ( 13 C)-labeled substrates (lactate and medium-chain and long-chain fatty acids) were systemically infused as metabolic tracers. Analyses by nuclear magnetic resonance showed that both ventricles have similar trends of fractional 13 C-labeled substrate contributions to the citric acid cycle under control conditions. VA-ECMO produced higher long-chain fatty acids and lower lactate contribution to the citric acid cycle via inhibition of pyruvate dehydrogenase, whereas T 3 promoted lactate metabolism in both ventricles. However, these metabolic shifts were smaller in RV, and RV fatty acid contributions showed minimal response to perturbations. Furthermore, VA-ECMO and T 3 also achieved high [phosphocreatine]/[ATP] and low [NADH]/[NAD + ] in LV but not in RV. These data suggest that the RV shows decreased ability to modify substrate utilization and achieve improvements in energy supply/demand during VA-ECMO. NEW & NOTEWORTHY We showed that the right ventricle unloaded by venoarterial extracorporeal membrane oxygenation (VA-ECMO) has diminished

  9. [Recent progress of mitochondrial quality control in ischemic heart disease and its role in cardio-protection of vagal nerve].

    Science.gov (United States)

    Xue, Run-Qing; Xu, Man; Yu, Xiao-Jiang; Liu, Long-Zhu; Zang, Wei-Jin

    2017-10-25

    Ischemic heart disease (IHD) is the life-threatening cardiovascular disease. Mitochondria have emerged as key participants and regulators of cellular energy demands and signal transduction. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission, fusion and mitophagy, which plays an important role in maintaining healthy mitochondria and cardiac function. Recently, dysfunction of each process in mitochondrial quality control has been observed in the ischemic hearts. This review describes the mechanism of mitochondrial dynamics and mitophagy as well as its performance linked to myocardial ischemia. Moreover, in combination with our study, we will discuss the effect of vagal nerve on mitochondria in cardio-protection.

  10. Thermal acclimation and subspecies-specific effects on heart and brain mitochondrial performance in a eurythermal teleost (Fundulus heteroclitus).

    Science.gov (United States)

    Chung, Dillon James; Bryant, Heather J; Schulte, Patricia M

    2017-04-15

    Mitochondrial performance may play a role in setting whole-animal thermal tolerance limits and their plasticity, but the relative roles of adjustments in mitochondrial performance across different highly aerobic tissues remain poorly understood. We compared heart and brain mitochondrial responses to acute thermal challenges and to thermal acclimation using high-resolution respirometry in two locally adapted subspecies of Atlantic killifish ( Fundulus heteroclitus ). We predicted that 5°C acclimation would result in compensatory increases in mitochondrial performance, while 33°C acclimation would cause suppression of mitochondrial function to minimize the effects of high temperature on mitochondrial metabolism. In contrast, acclimation to both 33 and 5°C decreased mitochondrial performance compared with fish acclimated to 15°C. These adjustments could represent an energetic cost-saving mechanism at temperature extremes. Acclimation responses were similar in both heart and brain; however, this effect was smaller in the heart, which might indicate its importance in maintaining whole-animal thermal performance. Alternatively, larger acclimation effects in the brain might indicate greater thermal sensitivity compared with the heart. We detected only modest differences between subspecies that were dependent on the tissue assayed. These data demonstrate extensive plasticity in mitochondrial performance following thermal acclimation in killifish, and indicate that the extent of these responses differs between tissues, highlighting the importance and complexity of mitochondrial regulation in thermal acclimation in eurytherms. © 2017. Published by The Company of Biologists Ltd.

  11. Myocardial microcirculation and mitochondrial energetics in the isolated rat heart

    NARCIS (Netherlands)

    Ashruf, J.F.

    2015-01-01

    Jesse Ashruf describes how the anatomy of the myocardial microcirculation determines the distribution pattern of oxygen to tissue and mitochondria, as evaluated with NADH- and Pd-porphyrin-videofluori-/phosphorimetry. In normal hearts this pattern reveals so-called weak microcirculatory units,

  12. Common Deletion (CD) in mitochondrial DNA of irradiated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Raquel Gomes; Ferreira-Machado, Samara C.; Almeida, Carlos E.V. de, E-mail: raquelgsiqueira@gmail.com [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Ciencias Radiologicas; Silva, Dayse A. da; Carvalho, Elizeu F. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Diagnosticos por DNA; Melo, Luiz D.B. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biofisica Carlos Chagas Filho. Lab. de Parasitologia Molecular

    2014-05-15

    The purpose of this study was to map the common deletion (CD) area in mtDNA and investigate the levels of this deletion in irradiated heart. The assays were developed in male Wistar rats that were irradiated with three different single doses (5, 10 or 15 Gy) delivered directly to the heart and the analyses were performed at various times post-irradiation (3, 15 or 120 days). The CDs area were sequenced and the CD quantified by real-time PCR. Our study demonstrated that the CD levels progressively decreased from the 3rd until the 15th day after irradiation, and then increased thereafter. Additionally, it was observed that the levels of CD are modulated differently according to the different categories of doses (moderate and high). This study demonstrated an immediate response to ionizing radiation, measured by the presence of mutations in the CD area and a decrease in the CD levels. (author)

  13. 3D IMAGING OF THE MITOCHONDRIAL REDOX STATE OF RAT HEARTS UNDER NORMAL AND FASTING CONDITIONS.

    Science.gov (United States)

    Xu, He N; Zhou, Rong; Moon, Lily; Feng, Min; Li, Lin Z

    2014-03-01

    The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo . Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD + couple acting as a central electron carrier. We employed the Chance redox scanner - the low-temperature fluorescence scanner to image the three-dimensional (3D) spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH ( p = 0.038). No significant change in Fp was found ( p = 0.4). The NADH/Fp ratio decreased with a marginal p value (0.076). The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the feasibility of 3D

  14. 3D imaging of the mitochondrial redox state of rat hearts under normal and fasting conditions

    Directory of Open Access Journals (Sweden)

    He N. Xu

    2014-03-01

    Full Text Available The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD+ couple acting as a central electron carrier. We employed the Chance redox scanner — the low-temperature fluorescence scanner to image the three-dimensional (3D spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p = 0.038. No significant change in Fp was found (p = 0.4. The NADH/Fp ratio decreased with a marginal p value (0.076. The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the

  15. Mitochondrial damage: An important mechanism of ambient PM2.5 exposure-induced acute heart injury in rats

    International Nuclear Information System (INIS)

    Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing; Cai, Zongwei; Dong, Chuan

    2015-01-01

    Highlights: • PM 2.5 induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM 2.5 ) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM 2.5 -induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM 2.5 with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM 2.5 exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM 2.5 exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na + K + -ATPase and Ca 2+ -ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM 2.5 -induced heart injury, and may have relations with cardiovascular disease

  16. PFOS prenatal exposure induce mitochondrial injury and gene expression change in hearts of weaned SD rats

    International Nuclear Information System (INIS)

    Xia, Wei; Wan, Yanjian; Li, Yuan-yuan; Zeng, Huaicai; Lv, Ziquan; Li, Gengqi; Wei, Zhengzheng; Xu, Shun-qing

    2011-01-01

    Xenobiotics exposure in early life may have adverse effects on animals' development through mitochondrial injury or dysfunction. The current study demonstrated the possibility of cardiac mitochondrial injury in prenatal PFOS-exposed weaned rat heart. Pregnant Sprague-Dawley (SD) rats were exposed to perfluorooctane sulfonate (PFOS) at doses of 0.1, 0.6 and 2.0 mg/kg/d and 0.05% Tween 80 as control by gavage from gestation days 2-21. The dams were allowed to give nature delivery and then heart tissues from weaned (postnatal day 21) offspring rats were analyzed for mitochondrial injury through ultrastructure observation by electron microscope, global gene expression profile by microarray, as well as related mRNA and proteins expression levels by quantitative PCR and western blot. Ultrastructural analysis revealed significant vacuolization and inner membrane injury occurred at the mitochondria of heart tissues from 2.0 mg/kg/d dosage group. Meanwhile, the global gene expression profile showed significant difference in level of some mRNA expression associated with mitochondrial function at 2.0 mg/kg/d dosage group, compared to the control. Furthermore, dose-response trends for the expression of selected genes were analyzed by quantitative PCR and western blot analysis. The selected genes were mainly focused on those encoding for proteins involved in energy production, control of ion levels, and maintenance of heart function. The down-regulation of mitochondrial ATP synthetase (ATP5E, ATP5I and ATP5O) implicated a decrease in energy supply. This was accompanied by down-regulation of gene transcripts involved in energy consumption such as ion transporting ATPase (ATP1A3 and ATP2B2) and inner membrane protein synthesis (SLC25A3, SLC25A4, SLC25A10, SLC25A29). The up-regulation of gene transcripts encoding for uncoupling proteins (UCP1 and UCP3), epidermal growth factor receptor (EGFR) and connective tissue growth factor (CTGF), was probably a protective process to maintain

  17. Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure.

    Science.gov (United States)

    Guichard, Jason L; Rogowski, Michael; Agnetti, Giulio; Fu, Lianwu; Powell, Pamela; Wei, Chih-Chang; Collawn, James; Dell'Italia, Louis J

    2017-07-01

    Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later. Desmin/mitochondrial ultrastructure was examined by transmission electron microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40% decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4 and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering, IHC evidence of disorganization associated with desmin breakdown, and desmin protein cleavage verified by Western blot analysis and mass spectrometry. IHC results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear translocation of αB-crystallin from the Z disk with increased α, β-unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is indicative of an inability to complete autophagy. An early and continuous disruption of the desmin/mitochondrial architecture, accompanied by oxidative stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV dilatation and systolic dysfunction in VO. NEW & NOTEWORTHY This study provides new evidence of early onset (24 h) and continuous (4-12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial

  18. Mitochondrial phospholipase A2 activated by reactive oxygen species in heart mitochondria induces mild uncoupling

    Czech Academy of Sciences Publication Activity Database

    Ježek, Jan; Jabůrek, Martin; Zelenka, Jaroslav; Ježek, Petr

    2010-01-01

    Roč. 59, č. 5 (2010), s. 737-747 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA303/07/0105; GA MŠk ME09018; GA AV ČR(CZ) KJB500110902 Institutional research plan: CEZ:AV0Z50110509 Keywords : Heart mitochondrial phospholipase A2 * Fatty Acids * Adenine nucleotide translocase Subject RIV: ED - Physiology Impact factor: 1.646, year: 2010

  19. Posttranslational modifications and dysfunction of mitochondrial enzymes in human heart failure.

    Science.gov (United States)

    Sheeran, Freya L; Pepe, Salvatore

    2016-08-01

    Deficiency of energy supply is a major complication contributing to the syndrome of heart failure (HF). Because the concurrent activity profile of mitochondrial bioenergetic enzymes has not been studied collectively in human HF, our aim was to examine the mitochondrial enzyme defects in left ventricular myocardium obtained from explanted end-stage failing hearts. Compared with nonfailing donor hearts, activity rates of complexes I and IV and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase, and aconitase were lower in HF, as determined spectrophotometrically. However, activity rates of complexes II and III and citrate synthase did not differ significantly between the two groups. Protein expression, determined by Western blotting, did not differ between the groups, implying posttranslational perturbation. In the face of diminished total glutathione and coenzyme Q10 levels, oxidative modification was explored as an underlying cause of enzyme dysfunction. Of the three oxidative modifications measured, protein carbonylation was increased significantly by 31% in HF (P human left ventricle involves impaired activity of key electron transport chain and Krebs cycle enzymes without altered expression of protein levels. Augmented oxidative modification of crucial enzyme subunit structures implicates dysfunction due to diminished capacity for management of mitochondrial reactive oxygen species, thus contributing further to reduced bioenergetics in human HF. Copyright © 2016 the American Physiological Society.

  20. Diclofenac induces proteasome and mitochondrial dysfunction in murine cardiomyocytes and hearts.

    Science.gov (United States)

    Ghosh, Rajeshwary; Goswami, Sumanta K; Feitoza, Luis Felipe B B; Hammock, Bruce; Gomes, Aldrin V

    2016-11-15

    One of the most common nonsteroidal anti-inflammatory drugs (NSAIDs) used worldwide, diclofenac (DIC), has been linked to increased risk of cardiovascular disease (CVD). The molecular mechanism(s) by which DIC causes CVD is unknown. Proteasome activities were studied in hearts, livers, and kidneys from male Swiss Webster mice treated with either 100mg/kg DIC for 18h (acute treatment) or 10mg/kg DIC for 28days (chronic treatment). Cultured H9c2 cells and neonatal cardiomyocytes were also treated with different concentrations of DIC and proteasome function, cell death and ROS generation studied. Isolated mouse heart mitochondria were utilized to determine the effect of DIC on various electron transport chain complex activities. DIC significantly inhibited the chymotrypsin-like proteasome activity in rat cardiac H9c2 cells, murine neonatal cardiomyocytes, and mouse hearts, but did not affect proteasome subunit expression levels. Proteasome activity was also affected in liver and kidney tissues from DIC treated animals. The levels of polyubiquitinated proteins increased in hearts from DIC treated mice. Importantly, the levels of oxidized proteins increased while the β5i immunoproteasome activity decreased in hearts from DIC treated mice. DIC increased ROS production and cell death in H9c2 cells and neonatal cardiomyocytes while the cardioprotective NSAID, aspirin, had no effect on ROS levels or cell viability. DIC inhibited mitochondrial Complex III, a major source of ROS, and impaired mitochondrial membrane potential suggesting that mitochondria are the major sites of ROS generation. These results suggest that DIC induces cardiotoxicity by a ROS dependent mechanism involving mitochondrial and proteasome dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Heart donation after cardiac death: preliminary study on an isolated, perfused swine heart after 20 minutes of normothermic ischemia.

    Science.gov (United States)

    Desrois, M; Piccardo, A; Zogheib, E; Dalmasso, C; Lan, C; Fourré, D; Cozzone, P J; Caus, T; Bernard, M

    2014-12-01

    We measured the functional and metabolic status of hearts submitted to normothermic ischemia before preservation through the use of an ex vivo pig heart model to assess the feasibility of donation after cardiac death (DCD) in heart transplantation. Ten pigs were separated into 2 groups: control (n = 6, brain-dead group) and DCD (n = 4, heart donation after cardiac death). In the control group, hearts were excised 20 minutes after the brachiocephalic trunk cross-clamping and were immediately reperfused. In DCD, hearts were excised 20 minutes after exsanguination and asphyxia, stored in the Centre de Résonance Magnétique Biologique et Médicale (CRMBM) solution for 2 hours, and then were reperfused. Cardioplegic arrest was induced with the use of 1 L of CRMBM solution (4°C) and the heart was reperfused for 60 minutes through the use of an ex vivo perfusion system in Langendorff mode with normothermic autologous blood. During reperfusion, functional parameters were analyzed. Biochemical assays were performed in myocardial effluents and freeze-clamped hearts. No electromechanical activity was found in DCD compared with control. Creatine kinase (CK) was higher at 2 minutes of reperfusion in DCD versus control (P = .005). Adenosine triphosphate was lower in DCD versus control (P = .0019). Malondialdehyde, an oxidative stress index, was present only in DCD. The nitric oxide (NO) pathway was impaired in DCD versus control, with lower eNOS expression (P heart preservation are necessary for recruiting heart donation after cardiac death. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Aging-dependent changes in rat heart mitochondrial glutaredoxins—Implications for redox regulation

    Directory of Open Access Journals (Sweden)

    Xing-Huang Gao

    2013-01-01

    Full Text Available Clinical and animal studies have documented that hearts of the elderly are more susceptible to ischemia/reperfusion damage compared to young adults. Recently we found that aging-dependent increase in susceptibility of cardiomyocytes to apoptosis was attributable to decrease in cytosolic glutaredoxin 1 (Grx1 and concomitant decrease in NF-κB-mediated expression of anti-apoptotic proteins. Besides primary localization in the cytosol, Grx1 also exists in the mitochondrial intermembrane space (IMS. In contrast, Grx2 is confined to the mitochondrial matrix. Here we report that Grx1 is decreased by 50–60% in the IMS, but Grx2 is increased by 1.4–2.6 fold in the matrix of heart mitochondria from elderly rats. Determination of in situ activities of the Grx isozymes from both subsarcolemmal (SSM and interfibrillar (IFM mitochondria revealed that Grx1 was fully active in the IMS. However, Grx2 was mostly in an inactive form in the matrix, consistent with reversible sequestration of the active-site cysteines of two Grx2 molecules in complex with an iron–sulfur cluster. Our quantitative evaluations of the active/inactive ratio for Grx2 suggest that levels of dimeric Grx2 complex with iron–sulfur clusters are increased in SSM and IFM in the hearts of elderly rats. We found that the inactive Grx2 can be fully reactivated by sodium dithionite or exogenous superoxide production mediated by xanthine oxidase. However, treatment with rotenone, which generates intramitochondrial superoxide through inhibition of mitochondrial respiratory chain Complex I, did not lead to Grx2 activation. These findings suggest that insufficient ROS accumulates in the vicinity of dimeric Grx2 to activate it in situ.

  3. Effects of Air Pollution and Blood Mitochondrial DNA Methylation on Markers of Heart Rate Variability.

    Science.gov (United States)

    Byun, Hyang-Min; Colicino, Elena; Trevisi, Letizia; Fan, Tianteng; Christiani, David C; Baccarelli, Andrea A

    2016-04-22

    The mitochondrion is the primary target of oxidative stress in response to exogenous environments. Mitochondrial DNA (mtDNA) is independent from nuclear DNA and uses separate epigenetic machinery to regulate mtDNA methylation. The mtDNA damage induced by oxidative stress can cause mitochondrial dysfunction and is implicated in human diseases; however, mtDNA methylation has been largely overlooked in environmental studies relating to human disease. The purpose of this study was to examine the association between exposure to fine metal-rich particulates (particulate matter heart rate variability. Forty-eight healthy men were recruited on multiple sampling cycles at the Boilermaker Union Local 29, located in Quincy, Massachusetts. We measured personal PM2.5 in the background ambient environment. We measured blood mtDNA methylation in the mtDNA promoter (D-loop) and genes essential for ATP synthesis (MT-TF and MT-RNR1) by bisulfite pyrosequencing. All analyses were adjusted for demographics, type of job, season, welding-work day, and mtDNA methylation experimental batch effect. The participants' PM2.5 exposure was significantly higher after a welding-work day (mean 0.38 mg/m(3)) than the background personal level (mean 0.15 mg/m(3), Pmarkers of heart rate variability. Blood mtDNA methylation levels were negatively associated with PM2.5 exposure and modified the adverse relationships between PM2.5 exposure and heart rate variability outcomes. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  4. Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction

    Directory of Open Access Journals (Sweden)

    Yasuharu Shinoda

    2016-07-01

    Full Text Available Haloperidol is an antipsychotic drug that inhibits the dopamine D2 receptor among others. Haloperidol also binds the sigma-1 receptor (σ1R and inhibits it irreversibly. A serious outcome of haloperidol treatment of schizophrenia patients is death due to sudden cardiac failure. Although the cause remains unclear, we hypothesized that these effects were mediated by chronic haloperidol inhibition of cardiac σ1R. To test this, we treated neonatal rat cardiomyocytes with haloperidol, exposed them to angiotensin II and assessed hypertrophy, σ1R expression, mitochondrial Ca2+ transport and ATP levels. In this context, haloperidol treatment altered mitochondrial Ca2+ transport resulting in decreased ATP content by inactivating cardiac σ1R and/or reducing its expression. We also performed transverse aortic constriction (TAC and then treated mice with haloperidol. After two weeks, haloperidol-treated mice showed enhanced heart failure marked by deteriorated cardiac function, reduced ATP production and increasing mortality relative to TAC only mice. ATP supplementation via sodium pyruvate rescued phenotypes seen in haloperidol-treated TAC mice. We conclude that σ1R inactivation or downregulation in response to haloperidol treatment impairs mitochondrial Ca2+ mobilization, depleting ATP depletion from cardiomyocytes. These findings suggest a novel approach to mitigate haloperidol-related adverse effects in schizophrenia patients by ATP supplementation.

  5. New Insights into the Role of Mitochondrial Dynamics and Autophagy during Oxidative Stress and Aging in the Heart

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ikeda

    2014-01-01

    Full Text Available The heart is highly sensitive to the aging process. In the elderly, the heart tends to become hypertrophic and fibrotic. Stiffness increases with ensuing systolic and diastolic dysfunction. Aging also affects the cardiac response to stress. At the molecular level, the aging process is associated with accumulation of damaged proteins and organelles, partially due to defects in protein quality control systems. The accumulation of dysfunctional and abnormal mitochondria is an important pathophysiological feature of the aging process, which is associated with excessive production of reactive oxygen species. Mitochondrial fusion and fission and mitochondrial autophagy are crucial mechanisms for maintaining mitochondrial function and preserving energy production. In particular, mitochondrial fission allows for selective segregation of damaged mitochondria, which are afterward eliminated by autophagy. Unfortunately, recent evidence indicates that mitochondrial dynamics and autophagy are progressively impaired over time, contributing to the aging process. This suggests that restoration of these mechanisms could delay organ senescence and prevent age-associated cardiac diseases. Here, we discuss the current understanding of the close relationship between mitochondrial dynamics, mitophagy, oxidative stress, and aging, with a particular focus on the heart.

  6. Mitochondrial and genomic ancestry are associated with etiology of heart failure in Brazilian patients.

    Science.gov (United States)

    Cardena, M M S G; Ribeiro-Dos-Santos, A K; Santos, S E B; Mansur, A J; Bernardez-Pereira, S; Santos, P C J L; Pereira, A C; Fridman, C

    2016-02-01

    There is a high prevalence of heart failure (HF) in the general population, but it is more common in black people. We evaluated the association between genomic ancestry and mitochondrial haplogroups (mt-haplogroups) with HF etiology in 503 Brazilian patients. We elicited Mt-haplogroups by analyzing the control region of mitochondrial DNA, and genomic ancestry, by using 48 autosomal insertion-deletion ancestry informative markers. Hypertensive (28.6%, n=144) and ischemic (28.4%, n=143) etiologies of HF were the most prevalent herein. Our results showed that 233 individuals (46.3%) presented African mitochondrial (mt)-haplogroups, and the major contribution in the genomic ancestry analysis was the European ancestry (57.5% (±22.1%)). African mt-haplogroups were positively associated with a diagnosis of hypertensive cardiomyopathy (odds ratio, OR 1.55, confidence interval, CI 95% 1.04-2.44, P=0.04) when compared with European mt-haplogroups. Regarding the genomic ancestry, the African ancestry variant had higher risks (OR 7.84, 95% CI 2.81-21.91, Pancestry variant had lower risks (OR 0.14, 95% CI 0.04-5.00, Pancestry showed an OR of 4.05 (CI 95% 1.53-10.74, P=0.005), whereas African ancestry showed an OR of 0.17 (CI 95% 0.06-0.48, P=0.001) for developing ischemic etiology. In conclusion, this study supports the importance of using ancestry informative markers and mitochondrial DNA to study the genetics of complex diseases in admixed populations to improve the management, treatment and prevention of these illnesses. Therefore, the ancestry informative markers and mt-haplogroups could provide new biomarkers to be associated with HF etiologies and be used as a premise for more specific management.

  7. Overexpression of Chromosome 21 miRNAs May Affect Mitochondrial Function in the Hearts of Down Syndrome Fetuses

    Directory of Open Access Journals (Sweden)

    Antonella Izzo

    2017-01-01

    Full Text Available Dosage-dependent upregulation of most of chromosome 21 (Hsa21 genes has been demonstrated in heart tissues of fetuses with Down syndrome (DS. Also miRNAs might play important roles in the cardiac phenotype as they are highly expressed in the heart and regulate cardiac development. Five Hsa21 miRNAs have been well studied in the past: miR-99a-5p, miR-125b-2-5p, let-7c-5p, miR-155-5p, and miR-802-5p but few information is available about their expression in trisomic tissues. In this study, we evaluated the expression of these miRNAs in heart tissues from DS fetuses, showing that miR-99a-5p, miR-155-5p, and let-7c-5p were overexpressed in trisomic hearts. To investigate their role, predicted targets were obtained from different databases and cross-validated using the gene expression profiling dataset we previously generated for fetal hearts. Eighty-five targets of let-7c-5p, 33 of miR-155-5p, and 10 of miR-99a-5p were expressed in fetal heart and downregulated in trisomic hearts. As nuclear encoded mitochondrial genes were found downregulated in trisomic hearts and mitochondrial dysfunction is a hallmark of DS phenotypes, we put special attention to let-7c-5p and miR-155-5p targets downregulated in DS fetal hearts and involved in mitochondrial function. The let-7c-5p predicted target SLC25A4/ANT1 was identified as a possible candidate for both mitochondrial and cardiac anomalies.

  8. Acetylation of mitochondrial proteins by GCN5L1 promotes enhanced fatty acid oxidation in the heart.

    Science.gov (United States)

    Thapa, Dharendra; Zhang, Manling; Manning, Janet R; Guimarães, Danielle A; Stoner, Michael W; O'Doherty, Robert M; Shiva, Sruti; Scott, Iain

    2017-08-01

    Lysine acetylation is a reversible posttranslational modification and is particularly important in the regulation of mitochondrial metabolic enzymes. Acetylation uses acetyl-CoA derived from fuel metabolism as a cofactor, thereby linking nutrition to metabolic activity. In the present study, we investigated how mitochondrial acetylation status in the heart is controlled by food intake and how these changes affect mitochondrial metabolism. We found that there was a significant increase in cardiac mitochondrial protein acetylation in mice fed a long-term high-fat diet and that this change correlated with an increase in the abundance of the mitochondrial acetyltransferase-related protein GCN5L1. We showed that the acetylation status of several mitochondrial fatty acid oxidation enzymes (long-chain acyl-CoA dehydrogenase, short-chain acyl-CoA dehydrogenase, and hydroxyacyl-CoA dehydrogenase) and a pyruvate oxidation enzyme (pyruvate dehydrogenase) was significantly upregulated in high-fat diet-fed mice and that the increase in long-chain and short-chain acyl-CoA dehydrogenase acetylation correlated with increased enzymatic activity. Finally, we demonstrated that the acetylation of mitochondrial fatty acid oxidation proteins was decreased after GCN5L1 knockdown and that the reduced acetylation led to diminished fatty acid oxidation in cultured H9C2 cells. These data indicate that lysine acetylation promotes fatty acid oxidation in the heart and that this modification is regulated in part by the activity of GCN5L1. NEW & NOTEWORTHY Recent research has shown that acetylation of mitochondrial fatty acid oxidation enzymes has greatly contrasting effects on their activity in different tissues. Here, we provide new evidence that acetylation of cardiac mitochondrial fatty acid oxidation enzymes by GCN5L1 significantly upregulates their activity in diet-induced obese mice. Copyright © 2017 the American Physiological Society.

  9. Reducing mitochondrial bound hexokinase II mediates transition from non-injurious into injurious ischemia/reperfusion of the intact heart

    NARCIS (Netherlands)

    R. Nederlof (Rianne); Gürel-Gurevin, E. (Ebru); O. Eerbeek (Otto); C. Xie (Chaoqin); Deijs, G.S.; Konkel, M. (Moritz); Hu, J. (Jun); N.C. Weber (Nina); C. Schumacher (Cees); A. Baartscheer (Antonius); E.G. Mik (Egbert); M.W. Hollmann (Markus); F.G. Akar (Fadi); C.J. Zuurbier (Coert J.)

    2016-01-01

    textabstractIschemia/reperfusion (I/R) of the heart becomes injurious when duration of the ischemic insult exceeds a certain threshold (approximately ≥20 min). Mitochondrial bound hexokinase II (mtHKII) protects against I/R injury, with the amount of mtHKII correlating with injury. Here, we examine

  10. Mitochondrial Dynamics in Mitochondrial Diseases

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    Juan M. Suárez-Rivero

    2016-12-01

    Full Text Available Mitochondria are very versatile organelles in continuous fusion and fission processes in response to various cellular signals. Mitochondrial dynamics, including mitochondrial fission/fusion, movements and turnover, are essential for the mitochondrial network quality control. Alterations in mitochondrial dynamics can cause neuropathies such as Charcot-Marie-Tooth disease in which mitochondrial fusion and transport are impaired, or dominant optic atrophy which is caused by a reduced mitochondrial fusion. On the other hand, mitochondrial dysfunction in primary mitochondrial diseases promotes reactive oxygen species production that impairs its own function and dynamics, causing a continuous vicious cycle that aggravates the pathological phenotype. Mitochondrial dynamics provides a new way to understand the pathophysiology of mitochondrial disorders and other diseases related to mitochondria dysfunction such as diabetes, heart failure, or Hungtinton’s disease. The knowledge about mitochondrial dynamics also offers new therapeutics targets in mitochondrial diseases.

  11. Improvement of heart function in postinfarct heart failure swine models after hepatocyte growth factor gene transfer: comparison of low-, medium- and high-dose groups.

    Science.gov (United States)

    Yang, Zhi-jian; Chen, Bo; Sheng, Zhang; Zhang, Ding-guo; Jia, En-zhi; Wang, Wei; Ma, Dong-chao; Zhu, Tie-bing; Wang, Lian-sheng; Li, Chun-jian; Wang, Hui; Cao, Ke-jiang; Ma, Wen-zhu

    2010-04-01

    Despite advances in surgical and reperfusion therapy, there is no effective therapy currently exists to prevent the progressive decline in cardiac function following myocardial infarction. Hepatocyte growth factor has potent angiogenic and anti-apoptotic activities. The aim of this study was to investigate the therapeutic effect and dose-effect relationship on postinfarction heart failure with different doses of adenovirus-mediated human hepatocyte growth factor (Ad(5)-HGF) transference in swine models. Totally twenty swine were randomly divided into four groups: (a) control group (null- Ad(5), 1 ml); (b) low-dose group (1 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (c) medium-dose group (5 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (d) high-dose group (1 x 10(10) Pfu/ml Ad(5)-HGF, 1 ml). Four weeks after left anterior descending coronary artery (LAD) ligation, different doses of Ad(5)-HGF were transferred in three therapeutic groups via right coronary artery. Four and seven weeks after LAD ligation, gate cardiac perfusion imaging was performed to evaluate cardiac perfusion and left ventricular ejection fraction (LVEF). Seven weeks after surgery, the apoptotic index of cardiocyte was observed by TUNEL, the expression of Bcl-2, Bax, alpha-SMA and Factor VIII in the border zones were evaluated by immunohistochemistry, respectively. Four weeks after myocardial infarction, no significant difference was observed among four groups. Three weeks after Ad(5)-HGF transfer, the improvement of cardiac perfusion and LVEF was obviously observed, especially after 1 x 10(10) Pfu Ad(5)-HGF transfer. TUNEL assay showed that 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF treatment had a obvious reduction in the apoptotic index compared with the null-Ad(5) group, especially after 1 x 10(10) Pfu Ad(5)-HGF treatment. The expression of Bcl-2 protein was increased and the expression of Bax protein was inhibited in the 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF groups compared with the null-Ad(5) group. The vessel

  12. Quantification of fibrosis in infarcted swine hearts by ex vivo late gadolinium-enhancement and diffusion-weighted MRI methods

    Science.gov (United States)

    Pop, Mihaela; Ghugre, Nilesh R.; Ramanan, Venkat; Morikawa, Lily; Stanisz, Greg; Dick, Alexander J.; Wright, Graham A.

    2013-08-01

    Many have speculated that MRI signal characteristics can be used to identify regions of heterogeneous infarct associated with an arrhythmogenic substrate; however, direct evidence of this relationship is limited. The aim of this study was to demonstrate the remodelling characteristics of fibrosis by means of histology and high-resolution MR imaging. For this purpose, we performed whole-mount histology in heart samples (n = 9) collected from five swine at six weeks post-infarction and compared the extent of fibrosis in the infarcted areas delineated in these histological images with that obtained ex vivo by MRI using late gadolinium-enhancement (LGE) and diffusion-weighted imaging (DWI) methods. All MR images were obtained at a submillimetre resolution (i.e., voxel size of 0.6×0.6×1.2 mm3). Specifically, in the histology images, we differentiated moderate fibrosis (consisting of a mixture of viable and non-viable myocytes, known as border zone, BZ) from severe fibrosis (i.e., the dense scar). Correspondingly, tissue heterogeneities in the MR images were categorized by a Gaussian mixture model into healthy, BZ and scar. Our results showed that (a) both MRI methods were capable of qualitatively distinguishing sharp edges between dense scar and healthy tissue from regions of heterogeneous BZ; (b) the BZ and dense scar areas had intermediate-to-high increased values of signal intensity in the LGE images and of apparent diffusion coefficient in the DWI, respectively. In addition, as demonstrated by the Picrosirius Red and immunohistochemistry stains, the viable bundles in the BZ were clearly separated by thin collagen strands and had reduced expression of Cx43, whereas the core scar was composed of dense fibrosis. A quantitative analysis demonstrated that the comparison between BZ/scar extent in LGE and DWI to the corresponding areas identified in histology yielded very good correlations (i.e., for the scar identified by LGE, R2 was 0.96 compared to R2 = 0.93 for the

  13. Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism.

    Science.gov (United States)

    Sun, Dan; Yang, Fei

    2017-04-29

    To investigate whether metformin can improve the cardiac function through improving the mitochondrial function in model of heart failure after myocardial infarction. Male C57/BL6 mice aged about 8 weeks were selected and the anterior descending branch was ligatured to establish the heart failure model after myocardial infarction. The cardiac function was evaluated via ultrasound after 3 days to determine the modeling was successful, and the mice were randomly divided into two groups. Saline group (Saline) received the intragastric administration of normal saline for 4 weeks, and metformin group (Met) received the intragastric administration of metformin for 4 weeks. At the same time, Shame group (Sham) was set up. Changes in cardiac function in mice were detected at 4 weeks after operation. Hearts were taken from mice after 4 weeks, and cell apoptosis in myocardial tissue was detected using TUNEL method; fresh mitochondria were taken and changes in oxygen consumption rate (OCR) and respiratory control rate (RCR) of mitochondria in each group were detected using bio-energy metabolism tester, and change in mitochondrial membrane potential (MMP) of myocardial tissue was detected via JC-1 staining; the expressions and changes in Bcl-2, Bax, Sirt3, PGC-1α and acetylated PGC-1α in myocardial tissue were detected by Western blot. RT-PCR was used to detect mRNA levels in Sirt3 in myocardial tissues. Metformin improved the systolic function of heart failure model rats after myocardial infarction and reduced the apoptosis of myocardial cells after myocardial infarction. Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1α in myocardial tissue of heart failure after myocardial infarction. Metformin decreases the

  14. Mitochondrial damage: An important mechanism of ambient PM{sub 2.5} exposure-induced acute heart injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China); Cai, Zongwei, E-mail: zwcai@hkbu.edu.hk [State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR (China); Dong, Chuan, E-mail: dc@sxu.edu.cn [Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University, Taiyuan (China)

    2015-04-28

    Highlights: • PM{sub 2.5} induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM{sub 2.5}) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM{sub 2.5}-induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM{sub 2.5} with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM{sub 2.5} exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM{sub 2.5} exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na{sup +}K{sup +}-ATPase and Ca{sup 2+}-ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM{sub 2.5}-induced heart injury, and may have relations with cardiovascular disease.

  15. Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells

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    Dehai Yu

    2017-01-01

    Full Text Available Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal. By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.

  16. Protein Phosphatase Inhibitor-1 Gene Therapy in a Swine Model of Nonischemic Heart Failure.

    Science.gov (United States)

    Watanabe, Shin; Ishikawa, Kiyotake; Fish, Kenneth; Oh, Jae Gyun; Motloch, Lukas J; Kohlbrenner, Erik; Lee, Philyoung; Xie, Chaoqin; Lee, Ahyoung; Liang, Lifan; Kho, Changwon; Leonardson, Lauren; McIntyre, Maritza; Wilson, Scott; Samulski, R Jude; Kranias, Evangelia G; Weber, Thomas; Akar, Fadi G; Hajjar, Roger J

    2017-10-03

    Increased protein phosphatase-1 in heart failure (HF) induces molecular changes deleterious to the cardiac cell. Inhibiting protein phosphatase-1 through the overexpression of a constitutively active inhibitor-1 (I-1c) has been shown to reverse cardiac dysfunction in a model of ischemic HF. This study sought to determine the therapeutic efficacy of a re-engineered adenoassociated viral vector carrying I-1c (BNP116.I-1c) in a preclinical model of nonischemic HF, and to assess thoroughly the safety of BNP116.I-1c gene therapy. Volume-overload HF was created in Yorkshire swine by inducing severe mitral regurgitation. One month after mitral regurgitation induction, pigs were randomized to intracoronary delivery of either BNP116.I-1c (n = 6) or saline (n = 7). Therapeutic efficacy and safety were evaluated 2 months after gene delivery. Additionally, 24 naive pigs received different doses of BNP116.I-1c for safety evaluation. At 1 month after mitral regurgitation induction, pigs developed HF as evidenced by increased left ventricular end-diastolic pressure and left ventricular volume indexes. Treatment with BNP116.I-1c resulted in improved left ventricular ejection fraction (-5.9 ± 4.2% vs. 5.5 ± 4.0%; p pigs also exhibited a significant increase in left atrial ejection fraction at 2 months after gene delivery (-4.3 ± 3.1% vs. 7.5 ± 3.1%; p = 0.02). In vitro I-1c gene transfer in isolated left atrial myocytes from both pigs and rats increased calcium transient amplitude, consistent with its positive impact on left atrial contraction. We found no evidence of adverse electrical remodeling, arrhythmogenicity, activation of a cellular immune response, or off-target organ damage by BNP116.I-1c gene therapy in pigs. Intracoronary delivery of BNP116.I-1c was safe and improved contractility of the left ventricle and atrium in a large animal model of nonischemic HF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights

  17. Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts.

    Science.gov (United States)

    Duicu, Oana M; Privistirescu, Andreea; Wolf, Adrian; Petruş, Alexandra; Dănilă, Maria D; Raţiu, Corina D; Muntean, Danina M; Sturza, Adrian

    2017-11-01

    Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox drug with reported protective effects mainly on brain mitochondria. The purpose of the present study was to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H 2 O 2 production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats. Mitochondrial respiratory function was assessed by high-resolution respirometry. H 2 O 2 production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μmol·L -1 ) elicited an increase in oxygen consumption of mitochondria energized with complex I and II substrates in both normal and diseased mitochondria. Interestingly, methylene blue elicited a significant increase in H 2 O 2 release in the presence of complex I substrates (glutamate and malate), but had an opposite effect in mitochondria energized with complex II substrate (succinate). No changes in the calcium retention capacity of healthy or diabetic mitochondria were found in the presence of methylene blue. In conclusion, in cardiac mitochondria isolated from diabetic and nondiabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production.

  18. Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart.

    Science.gov (United States)

    Ashmore, Tom; Fernandez, Bernadette O; Branco-Price, Cristina; West, James A; Cowburn, Andrew S; Heather, Lisa C; Griffin, Julian L; Johnson, Randall S; Feelisch, Martin; Murray, Andrew J

    2014-11-01

    Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n = 40) were given water supplemented with 0.7 mmol l(-1) NaCl (as control) or 0.7 mmol l(-1) NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n = 10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac l-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  19. Nitric oxide protects the heart from ischemia-induced apoptosis and mitochondrial damage via protein kinase G mediated blockage of permeability transition and cytochrome c release

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    Jekabsone Aiste

    2009-08-01

    Full Text Available Abstract Background Heart ischemia can rapidly induce apoptosis and mitochondrial dysfunction via mitochondrial permeability transition-induced cytochrome c release. We tested whether nitric oxide (NO can block this damage in isolated rat heart, and, if so, by what mechanisms. Methods Hearts were perfused with 50 μM DETA/NO (NO donor, then subjected to 30 min stop-flow ischemia or ischemia/reperfusion. Isolated heart mitochondria were used to measure the rate of mitochondrial oxygen consumption and membrane potential using oxygen and tetraphenylphosphonium-selective electrodes. Mitochondrial and cytosolic cytochrome c levels were measured spectrophotometrically and by ELISA. The calcium retention capacity of isolated mitochondria was measured using the fluorescent dye Calcium Green-5N. Apoptosis and necrosis were evaluated by measuring the activity of caspase-3 in cytosolic extracts and the activity of lactate dehydrogenase in perfusate, respectively. Results 30 min ischemia caused release of mitochondrial cytochrome c to the cytoplasm, inhibition of the mitochondrial respiratory chain, and stimulation of mitochondrial proton permeability. 3 min perfusion with 50 μM DETA/NO of hearts prior to ischemia decreased this mitochondrial damage. The DETA/NO-induced blockage of mitochondrial cytochrome c release was reversed by a protein kinase G (PKG inhibitor KT5823, or soluble guanylate cyclase inhibitor ODQ or protein kinase C inhibitors (Ro 32-0432 and Ro 31-8220. Ischemia also stimulated caspase-3-like activity, and this was substantially reduced by pre-perfusion with DETA/NO. Reperfusion after 30 min of ischemia caused no further caspase activation, but was accompanied by necrosis, which was completely prevented by DETA/NO, and this protection was blocked by the PKG inhibitor. Incubation of isolated heart mitochondria with activated PKG blocked calcium-induced mitochondrial permeability transition and cytochrome c release. Perfusion of non

  20. Radiation-induced signaling results in mitochondrial impairment in mouse heart at 4 weeks after exposure to X-rays.

    Science.gov (United States)

    Barjaktarovic, Zarko; Schmaltz, Dominik; Shyla, Alena; Azimzadeh, Omid; Schulz, Sabine; Haagen, Julia; Dörr, Wolfgang; Sarioglu, Hakan; Schäfer, Alexander; Atkinson, Michael J; Zischka, Hans; Tapio, Soile

    2011-01-01

    Radiation therapy treatment of breast cancer, Hodgkin's disease or childhood cancers expose the heart to high local radiation doses, causing an increased risk of cardiovascular disease in the survivors decades after the treatment. The mechanisms that underlie the radiation damage remain poorly understood so far. Previous data show that impairment of mitochondrial oxidative metabolism is directly linked to the development of cardiovascular disease. In this study, the radiation-induced in vivo effects on cardiac mitochondrial proteome and function were investigated. C57BL/6N mice were exposed to local irradiation of the heart with doses of 0.2 Gy or 2 Gy (X-ray, 200 kV) at the age of eight weeks, the control mice were sham-irradiated. After four weeks the cardiac mitochondria were isolated and tested for proteomic and functional alterations. Two complementary proteomics approaches using both peptide and protein quantification strategies showed radiation-induced deregulation of 25 proteins in total. Three main biological categories were affected: the oxidative phophorylation, the pyruvate metabolism, and the cytoskeletal structure. The mitochondria exposed to high-dose irradiation showed functional impairment reflected as partial deactivation of Complex I (32%) and Complex III (11%), decreased succinate-driven respiratory capacity (13%), increased level of reactive oxygen species and enhanced oxidation of mitochondrial proteins. The changes in the pyruvate metabolism and structural proteins were seen with both low and high radiation doses. This is the first study showing the biological alterations in the murine heart mitochondria several weeks after the exposure to low- and high-dose of ionizing radiation. Our results show that doses, equivalent to a single dose in radiotherapy, cause long-lasting changes in mitochondrial oxidative metabolism and mitochondria-associated cytoskeleton. This prompts us to propose that these first pathological changes lead to an increased

  1. Mitochondrial DNA analysis of the putative heart of Louis XVII, son of Louis XVI and Marie-Antoinette.

    Science.gov (United States)

    Jehaes, E; Pfeiffer, H; Toprak, K; Decorte, R; Brinkmann, B; Cassiman, J J

    2001-03-01

    According to official historiography, the 10-year-old Louis XVII died in the Temple of Paris on June 8, 1795. However, public rumour spread the theory that Louis XVII escaped and that his descendants would be alive today. One such putative 'Louis XVII' was Carl Wilhelm Naundorff, who died in 1845 in Delft (the Netherlands). Comparative mitochondrial DNA (mtDNA) analysis gave evidence that his remains could not be identified as those of Louis XVII. In the present study, mtDNA analysis was performed on the heart of the young boy who died in the prison of Paris in 1795. In order to obtain the strongest evidence possible, two laboratories independently analysed the heart. The results showed that the consensus mtDNA sequence of the heart was identical to that of the maternal relatives of Louis XVII.

  2. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in swine hearts: a novel therapeutic approach for acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Hisaaki eIshiguro

    2011-06-01

    Full Text Available Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigate the cardioprotective effect of midkine (MK in swine subjected to ischemia/reperfusion (I/R. I/R was created in swine by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion (midkine injected group; MKT. Saline was injected in controls (CONT. Survival rate 24h after I/R was significantly higher in MKT than in CONT, whereas infarct size/area at risk was almost 5 times smaller. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher % fractional shortening and a lower E/e’ compared with CONT. LV catheterization in MKT showed a lower LVEDP, and a higher dP/dtmax compared with CONT. TUNEL-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we showed that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and mortality and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

  3. Megaconial muscular dystrophy caused by mitochondrial membrane homeostasis defect, new insights from skeletal and heart muscle analyses.

    Science.gov (United States)

    Vanlander, Arnaud V; Muiño Mosquera, Laura; Panzer, Joseph; Deconinck, Tine; Smet, Joél; Seneca, Sara; Van Dorpe, Jo; Ferdinande, Liesbeth; Ceuterick-de Groote, Chantal; De Jonghe, Peter; Van Coster, Rudy; Baets, Jonathan

    2016-03-01

    Megaconial congenital muscular dystrophy is a disease caused by pathogenic mutations in the gene encoding choline kinase beta (CHKB). Microscopically, the disease is hallmarked by the presence of enlarged mitochondria at the periphery of skeletal muscle fibres leaving the centre devoid of mitochondria. Clinical characteristics are delayed motor development, intellectual disability and dilated cardiomyopathy in half of reported cases. This study describes a patient presenting with the cardinal clinical features, in whom a homozygous nonsense mutation (c.248_249insT; p.Arg84Profs*209) was identified in CHKB and who was treated by heart transplantation. Microscopic evaluation of skeletal and heart muscles typically showed enlarged mitochondria. Spectrophotometric evaluation in both tissues revealed a mild decrease of all OXPHOS complexes. Using BN-PAGE analysis followed by activity staining subcomplexes of complex V were detected in both tissues, indicating incomplete complex V assembly. Mitochondrial DNA content was not depleted in analysed tissues. This is the first report describing the microscopic and biochemical abnormalities in the heart from an affected patient. A likely hypothesis is that the biochemical findings are caused by an abnormal lipid profile in the inner mitochondrial membrane resulting from a defective choline kinase B activity. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  4. Swine Influenza (Swine Flu) in Pigs

    Science.gov (United States)

    ... Avian Swine Variant Pandemic Other Key Facts about Swine Influenza (Swine Flu) in Pigs Language: English (US) Español Recommend on Facebook Tweet ... visit the CDC seasonal flu website . What is Swine Influenza? Swine Influenza (swine flu) is a respiratory ...

  5. Padronização de modelo de coração isolado "working heart" com circulação parabiótica Development of isolated swine "working heart model" with parabiotic circulation

    Directory of Open Access Journals (Sweden)

    Lindemberg da Mota Silveira Filho

    2008-03-01

    Full Text Available OBJETIVO: Desenvolver modelo de coração isolado de suíno "working heart" sob suporte por circulação parabiótica e verificar se o mesmo é estável e se possibilitou de forma efetiva a mensuração dos dados propostos. MÉTODOS: O modelo foi padronizado durante preparação para estudo de associação de agente à solução cardioplégica. Foram realizados 18 experimentos com um animal suporte e um animal doador em cada. O coração do animal doador foi perfundido como coração isolado pelo animal suporte em modo de execução de trabalho ("coração ejetante". O coração isolado foi submetido à isquemia regional por pinçamento da artéria interventricular anterior seguido de isquemia global. Durante reperfusão, com o coração ejetante (em modo "working heart", aos 30, 60 e 90 minutos foram medidos parâmetros hemodinâmicos de contratilidade e metabólicos, obtendo-se assim a elastância máxima (Emáx, o trabalho sistólico pré-recrutável (PRSW, rigidez do ventrículo (EDPRV, fluxo coronariano, consumo de oxigênio e dosagens de lactato e glicose. RESULTADOS: Os animais suporte ficaram estáveis durante todo o experimento. O pH, a pressão parcial de oxigênio e o hematócrito foram mantidos estáveis e dentro da faixa fisiológica. O coração isolado foi perfundido de forma adequada durante todo o experimento. Os dados hemodinâmicos e metabólicos propostos puderam ser mensurados adequadamente e sempre com o coração ejetante, em modo de execução de trabalho ("working heart". CONCLUSÃO: O modelo de coração isolado desenvolvido tipo "working heart" se manteve estável durante todo o experimento, sem a administração de drogas cardiotônicas e possibilitou a mensuração de todos os dados propostos de forma efetiva com o coração executando trabalho.OBJECTIVE: To develop an isolated working heart model with parabiotic circulaton in swines and verify its stability and possibility to allow effective measurements of

  6. Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes.

    Science.gov (United States)

    Feng, Li; Gong, Jing; Jin, Zhen-yi; Li, Ning; Sun, Li-ping; Wu, Yi-ling; Pu, Jie-lin

    2009-07-05

    Shen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels. The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n = 8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP). SSYX treatment accelerated the HR from (141.8 +/- 36.0) beats per minute to (163.0 +/- 38.0) beats per minute (P = 0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD(30), APD(50) and APD(90) were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD(30) and APD(90) did not significantly change. The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

  7. Sericin improves heart and liver mitochondrial architecture in hypercholesterolaemic rats and maintains pancreatic and adrenal cell biosynthesis.

    Science.gov (United States)

    Ampawong, Sumate; Isarangkul, Duangnate; Aramwit, Pornanong

    2017-09-15

    Hypercholesterolaemia is well known to be associated with mitochondrial dysfunction, subsequently leading to multiple organ failure. Similar to other natural products, sericin is a candidate for adjunctive therapy in hyperlipidaemic conditions. However, the cholesterol-lowering mechanisms of sericin are multifactorial and controversial. Here, a high-cholesterol-fed rat model with or without sericin treatment was established using a dosage of 1000mg/kg/day for 30 days. Blood lipid profiles, oxidative stress markers (superoxide dismutase, SOD; malondialdehyde, MDA; nuclear factor erythroid 2-related factor, Nrf-2), dysmorphic mitochondria in relation to fission (dynamin-related protein-1; Drp-1) and fusion (guanosine triphosphatase mutated in dominant optic atrophy; OPA-1) markers and biosynthetic markers (aquaporin, AQP-1; tubulin-4β, Tb4B) in the pancreas and adrenal gland were evaluated. The results showed that sericin reduced blood cholesterol and increased high-density lipoprotein (HDL) by acting against oxidative stress. Hypocholesterolaemic and antioxidant conditions further preserved heart and liver mitochondrial architecture; however, this protection was not exhibited in the kidney, where a high level of renal mitophagy, indicating by LC-3 up-regulation, was presented. The steps of ultrastructural alteration of mitochondria from degenerative changes to necrosis were also demonstrated. Sericin also conserved AQP-1 and Tb4B levels in the exocrine pancreatic acinar cells and zona glomerulosa cells, which were positively correlated with serum lipase, HDL, antioxidative markers and mitochondrial integrity. The present study revealed that sericin not only has antioxidant capacity but also balances pancreatic and adrenal cell biosynthesis, especially lipase activity, which may have played an important role in improving lipid dysregulation in the hypercholesterolaemic rat model, leading to the reduction of dysmorphic mitochondria, particularly in the heart and

  8. Global intracoronary infusion of allogeneic cardiosphere-derived cells improves ventricular function and stimulates endogenous myocyte regeneration throughout the heart in swine with hibernating myocardium.

    Directory of Open Access Journals (Sweden)

    Gen Suzuki

    Full Text Available Cardiosphere-derived cells (CDCs improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the "stop-flow" technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation.Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25. CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼ 33 × 10(6 icCDCs. Global icCDC infusion was safe and while ∼ 3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23 ± 6 to 51 ± 5% (p<0.01. In diseased hearts, myocyte proliferation (phospho-histone-H3 increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs.Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair.

  9. Trimetazidine As Cardioplegia Addictive Without Pre-treatment Does Not Improve Myocardial Protection: Study In A Swine Working Heart Model [trimetazidina Como Aditivo Em Solução Cardioplégica Sem Pré-tratamento Não Traz Proteção Adicional Ao Miocárdio Isquêmico: Estudo Em Modelo Suíno De Coração Isolado

    OpenAIRE

    Silveira Filho L.D.M.; Petrucci Jr. O.; Do Carmo M.R.; De Oliveira P.P.M.; Vilarinho K.A.S.; Vieira R.W.; Braile D.M.

    2008-01-01

    Objective: The aim of this study is to verify in an isolated working heart swine model if the acute administration of trimetazidine to cardioplegia, without pre=treatment improves heart performance. Methods: Eighteen pairs of swines were used in this working heart model, divided into three groups (n = 6) that underwent regional and global ischemia. Each group was selected to a different treatment: St Thomas cardioplegia (ST), St Thomas enriched with trimetazidine (TMZ) and control group (Co)....

  10. Isolation and characterization of a Ca/sup 2 +/ carrier candidate from calf heart inner mitochondrial membrane

    Energy Technology Data Exchange (ETDEWEB)

    Jeng, A.Y.

    1979-01-01

    A protein was isolated from calf heart inner mitochondrial membrane with the aid of an electron paramagnetic resonance assay based on the relative binding properties of Ca/sup 2 +/, Mn/sup 2 +/, and Mg/sup 2 +/ to the protein. Partial delipidation of the protein was performed by using either the organic solvent extraction procedure or the silicic acid column chromatography. Control experiments indicated that the Ca/sup 2 +/ transport properties of the isolated protein were not due to the contaminating phospholipids. A complete delipidation procedure was developd by using Sephadex LH-20 column chromatography. Further characterization of the physical and chemical properties of the delipidated protein showed that delipidated protein becomes more hydrophobic in the presence of Ca/sup 2 +/ and alkaline pH in the organic solvent extraction experiments. Two possible models of calciphorin-mediated Ca/sup 2 +/ transport in mitochondria are proposed. (PCS)

  11. Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

    Science.gov (United States)

    Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

    2014-01-01

    Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (pmyocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

  12. Heart rate variability in conscious neonatal swine: spectral features and responses to short-term intermittent hypoxia

    Directory of Open Access Journals (Sweden)

    Zhao Ning

    2006-06-01

    Full Text Available Abstract Background Spectral analysis of the cardiac time series has been used as a tool for assessing levels of parasympathetic and sympathetic modulation of the sinoatrial node. In the present investigation we evaluated daily changes in heart rate variability spectra in conscious neonatal piglets that were either neurally intact (n = 5 or had undergone right stellate ganglionectomy (n = 5. The partial stellectomized animals and their intact litter mates were exposed to four days of intermittent hypoxia, each day comprising nine episodes of hypoxia alternating with nine episodes of normoxia. A time control group (n = 7 comprised animals from different litters that were not exposed to intermittent hypoxia. We hypothesized that exposure to intermittent hypoxia would increase sympathetic efferent neuronal modulation of heart rate variability spectra in neurally intact animals and in those with right stellate ganglionectomy, and that his effect would be observed in heart rate variability spectra computed from baseline recordings. Results Overall, heart rate variability spectra during baseline conditions were dominated by high frequency activity, a reflection of parasympathetic efferent neuronal innervation and linkage to the ventilatory cycle manifested as respiratory sinus arrhythmia. Exposure to intermittent hypoxia did not alter daily baseline spectral features that would indicate an increase of sympathetic cardiac activity: low frequency (0.05 – 0.15 Hz activity was unaffected and the ratio of low- to -high frequency activity remained less than unity indicating a predominance of high frequency activity. The resultant spectra were remarkably similar despite differences in cardiac sympathetic efferent neuronal innervation and experimental treatment. When spectra were computed from cardiac time series during representative hypoxic episodes, significant increases in activity across the low frequency region (0.05 – 0.15 Hz of heart rate

  13. Mitochondrial Enzyme Plays Critical Role in Chemotherapy-Induced Heart Damage | Center for Cancer Research

    Science.gov (United States)

    Doxorubicin (DOX) is an effective drug for treating cancers ranging from leukemia and lymphoma to solid tumors, such as breast cancer. DOX kills dividing cells in two ways: inserting between the base pairs of DNA and trapping a complex of DNA and an enzyme that cuts DNA, topoisomerase 2α, preventing DNA repair. However, DOX also causes congestive heart failure in about 30 percent of adult cancer patients and delayed onset heart failure in a significant number of pediatric cancer patients. The mechanism of this DOX-mediated cardiotoxicity is not well understood since heart muscle cells neither divide nor express Top2α, and there are currently no genetic factors that identify patients who are susceptible to cardiac damage from DOX. However, a recent study showed that mice lacking another topoisomerase, Top2β, did not experience cardiac damage after treatment with DOX.

  14. Altered Mitochondrial Metabolism and Mechanosensation in the Failing Heart: Focus on Intracellular Calcium Signaling

    Directory of Open Access Journals (Sweden)

    Aderville Cabassi

    2017-07-01

    Full Text Available The heart consists of millions of cells, namely cardiomyocytes, which are highly organized in terms of structure and function, at both macroscale and microscale levels. Such meticulous organization is imperative for assuring the physiological pump-function of the heart. One of the key players for the electrical and mechanical synchronization and contraction is the calcium ion via the well-known calcium-induced calcium release process. In cardiovascular diseases, the structural organization is lost, resulting in morphological, electrical, and metabolic remodeling owing the imbalance of the calcium handling and promoting heart failure and arrhythmias. Recently, attention has been focused on the role of mitochondria, which seem to jeopardize these events by misbalancing the calcium processes. In this review, we highlight our recent findings, especially the role of mitochondria (dysfunction in failing cardiomyocytes with respect to the calcium machinery.

  15. Two- and three-dimensional transoesophageal echocardiography in large swine used as model for transcatheter heart valve therapies: standard planes and values.

    Science.gov (United States)

    Sündermann, Simon H; Cesarovic, Nikola; Falk, Volkmar; Bettex, Dominique

    2016-05-01

    Swine models are widely used to develop new techniques and materials for the treatment of heart valve disease like aortic valve and mitral valve transcatheter interventions and to train physicians in these techniques. Transoesophageal echocardiography (TOE) is crucial in these models. We defined standard planes of 2D and 3D TOE in healthy pigs undergoing transcatheter heart valve interventions. Twenty healthy pigs (weight 56-106 kg) underwent different mitral and aortic valve interventions (transcatheter aortic valve implantations, implantations of a mitral band, bicuspidization of the aortic valve, trans-septal punctures). For image guidance of the procedures, an adult TOE probe was introduced under direct vision in the oesophagus. Before the procedure itself was performed, a standardized protocol was used to determine normal values for anatomical and functional echocardiographic parameters. Positioning of the probe was possible in all animals and ideal when achieving a distance from the front teeth (incisors) of 40-60 cm. Anteflexion and lateroflexion of the probe was necessary to achieve optimal imaging quality. 2D visualization of all relevant cardiac structures was possible. The aortic annulus diameter was 24.1 ± 2.5 mm, the sinus of valsalva diameter was 30.6 ± 4 mm and the sinotubular junction diameter was 25.2 ± 4 mm. The ascending aorta had a diameter of 24 ± 4 mm and the descending aorta a diameter of 16 ± 5 mm. The mitral valve anterior-posterior diameter was 31.8 ± 4 mm and the commissure to commissure diameter was 40.5 ± 5 mm resulting in a mitral valve area of 10.7 ± 1.5 cm(2). 3D visualization was possible for the aortic and the mitral valve. None of the animals showed any pathology except one that had a dilated left ventricle and moderate mitral valve insufficiency. Left and right ventricular dimensions and the anatomy of the aortic-, mitral-, tricuspid and pulmonary valve as well as of the aorta were comparable with those of the human

  16. Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.

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    Amy Botta

    Full Text Available PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα and systemic (circulating chemokines and cytokines inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.

  17. Effect of Ginkgo biloba extract on the rat heart mitochondrial function.

    Science.gov (United States)

    Trumbeckaite, Sonata; Bernatoniene, Jurga; Majiene, Daiva; Jakstas, Valdas; Savickas, Arunas; Toleikis, Adolfas

    2007-05-22

    Ginkgo biloba L. (Ginkgoaceae) originated from China, first introduced to Europe in the 18th century, it is now distributed all over the world. The leaves of Ginkgo biloba include a rich complex of active compounds responsible for various pharmacological properties. Ginkgo biloba extract improves blood circulation, protects against oxidative cell damage, blocks platelet aggregation that could be important for prevention of cardiovascular diseases. Therefore the fluid extract from Ginkgo biloba leaves was prepared and tested for it is effect on rat mitochondrial function. Our data showed that 0.5 microl/ml of GE (containing 0.57 ng/ml of rutin, 0.23 ng/ml of quercitrin, 0.105 ng/ml of hyperosid and 0.02 ng/ml of quercetin) had no effect on the State 2 respiration rate of mitochondria with all used substrates: pyruvate+malate, succinate and palmitoyl-L-carnitine. Further increase in GE concentration (2 and 4 microl/ml), increased the State 2 respiration rate with all respiratory substrates in a dose-dependent manner (by 35-116%). The State 3 respiration rate was not affected by GE. In order to identify which compounds of GE could be responsible for the observed effects, we measured the effect of pure flavonoids: rutin, quercetin, hyperosid and quercitrin on mitochondrial respiration. All flavonoids (except of hyperosid) at maximal used concentration, comparable/identical to that in GE, stimulated the State 2 respiration rate only by 8-20%, i.e. less effectively as compared to GE. Therefore, for the explanation of the GE-induced uncoupling of oxidative phosphorylation, other biologically active compounds of GE have to be taken into account in future studies.

  18. Increased intraventricular pressures are as harmful as the electrophysiological substrate of heart failure in favoring sustained reentry in the swine heart.

    Science.gov (United States)

    Quintanilla, Jorge G; Moreno, Javier; Archondo, Tamara; Usandizaga, Elena; Molina-Morúa, Roberto; Rodríguez-Bobada, Cruz; González, Pablo; García-Torrent, María Jesús; Filgueiras-Rama, David; Pérez-Castellano, Nicasio; Macaya, Carlos; Pérez-Villacastín, Julián

    2015-10-01

    Heart failure (HF) electrophysiological remodeling (HF-ER) often includes the effect of chronically increased intraventricular pressures (IVPs) and promotes ventricular tachycardia/ventricular fibrillation (VT/VF). In addition, acutely increased IVPs have been associated with a higher rate of VT/VF episodes in chronic HF. We hypothesized that increased IVPs and/or an ionic-imbalanced (acidified), catecholamine-rich (adrenergic) milieu (AA milieu) may contribute as much as HF-ER to the substrate for reentry in HF. We used a porcine model of tachycardiomyopathy and evaluated the individual/combined contributions of (1) increased IVPs, (2) HF-ER, and (3) an AA milieu. HF-ER was induced in 7 pigs by rapid pacing. Seven pigs were used as controls. Hearts were isolated and Langendorff perfused. Programmed ventricular stimulation was conducted under low or increased IVP and normal/AA milieu (4 combinations). Epicardial optical mapping was used to quantify conduction velocity (CV), action potential duration (APD), and dispersion of repolarization (DoR). HF-ER decreased CV (-34%; P = .002) and increased APD (11%; P = .024) and DoR (21%; P = .007). Increased IVP amplified DoR (36%; P 6-fold). By magnifying DoR, decreasing CV, and shortening APD, increased IVP was as harmful as HF-ER in favoring the substrate for sustained reentry in this model. The AA milieu contributed to a much lesser extent. Thus, a stricter control of IVP might be postulated as a useful add-on antiarrhythmic strategy in HF. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  19. Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis

    Czech Academy of Sciences Publication Activity Database

    Melenovský, V.; Petrák, J.; Mráček, Tomáš; Beneš, J.; Borlaug, B. A.; Nůsková, Hana; Pluháček, T.; Špatenka, J.; Kovalčíková, Jana; Drahota, Zdeněk; Kautzner, J.; Pirk, J.; Houštěk, Josef

    2017-01-01

    Roč. 19, č. 4 (2017), s. 522-530 ISSN 1388-9842 R&D Projects: GA ČR(CZ) GB14-36804G; GA MZd(CZ) NT14050; GA MŠk(CZ) LQ1604; GA MZd NT14250; GA MŠk(CZ) ED1.1.00/02.0109; GA MZd(CZ) NV16-27496A Institutional support: RVO:67985823 Keywords : heart failure * mitochondria * iron deficiency * bioenergetics * metabolism * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 6.968, year: 2016

  20. LMNA E82K mutation activates FAS and mitochondrial pathways of apoptosis in heart tissue specific transgenic mice.

    Directory of Open Access Journals (Sweden)

    Dan Lu

    Full Text Available The lamin A/C (LMNA, nuclear intermediate filament proteins, is a basic component of the nuclear lamina. Mutations in LMNA are associated with a broad range of laminopathies, congenital diseases affecting tissue regeneration and homeostasis. Heart tissue specific transgenic mice of human LMNA E82K, a mutation causing dilated cardiomyopathy, were generated. Lmna(E82K transgenic mouse lines exhibited thin-walled, dilated left and right ventricles, a progressive decrease of contractile function assessed by echocardiography. Abnormalities of the conduction system, myocytes disarray, collagen accumulation and increased levels of B-type natriuretic peptide (BNP, procollagen type III α1 (Col3α1 and skeletal muscle actin α1 (Actα1 were detected in the hearts of Lmna(E82K transgenic mice. The LMNA E82K mutation caused mislocation of LMNA in the nucleus and swollen mitochondria with loss of critae, together with the loss of nuclear envelope integrity. Most interestingly, we found that the level of apoptosis was 8.5-fold higher in the Lmna(E82K transgenic mice than that of non-transgenic (NTG mice. In the presence of the LMNA E82K, both of FAS and mitochondrial pathways of apoptosis were activated consistent with the increase of FAS expression, the release of cytochrome c from mitochondria to cytosol and activation of caspase-8, -9 and -3. Our results suggested that the apoptosis, at least for the LMNA E82K or the mutations in the rod region of Lamin A/C, might be an important mechanism causing continuous loss of myocytes and lead to myocardial dysfunction. It could be a potential therapeutic means to suppress and/or prevent inappropriate cardiac cell death in patients carrying LMNA mutation.

  1. Further investigations on the inorganic phosphate binding site of beef heart mitochondrial F1-ATPase

    International Nuclear Information System (INIS)

    Pougeois, R.; Lauquin, G.J.

    1985-01-01

    The possibility that 4-azido-2-nitrophenyl phosphate (ANPP), a photoreactive derivative of inorganic phosphate (P /sub i/ ), could mimic ATP was investigated. ANPP was hydrolyzed in the dark by sarcoplasmic reticulum Ca 2+ -ATPase in the presence of Ca 2+ but not in the presence of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. ANPP was not hydrolyzed by purified mitochondrial F1-ATPase; however, ADP and ATP protected F1-ATPase against ANPP photoinactivation. On the other hand, the trinitrophenyl nucleotide analogues (TNP-ADP, TNP-ATP, and TNP-AMP-PNP), which bind specifically at the two catalytic sites of F1-ATPase, abolished P /sub i/ binding on F1-ATPase; they do not protect F1-ATPase against ANPP photoinactivation. Furthermore, ANPP-photoinactivated F1-ATPase binds the TNP analogues in the same way as the native enzyme. The Pi binding site of F1-ATPase, which is shown to be photolabeled by ANPP, does not appear to be at the gamma-phosphate position of the catalytic sites

  2. Identification of low and high frequency ranges for heart rate variability and blood pressure variability analyses using pharmacological autonomic blockade with atropine and propranolol in swine.

    Science.gov (United States)

    Poletto, Rosangela; Janczak, Andrew M; Marchant-Forde, Ruth M; Marchant-Forde, Jeremy N; Matthews, Donald L; Dowell, Carol A; Hogan, Daniel F; Freeman, Lynetta J; Lay, Donald C

    2011-05-03

    Understanding autonomic nervous system functioning, which mediates behavioral and physiological responses to stress, offers great potential for assessing farm animal stress and welfare. Evaluation of heart rate variability (HRV) and blood pressure variability (BPV), using time and frequency domain analyses may provide a sensitive and reliable measure of affective states and stress-mediated changes in sympathetic and parasympathetic tones. The aim of this research was to define low (LF) and high frequency (HF) power spectral ranges using pharmacological autonomic blockade, and to examine HRV and BPV parameter changes in response to atropine and propranolol in swine. Ten, 13-week old, barrows (n=6) and gilts (n=4) underwent surgery to place an intra-cardiac electrode and a blood pressure catheter attached to a biotelemetric transmitter; pigs had a 3-week recovery period prior to data collection. Each pig was subjected to administration of 4 intravenous (i.v.) drug treatments: a control treatment, 3 mL of saline, and 3 blockade treatments; 0.1 mg/kg of atropine, 1.0 mg/kg of propranolol, and .1 mg/kg of atropine together with 1.0 mg/kg of propranolol. All treatments were delivered by injection in the jugular vein with a minimum of 48 h between individual treatments. Behavior, ECG and blood pressure data were recorded continuously for a total of 1h, from 30 min pre-injection to 30 min post-injection. For data analyses, two 512-beat intervals were selected for each treatment while the pig was lying and inactive. The first interval was selected from the pre-injection period (baseline), and the second was selected between 10 and 30 min post-injection. Time and frequency domain (power spectral density) analyses were performed on each data interval. Subsequent, LF and HF bands from the power spectral densities were defined based on general linear and regression analyses. The HRV and BPV were computed with a covariate (baseline) factorial analysis of treatment by sex

  3. Mitochondrial cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Ayman W. El-Hattab

    2016-07-01

    Full Text Available Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA while more than 99% of them are encoded by nuclear DNA (nDNA. Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs of various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular noncompaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain (ETC complexes subunits and their assembly factors, mitochondrial tRNAs, rRNAs, ribosomal proteins, and translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia.

  4. Chemical labeling studies on isolated and vesicular bovine heart mitochondrial cytochrome c oxidase

    International Nuclear Information System (INIS)

    Venzke, K.S.; Reynolds, K.A.; Prochaska, L.J.

    1987-01-01

    Bovine heart cytochrome c oxidase dispersed in Triton X-100, Tween 80, or dodecyl maltoside was reacted with the water-soluble reagents [ 35 S]-diazonium benzene sulfonate (DABS) (10-100 μM) or [ 125 I]-iodo-DABS (34-55 nM) to map the surface topography of the enzyme in different protein aggregation states. Both reagents gave similar labeling profiles of the enzyme under all conditions. Subunits II, III, and VII were extensively labeled by DABS, while subunits I and VI were unreactive with DABS in each detergent. Subunit V exhibited an increase in DABS labeling when the enzyme was reacted in Tween 80 as compared to the enzyme in Triton X-100 or dodecyl maltoside. Also, components b and c showed an increase in DABS reactivity when the enzyme was modified in dodecyl maltoside. In general, the labeling profile of the enzyme in dodecyl maltoside resembled that of the enzyme in Triton X-100, emphasizing that the mechanism of dispersal of the enzyme by both detergents is similar. Cytochrome c oxidase incorporated into phosphatidylglycerol:phosphatidylcholine(1:20)(w:w) phospholipid vesicles (COV) by cholate dialysis was reacted with DABS and subunits II and III were significantly labeled. Approximately 65-70% of the enzyme in COV was oriented with the cytochrome c binding domain facing the extravesicular medium, as determined by comparison of the DABS labeling in subunit IV in detergent-lysed and intact COV

  5. Alterations in Glutathione Redox Metabolism, Oxidative Stress, and Mitochondrial Function in the Left Ventricle of Elderly Zucker Diabetic Fatty Rat Heart

    Directory of Open Access Journals (Sweden)

    Haider Raza

    2012-11-01

    Full Text Available The Zucker diabetic fatty (ZDF rat is a genetic model in which the homozygous (FA/FA male animals develop obesity and type 2 diabetes. Morbidity and mortality from cardiovascular complications, due to increased oxidative stress and inflammatory signals, are the hallmarks of type 2 diabetes. The precise molecular mechanism of contractile dysfunction and disease progression remains to be clarified. Therefore, we have investigated molecular and metabolic targets in male ZDF (30–34 weeks old rat heart compared to age matched Zucker lean (ZL controls. Hyperglycemia was confirmed by a 4-fold elevation in non-fasting blood glucose (478.43 ± 29.22 mg/dL in ZDF vs. 108.22 ± 2.52 mg/dL in ZL rats. An increase in reactive oxygen species production, lipid peroxidation and oxidative protein carbonylation was observed in ZDF rats. A significant increase in CYP4502E1 activity accompanied by increased protein expression was also observed in diabetic rat heart. Increased expression of other oxidative stress marker proteins, HO-1 and iNOS was also observed. GSH concentration and activities of GSH-dependent enzymes, glutathione S-transferase and GSH reductase, were, however, significantly increased in ZDF heart tissue suggesting a compensatory defense mechanism. The activities of mitochondrial respiratory enzymes, Complex I and Complex IV were significantly reduced in the heart ventricle of ZDF rats in comparison to ZL rats. Western blot analysis has also suggested a decreased expression of IκB-α and phosphorylated-JNK in diabetic heart tissue. Our results have suggested that mitochondrial dysfunction and increased oxidative stress in ZDF rats might be associated, at least in part, with altered NF-κB/JNK dependent redox cell signaling. These results might have implications in the elucidation of the mechanism of disease progression and designing strategies for diabetes prevention.

  6. Swine mycoplasmoses

    DEFF Research Database (Denmark)

    Kobisch, M.; Friis, N.F.

    1996-01-01

    /tonsillar samples and can induce antibodies in blood and joint fluid. Predisposing factors play an important role. M. flocculare is widely distributed in swine, in normal and pneumonic lungs and in nasal cavities, but no pathogenic capability has been described. There is great interest in this mycoplasma because......Mycoplasma hyopneumoniae is the primary agent of enzootic pneumonia in pigs. The lung lesions, generally observed in young pigs, are characterised by a hyperplasia of the epithelial cells and an increased perivascular and peribronchiolar accumulation of mononuclear cells. Following M. hyopneumoniae...

  7. Cadmium affects the mitochondrial viability and the acid soluble thiols concentration in liver, kidney, heart and gills of Ancistrus brevifilis (Eigenmann, 1920)

    Science.gov (United States)

    Velasquez-Vottelerd, P.; Anton, Y.; Salazar-Lugo, R.

    2015-01-01

    The freshwater fish Ancistrus brevifilis, which is found in Venezuelan rivers, is considered a potential sentinel fish in ecotoxicological studies. The cadmium (Cd) effect on the mitochondrial viability (MV) and acid soluble thiols levels (AST) in A. brevifilis tissues (liver, kidney, heart, and gill) was evaluated. Forty-two fish with similar sizes and weights were randomly selected, of which 7 fish (with their respective replicate) were exposed for 7 and 30 days to a Cd sublethal concentration (0.1 mg.l-1). We determined the MV through a Janus Green B colorimetric assay and we obtained the concentration of AST by Ellman’s method. Mitochondrial viability decreased in fish exposed to Cd for 30 days with the liver being the most affected tissue. We also detected a significant decrease in AST levels was in fishes exposed to Cd for 7 days in liver and kidney tissues; these results suggests that AST levels are elevated in some tissues may act as cytoprotective and adaptive alternative mechanism related to the ROS detoxification, maintenance redox status and mitochondrial viability. Organ-specifics variations were observed in both assays. We conclude that the Cd exposure effect on AST levels and MV, vary across fish tissues and is related to the exposure duration, the molecule dynamics in different tissues, the organism and environmental conditions. PMID:26623384

  8. Cadmium affects the mitochondrial viability and the acid soluble thiols concentration in liver, kidney, heart and gills of Ancistrus brevifilis (Eigenmann, 1920

    Directory of Open Access Journals (Sweden)

    P. Velasquez-Vottelerd

    2015-11-01

    Full Text Available The freshwater fish Ancistrus brevifilis, which is found in Venezuelan rivers, is considered a potential sentinel fish in ecotoxicological studies. The cadmium (Cd effect on the mitochondrial viability (MV and acid soluble thiols levels (AST in A. brevifilis tissues (liver, kidney, heart, and gill was evaluated. Forty-two fish with similar sizes and weights were randomly selected, of which 7 fish (with their respective replicate were exposed for 7 and 30 days to a Cd sublethal concentration (0.1 mg.l-1. We determined the MV through a Janus Green B colorimetric assay and we obtained the concentration of AST by Ellman’s method. Mitochondrial viability decreased in fish exposed to Cd for 30 days with the liver being the most affected tissue. We also detected a significant decrease in AST levels was in fishes exposed to Cd for 7 days in liver and kidney tissues; these results suggests that AST levels are elevated in some tissues may act as cytoprotective and adaptive alternative mechanism related to the ROS detoxification, maintenance redox status and mitochondrial viability. Organ-specifics variations were observed in both assays. We conclude that the Cd exposure effect on AST levels and MV, vary across fish tissues and is related to the exposure duration, the molecule dynamics in different tissues, the organism and environmental conditions.

  9. Powering Up Mitochondrial Functions to Treat Mitochondrial Disease

    Science.gov (United States)

    2017-10-01

    Philadelphia, PA. “Listen to your heart” *05/2017 Keystone Symposia—Mitochondria, Metabolism and Heart. Santa Fe, NM. “A heart-derived hormone that...ND6P25L combination was associated with impaired mitochondrial complex I activity, altered mitochondrial morphology, increased reactive oxygen species ...oxygen species production, sensitization of the mitochondrial permeability transition pore, increased somatic mtDNA mutation levels, and shortened

  10. Expression of mitochondrial uncoupling protein 3 and adenine nucleotide translocase 1 genes in developing rat heart: putative involvement in control of mitochondrial membrane potential

    Czech Academy of Sciences Publication Activity Database

    Škárka, Libor; Bardová, Kristina; Brauner, Petr; Flachs, Pavel; Jarkovská, D.; Kopecký, Jan; Ošťádal, Bohuslav

    2003-01-01

    Roč. 35, č. 3 (2003), s. 321-330 ISSN 0022-2828 R&D Projects: GA MŠk LN00A079; GA MŠk LN00A069; GA ČR GA305/00/1659; GA MZd NE6430 Grant - others:GA UK(CZ) 56/2000; March of Dimes Birth Defects Foundation(US) 6-FY00-331 Institutional research plan: CEZ:AV0Z5011922 Keywords : development * heart * mitochondria Subject RIV: ED - Physiology Impact factor: 4.954, year: 2003

  11. Use of Raman spectroscopy to study reduction state of mitochondrial cytochromes in an isolated heart under normoxic and hypoxic conditions

    DEFF Research Database (Denmark)

    Brazhe, N. A.; Treiman, M.; Faricelli, B.

    2013-01-01

    (1). The mitochondrial peaks reflected essentially the reduced forms of b- and c-type cytochromes. Major peaks were mainly contributed by cytochromes c and c1 (750 cm-1) and b (1127 cm-1). Several less intense peaks were also assigned. Main myoglobin (Mb) peaks were present at 1587 and 1556 cm-1...

  12. Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain acyl-CoA dehydrogenase

    NARCIS (Netherlands)

    Exil, VJ; Gardner, CD; Rottman, JN; Sims, H; Bartelds, B; Khuchua, Z; Sindhal, R; Ni, GM; Strauss, AW

    Mitochondrial very-long-chain acyl-CoA dehydrogenase ( VLCAD) deficiency is associated with severe hypoglycemia, cardiac dysfunction, and sudden death in neonates and children. Sudden death is common, but the underlying mechanisms are not fully understood. We report on a mouse model of VLCAD

  13. 9 CFR 85.10 - Interstate movement of swine semen and swine embryos for insemination of or implantation into swine.

    Science.gov (United States)

    2010-01-01

    ... swine embryos for insemination of or implantation into swine. 85.10 Section 85.10 Animals and Animal... and swine embryos for insemination of or implantation into swine. Swine semen and swine embryos moved interstate for insemination of swine or implantation into swine shall be accompanied by a document issued by...

  14. Identification of low and high frequency ranges for heart rate variability and blood pressure variability analyses using pharmacological autonomic blockade with atropine and propranolol in swine.

    Science.gov (United States)

    Understanding autonomic nervous system functioning, which mediates behavioral and physiological responses to stress, offers great potential for evaluation of farm animal stress and welfare. Evaluation of heart rate variability (HRV) and blood pressure variability (BPV), using time and frequency doma...

  15. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

    1986-01-01

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  16. Enhanced acyl-CoA dehydrogenase activity is associated with improved mitochondrial and contractile function in heart failure

    Science.gov (United States)

    Heart failure is associated with decreased myocardial fatty acid oxidation capacity and has been likened to energy starvation. Increased fatty acid availability results in an induction of genes promoting fatty acid oxidation. The aim of the present study was to investigate possible mechanisms by whi...

  17. Supplementation of selenium-enriched yeast attenuates age-dependent transcriptional changes of heart in mitochondrial DNA mutator mice

    Directory of Open Access Journals (Sweden)

    Rijin Xiao

    2014-03-01

    Full Text Available Background: Age is a major risk factor in developing heart diseases and has been associated with profound transcriptional changes in mammalian tissues. Low tissue selenium has recently been linked to several age-related diseases, including cardiovascular disease. This study investigated the global effects of age and dietary supplementation of selenium on heart transcriptional profiles in POLG mutator mice. Methods: Heart transcription profiles from young (2-month-old and old (13-month-old animals fed either a control diet or a diet supplemented with 1.0 mg selenium from seleniumenriched yeast (SP/kg diet were obtained and validated using microarray and real-time RTPCR techniques. Results: Aging led to significant transcriptional changes, where the expression of 1942 genes in old animals was changed by a fold change larger than 2.0, when compared to young animals. Age-regulated genes are associated with cardiovascular system development, immune and inflammatory response, and cellular oxidative stress response. Multiple genes linked with cardiomyocyte apoptosis, hypertrophy, and cardiac fibrosis, such as Myh7, Lcn2, Spp1, and Serpine1, were significantly up-regulated in old animals. SP supplementation also caused significant transcriptional changes in the heart, especially in old mice where many age-dependent transcriptional changes were totally or partially reversed by SP. Upstream regulator analysis further indicated that genes for Foxo1 and Foxo3, two transcriptional regulators involved in the regulation of cardiac muscle remodeling, were significantly activated by SP, suggesting that Foxo-mediated transcriptional activities play important roles in the anti-aging properties of SP. Functional Foods in Health and Disease 2014; 4(3:98- 119 Page 99 of 119 Conclusions: Results of this study indicate that SP supplementation attenuated age-related transcriptional changes in the heart of old POLG mice, which implies a potential clinical application of

  18. Hypercholesterolemia abrogates the cardioprotection of ischemic postconditioning in isolated rat heart: roles of glycogen synthase kinase-3β and the mitochondrial permeability transition pore.

    Science.gov (United States)

    Wu, Nan; Zhang, Xiaowen; Guan, Yuee; Shu, Wenqi; Jia, Pengyu; Jia, Dalin

    2014-05-01

    Ischemic postconditioning (IPO) reduces lethal reperfusion injury under normal conditions, but its effectiveness in hypercholesterolemia (HC) is disputed. We measured the cardioprotection of IPO in hypercholesterolemic rats and determined the roles of glycogen synthase kinase-3β (GSK-3β) and the mitochondrial permeability transition pore (mPTP). Isolated rat hearts underwent 30-min global ischemia and 120-min reperfusion. Postconditioning protocol induced six cycles of 10s ischemia and 10s reperfusion at the onset of the reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride staining and cardiomyocyte apoptosis was assessed by TUNEL staining. GSK-3β phosphorylation was measured by immunoblotting. The opening of mPTP was measured by NAD(+) content in myocardium. In normocholesterolemia (NC) groups, infarct size and cardiomyocyte apoptosis were significantly reduced after IPO. These reductions were completely abolished by HC, as evidenced by a similar infarct size and cardiomyocyte apoptosis observed between the IPO-HC and IR (ischemia-reperfusion)-HC groups. GSK-3β phosphorylation was significantly higher in the IPO-NC than the IPO-HC group. In addition, NAD(+) content in myocardium, a marker of mPTP opening, was higher in the IPO-NC group than the IPO-HC group. In conclusion, cardioprotection of IPO is blocked by hypercholesterolemia. This might be due to the impairment of phosphorylation of GSK-3β and attenuation of mPTP opening.

  19. Nanoparticle-Mediated Delivery of Mitochondrial Division Inhibitor 1 to the Myocardium Protects the Heart From Ischemia-Reperfusion Injury Through Inhibition of Mitochondria Outer Membrane Permeabilization: A New Therapeutic Modality for Acute Myocardial Infarction.

    Science.gov (United States)

    Ishikita, Ayako; Matoba, Tetsuya; Ikeda, Gentaro; Koga, Jun-Ichiro; Mao, Yajing; Nakano, Kaku; Takeuchi, Osamu; Sadoshima, Junichi; Egashira, Kensuke

    2016-07-22

    Mitochondria-mediated cell death plays a critical role in myocardial ischemia-reperfusion (IR) injury. We hypothesized that nanoparticle-mediated drug delivery of mitochondrial division inhibitor 1 (Mdivi1) protects hearts from IR injury through inhibition of mitochondria outer membrane permeabilization (MOMP), which causes mitochondrial-mediated cell death. We formulated poly (lactic-co-glycolic acid) nanoparticles containing Mdivi1 (Mdivi1-NP). We recently demonstrated that these nanoparticles could be successfully delivered to the cytosol and mitochondria of cardiomyocytes under H2O2-induced oxidative stress that mimicked IR injury. Pretreatment with Mdivi1-NP ameliorated H2O2-induced cell death in rat neonatal cardiomyocytes more potently than Mdivi1 alone, as indicated by a lower estimated half-maximal effective concentration and greater maximal effect on cell survival. Mdivi1-NP treatment of Langendorff-perfused mouse hearts through the coronary arteries at the time of reperfusion reduced infarct size after IR injury more effectively than Mdivi1 alone. Mdivi1-NP treatment also inhibited Drp1-mediated Bax translocation to the mitochondria and subsequent cytochrome c leakage into the cytosol, namely, MOMP, in mouse IR hearts. MOMP inhibition was also observed in cyclophilin D knockout (CypD-KO) mice, which lack the mitochondrial permeability transition pore (MPTP) opening. Intravenous Mdivi1-NP treatment in vivo at the time of reperfusion reduced IR injury in wild-type and CypD-KO mice, but not Bax-KO mice. Mdivi1-NP treatment reduced IR injury through inhibition of MOMP, even in the absence of a CypD/MPTP opening. Thus, nanoparticle-mediated drug delivery of Mdivi1 may be a novel treatment strategy for IR injury. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  20. Bupivacaine mandibular nerve block affects intraoperative blood pressure and heart rate in a Yucatan miniature swine mandibular condylectomy model: a pilot study.

    Science.gov (United States)

    Bova, Jonathan F; da Cunha, Anderson F; Stout, Rhett W; Bhumiratana, Sarindr; Alfi, David M; Eisig, Sidney B; Vunjak-Novakovic, Gordana; Lopez, Mandi J

    2015-02-01

    The primary objective was to evaluate the effect of a bupivacaine mandibular nerve block on intraoperative blood pressure (BP) and heart rate (HR) in response to surgical stimulation and the need for systemic analgesics postoperatively. We hypothesized that a mandibular nerve block would decrease the need for systemic analgesics both intraoperatively and postoperatively. Fourteen adult male Yucatan pigs were purchased. Pigs were chemically restrained with ketamine, midazolam, and dexmedetomidine and anesthesia was maintained with isoflurane inhalant anesthesia. Pigs were randomized to receive a mandibular block with either bupivacaine (bupivacaine group) or saline (control group). A nerve stimulator was used for administration of the block with observation of masseter muscle twitch to indicate the injection site. Invasive BP and HR were measured with the aid of an arterial catheter in eight pigs. A rescue analgesic protocol consisting of fentanyl and lidocaine was administered if HR or BP values increased 20% from baseline. Postoperative pain was quantified with a customized ethogram. HR and BP were evaluated at base line, pre-rescue, 10 and 20 min post-rescue. Pre-rescue mean BP was significantly increased (p = .001) for the bupivacaine group. Mean intraoperative HR was significantly lower (p = .044) in the bupivacaine versus saline group. All other parameters were not significant. Addition of a mandibular nerve block to the anesthetic regimen in the miniature pig condylectomy model may improve variations in intraoperative BP and HR. This study establishes the foundation for future studies with larger animal numbers to confirm these preliminary findings.

  1. Swine brucellosis: current perspectives

    Directory of Open Access Journals (Sweden)

    Olsen SC

    2016-12-01

    Full Text Available SC Olsen, FM Tatum Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, USA Abstract: Brucella suis is a significant zoonotic species that is present in domestic livestock and wildlife in many countries worldwide. Transmission from animal reservoirs is the source of human infection as human-to-human transmission is very rare. Although swine brucellosis causes economic losses in domestic livestock, preventing human infection is the primary reason for its emphasis in disease control programs. Although disease prevalence varies worldwide, in areas outside of Europe, swine brucellosis is predominantly caused by B. suis biovars 1 and 3. In Europe, swine are predominantly infected with biovar 2 which is much less pathogenic in humans. In many areas worldwide, feral or wild populations of swine are important reservoir hosts. Like other Brucella spp. in their natural host, B. suis has developed mechanisms to survive in an intracellular environment and evade immune detection. Limitations in sensitivity and specificity of current diagnostics require use at a herd level, rather for individual animals. There is currently no commercial vaccine approved for preventing brucellosis in swine. Although not feasible in all situations, whole-herd depopulation is the most effective regulatory mechanism to control swine brucellosis. Keywords: livestock, transmission, pathogenicity, vaccine, host, infection

  2. Effects of Continuous Triiodothyronine Infusion on Citric Acid Cycle in the Normal Immature Swine Heart under Extracorporeal Membrane Oxygenation in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Kajimoto, Masaki [Seattle Children' s Research Inst., Seattle, WA (United States); O' Kelly-Priddy, Colleen M. [Seattle Children' s Research Inst., Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States); Ledee, Dolena R. [Seattle Children' s Research Inst., Seattle, WA (United States); Xu, Chun [Seattle Children' s Research Inst., Seattle, WA (United States); Isern, Nancy G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Olson, Aaron [Seattle Children' s Research Inst., Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States); Portman, Michael A. [Seattle Children' s Research Inst., Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)

    2014-02-13

    Extracorporeal membrane oxygenation (ECMO) is frequently used in infants with postoperative cardiopulmonary failure. ECMO also suppresses circulating triiodothyronine (T3) levels and modifies myocardial metabolism. We assessed the hypothesis that T3 supplementation reverses ECMO induced metabolic abnormalities in the immature heart. Twenty-two male Yorkshire pigs (age 25-38 days) with ECMO were received [2-13C]lactate, [2,4,6,8-13C]octanoate (medium chain fatty acid) and [U-13C]long-chain fatty acids as metabolic tracers either systemically (totally physiological intracoronary concentration) or directly into the coronary artery (high substrate concentration) for the last 60 minutes of each protocol. Nuclear magnetic resonance (NMR) analysis of left ventricular tissue determined the fractional contribution (Fc) of these substrates to the citric acid cycle (CAC). Fifty percent of the pigs in each group received intravenous T3 supplement (bolus at 0.6 μg/kg and then continuous infusion at 0.2 μg/kg/hour) during ECMO. Under both substrate loading conditions T3 significantly increased lactate-Fc with a marginal increase in octanoate-Fc. Both T3 and high substrate provision increased myocardial energy status indexed by [Phosphocreatine]/[ATP]. In conclusion, T3 supplementation promoted lactate metabolism to the CAC during ECMO suggesting that T3 releases inhibition of pyruvate dehydrogenase. Manipulation of substrate utilization by T3 may be used therapeutically during ECMO to improve resting energy state and facilitate weaning.

  3. Mitochondrial Diseases

    Science.gov (United States)

    ... disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are ... cells and cause damage. The symptoms of mitochondrial disease can vary. It depends on how many mitochondria ...

  4. Atrophic Rhinitis of Swine

    Science.gov (United States)

    This book chapter for the 8th edition of the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals describes the current state of knowledge regarding progressive atrophic rhinitis of swine. Topics covered include clinical signs and lesions, characteristics and methods of detection for...

  5. Swine Brucellosis: Current Perspectives

    Science.gov (United States)

    Brucella suis is a significant zoonosis that is present in domestic livestock and wildlife in many countries worldwide. Transmission from animal reservoirs is the source of human infection as human to human transmission is very rare. Although swine brucellosis causes economic losses in domestic liv...

  6. The effect of captopril on nitric oxide formation and on generation of radical forms of mitochondrial respiratory chain compounds in ischemic rat heart

    Czech Academy of Sciences Publication Activity Database

    Vavřínková, H.; Tutterová, M.; Stopka, Pavel; Divišová, J.; Kazdová, L.; Drahota, Zdeněk

    2001-01-01

    Roč. 50, č. 5 (2001), s. 481-489 ISSN 0862-8408 R&D Projects: GA ČR GA203/97/0642; GA MZd NB5299 Keywords : ACE inhibitors * L- arginine * mitochondrial radicals Subject RIV: BO - Biophysics Impact factor: 1.027, year: 2001

  7. Genotoxicity of swine effluents.

    Science.gov (United States)

    Techio, V H; Stolberg, J; Kunz, A; Zanin, E; Perdomo, C C

    2011-01-01

    This study aimed at the investigation of genotoxic effects of swine effluents from different stages of a treatment system for swine wastes through bioassay of stamen hairs and micronuclei in Tradescantia (clone BNL 4430). No significant differences (p≥0.05) regarding the genic mutations were found in the bioassay of stamen hairs, independently of the effluent analysed. For the genotoxicity test with micronuclei, the plants exposed to raw wastes, to sludge, and to effluent of the biodigester have presented higher rates of chromosomal damages (micronuclei), with significant differences in relation to the control group and other effluent of the waste treatment system (p≤0.05). The association between the chemical parameters and the genotoxicity data have shown that the variables COD and TKN have presented significant correlation (p≤0.05) with the number of mutagenic events in the tetrads.

  8. Crystallization of Mitochondrial Respiratory Complex II fromChicken Heart: A Membrane-Protein Complex Diffracting to 2.0Angstrom

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Li-shar; Borders, Toni M.; Shen, John T.; Wang, Chung-Jen; Berry, Edward A.

    2004-12-17

    Procedure is presented for preparation of diffraction-quality crystals of a vertebrate mitochondrial respiratory Complex II. The crystals have the potential to diffract to at least 2.0 Angstrom with optimization of post-crystal-growth treatment and cryoprotection. This should allow determination of the structure of this important and medically relevant membrane protein complex at near-atomic resolution and provide great detail of the mode of binding of substrates and inhibitors at the two substrate-binding sites.

  9. Circoviral infections in swine

    Directory of Open Access Journals (Sweden)

    Ivetić Vojin

    2002-01-01

    Full Text Available Circoviral infections in swine have appeared only recently and they today attract the attention of large numbers of researchers all over the world. They represent a great mystery, an unknown in veterinary medicine, both in our country and in the world. The causes of these infections are circoviruses, called after the DNA which is shaped like a circle. A large number of authors today believe the PCV-2 causes two pathological entities in weaned piglets which are known as porcine multisystemic wasting syndrome (PMWS and porcine dermatitis nephropathy syndrome (PDNS. Current investigations indicate that there is a causal connection between these two syndromes. These two new diseases, which have recently spread all over the world, cause serious losses, great concern and confusion, especially when they occur simultaneously or in a sequence in the same herd, or in parallel with other pathogenes, primarily with the porcine reproductive and respiratory syndrome virus (PRRSV and the porcine parvovirus (PPV. PMWS was first described in Canada in 1991. It most often affect pigs aged 5-12 weeks. The main clinical expression, depending on the stage of progression is diarrhea, delayed development or depressed growth, stuntedness, dyspnea ictherus, eyelid swelling, and lymphadenopathy. More rarely, there are neurological symptoms. Prominent suppression of the immune system is the main characteristic of PMWS, and a wave of secondary bacterial infection is also observed. PDNS is a new disease of economic importance, which mostly affects older swine, from 5 weeks to 5 months of age. The most prominent clinical symptoms in seriously ill piglets is extensive dermatitis, mostly on the chest, abdomen, haunches and forelegs, with the appearance of purple-red swellings of different shape and size. The swine are depressive febrile, anorectic, all of which leads to stunted growth. They are inactive. Mortality is often about 15%. PDNS is a differentially diagnostically

  10. Mitochondrial DNA.

    Science.gov (United States)

    Wright, Russell G.; Bottino, Paul J.

    1986-01-01

    Provides background information for teachers on mitochondrial DNA, pointing out that it may have once been a free-living organism. Includes a ready-to-duplicate exercise titled "Using Microchondrial DNA to Measure Evolutionary Distance." (JN)

  11. Mitochondrial Myopathy

    Science.gov (United States)

    ... fact, many cases of mitochondrial disease are sporadic, meaning that they occur without any family history. To ... temporary vision loss, difficulty speaking, or difficulty understanding speech) and lead to progressive brain injury. The cause ...

  12. Antibody repertoire development in swine

    Czech Academy of Sciences Publication Activity Database

    Butler, J. E.; Sun, J.; Wertz, N.; Šinkora, Marek

    2006-01-01

    Roč. 30, - (2006), s. 199-221 ISSN 0145-305X Institutional research plan: CEZ:AV0Z50200510 Keywords : swine * b cells * immunoglobulins Subject RIV: EE - Microbiology, Virology Impact factor: 3.399, year: 2006

  13. Swine Flu: Prevention to Pandemic

    Directory of Open Access Journals (Sweden)

    Preeti Padda

    2015-03-01

    Full Text Available Swine flu, also known as swine influenza, pig influenza, hog flu and pig flu, is a respiratory disease caused by viruses (influenza viruses that infect the respiratory tract of pigs, resulting in nasal secretions, a barking cough, decreased appetite, and listless behaviour. Swine flu produces most of the same symptoms in pigs as human flu produces in people. Mostly people who are closely associated with pigs (for example, pork processors and farmers acquire the infection and similarly pigs get infected occasionally human flu infection. The cross-species infections (swine virus to man; human flu virus to pigs have always been confined to local areas and have not spread across borders in either pigs or humans. Unfortunately, this cross-species situation with influenza viruses has had the potential to change and cause epidemics and pandemics. Most recent pandemic has been reported in 2009,  where "swine flu" strain, first seen in Mexico, was termed as H1N1 as it was mainly infecting people and exhibited two main surface antigens, H1 (hemagglutinin type 1 and N1 (neuraminidase type1. This unique eight RNA strands from novel H1N1 flu have one strand derived from human flu strains, two from avian (bird strains, and five from swine strains. Since then it has been infecting people here and there. 

  14. MITOCHONDRIAL BKCa CHANNEL

    Directory of Open Access Journals (Sweden)

    Enrique eBalderas

    2015-03-01

    Full Text Available Since its discovery in a glioma cell line 15 years ago, mitochondrial BKCa channel (mitoBKCa has been studied in brain cells and cardiomyocytes sharing general biophysical properties such as high K+ conductance (~300 pS, voltage-dependency and Ca2+-sensitivity. Main advances in deciphering the molecular composition of mitoBKCa have included establishing that it is encoded by the Kcnma1 gene, that a C-terminal splice insert confers mitoBKCa ability to be targeted to cardiac mitochondria, and evidence for its potential coassembly with β subunits. Notoriously, β1 subunit directly interacts with cytochrome c oxidase and mitoBKCa can be modulated by substrates of the respiratory chain. mitoBKCa channel has a central role in protecting the heart from ischemia, where pharmacological activation of the channel impacts the generation of reactive oxygen species and mitochondrial Ca2+ preventing cell death likely by impeding uncontrolled opening of the mitochondrial transition pore. Supporting this view, inhibition of mitoBKCa with Iberiotoxin, enhances cytochrome c release from glioma mitochondria. Many tantalizing questions remain. Some of them are: how is mitoBKCa coupled to the respiratory chain? Does mitoBKCa play non-conduction roles in mitochondria physiology? Which are the functional partners of mitoBKCa? What are the roles of mitoBKCa in other cell types? Answers to these questions are essential to define the impact of mitoBKCa channel in mitochondria biology and disease.

  15. 9 CFR 94.10 - Swine from regions where classical swine fever exists.

    Science.gov (United States)

    2010-01-01

    ... swine fever exists. 94.10 Section 94.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY: PROHIBITED AND RESTRICTED...

  16. Maintaining ancient organelles: mitochondrial biogenesis and maturation.

    Science.gov (United States)

    Vega, Rick B; Horton, Julie L; Kelly, Daniel P

    2015-05-22

    The ultrastructure of the cardiac myocyte is remarkable for the high density of mitochondria tightly packed between sarcomeres. This structural organization is designed to provide energy in the form of ATP to fuel normal pump function of the heart. A complex system comprised of regulatory factors and energy metabolic machinery, encoded by both mitochondrial and nuclear genomes, is required for the coordinate control of cardiac mitochondrial biogenesis, maturation, and high-capacity function. This process involves the action of a transcriptional regulatory network that builds and maintains the mitochondrial genome and drives the expression of the energy transduction machinery. This finely tuned system is responsive to developmental and physiological cues, as well as changes in fuel substrate availability. Deficiency of components critical for mitochondrial energy production frequently manifests as a cardiomyopathic phenotype, underscoring the requirement to maintain high respiration rates in the heart. Although a precise causative role is not clear, there is increasing evidence that perturbations in this regulatory system occur in the hypertrophied and failing heart. This review summarizes current knowledge and highlights recent advances in our understanding of the transcriptional regulatory factors and signaling networks that serve to regulate mitochondrial biogenesis and function in the mammalian heart. © 2015 American Heart Association, Inc.

  17. Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, C. [Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou (China); Institute of Neuroscience, Soochow University, Suzhou (China); Hu, S.M. [Institute of Neuroscience, Soochow University, Suzhou (China); Xie, H.; Qiao, S.G. [Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou (China); Liu, H. [Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Davis, CA (United States); Liu, C.F. [Institute of Neuroscience, Soochow University, Suzhou (China)

    2015-03-27

    This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoK{sub ATP}) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoK{sub ATP} channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoK{sub ATP} channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.

  18. Variant (Swine Origin) Influenza Viruses in Humans

    Science.gov (United States)

    ... Types Seasonal Avian Swine Variant Other Variant Influenza Viruses: Background and CDC Risk Assessment and Reporting Language: ... Background CDC Assessment Reporting Background On Variant Influenza Viruses Swine flu viruses do not normally infect humans. ...

  19. Development and Use of a Swine Model for Evaluating Anesthetic Agents and Devices

    Science.gov (United States)

    1990-09-01

    anaesthesia in patients with valvular heart disease . Canad. Anaesth. Soc. J., 26: 463-467, 1979. ...341Ketamine has been advocated for the induction of anesthesia in the acutely hypovolemic patient because of its ability to preserve blood pressure which...hypovolemia. The effects of anesthetic induction doses of Ketamine and thiopental were evaluated in a hypovolemic swine model. Sixteen acutely in

  20. Swine Flu -A Comprehensive View

    Science.gov (United States)

    Singh, Vandana; Sood, Meenakshi

    2012-07-01

    The present article is aimed on comprehensive view of Swine flu. It was first isolated from pigs in 1930 in USA. Pandemic caused by H1N1 in 2009 brought it in limelight. Itís a viral respiratory disease caused by viruses that infects pigs, resulting in nasal secretions, barking cough, decreased appetite, and listless behavior. Swine virus consist of eight RNA strands, one strand derived from human flu strains, two from avian (bird) strains, and five from swine strains. Swine flu spreads from infected person to healthy person by inhalation or ingestion of droplets contaminated with virus while sneezing or coughing. Two antiviral agents have been reported to help prevent or reduce the effects of swine flu, flu shot and nasal spray. WHO recommended for pandemic period to prevent its future outbreaks through vaccines or non-vaccines means. Antiviral drugs effective against this virus are Tamiflu and Relenza. Rapid antigen testing (RIDT), DFA testing, viral culture, and molecular testing (RT-PCR) are used for its diagnosis in laboratory

  1. Engineered Swine Models of Cancer

    Directory of Open Access Journals (Sweden)

    Adrienne L. Watson

    2016-05-01

    Full Text Available Over the past decade, the technology to engineer genetically modified swine has seen many advancements, and because their physiology is remarkably similar to that of humans, swine models of cancer may be extremely valuable for preclinical safety studies as well as toxicity testing of pharmaceuticals prior to the start of human clinical trials. Hence, the benefits of using swine as a large animal model in cancer research and the potential applications and future opportunities of utilizing pigs in cancer modeling are immense. In this review, we discuss how pigs have been and can be used as a biomedical models for cancer research, with an emphasis on current technologies. We have focused on applications of precision genetics that can provide models that mimic human cancer predisposition syndromes. In particular, we describe the advantages of targeted gene-editing using custom endonucleases, specifically TALENs and CRISPRs, and transposon systems, to make novel pig models of cancer with broad preclinical applications.

  2. Trimetazidina como aditivo em solução cardioplégica sem pré-tratamento não traz proteção adicional ao miocárdio isquêmico: estudo em modelo suíno de coração isolado Trimetazidine as cardioplegia addictive without pre-treatment does not improve myocardial protection: study in a swine working heart model

    Directory of Open Access Journals (Sweden)

    Lindemberg da Mota Silveira Filho

    2008-06-01

    Full Text Available OBJETIVO: Verificar, em modelo experimental de coração isolado de suínos, se a associação da trimetazidina à solução cardioplégica promove melhora no desempenho do coração. MÉTODOS: O modelo experimental utilizou suínos Large-White, com coração isolado perfundido por suporte de outro animal em modo de execução de trabalho ("working heart state". Foram divididos em três grupos (n = 6, submetidos a isquemia regional seguida de isquemia global, que recebiam um dos três tratamentos: solução St Thomas (ST, solução St Thomas acrescida de trimetazidina (TMZ e grupo controle (Co. Durante período de reperfusão, aos 30, 60 e 90 minutos, foram medidos parâmetros hemodinâmicos de contratilidade e metabólicos, obtendo-se assim a elastância máxima (Emáx, o índice de trabalho sistólico pré-recrutável (PRSW, "dureza" do ventrículo (EDPRV, fluxo coronariano, consumo de oxigênio e dosagens de lactato e glicose. Os resultados foram analisados estatisticamente. RESULTADOS: Em relação aos parâmetros hemodinâmicos de contratilidade, não houve diferença estatística significante entre os três grupos. Houve produção crescente de lactato nos três grupos de forma uniforme quanto maior o tempo de reperfusão. O fluxo coronariano, o consumo de oxigênio e o consumo de glicose tiveram grande variação entre os diferentes tempos medidos, mas sem diferença entre os três tratamentos. O peso final do ventrículo esquerdo foi significativamente menor no grupo trimetazidina (TMZ do que nos demais. CONCLUSÃO: A administração da trimetazidina associada como adjuvante à solução cardioplégica, sem pré-tratamento, não demonstrou benefício hemodinâmico ou metabólico em modelo experimental "working heart" de coração isolado em porcos.OBJECTIVE: The aim of this study is to verify in an isolated working heart swine model if the acute administration of trimetazidine to cardioplegia, without pre=treatment improves heart

  3. Swine in biomedical research. Vol. 3

    Energy Technology Data Exchange (ETDEWEB)

    Tumbleson, M.E.

    1986-01-01

    This volume presents information on the following topics: hemodynamic characteristics of the conscious resting pig; cardiovascular and metabolic responses to acute and chronic exercise in swine (ILLEGIBLE) a large animal model for studies (ILLEGIBLE) effects of heparin-protamine interaction in swine - intravenous vs. intraarterial; swine as animal models in cardiovascular research; studies of coronary thrombosis in swine with von Willebrand's disease; role of plasma intermediate and low density lipoproteins in early atherogenesis in hyperlipidemic swine; swine as a model in renal physiology and nephrology; the pig as a model for studying kidney disease in man; hypertension of renal origin and the effects of Captopril in miniature pigs; porcine natural killer/killer cell system; the behavior of pig lymphocyte populations in vivo; a review of spontaneous and experimental porcine eperythrozoonosis; and Sinclair swine melanoma.

  4. Cadmium affects the mitochondrial viability and the acid soluble ...

    African Journals Online (AJOL)

    Cadmium affects the mitochondrial viability and the acid soluble thiols concentration in liver, kidney, heart and gills of Ancistrus brevifilis (Eigenmann, 1920). P Velasquez-Vottelerd, Y Anton, R Salazar-Lugo ...

  5. Overview of Classical Swine Fever (Hog Cholera, Classical Swine fever)

    Science.gov (United States)

    Classical swine fever is a contagious often fatal disease of pigs clinically characterized by high body temperature, lethargy, yellowish diarrhea, vomits and purple skin discoloration of ears, lower abdomen and legs. It was first described in the early 19th century in the USA. Later, a condition i...

  6. Control of African swine fever epidemics in industrialized swine populations

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Bøtner, Anette; Mortensen, Sten

    2016-01-01

    resulted in marginal improvements to the control of the epidemics. However, adding testing of dead animals in the protection and surveillance zones was predicted to be the optimal control scenario for an ASF epidemic in industrialized swine populations without contact to wild boar. This optimal scenario...

  7. What Is Mitochondrial DNA?

    Science.gov (United States)

    ... DNA What is mitochondrial DNA? What is mitochondrial DNA? Although most DNA is packaged in chromosomes within ... proteins. For more information about mitochondria and mitochondrial DNA: Molecular Expressions, a web site from the Florida ...

  8. Heart Health - Brave Heart

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Brave Heart Past Issues / Winter 2009 Table of Contents For ... you can have a good life after a heart attack." Lifestyle Changes Surviving—and thriving—after such ...

  9. CSFV induced mitochondrial fission and mitophagy to inhibit apoptosis.

    Science.gov (United States)

    Gou, Hongchao; Zhao, Mingqiu; Xu, Hailuan; Yuan, Jin; He, Wencheng; Zhu, Mengjiao; Ding, Hongxing; Yi, Lin; Chen, Jinding

    2017-06-13

    Classical swine fever virus (CSFV), which causes typical clinical characteristics in piglets, including hemorrhagic syndrome and immunosuppression, is linked to hepatitis C and dengue virus. Oxidative stress and a reduced mitochondrial transmembrane potential are disturbed in CSFV-infected cells. The balance of mitochondrial dynamics is essential for cellular homeostasis. In this study, we offer the first evidence that CSFV induces mitochondrial fission and mitophagy to inhibit host cell apoptosis for persistent infection. The formation of mitophagosomes and decline in mitochondrial mass relevant to mitophagy were detected in CSFV-infected cells. CSFV infection increased the expression and mitochondrial translocation of Pink and Parkin. Upon activation of the PINK1 and Parkin pathways, Mitofusin 2 (MFN2), a mitochondrial fusion mediator, was ubiquitinated and degraded in CSFV-infected cells. Mitophagosomes and mitophagolysosomes induced by CSFV were, respectively, observed by the colocalization of LC3-associated mitochondria with Parkin or lysosomes. In addition, a sensitive dual fluorescence reporter (mito-mRFP-EGFP) was utilized to analyze the delivery of mitophagosomes to lysosomes. Mitochondrial fission caused by CSFV infection was further determined by mitochondrial fragmentation and Drp1 translocation into mitochondria using a confocal microscope. The preservation of mitochondrial proteins, upregulated apoptotic signals and decline of viral replication resulting from the silencing of Drp1 and Parkin in CSFV-infected cells suggested that CSFV induced mitochondrial fission and mitophagy to enhance cell survival and viral persistence. Our data for mitochondrial fission and selective mitophagy in CSFV-infected cells reveal a unique view of the pathogenesis of CSFV infection and provide new avenues for the development of antiviral strategies.

  10. Microbiome overview in swine lungs.

    Science.gov (United States)

    Siqueira, Franciele Maboni; Pérez-Wohlfeil, Esteban; Carvalho, Fabíola Marques; Trelles, Oswaldo; Schrank, Irene Silveira; Vasconcelos, Ana Tereza Ribeiro; Zaha, Arnaldo

    2017-01-01

    Mycoplasma hyopneumoniae is the etiologic agent of swine enzootic pneumonia. However other mycoplasma species and secondary bacteria are found as inhabitants of the swine respiratory tract, which can be also related to disease. In the present study we have performed a total DNA metagenomic analysis from the lungs of pigs kept in a field condition, with suggestive signals of enzootic pneumonia and without any infection signals to evaluate the bacteria variability of the lungs microbiota. Libraries from metagenomic DNA were prepared and sequenced using total DNA shotgun metagenomic pyrosequencing. The metagenomic distribution showed a great abundance of bacteria. The most common microbial families identified from pneumonic swine's lungs were Mycoplasmataceae, Flavobacteriaceae and Pasteurellaceae, whereas in the carrier swine's lungs the most common families were Mycoplasmataceae, Bradyrhizobiaceae and Flavobacteriaceae. Analysis of community composition in both samples confirmed the high prevalence of M. hyopneumoniae. Moreover, the carrier lungs had more diverse family population, which should be related to the lungs normal flora. In summary, we provide a wide view of the bacterial population from lungs with signals of enzootic pneumonia and lungs without signals of enzootic pneumonia in a field situation. These bacteria patterns provide information that may be important for the establishment of disease control measures and to give insights for further studies.

  11. Microbiome overview in swine lungs.

    Directory of Open Access Journals (Sweden)

    Franciele Maboni Siqueira

    Full Text Available Mycoplasma hyopneumoniae is the etiologic agent of swine enzootic pneumonia. However other mycoplasma species and secondary bacteria are found as inhabitants of the swine respiratory tract, which can be also related to disease. In the present study we have performed a total DNA metagenomic analysis from the lungs of pigs kept in a field condition, with suggestive signals of enzootic pneumonia and without any infection signals to evaluate the bacteria variability of the lungs microbiota. Libraries from metagenomic DNA were prepared and sequenced using total DNA shotgun metagenomic pyrosequencing. The metagenomic distribution showed a great abundance of bacteria. The most common microbial families identified from pneumonic swine's lungs were Mycoplasmataceae, Flavobacteriaceae and Pasteurellaceae, whereas in the carrier swine's lungs the most common families were Mycoplasmataceae, Bradyrhizobiaceae and Flavobacteriaceae. Analysis of community composition in both samples confirmed the high prevalence of M. hyopneumoniae. Moreover, the carrier lungs had more diverse family population, which should be related to the lungs normal flora. In summary, we provide a wide view of the bacterial population from lungs with signals of enzootic pneumonia and lungs without signals of enzootic pneumonia in a field situation. These bacteria patterns provide information that may be important for the establishment of disease control measures and to give insights for further studies.

  12. Induction of anaesthesia with remifentanil after bolus midazolam administration in Landrace/Large White swine

    DEFF Research Database (Denmark)

    Zacharioudaki, Argyro; Lelovas, Pavlos; Sergentanis, Theodoros N.

    2017-01-01

    Objective To investigate an alternative combination for anaesthesia induction in swine. Study design Randomized, ‘blinded’ experimental study. Animals Forty-five Landrace/Large White swine weighing 20.0 ± 1.5 kg. Methods Pulse oximetry, heart rate (HR) and blood pressure were measured after.......001), better response to intubation (p animals required additional midazolam. In groups R1, R4 and R5, there were decreases in HRs (p = 0.009, p...... variables. One animal developed apnoea and four electrocardiographic anomalies; all resolved without pharmaceutical interventions. Conclusions and clinical relevance A combination of 0.2 mg kg−1 midazolam with 4 or 5 μg kg−1 remifentanil may provide an alternative method of anaesthesia induction for swine....

  13. Microbiota in fermented feed and swine gut.

    Science.gov (United States)

    Wang, Cheng; Shi, Changyou; Zhang, Yu; Song, Deguang; Lu, Zeqing; Wang, Yizhen

    2018-04-01

    Development of alternatives to antibiotic growth promoters (AGP) used in swine production requires a better understanding of their impacts on the gut microbiota. Supplementing fermented feed (FF) in swine diets as a novel nutritional strategy to reduce the use of AGP and feed price, can positively affect the porcine gut microbiota, thereby improving pig productivities. Previous studies have noted the potential effects of FF on the shift in benefit of the swine microbiota in different regions of the gastrointestinal tract (GIT). The positive influences of FF on swine gut microbiota may be due to the beneficial effects of both pre- and probiotics. Necessarily, some methods should be adopted to properly ferment and evaluate the feed and avoid undesired problems. In this mini-review, we mainly discuss the microbiota in both fermented feed and swine gut and how FF influences swine gut microbiota.

  14. Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

    DEFF Research Database (Denmark)

    Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus

    2014-01-01

    and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

  15. Swine in biomedical research. V. 1

    Energy Technology Data Exchange (ETDEWEB)

    Tumbleson, M.E.

    1986-01-01

    This volume presents information on the following topics: the history of pigs; conceptual and operational history of the development of miniature swine; breeding program and population standards of the Gottingen miniature swine; moral, social and scientific aspects of the use of swine in research; fertility in gilts inseminated with frozen boar semen stored at -196 C for eight years; ultrastructure of piglet liver; porcine models in surgical research; anesthesia in swine; pulse monitoring, intravascular and instramuscular injection sites in pigs; collagen biosynthesis and collagen content as a measure of dermal healing in experimental wounds in domestic swine; methods for hair removal; swine as a cardiac surgical model; bone marrow transplantation in miniature swine; technical aspects of small intestinal transplantation in young pigs; models; the pig in studies of diarrhea pathophysiology; use of swine to validate airflow perturbation device for airways resistance measurements in humans; swine as a model for human diabetes; and the weanling Yorkshire pig as an animal model for measuring percutaneous penetration.

  16. Porcine heart interatrial septum anatomy.

    Science.gov (United States)

    Holda, Mateusz K; Holda, Jakub; Koziej, Mateusz; Piatek, Katarzyna; Klimek-Piotrowska, Wieslawa

    2018-02-16

    The left-sided atrial septal pouch (SP), a recently re-discovered anatomical structure within the human interatrial septum, has emerged as a possible source of thrombi formation and a trigger for atrial fibrillation, thereby potentially increasing the risk for ischemic stroke. In many studies, the swine interatrial septum has been used as model of the human heart. Also, possible new strategies and devices for management of the SPs may first be tested in this pig model. Therefore, in this study, we aimed to evaluate swine interatrial septum morphology and to compare it with the human analog, especially in the light of SP occurrence. A total of 75 swine (Sus scrofa f. domestica) hearts were examined. The interatrial septum morphology was assessed, and SPs were measured. The most common variant of the interatrial septum was smooth septum (26.6%) followed by the patent foramen ovale channel and right SP (both 22.7%). No left or double SPs were observed. In 28.0% of all cases the fold of tissue (left septal ridge) was observed on the left side of the interatrial septum in the location where the left-sided SP should be expected. The mean length of the patent foramen ovale channel was 7.1±1.5mm. The mean right SP depth was 6.3±2.2mm, and its ostium width and height were 5.8±1.2 and 5.3±1.6mm, respectively. There are significant differences between human and porcine interatrial septum morphology that should be taken into account during experimental studies. The absence of the left SP in swine results in the inability to use porcine heart as an experimental model for left-sided SP management. Copyright © 2018 Elsevier GmbH. All rights reserved.

  17. Antibody Repertoire Development in Swine

    Czech Academy of Sciences Publication Activity Database

    Butler, J. E.; Wertz, N.; Šinkora, Marek

    2017-01-01

    Roč. 5, FEB 17 (2017), s. 255-279 ISSN 2165-8102 R&D Projects: GA ČR GA15-02274S; GA ČR(CZ) GA16-09296S Institutional support: RVO:61388971 Keywords : swine * pre-immune antibody repertoire * ileal Peyer's patches Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.708, year: 2016

  18. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Tomoyuki [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Saotome, Masao, E-mail: msaotome@hama-med.ac.jp [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Funaki, Makoto [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Hayashi, Hideharu [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan)

    2014-05-01

    Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin

  19. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

    International Nuclear Information System (INIS)

    Watanabe, Tomoyuki; Saotome, Masao; Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Funaki, Makoto; Hayashi, Hideharu

    2014-01-01

    Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ m ) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H 2 O 2 ), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ m depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H 2 O 2 -induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ m depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance. • Inhibition of DRP or ROS

  20. Antibody levels to hepatitis E virus in North Carolina swine workers, non-swine workers, swine, and murids.

    Science.gov (United States)

    Withers, Mark R; Correa, Maria T; Morrow, Morgan; Stebbins, Martha E; Seriwatana, Jitvimol; Webster, W David; Boak, Marshall B; Vaughn, David W

    2002-04-01

    In a cross-sectional serosurvey, eastern North Carolina swine workers (n = 165) were compared with non-swine workers (127) for the presence of antibodies to hepatitis E virus as measured by a quantitative immunoglobulin enzyme-linked immunosorbent assay. Using a cutoff of 20 Walter Reed U/ml, swine-exposed subjects had a 4.5-fold higher antibody prevalence (10.9%) than unexposed subjects (2.4%). No evidence of past clinical hepatitis E or unexplained jaundice could be elicited. Swine (84) and mice (61), from farm sites in the same region as exposed subjects, were also tested. Antibody prevalence in swine (overall = 34.5%) varied widely (10.0-91.7%) according to site, but no antibody was detected in mice. Our data contribute to the accumulating evidence that hepatitis E may be a zoonosis and specifically to the concept of it as an occupational infection of livestock workers.

  1. Heart murmurs

    Science.gov (United States)

    Chest sounds - murmurs; Heart sounds - abnormal; Murmur - innocent; Innocent murmur; Systolic heart murmur; Diastolic heart murmur ... The heart has 4 chambers: Two upper chambers (atria) Two lower chambers (ventricles) The heart has valves that close ...

  2. Classical Swine Fever Virus-Rluc Replicons

    DEFF Research Database (Denmark)

    Risager, Peter Christian; Belsham, Graham J.; Rasmussen, Thomas Bruun

    Classical swine fever virus (CSFV) is the etiologic agent of the severe porcine disease, classical swine fever. Unraveling the molecular determinants of efficient replication is crucial for gaining proper knowledge of the pathogenic traits of this virus. Monitoring the replication competence within...

  3. 9 CFR 93.517 - Swine from Canada.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Swine from Canada. 93.517 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Swine Canada 7 § 93.517 Swine from Canada. (a) For purposes other than immediate slaughter. Swine offered for importation from Canada for purposes other than immediate slaughter...

  4. 9 CFR 206.2 - Swine contract library.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Swine contract library. 206.2 Section... STOCKYARDS PROGRAMS), DEPARTMENT OF AGRICULTURE SWINE CONTRACT LIBRARY § 206.2 Swine contract library. (a) Do... swine contract library will be made available to the public? GIPSA will summarize the information it has...

  5. Genetic evolution of recently emerged novel human-like swine H3 influenza A viruses (IAV) in United States swine

    Science.gov (United States)

    Introduction Influenza A virus (IAV) is a major cause of respiratory disease in swine. IAV transmission from humans to swine is a major contributor to swine IAV diversity. In 2012, a novel H3N2 with an HA (hu-H3) and NA derived from human seasonal H3N2 was detected in United States (US) swine. The h...

  6. The mitochondrial ROMK channel is a molecular component of Mitokatp

    Science.gov (United States)

    Foster, D. Brian; Ho, Alice S.; Rucker, Jasma; Garlid, Anders O.; Chen, Ling; Sidor, Agnieszka; Garlid, Keith D.; O’Rourke, Brian

    2013-01-01

    Rationale Activation of the mitochondrial ATP-sensitive potassium channel (mitoKATP) has been implicated in the mechanism of cardiac ischemic preconditioning, yet its molecular composition is unknown. Objective To use an unbiased proteomic analysis of the mitochondrial inner membrane to identify the mitochondrial K+ channel underlying mitoKATP. Methods and Results Mass spectrometric analysis was used to identify KCNJ1(ROMK) in purified bovine heart mitochondrial inner membrane and confirmed that ROMK mRNA is present in neonatal rat ventricular myocytes and adult hearts. ROMK2, a short form of the channel, is shown to contain an N-terminal mitochondrial targeting signal and a full length epitope-tagged ROMK2 colocalizes with mitochondrial ATP synthase β. The high-affinity ROMK toxin, tertiapin Q, inhibits mitoKATP activity in isolated mitochondria and in digitonin-permeabilized cells. Moreover, shRNA-mediated knockdown of ROMK inhibits the ATP-sensitive, diazoxide activated, component of mitochondrial thallium uptake. Finally, the heart-derived cell line, H9C2, is protected from cell death stimuli by stable ROMK2 overexpression, while knockdown of the native ROMK exacerbates cell death. Conclusions The findings support ROMK as the pore-forming subunit of the cytoprotective mitoKATP channel. PMID:22811560

  7. Cardioprotection by modulation of mitochondrial respiration during ischemia–reperfusion: Role of apoptosis-inducing factor

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Aijun [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030 (China); Szczepanek, Karol; Hu, Ying [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Lesnefsky, Edward J. [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298 (United States); McGuire Department of Veterans Affairs Medical Center, Richmond, VA 23249 (United States); Chen, Qun, E-mail: qchen8@vcu.edu [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States)

    2013-06-14

    Highlights: •Blockade of electron transport prevents the loss of AIF from mitochondria during IR. •Blockade of electron transport decreases caspase-independent cell death during IR. •Mitochondrial AIF content is down-regulated in Harlequin mice. •Blockade of electron transport protects Harlequin mouse hearts during IR. •Amobarbital protection is partially dependent on mitochondrial AIF content. -- Abstract: The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia–reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia–reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in

  8. Power Grid Protection of the Muscle Mitochondrial Reticulum

    Directory of Open Access Journals (Sweden)

    Brian Glancy

    2017-04-01

    Full Text Available Summary: Mitochondrial network connectivity enables rapid communication and distribution of potential energy throughout the cell. However, this connectivity puts the energy conversion system at risk, because damaged elements could jeopardize the entire network. Here, we demonstrate the mechanisms for mitochondrial network protection in heart and skeletal muscle (SKM. We find that the cardiac mitochondrial reticulum is segmented into subnetworks comprising many mitochondria linked through abundant contact sites at highly specific intermitochondrial junctions (IMJs. In both cardiac and SKM subnetworks, a rapid electrical and physical separation of malfunctioning mitochondria occurs, consistent with detachment of IMJs and retraction of elongated mitochondria into condensed structures. Regional mitochondrial subnetworks limit the cellular impact of local dysfunction while the dynamic disconnection of damaged mitochondria allows the remaining mitochondria to resume normal function within seconds. Thus, mitochondrial network security is comprised of both proactive and reactive mechanisms in striated muscle cells. : Network connectivity allows information sharing and distribution but also enables propagation of localized dysfunction. Glancy et al. demonstrate the existence of both proactive and reactive network protection mechanisms designed to minimize the spread of dysfunction throughout the coupled mitochondrial networks in heart and skeletal muscle cells. Keywords: energy distribution, muscle energetics, oxidative phosphorylation, 3D electron microscopy, mitochondrial retraction, mitochondrial dynamics

  9. Mitochondrial multiorgan disorder syndrome score generated from definite mitochondrial disorders

    Directory of Open Access Journals (Sweden)

    Finsterer J

    2017-10-01

    Full Text Available Josef Finsterer,1 Sinda Zarrouk-Mahjoub2 1Municipal Hospital Rudolfstiftung, Vienna, Austria; 2Genomics Platform, Pasteur Institute of Tunis, Tunis, Tunisia Objectives: Mitochondrial disorders (MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS at onset or evolve into MIMODS during the course. This study aimed to find which organs and/or tissues are most frequently affected by MIMODS, which are the most frequent abnormalities within an affected organ, whether there are typical MIMODS patterns, and to generate an MIMODS score to assess the diagnostic probability for an MID.Methods: This is a retrospective evaluation of clinical, biochemical, and genetic investigations of adult patients with definite MIDs. A total of 36 definite MID patients, 19 men and 17 women, aged 29–82 years were included in this study. The diagnosis was based on genetic testing (n=21, on biochemical investigations (n=17, or on both (n=2.Results: The number of organs most frequently affected was 4 ranging from 1 to 9. MIMODS was diagnosed in 97% of patients. The organs most frequently affected were the muscle (97%, central nervous system (CNS; 72%, endocrine glands (69%, heart (58%, intestines (55%, and peripheral nerves (50%. The most frequent CNS abnormalities were leukoencephalopathy, prolonged visually evoked potentials, and atrophy. The most frequent endocrine abnormalities included thyroid dysfunction, short stature, and diabetes. The most frequent cardiac abnormalities included arrhythmias, systolic dysfunction, and hypertrophic cardiomyopathy. The most frequent MIMODS patterns were encephalomyopathy, encephalo-myo-endocrinopathy, and encepalo-myo-endocrino-cardiopathy. The mean ± 2SD MIMODS score was 35.97±27.6 (range =11–71. An MIMODS score >10 was regarded as indicative of an MID.Conclusion: Adult MIDs manifest as MIMODS in the vast majority of the cases. The organs most frequently affected in MIMODS are muscles, CNS, endocrine

  10. Source tracking swine fecal waste in surface water proximal to swine concentrated animal feeding operations

    OpenAIRE

    Heaney, Christopher D.; Myers, Kevin; Wing, Steve; Hall, Devon; Baron, Dothula; Stewart, Jill R.

    2015-01-01

    Swine farming has gone through many changes in the last few decades, resulting in operations with a high animal density known as confined animal feeding operations (CAFOs). These operations produce a large quantity of fecal waste whose environmental impacts are not well understood. The purpose of this study was to investigate microbial water quality in surface waters proximal to swine CAFOs including microbial source tracking of fecal microbes specific to swine. For one year, surface water sa...

  11. Deciphering Modifications in Swine Cardiac Troponin I by Top-Down High-Resolution Tandem Mass Spectrometry

    Science.gov (United States)

    Zhang, Jiang; Dong, Xintong; Hacker, Timothy A.; Ge, Ying

    2011-01-01

    Cardiac troponin I (cTnI) is an important regulatory protein in cardiac muscle and its modification represents a key mechanism in the regulation of cardiac muscle contraction and relaxation. cTnI is often referred to as the “gold-standard” serum biomarker for diagnosing patients with acute cardiac injury since it is unique to the heart and released into the circulation following necrotic death of cardiac tissue. The swine (Sus scrofa) heart model is extremely valuable for cardiovascular research since the heart anatomy and coronary artery distribution of swine are almost identical to those of humans. Herein we report a comprehensive characterization of the modifications in swine cTnI using top-down high-resolution tandem mass spectrometry in conjugation with immunoaffinity chromatography purification. High-resolution high accuracy mass spectrometry revealed that swine cTnI affinity purified from domestic pig hearts was N-terminally acetylated and phosphorylated. Electron capture disassociation is uniquely suited for localization of labile phosphorylations, which unambiguously identified Ser22/Ser23 as the only basally phosphorylation sites that are well-known to be regulated by protein kinase A and protein kinase C. Moreover, a combination of tandem mass spectrometry with sequence homology alignment effectively localized a single amino acid polymorphism, V116A, representing a novel genetic variant of swine cTnI. Overall, our studies demonstrated the unique power of top-down high-resolution tandem mass spectrometry in the characterization of protein modifications including labile phosphorylation and unexpected sequence variants. PMID:20223681

  12. Deciphering modifications in swine cardiac troponin I by top-down high-resolution tandem mass spectrometry.

    Science.gov (United States)

    Zhang, Jiang; Dong, Xintong; Hacker, Timothy A; Ge, Ying

    2010-06-01

    Cardiac troponin I (cTnI) is an important regulatory protein in cardiac muscle, and its modification represents a key mechanism in the regulation of cardiac muscle contraction and relaxation. cTnI is often referred to as the "gold-standard" serum biomarker for diagnosing patients with acute cardiac injury since it is unique to the heart and released into the circulation following necrotic death of cardiac tissue. The swine (Sus scrofa) heart model is extremely valuable for cardiovascular research since the heart anatomy and coronary artery distribution of swine are almost identical to those of humans. Herein, we report a comprehensive characterization of the modifications in swine cTnI using top-down high-resolution tandem mass spectrometry in conjugation with immunoaffinity chromatography purification. High-resolution high accuracy mass spectrometry revealed that swine cTnI affinity purified from domestic pig hearts was N-terminally acetylated and phosphorylated. Electron capture disassociation is uniquely suited for localization of labile phosphorylations, which unambiguously identified Ser22/Ser23 as the only basally phosphorylated sites that are well-known to be regulated by protein kinase A and protein kinase C. Moreover, a combination of tandem mass spectrometry with sequence homology alignment effectively localized a single amino acid polymorphism, V116A, representing a novel genetic variant of swine cTnI. Overall, our studies demonstrated the unique power of top-down high-resolution tandem mass spectrometry in the characterization of protein modifications, including labile phosphorylation and unexpected sequence variants. Copyright 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

  13. The cholesterol system of the swine

    International Nuclear Information System (INIS)

    Aigueperse, Jocelyne

    1979-01-01

    The purpose of this work was to characterize the dynamic system of adult female Large White swine. The content of this system and its relationships with both the external environment and between the different parts of the system were explained. The analysis of these results in terms of compared physiology showed that the structure of the cholesterol system was the same in man and in the swine. Consequently, the swine constitutes a good biological tool to study human cholesterol indirectly and to foresee the changes that might be induced in various physio-pathological cases. (author) [fr

  14. Swine flu - A pandemic outbreak

    Directory of Open Access Journals (Sweden)

    Jini George

    Full Text Available Hippocrates had described influenza like outbreak in 412 B.C. and since then repeated influenza like epidemics and pandemics have been recorded in recent times. One of the greatest killers of all time was the pandemic of swine flu (Spanish flu of 1918-1919, when 230 million people died. Annual influenza epidemics are estimated to affect 5–15% of the global population, resulting in severe illness in 3–5 million patients causing 250,000–500,000 deaths worldwide. Severe illness and deaths occur mainly in the high-risk populations of infants, the elderly and chronically ill patients. The 2009 outbreak of swine flu is thought to be a mutation more specifically a reassortment of four known strains of influenza A virus subtype H1N1; one endemic in humans, one endemic in birds, and two endemic in pigs. WHO officially declared the outbreak to be a pandemic on June 11, 2009, but stressed that the new designation was a result of the global "spread of the virus," not its severity. [Vet World 2009; 2(12.000: 472-474

  15. Solid organ transplantation in primary mitochondrial disease: Proceed with caution.

    Science.gov (United States)

    Parikh, Sumit; Karaa, Amel; Goldstein, Amy; Ng, Yi S; Gorman, Grainne; Feigenbaum, Annette; Christodoulou, John; Haas, Richard; Tarnopolsky, Mark; Cohen, Bruce K; Dimmock, David; Feyma, Tim; Koenig, Mary K; Mundy, Helen; Niyazov, David; Saneto, Russell P; Wainwright, Mark S; Wusthoff, Courtney; McFarland, Robert; Scaglia, Fernando

    2016-07-01

    Solid organ transplants are rarely performed in both adult and pediatric patients with primary mitochondrial disease. Poor outcomes have been described in case reports and small case series. It is unclear whether the underlying genetic disease has a significant impact on post-transplant morbidity and mortality. Data were obtained for 35 patients from 17 Mitochondrial Disease Centers across North America, the United Kingdom and Australia. Patient outcomes were noted after liver, kidney or heart transplantation. Excluding patients with POLG-related disease, post-transplant survival approached or met outcomes seen in non-mitochondrial disease transplant patients. The majority of mitochondrial disease patients did not have worsening of their mitochondrial disease within 90-days post-transplant. Post-transplant complications, including organ rejection, were not a common occurrence and were generally treatable. Many patients did not have a mitochondrial disease considered or diagnosed prior to transplantation. In conclusion, patients with mitochondrial disease in this cohort generally tolerated solid-organ transplantation. Such patients may not need to be excluded from transplant solely for their mitochondrial diagnosis; additional caution may be needed for patients with POLG-related disease. Transplant teams should be aware of mitochondrial disease as an etiology for organ-failure and consider appropriate consultation in patients without a known cause of their symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Vascularização arterial da região do nó sinoatrial em corações suínos: origem, distribuição e quantificação Arterial vascularization of the sinoatrial node in swine hearts: origin, distribution and quantification

    Directory of Open Access Journals (Sweden)

    Ana P. Vidotti

    2008-02-01

    superfície de área (Sv foi de 182 e a superfície de área (S - mm² - foi de 64,3x10(6µm². A estimação da densidade numérica vascular (Nv(vasc, quantidade de vasos por unidade de volume (cm³, foi de 2,19 10-5 e o número total de vasos no órgão (N(vasc, estimado pelo método dissector físico em combinação com a estimativa do número de Euler (Xv, foi de 773,6832 x10-2. A elevada densidade vascular e do número total de vasos na região do nó sinoatrial de suínos sugere a existência de uma complexa e densa rede vascular perinodal, ratificando a importância deste marca-passo pelo seu suprimento sangüíneo.The sinoatrial node, for being topographically installed as the initial component of the conduction system, is responsible for the production of the nervous impulses, which determines the cardiac contraction. There have been made studies related to the node's morphology in order to know the origin, distribution and quantification of the vases in this tissue, however, in spite of the results and quantitative data of the nodal irrigation - arterial vascular conduct and arterial vascular density, at the nodal level - the literature is scarce. With this objective 27 SRD swine hearts, injected with colored resin for macroscopic analysis of the origin and distribution of ANSA (sinoatrial node artery, 3 others injected with watery solution of colloidal coal (dyed nanquim were used, to mark the route of the vases on the node level for stereological analysis. The atrial arteries originated as well from the right coronary artery as from the left one, with predominance of the first (66.66% and 33.33%, respectively. When originated from the right coronary artery, there existed the following branches: AADAM (right cranial medial atrial artery in 14 cases, AADAI (right cranial intermedial atrial artery in 2 cases, and AADAL (right cranial lateral atrial artery in 2 cases. In 9 cases (33.33% the following branches originated from the left coronary artery: 4 through

  17. Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy

    Science.gov (United States)

    Abel, E. Dale; Doenst, Torsten

    2011-01-01

    Cardiac hypertrophy is a stereotypic response of the heart to increased workload. The nature of the workload increase may vary depending on the stimulus (repetitive, chronic, pressure, or volume overload). If the heart fully adapts to the new loading condition, the hypertrophic response is considered physiological. If the hypertrophic response is associated with the ultimate development of contractile dysfunction and heart failure, the response is considered pathological. Although divergent signalling mechanisms may lead to these distinct patterns of hypertrophy, there is some overlap. Given the close relationship between workload and energy demand, any form of cardiac hypertrophy will impact the energy generation by mitochondria, which are the key organelles for cellular ATP production. Significant changes in the expression of nuclear and mitochondrially encoded transcripts that impact mitochondrial function as well as altered mitochondrial proteome composition and mitochondrial energetics have been described in various forms of cardiac hypertrophy. Here, we review mitochondrial alterations in pathological and physiological hypertrophy. We suggest that mitochondrial adaptations to pathological and physiological hypertrophy are distinct, and we shall review potential mechanisms that might account for these differences. PMID:21257612

  18. 1998 BUSINESS ANALYSIS SUMMARY FOR SWINE FARMS

    OpenAIRE

    Nott, Sherrill B.

    1999-01-01

    This report is a summary of the financial and production records kept by swine farmers enrolled in the Telfarm/MicroTel record program through Michigan State University Extension. This report has three purposes: 1)to provide statistical information about the financial results on swine farms during 1997; 2)to provide production costs for comparative analysis and forward planning; and 3)to provide information on the trends in resource use, income and costs during the last few years.

  19. Magnetic Resonance Imaging of Heart Failure Using a Swine Model

    Science.gov (United States)

    2011-03-21

    artery in 3D dynamic contrast medium enhanced MR angiography of the thorax --a brief review of causes and prevention. Int J Cardiovasc Imaging 2003;19(2...America, Associated Sciences Consortium, Educational Planning Committee 2003-2004 Assisted with installation of Computerized Radiography at the US... Radiography , #237974 1992 Registry of MRI Technologists, #1048 1995-present American Registry of Radiologic Technologists, Magnetic Resonance

  20. Echinococcus canadensis (G7) and Echinococcus granulosus sensu stricto (G1) in swine of southern Brazil.

    Science.gov (United States)

    Monteiro, D U; Botton, S A; Tonin, A A; Azevedo, M I; Graichen, D A S; Noal, C B; de la Rue, M L

    2014-05-28

    The cystic echinococcosis (CE) is an important zoonotic disease caused by the parasite Echinococcus spp. In Brazil, this parasite is present in Rio Grande do Sul (RS) state, border with Argentina and Uruguay, causing several damages to human and animal health. This study aimed to identify Echinococcus spp. in hydatid cysts of swine and evaluate the similarity of the genotypes through the phylogenetic analysis. A total of 3,101,992 swine were slaughtered in the central/northern region of RS/Brazil, during 2008-2012. Five isolates were characterized as hydatid cyst by molecular analysis, based on the mitochondrial gene cytochrome c oxidase subunit I (cox-I). The genotypes E. granulosus sensu stricto (G1) (n=2) and E. canadensis (G7) (n=3) were identified in the hydatid cysts. The swine represents a potential intermediate host for different genotypes of Echinococcus spp., besides it can contribute to the perpetuation of the parasite's life cycle in rural areas. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Characteristics of Yorkshire swine natural killer cells

    International Nuclear Information System (INIS)

    Ferguson, F.G.; Botticelli, G.; Confer, F.L.; Pinto, A.J.

    1986-01-01

    Since natural killer (NK) cells have a role in immune surveillance, they are important to consider in disease pathogenesis and resistance. We examined cell aspects responsible for NK cell mediated cytotoxicity in Yorkshire swine. Using cell separation procedures, peripheral blood lymphocytes were examined for reactivity to a panel of tumor targets, kinetics of lysis, morphology, surface receptor characteristics and response to immunoregulators. YAC-1 lymphoma and K-562 myeloid leukemia cells were sensitive to swine NK cells; whereas, several other tumor lines were not. In kinetic studies, swine NK cells were slower in initiation of the lytic process than cells responsible for NK activity in other species; small agranular lymphocytes are responsible for this activity in swine. These cells were examined for the presence of a surface marker, asialo GM1, which is common to NK cells in several other species. Swine NK cells respond to an interferon inducer, poly I:C, with enhanced NK activity. Cells in Yorkshire swine have characteristics which are unique but also have characteristics common to NK cells in other species

  2. Feral Swine in the United States Have Been Exposed to both Avian and Swine Influenza A Viruses.

    Science.gov (United States)

    Martin, Brigitte E; Sun, Hailiang; Carrel, Margaret; Cunningham, Fred L; Baroch, John A; Hanson-Dorr, Katie C; Young, Sean G; Schmit, Brandon; Nolting, Jacqueline M; Yoon, Kyoung-Jin; Lutman, Mark W; Pedersen, Kerri; Lager, Kelly; Bowman, Andrew S; Slemons, Richard D; Smith, David R; DeLiberto, Thomas; Wan, Xiu-Feng

    2017-10-01

    Influenza A viruses (IAVs) in swine can cause sporadic infections and pandemic outbreaks among humans, but how avian IAV emerges in swine is still unclear. Unlike domestic swine, feral swine are free ranging and have many opportunities for IAV exposure through contacts with various habitats and animals, including migratory waterfowl, a natural reservoir for IAVs. During the period from 2010 to 2013, 8,239 serum samples were collected from feral swine across 35 U.S. states and tested against 45 contemporary antigenic variants of avian, swine, and human IAVs; of these, 406 (4.9%) samples were IAV antibody positive. Among 294 serum samples selected for antigenic characterization, 271 cross-reacted with ≥1 tested virus, whereas the other 23 did not cross-react with any tested virus. Of the 271 IAV-positive samples, 236 cross-reacted with swine IAVs, 1 with avian IAVs, and 16 with avian and swine IAVs, indicating that feral swine had been exposed to both swine and avian IAVs but predominantly to swine IAVs. Our findings suggest that feral swine could potentially be infected with both avian and swine IAVs, generating novel IAVs by hosting and reassorting IAVs from wild birds and domestic swine and facilitating adaptation of avian IAVs to other hosts, including humans, before their spillover. Continued surveillance to monitor the distribution and antigenic diversities of IAVs in feral swine is necessary to increase our understanding of the natural history of IAVs. IMPORTANCE There are more than 5 million feral swine distributed across at least 35 states in the United States. In contrast to domestic swine, feral swine are free ranging and have unique opportunities for contact with wildlife, livestock, and their habitats. Our serological results indicate that feral swine in the United States have been exposed to influenza A viruses (IAVs) consistent with those found in both domestic swine and wild birds, with the predominant infections consisting of swine-adapted IAVs

  3. Assessment of swine-specific bacteriophages of Bacteroides fragilis in swine farms with different antibiotic practices.

    Science.gov (United States)

    Leknoi, Yuranan; Mongkolsuk, Skorn; Sirikanchana, Kwanrawee

    2017-04-01

    We assessed the occurrence and specificity of bacteriophages of Bacteroides fragilis in swine farms for their potential application in microbial source tracking. A local B. fragilis host strain, SP25 (DSM29413), was isolated from a pooled swine feces sample taken from a non-antibiotic farm. This strain was highly specific to swine fecal materials because it did not detect bacteriophages in any samples from human sewage, sheep, goats, cattle, dogs, and cats. The reference B. fragilis strain, RYC2056, could detect phages in swine samples but also detected phages in most human sewage and polluted urban canal samples. Phages of SP25 exist in the proximity of certain swine farms, regardless of their antibiotic use (p > 0.05). B. fragilis strain SP25 exhibited relatively high resistance to most of the veterinary antimicrobial agents tested. Interestingly, most farms that were positive for SP25 phages were also positive for RYC2056 phages. In conclusion, the swine-specific SP25 strain has the potential to indicate swine fecal contamination in certain bodies of water. Bacterial isolates with larger distributions are being studied and validated. This study highlights the importance of assessing the abundance of phages in local swine populations before determining their potential applicability for source tracking in local surface waters.

  4. Antimicrobial use in swine production and its effect on the swine gut microbiota and antimicrobial resistance.

    Science.gov (United States)

    Holman, Devin B; Chénier, Martin R

    2015-11-01

    Antimicrobials have been used in swine production at subtherapeutic levels since the early 1950s to increase feed efficiency and promote growth. In North America, a number of antimicrobials are available for use in swine. However, the continuous administration of subtherapeutic, low concentrations of antimicrobials to pigs also provides selective pressure for antimicrobial-resistant bacteria and resistance determinants. For this reason, subtherapeutic antimicrobial use in livestock remains a source of controversy and concern. The swine gut microbiota demonstrates a number of changes in response to antimicrobial administration depending on the dosage, duration of treatment, age of the pigs, and gut location that is sampled. Both culture-independent and -dependent studies have also shown that the swine gut microbiota contains a large number of antimicrobial resistance determinants even in the absence of antimicrobial exposure. Heavy metals, such as zinc and copper, which are often added at relatively high doses to swine feed, may also play a role in maintaining antimicrobial resistance and in the stability of the swine gut microbiota. This review focuses on the use of antimicrobials in swine production, with an emphasis on the North American regulatory context, and their effect on the swine gut microbiota and on antimicrobial resistance determinants in the gut microbiota.

  5. Pre-ischemic mitochondrial substrate constraint by inhibition of malate-aspartate shuttle preserves mitochondrial function after ischemia-reperfusion

    DEFF Research Database (Denmark)

    Jespersen, Nichlas Riise; Yokota, Takashi; Støttrup, Nicolaj Brejnholt

    2017-01-01

    effects of MAS inhibition on the mitochondria were similar to those of IPC. Intriguingly, the protection of mitochondrial function by AOA treatment appears to be different from that of IPC because AOA treatment, but not IPC, downregulated myocardial tricarboxilic acid (TCA)-cycle intermediates...... at the onset of reperfusion. MAS inhibition thus preserved mitochondrial respiratory capacity and decreased mitochondrial oxidative stress during late reperfusion in the IR-injured heart, at least in part, via metabolic regulation of TCA cycle intermediates in the mitochondria at the onset of reperfusion....

  6. The mitochondrial contact site complex, a determinant of mitochondrial architecture

    OpenAIRE

    Harner, Max; Körner, Christian; Walther, Dirk; Mokranjac, Dejana; Kaesmacher, Johannes; Welsch, Ulrich; Griffith, Janice; Mann, Matthias; Reggiori, Fulvio; Neupert, Walter

    2011-01-01

    The outer and inner mitochondrial membranes are physically linked. Quantitative high resolution mass spectrometry now identifies the molecular nature of the Mitochondrial Contact Site complex (MICOS). MICOS is required for crista junctions formation, respiration and mitochondrial DNA inheritance.

  7. Magnetic resonance imaging guided transatrial electrophysiological studies in swine using active catheter tracking - experience with 14 cases

    Energy Technology Data Exchange (ETDEWEB)

    Grothoff, Matthias; Gutberlet, Matthias [University of Leipzig - Heart Center, Department of Radiology, Leipzig (Germany); Hindricks, Gerhard; Sommer, Philipp; Hilbert, Sebastian [University of Leipzig - Heart Center, Department of Electrophysiology, Leipzig (Germany); Fleiter, Christian [Helios Klinikum Berlin-Buch, Department of Orthopaedic Surgery, Berlin (Germany); Schnackenburg, Bernhard [Philips Healthcare, Hamburg (Germany); Weiss, Steffen; Krueger, Sascha [Philips Innovative Technologies, Hamburg (Germany); Piorkowski, Christopher; Gaspar, Thomas [University of Dresden - Heart Center, Department of Electrophysiology, Dresden (Germany); Wedan, Steve; Lloyd, Thomas [Imricor Medical Systems, Burnsville, MN (United States)

    2017-05-15

    To evaluate the feasibility of performing comprehensive Cardiac Magnetic resonance (CMR) guided electrophysiological (EP) interventions in a porcine model encompassing left atrial access. After introduction of two femoral sheaths 14 swine (41 ± 3.6 kg) were transferred to a 1.5 T MR scanner. A three-dimensional whole-heart sequence was acquired followed by segmentation and the visualization of all heart chambers using an image-guidance platform. Two MR conditional catheters were inserted. The interventional protocol consisted of intubation of the coronary sinus, activation mapping, transseptal left atrial access (n = 4), generation of ablation lesions and eventually ablation of the atrioventricular (AV) node. For visualization of the catheter tip active tracking was used. Catheter positions were confirmed by passive real-time imaging. Total procedure time was 169 ± 51 minutes. The protocol could be completed in 12 swine. Two swine died from AV-ablation induced ventricular fibrillation. Catheters could be visualized and navigated under active tracking almost exclusively. The position of the catheter tips as visualized by active tracking could reliably be confirmed with passive catheter imaging. Comprehensive CMR-guided EP interventions including left atrial access are feasible in swine using active catheter tracking. (orig.)

  8. 9 CFR 93.505 - Certificate for swine.

    Science.gov (United States)

    2010-01-01

    ... certificate shall show that the entire region of origin is free of classical swine fever. (b) Swine from.... (Approved by the Office of Management and Budget under control number 0579-0165) [55 FR 31495, Aug. 2, 1990...

  9. Heart Failure

    Science.gov (United States)

    Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped ... and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and ...

  10. Nanoparticle sensor for label free detection of swine DNA in mixed biological samples

    International Nuclear Information System (INIS)

    Ali, M E; Hashim, U; Mustafa, S; Che Man, Y B; Yusop, M H M; Bari, M F; Islam, Kh N; Hasan, M F

    2011-01-01

    We used 40 ± 5 nm gold nanoparticles (GNPs) as colorimetric sensor to visually detect swine-specific conserved sequence and nucleotide mismatch in PCR-amplified and non-amplified mitochondrial DNA mixtures to authenticate species. Colloidal GNPs changed color from pinkish-red to gray-purple in 2 mM PBS. Visually observed results were clearly reflected by the dramatic reduction of surface plasmon resonance peak at 530 nm and the appearance of new features in the 620-800 nm regions in their absorption spectra. The particles were stabilized against salt-induced aggregation upon the adsorption of single-stranded DNA. The PCR products, without any additional processing, were hybridized with a 17-base probe prior to exposure to GNPs. At a critical annealing temperature (55 0 C) that differentiated matched and mismatched base pairing, the probe was hybridized to pig PCR product and dehybridized from the deer product. The dehybridized probe stuck to GNPs to prevent them from salt-induced aggregation and retained their characteristic red color. Hybridization of a 27-nucleotide probe to swine mitochondrial DNA identified them in pork-venison, pork-shad and venison-shad binary admixtures, eliminating the need of PCR amplification. Thus the assay was applied to authenticate species both in PCR-amplified and non-amplified heterogeneous biological samples. The results were determined visually and validated by absorption spectroscopy. The entire assay (hybridization plus visual detection) was performed in less than 10 min. The LOD (for genomic DNA) of the assay was 6 μg ml -1 swine DNA in mixed meat samples. We believe the assay can be applied for species assignment in food analysis, mismatch detection in genetic screening and homology studies between closely related species.

  11. Nanoparticle sensor for label free detection of swine DNA in mixed biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Ali, M E; Hashim, U [Institute of Nano Electronic Engineering (INNE), Universiti Malaysia Perlis, Lot 104-108, Tingkat 1, Block A, Taman Pertiwi Indah, Jalan Kangar-Alor Star, Seriab, 01000 Kangar, Perlis (Malaysia); Mustafa, S; Che Man, Y B; Yusop, M H M [Halal Products Research Institute, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia); Bari, M F [School of Materials Engineering, University Malaysia Perlis, Seriab 01000, Kangar, Perlis (Malaysia); Islam, Kh N [Department of Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia); Hasan, M F, E-mail: uda@unimap.edu.my [Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor (Malaysia)

    2011-05-13

    We used 40 {+-} 5 nm gold nanoparticles (GNPs) as colorimetric sensor to visually detect swine-specific conserved sequence and nucleotide mismatch in PCR-amplified and non-amplified mitochondrial DNA mixtures to authenticate species. Colloidal GNPs changed color from pinkish-red to gray-purple in 2 mM PBS. Visually observed results were clearly reflected by the dramatic reduction of surface plasmon resonance peak at 530 nm and the appearance of new features in the 620-800 nm regions in their absorption spectra. The particles were stabilized against salt-induced aggregation upon the adsorption of single-stranded DNA. The PCR products, without any additional processing, were hybridized with a 17-base probe prior to exposure to GNPs. At a critical annealing temperature (55 {sup 0}C) that differentiated matched and mismatched base pairing, the probe was hybridized to pig PCR product and dehybridized from the deer product. The dehybridized probe stuck to GNPs to prevent them from salt-induced aggregation and retained their characteristic red color. Hybridization of a 27-nucleotide probe to swine mitochondrial DNA identified them in pork-venison, pork-shad and venison-shad binary admixtures, eliminating the need of PCR amplification. Thus the assay was applied to authenticate species both in PCR-amplified and non-amplified heterogeneous biological samples. The results were determined visually and validated by absorption spectroscopy. The entire assay (hybridization plus visual detection) was performed in less than 10 min. The LOD (for genomic DNA) of the assay was 6 {mu}g ml{sup -1} swine DNA in mixed meat samples. We believe the assay can be applied for species assignment in food analysis, mismatch detection in genetic screening and homology studies between closely related species.

  12. Mitochondrial multiorgan disorder syndrome score generated from definite mitochondrial disorders.

    Science.gov (United States)

    Finsterer, Josef; Zarrouk-Mahjoub, Sinda

    2017-01-01

    Mitochondrial disorders (MIDs) frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or evolve into MIMODS during the course. This study aimed to find which organs and/or tissues are most frequently affected by MIMODS, which are the most frequent abnormalities within an affected organ, whether there are typical MIMODS patterns, and to generate an MIMODS score to assess the diagnostic probability for an MID. This is a retrospective evaluation of clinical, biochemical, and genetic investigations of adult patients with definite MIDs. A total of 36 definite MID patients, 19 men and 17 women, aged 29-82 years were included in this study. The diagnosis was based on genetic testing (n=21), on biochemical investigations (n=17), or on both (n=2). The number of organs most frequently affected was 4 ranging from 1 to 9. MIMODS was diagnosed in 97% of patients. The organs most frequently affected were the muscle (97%), central nervous system (CNS; 72%), endocrine glands (69%), heart (58%), intestines (55%), and peripheral nerves (50%). The most frequent CNS abnormalities were leukoencephalopathy, prolonged visually evoked potentials, and atrophy. The most frequent endocrine abnormalities included thyroid dysfunction, short stature, and diabetes. The most frequent cardiac abnormalities included arrhythmias, systolic dysfunction, and hypertrophic cardiomyopathy. The most frequent MIMODS patterns were encephalomyopathy, encephalo-myo-endocrinopathy, and encepalo-myo-endocrino-cardiopathy. The mean ± 2SD MIMODS score was 35.97±27.6 (range =11-71). An MIMODS score >10 was regarded as indicative of an MID. Adult MIDs manifest as MIMODS in the vast majority of the cases. The organs most frequently affected in MIMODS are muscles, CNS, endocrine glands, and heart. An MIMODS score >10 suggests an MID.

  13. Mitochondrial approaches to protect against cardiac ischemia and reperfusion injury

    Directory of Open Access Journals (Sweden)

    Amadou K.S. Camara

    2011-04-01

    Full Text Available The mitochondrion is a vital component in cellular energy metabolism and intracellular signaling processes. Mitochondria are involved in a myriad of complex signaling cascades regulating cell death vs. survival. Importantly, mitochondrial dysfunction and the resulting oxidative and nitrosative stress are central in the pathogenesis of numerous human maladies including cardiovascular diseases, neurodegenerative diseases, diabetes, and retinal diseases, many of which are related. This review will examine the emerging understanding of the role of mitochondria in the etiology and progression of cardiovascular diseases and will explore potential therapeutic benefits of targeting the organelle in attenuating the disease process. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate or manipulate mitochondrial function, to the use of light therapy directed to the mitochondrial function, and to modification of the mitochondrial genome for potential therapeutic benefit. The approach to rationally treat mitochondrial dysfunction could lead to more effective interventions in cardiovascular diseases that to date have remained elusive. The central premise of this review is that if mitochondrial abnormalities contribute to the etiology of cardiovascular diseases (e.g. ischemic heart disease, alleviating the mitochondrial dysfunction will contribute to mitigating the severity or progression of the disease. To this end, this review will provide an overview of our current understanding of mitochondria function in cardiovascular diseases as well as the potential role for targeting mitochondria with potential drugs or other interventions that lead to protection against cell injury.

  14. 9 CFR 93.508 - Articles accompanying swine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Articles accompanying swine. 93.508 Section 93.508 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.508 Articles accompanying swine. No litter...

  15. 9 CFR 78.31 - Brucellosis reactor swine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Brucellosis reactor swine. 78.31... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Restrictions on Interstate Movement of Swine Because of Brucellosis § 78.31 Brucellosis reactor swine. (a...

  16. 9 CFR 78.32 - Brucellosis exposed swine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Brucellosis exposed swine. 78.32... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS BRUCELLOSIS Restrictions on Interstate Movement of Swine Because of Brucellosis § 78.32 Brucellosis exposed swine. (a...

  17. Heart Anatomy

    Science.gov (United States)

    ... kilometers), which is far enough to circle the earth more than twice! See also on other sites: ... For the Public Heart Information Center Project Heart Women’s Heart Health Clinical Trials 6770 Bertner Avenue Houston, ...

  18. Clinical manifestation of mitochondrial diseases.

    Science.gov (United States)

    Magner, Martin; Kolářová, Hana; Honzik, Tomáš; Švandová, Ivana; Zeman, Jiří

    2015-01-01

    Mitochondrial disorders (MD) represent a clinically, biochemically and genetically heterogeneous group of diseases associated with dysfunction of the oxidative phosphorylation system and pyruvate dehydrogenase complex. Our aim was to illustrate the most common clinical presentation of MD on the example of selected diseases and syndromes. The minimal prevalence of MD is estimated as 1 to 5,000. MD may manifest at any age since birth until late-adulthood with acute manifestation or as a chronic progressive disease. Virtually any organ may be impaired, but the organs with the highest energetic demands are most frequently involved, including brain, muscle, heart and liver. Some MD may manifest as a characteristic cluster of clinical features (e.g. MELAS syndrome, Kearns-Sayre syndrome). Diagnostics includes detailed history, the comprehensive clinical examination, results of specialized examinations (especially cardiology, visual fundus examination, brain imaging, EMG), laboratory testing of body fluids (lactate, aminoacids, organic acids), and analysis of bioptic samples of muscle, skin, and liver, eventually. Normal lactate level in blood does not exclude the possibility of MD. Although the aimed molecular genetic analyses may be indicated in some of mitochondrial diseases, the methods of next generation sequencing come into focus. Examples of treatment are arginine supplementation in MELAS syndrome, ketogenic diet in pyruvate oxidation disorders or quinone analogs in patients with LHON. Conclusion: The clinical suspicion of a mitochondrial disorder is often delayed, or the disease remains undiagnosed. The correct diagnosis and adequate treatment can improve prognosis of the patient. Access to genetic counseling is also of great importance.

  19. Prevention of swine dysentery with a combination of lincomycin and spectinomycin and resistance of swine dysentery to tylosin and sodium arsanilate.

    Science.gov (United States)

    Olson, L D; Rodabaugh, D E

    1976-07-01

    The addition of a combination of lincomycin and spectinomycin to feed at the total concentrations of 44 and 77 mg/kg, beginning at the time of exposure and continuing for 8 weeks, prevented experimentally induced swine dysentery in swine. The disease did not develop after the medication was withdrawn. In contrast, swine dysentery, similar to that seen in the nonmedicated swine, did develop in simultaneously exposed swine treated with feed containing either 44 mg of tylosin or 99 mg sodium arsanilate/kg. The swine fed sodium arsanilate and which developed hemorrhagic diarrhea had a more severe form of this type of diarrhea than did the nonmedicated swine. After reexposure to inefective inoculum of swine dysentery 86 days after initial exposure, all remaining swine previously medicated with either tylosin or sodium arsanilate and all nonmedicated swine were immune; whereas 17 of the 24 swine fed the combination of lincomycin and spectinomycin were susceptible to swine dysentery and developed diarrhea.

  20. New biotechnological procedures in swine reproduction

    Directory of Open Access Journals (Sweden)

    Petrujkić Tihomir

    2002-01-01

    Full Text Available New biotechnological procedures and the use of hormones in swine breeding are aimed at increasing the number of piglets in the litter. In small herds and groups, selected sows with 16 mammary complexes (tits can yield up to 32 piglets, or porkers, per year per sow. In order to achieve such reproduction results, special, individual stalls for sow deliveries are used, in addition to biotechnological methods, with a warm core and floor heating, phased diet and clean facilities. The ovulation value in swine is determined by their genetic and paragenetic effects, and it is often provoked and increased with injections and preparations for superovulation. However, the results vary, since any administration of hormone injecions can reduce the reproductive cycle, shorten the duration of estrus, or disrupt the work of ovaries and create cystic follicles. The use of follicle-stimulating hormones in quantities up to 1000 IU per animal for the induction and synchronization of estrus has become customary for sows and gilts, as well as the use of prostaglandins, the use of GnRH for increasing ovulation in swine and increasing the number of follicles >4 mm in diameter in the implementation of new biotechnologies in swine breeding, increases the number of ovulations and fertility in swine. In this way, reproduction is raised to the highest possible level, and artificial insemination of sows has 12 separate rules which enable better and more successful artificial insemination of sows.

  1. A Pilot Study of Peritoneal Perfusion with a Novel Hemoglobin Based Oxygen Carrier in Swine (Sus scrofa)

    Science.gov (United States)

    2016-10-12

    peritoneum for gas exchange and lung replacement. Ten Yorkshire-cross swine were anesthetized, mechanically ventilated, instrumented, and laparotomized...Inflow and outflow tubing were be placed in the abdomen, and connected to a heart- lung bypass circuit, and the abdomen closed. Animals were then...the endotracheal tube was clamped, ceasing gas exchange in the lung . Arterial blood gases and time to death were then recorded. No differences were

  2. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

    Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease. © The Author(s) 2014.

  3. Mitochondrial events responsible for morphine's cardioprotection against ischemia/reperfusion injury

    International Nuclear Information System (INIS)

    He, Haiyan; Huh, Jin; Wang, Huihua; Kang, Yi; Lou, Jianshi; Xu, Zhelong

    2016-01-01

    Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30 min ischemia and 2 h of reperfusion. Morphine was given before the onset of ischemia. Infarct size and troponin I release were measured to evaluate cardiac injury. Oxidative stress was evaluated by measuring mitochondrial protein carbonylation and mitochondrial ROS generation. HL-1 cells were subjected to simulated ischemia/reperfusion and LDH release and mitochondrial membrane potential (ΔΨm) were measured. Morphine reduced infarct size as well as cardiac troponin I release which were aborted by the selective Src tyrosine kinase inhibitors PP2 and Src-I1. Morphine also attenuated LDH release and prevented a loss of ΔΨm at reperfusion in a Src tyrosine kinase dependent manner in HL-1 cells. However, morphine failed to reduce LDH release in HL-1 cells transfected with Src siRNA. Morphine increased mitochondrial Src phosphorylation at reperfusion and this was abrogated by PP2. Morphine attenuated mitochondrial protein carbonylation and mitochondrial superoxide generation at reperfusion through Src tyrosine kinase. The inhibitory effect of morphine on the mitochondrial complex I activity was reversed by PP2. These data suggest that morphine induces cardioprotection by preventing mitochondrial oxidative stress through mitochondrial Src tyrosine kinase. Inhibition of mitochondrial complex I at reperfusion by Src tyrosine kinase may account for the prevention of mitochondrial oxidative stress by morphine. - Highlights: • Morphine induced mito-Src phosphorylation and reduced infarct size in rat hearts. • Morphine failed to reduce I/R-induced LDH release in Src-silencing HL-1 cells. • Morphine prevented mitochondria damage caused by I/R through Src. • Morphine reduced

  4. Estimation of the transmission dynamics of African swine fever virus within a swine house

    DEFF Research Database (Denmark)

    Nielsen, J. P.; Larsen, T. S.; Hisham Beshara Halasa, Tariq

    2017-01-01

    The spread of African swine fever virus (ASFV) threatens to reach further parts of Europe. In countries with a large swine production, an outbreak of ASF may result in devastating economic consequences for the swine industry. Simulation models can assist decision makers setting up contingency plans......·00 (95% CI 0-1). Furthermore, we simulated the spread of ASFV within a pig house using a modified SEIR-model to establish the time from infection of one animal until ASFV is detected in the herd. Based on a chosen detection limit of 2·55% equivalent to 10 dead pigs out of 360, the disease would...

  5. Isolating the segment of the mitochondrial electron transport chain responsible for mitochondrial damage during cardiac ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qun; Yin, Guotian; Stewart, Sarah; Hu, Ying [Department of Medicine, Division of Cardiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Lesnefsky, Edward J., E-mail: edward.lesnefsky@va.gov [Department of Medicine, Division of Cardiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Medical Service, Louis Stokes Veterans Affairs Medical Center, Cleveland, OH 44106 (United States)

    2010-07-09

    Ischemia damages the mitochondrial electron transport chain (ETC), mediated in part by damage generated by the mitochondria themselves. Mitochondrial damage resulting from ischemia, in turn, leads to cardiac injury during reperfusion. The goal of the present study was to localize the segment of the ETC that produces the ischemic mitochondrial damage. We tested if blockade of the proximal ETC at complex I differed from blockade distal in the chain at cytochrome oxidase. Isolated rabbit hearts were perfused for 15 min followed by 30 min stop-flow ischemia at 37 {sup o}C. Amobarbital (2.5 mM) or azide (5 mM) was used to block proximal (complex I) or distal (cytochrome oxidase) sites in the ETC. Time control hearts were buffer-perfused for 45 min. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated. Ischemia decreased cytochrome c content in SSM but not in IFM compared to time control. Blockade of electron transport at complex I preserved the cytochrome c content in SSM. In contrast, blockade of electron transport at cytochrome oxidase with azide did not retain cytochrome c in SSM during ischemia. Since blockade of electron transport at complex III also prevented cytochrome c loss during ischemia, the specific site that elicits mitochondrial damage during ischemia is likely located in the segment between complex III and cytochrome oxidase.

  6. Elevated cytosolic Na+ increases mitochondrial formation of reactive oxygen species in failing cardiac myocytes.

    Science.gov (United States)

    Kohlhaas, Michael; Liu, Ting; Knopp, Andreas; Zeller, Tanja; Ong, Mei Fang; Böhm, Michael; O'Rourke, Brian; Maack, Christoph

    2010-04-13

    Oxidative stress is causally linked to the progression of heart failure, and mitochondria are critical sources of reactive oxygen species in failing myocardium. We previously observed that in heart failure, elevated cytosolic Na(+) ([Na(+)](i)) reduces mitochondrial Ca(2+) ([Ca(2+)](m)) by accelerating Ca(2+) efflux via the mitochondrial Na(+)/Ca(2+) exchanger. Because the regeneration of antioxidative enzymes requires NADPH, which is indirectly regenerated by the Krebs cycle, and Krebs cycle dehydrogenases are activated by [Ca(2+)](m), we speculated that in failing myocytes, elevated [Na(+)](i) promotes oxidative stress. We used a patch-clamp-based approach to simultaneously monitor cytosolic and mitochondrial Ca(2+) and, alternatively, mitochondrial H(2)O(2) together with NAD(P)H in guinea pig cardiac myocytes. Cells were depolarized in a voltage-clamp mode (3 Hz), and a transition of workload was induced by beta-adrenergic stimulation. During this transition, NAD(P)H initially oxidized but recovered when [Ca(2+)](m) increased. The transient oxidation of NAD(P)H was closely associated with an increase in mitochondrial H(2)O(2) formation. This reactive oxygen species formation was potentiated when mitochondrial Ca(2+) uptake was blocked (by Ru360) or Ca(2+) efflux was accelerated (by elevation of [Na(+)](i)). In failing myocytes, H(2)O(2) formation was increased, which was prevented by reducing mitochondrial Ca(2+) efflux via the mitochondrial Na(+)/Ca(2+) exchanger. Besides matching energy supply and demand, mitochondrial Ca(2+) uptake critically regulates mitochondrial reactive oxygen species production. In heart failure, elevated [Na(+)](i) promotes reactive oxygen species formation by reducing mitochondrial Ca(2+) uptake. This novel mechanism, by which defects in ion homeostasis induce oxidative stress, represents a potential drug target to reduce reactive oxygen species production in the failing heart.

  7. Mitochondrial Bioenergetics During Ischemia and Reperfusion.

    Science.gov (United States)

    Consolini, Alicia E; Ragone, María I; Bonazzola, Patricia; Colareda, Germán A

    2017-01-01

    During ischemia and reperfusion (I/R) mitochondria suffer a deficiency to supply the cardiomyocyte with chemical energy, but also contribute to the cytosolic ionic alterations especially of Ca 2+ . Their free calcium concentration ([Ca 2+ ]m) mainly depends on mitochondrial entrance through the uniporter (UCam) and extrusion in exchange with Na + (mNCX) driven by the electrochemical gradient (ΔΨm). Cardiac energetic is frequently estimated by the oxygen consumption, which determines metabolism coupled to ATP production and to the maintaining of ΔΨm. Nevertheless, a better estimation of heart energy consumption is the total heat release associated to ATP hydrolysis, metabolism, and binding reactions, which is measurable either in the presence or the absence of oxygenation or perfusion. Consequently, a mechano-calorimetrical approach on isolated hearts gives a tool to evaluate muscle economy. The mitochondrial role during I/R depends on the injury degree. We investigated the role of the mitochondrial Ca 2+ transporters in the energetic of hearts stunned by a model of no-flow I/R in rat hearts. This chapter explores an integrated view of previous and new results which give evidences to the mitochondrial role in cardiac stunning by ischemia o hypoxia, and the influence of thyroid alterations and cardioprotective strategies, such as cardioplegic solutions (high K-low Ca, pyruvate) and the phytoestrogen genistein in both sex. Rat ventricles were perfused in a flow-calorimeter at either 30 °C or 37 °C to continuously measure the left ventricular pressure (LVP) and total heat rate (Ht). A pharmacological treatment was done before exposing to no-flow I and R. The post-ischemic contractile (PICR as %) and energetical (Ht) recovery and muscle economy (Eco: P/Ht) were determined during stunning. The functional interaction between mitochondria (Mit) and sarcoplasmic reticulum (SR) was evaluated with selective mitochondrial inhibitors in hearts reperfused with Krebs-10 m

  8. Developmental and pathological changes in the human cardiac muscle mitochondrial DNA organization, replication and copy number.

    Directory of Open Access Journals (Sweden)

    Jaakko L O Pohjoismäki

    2010-05-01

    Full Text Available Adult human heart mitochondrial DNA (mtDNA has recently been shown to have a complex organization with abundant dimeric molecules, branched structures and four-way junctions. In order to understand the physiological significance of the heart-specific mtDNA maintenance mode and to find conditions that modify human heart mtDNA structure and replication, we analyzed healthy human heart of various ages as well as several different heart diseases, including ischemic heart disease, dilated as well as hypertrophic cardiomyopathies, and several mitochondrial disorders. By using one- and two-dimensional agarose gel electrophoresis, various enzymatic treatments and quantitative PCR we found that in human newborns heart mtDNA has a simple organization, lacking junctional forms and dimers. The adult-type branched forms are acquired in the early childhood, correlating with an increase in mtDNA copy number. Mitochondrial disorders involving either mutations in the mtDNA polymerase gamma (PolGalpha or mtDNA helicase Twinkle, while having no obvious cardiac manifestation, show distinct mtDNA maintenance phenotypes, which are not seen in various types of diseased heart or in mitochondrial disorders caused by point mutations or large-scale deletions of mtDNA. The findings suggest a link between cardiac muscle development, mtDNA copy number, replication mode and topological organization. Additionally, we show that Twinkle might have a direct role in the maintenance of four-way junctions in human heart mtDNA.

  9. Reassortment patterns in Swine influenza viruses.

    Directory of Open Access Journals (Sweden)

    Hossein Khiabanian

    Full Text Available Three human influenza pandemics occurred in the twentieth century, in 1918, 1957, and 1968. Influenza pandemic strains are the results of emerging viruses from non-human reservoirs to which humans have little or no immunity. At least two of these pandemic strains, in 1957 and in 1968, were the results of reassortments between human and avian viruses. Also, many cases of swine influenza viruses have reportedly infected humans, in particular, the recent H1N1 influenza virus of swine origin, isolated in Mexico and the United States. Pigs are documented to allow productive replication of human, avian, and swine influenza viruses. Thus it has been conjectured that pigs are the "mixing vessel" that create the avian-human reassortant strains, causing the human pandemics. Hence, studying the process and patterns of viral reassortment, especially in pigs, is a key to better understanding of human influenza pandemics. In the last few years, databases containing sequences of influenza A viruses, including swine viruses, collected since 1918 from diverse geographical locations, have been developed and made publicly available. In this paper, we study an ensemble of swine influenza viruses to analyze the reassortment phenomena through several statistical techniques. The reassortment patterns in swine viruses prove to be similar to the previous results found in human viruses, both in vitro and in vivo, that the surface glycoprotein coding segments reassort most often. Moreover, we find that one of the polymerase segments (PB1, reassorted in the strains responsible for the last two human pandemics, also reassorts frequently.

  10. Heart Attack

    Science.gov (United States)

    Each year almost 800,000 Americans have a heart attack. A heart attack happens when blood flow to the heart suddenly ... it's important to know the symptoms of a heart attack and call 9-1-1 if you or ...

  11. Heart Transplantation

    Science.gov (United States)

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes from a donor who has died. It is the last resort for people with heart failure when all other treatments have failed. The ...

  12. Heart Diseases

    Science.gov (United States)

    ... re like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the U.S. ... disability. There are many different forms of heart disease. The most common cause of heart disease is ...

  13. Mitochondrial reactive oxygen species production and elimination.

    Science.gov (United States)

    Nickel, Alexander; Kohlhaas, Michael; Maack, Christoph

    2014-08-01

    Reactive oxygen species (ROS) play an important role in cardiovascular diseases, and one important source for ROS are mitochondria. Emission of ROS from mitochondria is the net result of ROS production at the electron transport chain (ETC) and their elimination by antioxidative enzymes. Both of these processes are highly dependent on the mitochondrial redox state, which is dynamically altered under different physiological and pathological conditions. The concept of "redox-optimized ROS balance" integrates these aspects and implies that oxidative stress occurs when the optimal equilibrium of an intermediate redox state is disturbed towards either strong oxidation or reduction. Furthermore, mitochondria integrate ROS signals from other cellular sources, presumably through a process termed "ROS-induced ROS release" that involves mitochondrial ion channels. Here, we attempt to integrate these recent advances in our understanding of the control of mitochondrial ROS emission and develop a concept of how in heart failure, defects in ion handling can lead to mitochondrial oxidative stress. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System". Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. DNA methylation status of nuclear-encoded mitochondrial genes underlies the tissue-dependent mitochondrial functions

    Directory of Open Access Journals (Sweden)

    Takasugi Masaki

    2010-08-01

    Full Text Available Abstract Background Mitochondria are semi-autonomous, semi-self-replicating organelles harboring their own DNA (mitochondrial DNA, mtDNA, and their dysregulation is involved in the development of various diseases. While mtDNA does not generally undergo epigenetic modifications, almost all mitochondrial proteins are encoded by nuclear DNA. However, the epigenetic regulation of nuclear-encoded mitochondrial genes (nuclear mt genes has not been comprehensively analyzed. Results We analyzed the DNA methylation status of 899 nuclear mt genes in the liver, brain, and heart tissues of mouse, and identified 636 nuclear mt genes carrying tissue-dependent and differentially methylated regions (T-DMRs. These nuclar mt genes are involved in various mitochondrial functions and they also include genes related to human diseases. T-DMRs regulate the expression of nuclear mt genes. Nuclear mt genes with tissue-specific hypomethylated T-DMRs were characterized by enrichment of the target genes of specific transcription factors such as FOXA2 in the liver, and CEBPA and STAT1 in the brain. Conclusions A substantial proportion of nuclear mt genes contained T-DMRs, and the DNA methylation status of numerous T-DMRs should underlie tissue-dependent mitochondrial functions.

  15. Microbiological identification and analysis of Swine lungs collected from carcasses in Swine farms, china.

    Science.gov (United States)

    Zha, Yunfeng; Xie, Jiexiong; Chen, Ye; Wei, Chunya; Zhu, Wanjun; Chen, Jidang; Qi, Haitao; Zhang, Liangquan; Sun, Long; Zhang, Xiaozhan; Zhou, Pei; Cao, Zhenpeng; Qi, Wenbao; Zhang, Minze; Huang, Zhen; Zhang, Guihong

    2013-12-01

    The primary objective of this 3 years study was to determine the prevalence of porcine pathogens of the lungs of swine in swine farms in southern China. A total of 5,420 samples were collected from 200 swine farms. The bacterium that was most commonly isolated was Streptococcus suis, with 10.24 % of the samples being positive, 114 lungs (2.1 %) were positive for pseudorabies virus and 263 (4.85 %) were positive for classical swine fever virus; much lower than positive for PRRSV (15.1 %, p = 0.023) and PCV2 (13.8 %, p = 0.038). lungs that were positive for PRRSV and/or PCV-2 have significantly increased odds of being positive for any of the S. suis (9.79 vs. 0.44 %, p = 0.003).

  16. MitoMiner: a data warehouse for mitochondrial proteomics data.

    Science.gov (United States)

    Smith, Anthony C; Blackshaw, James A; Robinson, Alan J

    2012-01-01

    MitoMiner (http://mitominer.mrc-mbu.cam.ac.uk/) is a data warehouse for the storage and analysis of mitochondrial proteomics data gathered from publications of mass spectrometry and green fluorescent protein tagging studies. In MitoMiner, these data are integrated with data from UniProt, Gene Ontology, Online Mendelian Inheritance in Man, HomoloGene, Kyoto Encyclopaedia of Genes and Genomes and PubMed. The latest release of MitoMiner stores proteomics data sets from 46 studies covering 11 different species from eumetazoa, viridiplantae, fungi and protista. MitoMiner is implemented by using the open source InterMine data warehouse system, which provides a user interface allowing users to upload data for analysis, personal accounts to store queries and results and enables queries of any data in the data model. MitoMiner also provides lists of proteins for use in analyses, including the new MitoMiner mitochondrial proteome reference sets that specify proteins with substantial experimental evidence for mitochondrial localization. As further mitochondrial proteomics data sets from normal and diseased tissue are published, MitoMiner can be used to characterize the variability of the mitochondrial proteome between tissues and investigate how changes in the proteome may contribute to mitochondrial dysfunction and mitochondrial-associated diseases such as cancer, neurodegenerative diseases, obesity, diabetes, heart failure and the ageing process.

  17. Deciphering Modifications in Swine Cardiac Troponin I by Top-Down High-Resolution Tandem Mass Spectrometry

    OpenAIRE

    Zhang, Jiang; Dong, Xintong; Hacker, Timothy A.; Ge, Ying

    2010-01-01

    Cardiac troponin I (cTnI) is an important regulatory protein in cardiac muscle and its modification represents a key mechanism in the regulation of cardiac muscle contraction and relaxation. cTnI is often referred to as the “gold-standard” serum biomarker for diagnosing patients with acute cardiac injury since it is unique to the heart and released into the circulation following necrotic death of cardiac tissue. The swine (Sus scrofa) heart model is extremely valuable for cardiovascular resea...

  18. A Swine Model of Percutaneous Intracoronary Ethanol Induced Acute Myocardial Infarction and Ischemic Mitral Regurgitation.

    Science.gov (United States)

    Shi, Weiwei; McIver, Bryant V; Kalra, Kanika; Sarin, Eric L; Schmarkey, Susan; Duggan, Michael; Thourani, Vinod H; Guyton, Robert A; Padala, Muralidhar

    2017-08-01

    Ischemic mitral regurgitation (IMR) is a frequent complication after a myocardial infarction (MI), which doubles mortality. Transcatheter mitral repairs are emerging as alternative treatment options to open heart surgery for IMR, but animal models to test them are lacking. We report a percutaneous swine model of IMR. Seventeen swine were randomized to (group 1, n = 12) MI causing IMR, and (group 2, n = 5) controls. In group 1, MI was induced via percutaneous ethanol injection into the obtuse marginal branches of the left circumflex artery, resulting in ST elevating myocardial infarction. Nine animals were survived to 8-10 weeks with weekly echocardiograms and three swine were survived to 16-20 weeks with MRI at termination. In group 1 animals, average IMR fraction at termination was 26.6 ± 2.3% in the echo group, and 24.51 ± 0.41% in the MRI group. None of the animals in group 2 had IMR. Left ventricular dysfunction and significant dilatation were evident in group 1 animals, compared to the controls. In conclusion, a reproducible model of IMR is reported for use in pre-clinical testing of new mitral technologies.

  19. Mitochondrial biogenesis: pharmacological approaches.

    Science.gov (United States)

    Valero, Teresa

    2014-01-01

    Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS

  20. Transcription analysis on response of swine lung to H1N1 swine influenza virus.

    Science.gov (United States)

    Li, Yongtao; Zhou, Hongbo; Wen, Zhibin; Wu, Shujuan; Huang, Canhui; Jia, Guangmin; Chen, Huanchun; Jin, Meilin

    2011-08-08

    As a mild, highly contagious, respiratory disease, swine influenza always damages the innate immune systems, and increases susceptibility to secondary infections which results in considerable morbidity and mortality in pigs. Nevertheless, the systematical host response of pigs to swine influenza virus infection remains largely unknown. To explore it, a time-course gene expression profiling was performed for comprehensive analysis of the global host response induced by H1N1 swine influenza virus in pigs. At the early stage of H1N1 swine virus infection, pigs were suffering mild respiratory symptoms and pathological changes. A total of 268 porcine genes showing differential expression (DE) after inoculation were identified to compare with the controls on day 3 post infection (PID) (Fold change ≥ 2, p swine influenza virus infection in pigs. The observed gene expression profile could help to screen the potential host agents for reducing the prevalence of swine influenza virus and further understand the molecular pathogenesis associated with H1N1 infection in pigs.

  1. Proteomic analysis of swine serum following highly virulent classical swine fever virus infection

    Directory of Open Access Journals (Sweden)

    Guo Huan-cheng

    2011-03-01

    Full Text Available Abstract Background Classical swine fever virus (CSFV belongs to the genus Pestivirus within the family Flaviviridae. Virulent strains of classical swine fever virus (CSFV cause severe disease in pigs characterized by immunosuppression, thrombocytopenia and disseminated intravascular coagulation, which causes significant economic losses to the pig industry worldwide. Methods To reveal proteomic changes in swine serum during the acute stage of lethal CSFV infection, 5 of 10 pigs were inoculated with the virulent CSFV Shimen strain, the remainder serving as uninfected controls. A serum sample was taken at 3 days post-infection from each swine, at a stage when there were no clinical symptoms other than increased rectal temperatures (≥40°C. The samples were treated to remove serum albumin and immunoglobulin (IgG, and then subjected to two-dimension differential gel electrophoresis. Results Quantitative intensity analysis revealed 17 protein spots showing at least 1.5-fold quantitative alteration in expression. Ten spots were successfully identified by MALDI-TOF MS or LTQ MS. Expression of 4 proteins was increased and 6 decreased in CSFV-infected pigs. Functions of these proteins included blood coagulation, anti-inflammatory activity and angiogenesis. Conclusion These proteins with altered expression may have important implications in the pathogenesis of classical swine fever and provide a clue for identification of biomarkers for classical swine fever early diagnosis.

  2. In vitro effects of toxaphene on mitochondrial calcium ATPase and calcium uptake in selected rat tissues

    International Nuclear Information System (INIS)

    Trottman, C.H.; Rao, K.S.P.; Morrow, W.; Uzodinma, J.E.; Desaiah, D.

    1985-01-01

    In vitro effects of toxaphene on Ca 2+ -ATPase activity and 45 Ca 2+ -uptake were studied in mitochondrial fractions of heart, kidney and liver tissues of rat. Mitochondrial fractions were prepared by the conventional centrifugation method. Ca 2+ -ATPase activity was determined by measuring the inorganic phosphate liberated during ATP hydrolysis. Toxaphene inhibited Ca 2+ -ATPase in a concentration dependent manner in all the three tissues. Substrate activation kinetics, with heart, kidney and liver tissue fractions, revealed that toxaphene inhibited Ca 2+ -ATPase activity non-competetively by decreasing the maximum velocity of the enzyme without affecting the enzyme-substrate affinity. Toxaphene also inhibited mitochondrial 45 Ca 2+ -uptake in the three selected tissues in a concentration dependent manner. These results indicate that toxaphene is an inhibitor of mitochondrial Ca 2+ -ATPase and calcium transport in heart, kidney and liver tissues of rat. 19 references, 5 figures

  3. Epilepsy and Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    Russell P. Saneto DO, PhD

    2017-10-01

    Full Text Available Epilepsy is a common manifestation of mitochondrial disease. In a large cohort of children and adolescents with mitochondrial disease (n = 180, over 48% of patients developed seizures. The majority (68% of patients were younger than 3 years and medically intractable (90%. The electroencephalographic pattern of multiregional epileptiform discharges over the left and right hemisphere with background slowing occurred in 62%. The epilepsy syndrome, infantile spasms, was seen in 17%. Polymerase γ mutations were the most common genetic etiology of seizures, representing Alpers-Huttenlocher syndrome (14%. The severity of disease in those patients with epilepsy was significant, as 13% of patients experienced early death. Simply the loss of energy production cannot explain the development of seizures or all patients with mitochondrial dysfunction would have epilepsy. Until the various aspects of mitochondrial physiology that are involved in proper brain development are understood, epilepsy and its treatment will remain unsatisfactory.

  4. The plant mitochondrial proteome

    DEFF Research Database (Denmark)

    Millar, A.H.; Heazlewood, J.L.; Kristensen, B.K.

    2005-01-01

    The plant mitochondrial proteome might contain as many as 2000-3000 different gene products, each of which might undergo post-translational modification. Recent studies using analytical methods, such as one-, two- and three-dimensional gel electrophoresis and one- and two-dimensional liquid...... context to be defined for them. There are indications that some of these proteins add novel activities to mitochondrial protein complexes in plants....

  5. MITOCHONDRIAL DNA- REVOLUTIONARY EVOLUTION

    Directory of Open Access Journals (Sweden)

    Vaidhehi Narayan Nayak

    2017-07-01

    Full Text Available BACKGROUND Mitochondrion, the sausage-shaped organelle residing in the cytoplasm of all eukaryotic cells, apart from being the power house, represents endosymbiotic evolution of a free living organism to intracellular structure. Anthropologically, mitochondrial DNA is the fossilised source to trace the human ancestry particularly of maternal lineage. This article attempts to highlight the various biological functions of mitochondrial DNA (mtDNA with a note on its forensic application.

  6. USMARC update on swine reproduction research

    Science.gov (United States)

    Swine research at USMARC has continued to focus on meat quality, improvement of genomic resources and reproduction, specifically estrus traits, sow longevity and lifetime productivity. This report will focus on research in behavioral anestrus in gilts. Gilts that reach puberty at an earlier age are ...

  7. pandemic swine influenza virus: preparedness planning

    African Journals Online (AJOL)

    Zamzar

    pandemic planning. Keywords: Pandemic, swine, influenza, virus, preparedness. INTRODUCTION. Effective pandemic preparedness and response should involve all sectors of ... In less affluent countries, human and material resources are often scarce and other ... Once surge requirements have been estimated, policy ...

  8. Computerized management support for swine breeding farms

    NARCIS (Netherlands)

    Huirne, R.B.M.

    1990-01-01

    1. INTRODUCTION

    The investigations described in this thesis have been directed towards computerized management support for swine breeding farms, focused on sow productivity and profitability. The study is composed of three basic parts: (1) basic description and

  9. 75 FR 16641 - Swine Contract Library

    Science.gov (United States)

    2010-04-02

    ...;Prices of new books are listed in the first FEDERAL REGISTER issue of each #0;week. #0; #0; #0; #0;#0... types; (3) Adding definitions of terms used in several contract types to describe the market price that... rule will benefit swine producers by increasing their knowledge about contract terms and the number of...

  10. Replicon particle vaccine protects swine against influenza.

    Science.gov (United States)

    Bosworth, B; Erdman, M M; Stine, D L; Harris, I; Irwin, C; Jens, M; Loynachan, A; Kamrud, K; Harris, D L

    2010-12-01

    An alphavirus derived replicon particle (RP) vaccine expressing the cluster IV H3N2 swine influenza virus (SIV) hemagglutinin (HA) gene induced protective immunity against homologous influenza virus challenge. However, pigs with maternal antibody had no protective immunity against challenge after vaccination with RP vaccines expressing HA gene alone or in combination with nucleoprotein gene. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. H1N1 influenza (Swine flu)

    Science.gov (United States)

    Swine flu; H1N1 type A influenza ... The H1N1 virus is now considered a regular flu virus. It is one of the three viruses included in the regular (seasonal) flu vaccine . You cannot get H1N1 flu virus from ...

  12. Pandemic swine influenza virus: Preparedness planning | Ojogba ...

    African Journals Online (AJOL)

    The novel H1N1 influenza virus that emerged in humans in Mexico in early 2009 and transmitted efficiently in the human population with global spread was declared a pandemic strain. The introduction of different avian and human influenza virus genes into swine influenza viruses often result in viruses of increased fitness ...

  13. Preventing PRRS from Establishing in Utah Swine

    OpenAIRE

    Bagley, Clell V.

    2000-01-01

    Porcine Reproductive and Respiratory Syndrome (PRRS) is considered the most important disease affecting swine operations in North America and internationally. There has been no evidence of cross-infection to humans since discovery of PRRS in the U.S. in 1987.

  14. Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.

    Directory of Open Access Journals (Sweden)

    Martin Braun

    Full Text Available Adiponectin deficiency leads to increased myocardial infarct size following ischemia reperfusion and to exaggerated cardiac hypertrophy following pressure overload, entities that are causally linked to mitochondrial dysfunction. In skeletal muscle, lack of adiponectin results in impaired mitochondrial function. Thus, it was our objective to investigate whether adiponectin deficiency impairs mitochondrial energetics in the heart. At 8 weeks of age, heart weight-to-body weight ratios were not different between adiponectin knockout (ADQ-/- mice and wildtypes (WT. In isolated working hearts, cardiac output, aortic developed pressure and cardiac power were preserved in ADQ-/- mice. Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups. While myocardial oxygen consumption was slightly reduced (-24% in ADQ-/- mice in isolated working hearts, rates of maximal ADP-stimulated mitochondrial oxygen consumption and ATP synthesis in saponin-permeabilized cardiac fibers were preserved in ADQ-/- mice with glutamate, pyruvate or palmitoyl-carnitine as a substrate. In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups. Phosphorylation of AMP-activated protein kinase and SIRT1 activity were not decreased, expression and acetylation of PGC-1α were unchanged, and mitochondrial content of OXPHOS subunits was not decreased in ADQ-/- mice. Finally, increasing energy demands due to prolonged subcutaneous infusion of isoproterenol did not differentially affect cardiac contractility or mitochondrial function in ADQ-/- mice compared to WT. Thus, mitochondrial and contractile function are preserved in hearts of mice lacking adiponectin, suggesting that adiponectin may be expendable in the regulation of mitochondrial energetics and contractile function in the heart under non-pathological conditions.

  15. First description of a novel mitochondrial mutation in the MT-TI gene associated with multiple mitochondrial DNA deletion and depletion in family with severe dilated mitochondrial cardiomyopathy.

    Science.gov (United States)

    Alila-Fersi, Olfa; Tabebi, Mouna; Maalej, Marwa; Belguith, Neila; Keskes, Leila; Mkaouar-Rebai, Emna; Fakhfakh, Faiza

    2018-03-18

    Mitochondria are essential for early cardiac development and impaired mitochondrial function was described associated with heart diseases such as hypertrophic or dilated mitochondrial cardiomyopathy. In this study, we report a family including two individuals with severe dilated mitochondrial cardiomyopathy. The whole mitochondrial genome screening showed the presence of several variations and a novel homoplasmic mutation m.4318-4322delC in the MT-TI gene shared by the two patients and their mother and leading to a disruption of the tRNA Ile secondary structure. In addition, a mitochondrial depletion was present in blood leucocyte of the two affected brother whereas a de novo heteroplasmic multiple deletion in the major arc of mtDNA was present in blood leucocyte and mucosa of only one of them. These deletions in the major arc of the mtDNA resulted to the loss of several protein-encoding genes and also some tRNA genes. The mtDNA deletion and depletion could result to an impairment of the oxidative phosphorylation and energy metabolism in the respiratory chain in the studied patients. Our report is the first description of a family with severe lethal dilated mitochondrial cardiomyopathy and presenting several mtDNA abnormalities including punctual mutation, deletion and depletion. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Splenectomy Versus Sham Splenectomy in a Swine Model of Controlled Hemorrhagic Shock.

    Science.gov (United States)

    Boysen, Søren R; Caulkett, Nigel A; Brookfield, Caroline E; Warren, Amy; Pang, Jessica M

    2016-10-01

    Splenectomy is controversial in acute hemorrhagic shock models. To compare splenectomized (SP) versus sham-splenectomized (SSP) swine during acute controlled hemorrhage. Twenty-six male Landrace White swine (mean body weight ± standard deviation, 33.8 ± 2.9 kg) were used. Ethics approval was obtained. Landrace swine underwent splenectomy (n = 13) or sham-splenectomy (n = 13), were bled to mean arterial blood pressure (MAP) of 40 mm Hg, which was held for 60 min, given 125 mL IV RescueFlow, held for a further 60 min, given whole blood, and held for a final 60 min. Tissue oxygen saturation, thromboelastography, oncotic pressure, urine volume and specific gravity, complete blood count, serum chemistry, body temperature, hematocrit, total solids, arterial and mixed venous blood gas, bispectral index, SAP, MAP, DAP, cardiac index, total blood volume (TBV) removed and returned, rate of hemorrhage and transfusion, spleen weight, heart rate (HR), arterial pH, lactate, PaO2, PaCO2, respiratory rate, cranial mesenteric and renal artery blood flow were recorded. Groups were compared using two-way ANOVA with post hoc Bonferroni (P splenectomy for the duration of the experiment (P splenectomy (P Splenectomy likely accounts for the transient increase in hematocrit and the higher HR in SP swine prior to hemorrhage, and the differences in TBV removed between the two groups during hemorrhage. With a fixed end point model using a moderate rate of acute hemorrhage and an MAP of 40 mm Hg, splenectomy is not necessary and may confound results.

  17. Swine (Sus scrofa) as a Model of Postinfarction Mitral Regurgitation and Techniques to Accommodate Its Effects during Surgical Repair.

    Science.gov (United States)

    Sarin, Eric L; Shi, Weiwei; Duara, Rajnish; Melone, Todd A; Kalra, Kanika; Strong, Ashley; Girish, Apoorva; McIver, Bryant V; Thourani, Vinod H; Guyton, Robert A; Padala, Muralidhar

    2016-01-01

    Mitral regurgitation (MR) is a common heart-valve lesion after myocardial infarction in humans. Because it is considered a risk factor for accelerated heart failure and death, various surgical approaches and catheter-based devices to correct it are in development. Lack of a reproducible animal model of MR after myocardial infarction and reliable techniques to perform open-heart surgery in these diseased models led to the use of healthy animals to test new devices. Thus, most devices that are deemed safe in healthy animals have shown poor results in human efficacy studies, hampering progress in this area of research. Here we report our experience with a swine model of postinfarction MR, describe techniques to induce regurgitation and perform open-heart surgery in these diseased animals, and discuss our outcomes, complications, and solutions.

  18. Prostaglandin E1 protects coronary microvascular function via the glycogen synthase kinase 3β-mitochondrial permeability transition pore pathway in rat hearts subjected to sodium laurate-induced coronary microembolization.

    Science.gov (United States)

    Zhu, Houyong; Ding, Yu; Xu, Xiaoqun; Li, Meiya; Fang, Yangliang; Gao, Beibei; Mao, Hengyi; Tong, Guoxin; Zhou, Liang; Huang, Jinyu

    2017-01-01

    Prostaglandin E1 (PGE1) is used as a pretreatment for ischemia reperfusion injury in many biological systems. However, its value as a pretreatment for coronary microembolization (CME) is unknown. The goal of this study was to determine whether PGE1 would protect against CME. In a CME rat model, we observed microthrombi and early myocardial ischemia, with endothelium appearing exfoliated and mitochondria having irregular morphology and decreased internal complexity. The level of fibrinogen-like protein 2 prothrombinase was increased and superoxide dismutase and catalase levels were decreased. Moreover, mitochondria copy number and mitochondrial permeability transition pore (mPTP) opening were increased. Pretreatment with PGE1 (1 or 2 μg/kg) significantly improved these cardiological deficits, acting via the glycogen synthase kinase 3β (GSK-3β)-mPTP pathway. Unexpectedly, the phosphorylation of Akt at Ser473 decreased in the PGE1 at high dose. Overall, our findings suggested an important role for PGE1 in pretreatment of coronary microvascular dysfunction.

  19. Heart Failure

    DEFF Research Database (Denmark)

    Jorsal, Anders; Wiggers, Henrik; McMurray, John J V

    2018-01-01

    This article briefly discusses the epidemiology of heart failure and diabetes and summarizes the key findings from the recent cardiovascular outcome trials in patients with type 2 diabetes, with a focus on heart failure as an endpoint.......This article briefly discusses the epidemiology of heart failure and diabetes and summarizes the key findings from the recent cardiovascular outcome trials in patients with type 2 diabetes, with a focus on heart failure as an endpoint....

  20. Gastrointestinal manifestations of mitochondrial disease.

    Science.gov (United States)

    Gillis, Lynette A; Sokol, Ronald J

    2003-09-01

    Although non-specific gastrointestinal and hepatic symptoms are commonly found in most mitochondrial disorders, they are among the cardinal manifestations of several primary mitochondrial diseases, such as: mitochondrial neurogastrointestinal encephalomyopathy; mitochondrial DNA depletion syndrome; Alpers syndrome; and Pearson syndrome. Management of these heterogeneous disorders includes the empiric supplementation with various "mitochondrial cocktails," supportive therapies, and avoidance of drugs and conditions known to have a detrimental effect on the respiratory chain. There is a great need for improved methods of treatment and controlled clinical trials of existing therapies. Liver transplantation is successful in acquired cases; however neuromuscular involvement in primary mitochondrial disorders should be a contraindication for liver transplantation.

  1. Heart attack

    Science.gov (United States)

    ... part in support groups for people with heart disease . Outlook (Prognosis) After a heart attack, you have a higher ... P, Bonow RO, Braunwald E, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, PA: Elsevier Saunders; 2014: ...

  2. Mitochondrial dysfunction in obesity.

    Science.gov (United States)

    de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

    2018-01-01

    Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The global antigenic diversity of swine influenza A viruses

    DEFF Research Database (Denmark)

    Lewis, Nicola S; Russell, Colin A; Langat, Pinky

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled...... with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential...

  4. Mitochondrial ROMK channel is a molecular component of mitoK(ATP).

    Science.gov (United States)

    Foster, D Brian; Ho, Alice S; Rucker, Jasma; Garlid, Anders O; Chen, Ling; Sidor, Agnieszka; Garlid, Keith D; O'Rourke, Brian

    2012-08-03

    Activation of the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) has been implicated in the mechanism of cardiac ischemic preconditioning, yet its molecular composition is unknown. To use an unbiased proteomic analysis of the mitochondrial inner membrane to identify the mitochondrial K(+) channel underlying mitoK(ATP). Mass spectrometric analysis was used to identify KCNJ1(ROMK) in purified bovine heart mitochondrial inner membrane and ROMK mRNA was confirmed to be present in neonatal rat ventricular myocytes and adult hearts. ROMK2, a short form of the channel, is shown to contain an N-terminal mitochondrial targeting signal, and a full-length epitope-tagged ROMK2 colocalizes with mitochondrial ATP synthase β. The high-affinity ROMK toxin, tertiapin Q, inhibits mitoK(ATP) activity in isolated mitochondria and in digitonin-permeabilized cells. Moreover, short hairpin RNA-mediated knockdown of ROMK inhibits the ATP-sensitive, diazoxide-activated component of mitochondrial thallium uptake. Finally, the heart-derived cell line, H9C2, is protected from cell death stimuli by stable ROMK2 overexpression, whereas knockdown of the native ROMK exacerbates cell death. The findings support ROMK as the pore-forming subunit of the cytoprotective mitoK(ATP) channel.

  5. Cancer: Mitochondrial Origins.

    Science.gov (United States)

    Stefano, George B; Kream, Richard M

    2015-12-01

    The primacy of glucose derived from photosynthesis as an existential source of chemical energy across plant and animal phyla is universally accepted as a core principle in the biological sciences. In mammalian cells, initial processing of glucose to triose phosphate intermediates takes place within the cytosolic glycolytic pathway and terminates with temporal transport of reducing equivalents derived from pyruvate metabolism by membrane-associated respiratory complexes in the mitochondrial matrix. The intra-mitochondrial availability of molecular oxygen as the ultimate electron acceptor drives the evolutionary fashioned chemiosmotic production of ATP as a high-efficiency biological process. The mechanistic bases of carcinogenesis have demonstrated profound alteration of normative mitochondrial function, notably dysregulated respiratory processes. Accordingly, the classic Warburg effect functionally links aerobic glycolysis, aberrant production and release of lactate, and metabolic down-regulation of mitochondrial oxidative processes with the carcinogenetic phenotype. We surmise, however, that aerobic fermentation by cancer cells may also represent a developmental re-emergence of an evolutionarily conserved early phenotype, which was "sidelined" with the emergence of mitochondrial oxidative phosphorylation as a primary mechanism for ATP production in normal cells. Regardless of state-dependent physiological status in mixed populations of cancer cells, it has been established that mitochondria are functionally linked to the initiation of cancer and its progression. Biochemical, molecular, and physiological differences in cancer cell mitochondria, notably mtDNA heteroplasmy and allele-specific expression of selected nuclear genes, may represent major focal points for novel targeting and elimination of cancer cells in metastatic disease afflicting human populations. To date, and despite considerable research efforts, the practical realization of advanced mitochondrial

  6. Genetic monitoring in contemporary swine production

    OpenAIRE

    Savić Mila S.; Jovanović Slobodan J.; Trailović Ružica D.; Dimitrijević Vladimir M.

    2002-01-01

    The development of molecular techniques for genome studies has led to qualitative progress in the selection of domestic animals by enabling the use of genetic markers, in addition to phenotypic selection parameters in choosing an animal. Genetic montoring has a wide application in contemporary swine production. Namely, genetic control is in the basis of all procedures pertaining to the selection of parent couples. Genetic monitoring is thus used in the genetic characterization of breeds, line...

  7. Analysis of DNA methylation in various swine tissues.

    Directory of Open Access Journals (Sweden)

    Chun Yang

    Full Text Available DNA methylation is known to play an important role in regulating gene expression during biological development and tissue differentiation in eukaryotes. In this study, we used the fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP method to assess the extent and pattern of cytosine methylation in muscle, heart, liver, spleen, lung, kidney and stomach from the swine strain Laiwu, and we also examined specific methylation patterns in the seven tissues. In total, 96,371 fragments, each representing a recognition site cleaved by either or both EcoRI + HpaII and EcoRI + MspI, the HpaII and MspI are isoschizomeric enzymes, were amplified using 16 pairs of selective primers. A total of 50,094 sites were found to be methylated at cytosines in seven tissues. The incidence of DNA methylation was approximately 53.99% in muscle, 51.24% in the heart, 50.18% in the liver, 53.31% in the spleen, 51.97% in the lung, 51.15% in the kidney and 53.39% in the stomach, as revealed by the incidence of differential digestion. Additionally, differences in DNA methylation levels imply that such variations may be related to specific gene expression during tissue differentiation, growth and development. Three types of bands were generated in the F-MSAP profile, the total numbers of these three types of bands in the seven tissues were 46,277, 24,801 and 25,293, respectively.In addition, different methylation patterns were observed in seven tissues from pig, and almost all of the methylation patterns detected by F-MSAP could be confirmed by Southern analysis using the isolated amplified fragments as probes. The results clearly demonstrated that the F-MSAP technique can be adapted for use in large-scale DNA methylation detection in the pig genome.

  8. Initial psychological responses to swine flu.

    Science.gov (United States)

    Goodwin, Robin; Gaines, Stanley O; Myers, Lynn; Neto, Felix

    2011-06-01

    The emergence of influenza A ("swine flu") in early 2009 led to widespread public concern. However, little research has examined the factors that underlie initial worry about infection and subsequent behavioral responses to such worry. This study seeks to model some key predictors of worry and behavioral responses in the early stages of the swine flu pandemic (WHO pandemic stage 5). A cross-sectional internet questionnaire study (N = 186). Twenty-five percent of respondents rated themselves as worried about being a victim of swine flu, 40% that they were worried of a family member contracting the virus. Twenty percent had bought, or intended to buy, preparatory materials (e.g., face masks), 20% intended to delay or cancel air travel. In a structural equation model, conservation values and family or friends perception of risks predicted worry about infection, while worry correlated with the purchase of preparatory materials, a lesser willingness to travel by public transport, and difficulty in focusing on everyday activities. While previous research on pandemic risk perception has focused on cognitive risk judgments, our data suggests that initial "emotional" concerns about infection are also significant predictors of behavioral responses to pandemic threat. Such worry is likely to be influenced by a variety of individual factors, such as personal values, as well as normative pressures. Practitioners can use and expand on such models of pandemic response when tailoring health campaigns to meet newly emergent threats.

  9. Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction.

    Science.gov (United States)

    Alvino, Valeria Vincenza; Fernández-Jiménez, Rodrigo; Rodriguez-Arabaolaza, Iker; Slater, Sadie; Mangialardi, Giuseppe; Avolio, Elisa; Spencer, Helen; Culliford, Lucy; Hassan, Sakinah; Sueiro Ballesteros, Lorena; Herman, Andrew; Ayaon-Albarrán, Ali; Galán-Arriola, Carlos; Sánchez-González, Javier; Hennessey, Helena; Delmege, Catherine; Ascione, Raimondo; Emanueli, Costanza; Angelini, Gianni Davide; Ibanez, Borja; Madeddu, Paolo

    2018-01-22

    Transplantation of adventitial pericytes (APCs) promotes cardiac repair in murine models of myocardial infarction. The aim of present study was to confirm the benefit of APC therapy in a large animal model. We performed a blind, randomized, placebo-controlled APC therapy trial in a swine model of reperfused myocardial infarction. A first study used human APCs (hAPCs) from patients undergoing coronary artery bypass graft surgery. A second study used allogeneic swine APCs (sAPCs). Primary end points were (1) ejection fraction as assessed by cardiac magnetic resonance imaging and (2) myocardial vascularization and fibrosis as determined by immunohistochemistry. Transplantation of hAPCs reduced fibrosis but failed to improve the other efficacy end points. Incompatibility of the xenogeneic model was suggested by the occurrence of a cytotoxic response following in vitro challenge of hAPCs with swine spleen lymphocytes and the failure to retrieve hAPCs in transplanted hearts. We next considered sAPCs as an alternative. Flow cytometry, immunocytochemistry, and functional/cytotoxic assays indicate that sAPCs are a surrogate of hAPCs. Transplantation of allogeneic sAPCs benefited capillary density and fibrosis but did not improve cardiac magnetic resonance imaging indices of contractility. Transplanted cells were detected in the border zone. Immunologic barriers limit the applicability of a xenogeneic swine model to assess hAPC efficacy. On the other hand, we newly show that transplantation of allogeneic sAPCs is feasible, safe, and immunologically acceptable. The approach induces proangiogenic and antifibrotic benefits, though these effects were not enough to result in functional improvements. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  10. Swine models for cardiovascular research: a low stress transport and restraint system for large swine.

    Science.gov (United States)

    Lighty, G W; Spear, R S; Karatay, M C; Hare, C L; Carlson, R J

    1992-04-01

    A restraint and transport system was developed for handling large swine during cardiovascular research studies. The major design criteria provided for comfortable, low stress restraint of the swine, safety for laboratory personnel and ability to perform a wide variety of hemodynamic and echocardiographic measurements in the standing, supported standing and sedated, or in Panepinto sling positions. A head gate is provided for venipuncture procedures, and an auxiliary feeding and watering front panel can replace the head gate for use of the system as a post-operative "recovery room". Using this system animals weighing 22 to 150 kg can be easily managed.

  11. Insulin Signaling and Heart Failure

    Science.gov (United States)

    Riehle, Christian; Abel, E. Dale

    2016-01-01

    Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

  12. Mitochondrial dysfunction in epilepsy

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava; Kunz, W.S.

    2012-01-01

    Roč. 12, č. 1 (2012), s. 35-40 ISSN 1567-7249 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR GA309/08/0292 Institutional research plan: CEZ:AV0Z50110509 Keywords : epilepsy * mitochondrial dysfunction * neurodegeneration Subject RIV: FH - Neurology Impact factor: 4.025, year: 2012

  13. Mitochondrial Dysfunction in Gliomas

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Anni, H.; Dráber, Pavel

    2013-01-01

    Roč. 20, č. 3 (2013), s. 216-227 ISSN 1071-9091 R&D Projects: GA MŠk LH12050 Institutional support: RVO:68378050 Keywords : gliomas * mitochondrial dysfunction * microtubule proteins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.883, year: 2013

  14. Telomeres and Telomerase in The Aging Heart

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2017-12-01

    Full Text Available BACKGROUND: Aging per se is a risk factor for reduced cardiac function and heart diseases, even when adjusted for aging-associated cardiovascular risk factors. Accordingly, aging-related biochemical and cell-biological changes lead to pathophysiological conditions, especially reduced heart function and heart disease. CONTENT: Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC-1a and PGC-1b in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging. SUMMARY: The aging myocardium with telomere shortening and accumulation of senescent cells restricts the tissue regenerative ability, which contributes to systolic or diastolic heart failure. Moreover, patients with ion-channel defects might have genetic imbalance caused by oxidative stress-related accelerated telomere shortening, which may subsequently cause sudden cardiac death. Telomere length can serve as a marker for the biological status of previous cell divisions and DNA damage with inflammation and oxidative stress. It can be integrated into current risk prediction and stratification models for cardiovascular diseases and can be used in precise personalized treatments. KEYWORDS: aging, telomere, telomerase, aging heart, mitochondria, cardiac stem cell

  15. Cardiomyocyte specific deletion of Crif1 causes mitochondrial cardiomyopathy in mice.

    Directory of Open Access Journals (Sweden)

    Juhee Shin

    Full Text Available Mitochondria are key organelles dedicated to energy production. Crif1, which interacts with the large subunit of the mitochondrial ribosome, is indispensable for the mitochondrial translation and membrane insertion of respiratory subunits. To explore the physiological function of Crif1 in the heart, Crif1(f/f mice were crossed with Myh6-cre/Esr1 transgenic mice, which harbor cardiomyocyte-specific Cre activity in a tamoxifen-dependent manner. The tamoxifen injections were given at six weeks postnatal, and the mutant mice survived only five months due to hypertrophic heart failure. In the mutant cardiac muscles, mitochondrial mass dramatically increased, while the inner structure was altered with lack of cristae. Mutant cardiac muscles showed decreased rates of oxygen consumption and ATP production, suggesting that Crif1 plays a critical role in the maintenance of both mitochondrial structure and respiration in cardiac muscles.

  16. The global antigenic diversity of swine influenza A viruses

    NARCIS (Netherlands)

    N.S. Lewis (Nicola); C.A. Russell (Colin); P. Langat (Pinky); T.K. Anderson (Tavis); K. Berger (Kathryn); F. Bielejec (Filip); D.F. Burke (David); G. Dudas (Gytis); J.M. Fonville (Judith); R.A.M. Fouchier (Ron); P. Kellam (Paul); B.F. Koel (Björn); P. Lemey (Philippe); T. Nguyen (Tung); B. Nuansrichy (Bundit); J.S. Malik Peiris; T. Saito (Takehiko); G. Simon (Gaelle); E. Skepner (Eugene); N. Takemae (Nobuhiro); R.J. Webby (Richard J.); K. van Reeth; S.M. Brookes (Sharon M.); L. Larsen (Lars); S.J. Watson (Simon J.); I.H. Brown (Ian); A.L. Vincent (Amy L.); S. Reid (Scott); M.A. Garcia (Montserrat Auero); T.C. Harder (Timm); E. Foni (Emanuela); I. Markowska-Daniel (Iwona)

    2016-01-01

    textabstractSwine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds

  17. Oxygen radical-scavenging capacities of peptides from swine blood

    African Journals Online (AJOL)

    USER

    2010-08-02

    Aug 2, 2010 ... In China, about five hundred million swine are slaughtered yearly, which represents about 45% of the world´s production. Swine blood is generally discarded except for the small amount that is used in soybean curd and other food products. This not only wastes resources, but also contaminates the.

  18. Molecular characterization of African swine fever virus in apparently ...

    African Journals Online (AJOL)

    African swine fever (ASF) is a highly lethal and economically significant disease of domestic pigs in Uganda where outbreaks regularly occur. There is neither a vaccine nor treatment available for ASF control. Twenty two African swine fever virus (ASFV) genotypes (I - XXII) have been identified based on partial sequencing ...

  19. Economic Analysis Of Private Sector Participation In Swine ...

    African Journals Online (AJOL)

    In this study, the analysis of the economics of private sector participation in swine production in Ibadan metropolis, Oyo State, was conducted. Data were collected from sixty private operators of swine farms, who were randomly selected from the study area between March and October, 2002. Descriptive statistics and ...

  20. Prevalence, predisposing factors and antibiogram of swine skin ...

    African Journals Online (AJOL)

    These drugs therefore remain effective for first-line postsurgical chemotherapy in the management of swine skin abscess except Chloramphenicol which is banned in food animal therapy. Running title: Prevalence, Predisposing Factors and Antibiogram of Swine Skin Abscess. Keywords: Abscess, Antibiogram, Ibadan, ...

  1. Removal of nitrogen from anaerobically digested swine wastewater ...

    African Journals Online (AJOL)

    This result indicates that the sulfur-packed biofilter would be used as an efficient option for denitrification by autotrophic denitrifiers during swine wastewater treatment. Key words: Biological nitrogen removal, nitrification, denitrification, chemical oxygen demand (COD), intermittent aeration, sulfur-packed bed reactor, swine ...

  2. The global antigenic diversity of swine influenza A viruses

    Science.gov (United States)

    Lewis, Nicola S; Russell, Colin A; Langat, Pinky; Anderson, Tavis K; Berger, Kathryn; Bielejec, Filip; Burke, David F; Dudas, Gytis; Fonville, Judith M; Fouchier, Ron AM; Kellam, Paul; Koel, Bjorn F; Lemey, Philippe; Nguyen, Tung; Nuansrichy, Bundit; Peiris, JS Malik; Saito, Takehiko; Simon, Gaelle; Skepner, Eugene; Takemae, Nobuhiro; Webby, Richard J; Van Reeth, Kristien; Brookes, Sharon M; Larsen, Lars; Watson, Simon J; Brown, Ian H; Vincent, Amy L

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds complexity to the risk profiles for the movement of swine and the potential for swine-derived infections in humans. DOI: http://dx.doi.org/10.7554/eLife.12217.001 PMID:27113719

  3. Population dynamics of swine influenza virus in finishing pigs

    NARCIS (Netherlands)

    Loeffen, W.L.A.

    2008-01-01

    Influenza virus infections in swine were first noticed in the US in 1918, during the human pandemic of the Spanish flu. In Europe, seroprevalences for the three most common swine influenza strains at the moment, H1N1, H3N2 and H1N2, range from 20-80% in finishing pigs at the end of the finishing

  4. 9 CFR 93.511 - Swine quarantine facilities.

    Science.gov (United States)

    2010-01-01

    ...) Privately operated quarantine facilities. The importer, or his or her agent, of swine subject to quarantine... of any import permit. The facilities occupied by swine should be kept clean and sanitary to the... described in paragraph (b) of this section. The importer, or his or her agent, shall request in writing such...

  5. Economic losses to Iberian swine production from forest fires

    Science.gov (United States)

    Juan Ramon Molina Martinez; Miguel Herrera Machuca; Ricardo Zamora Diaz; Fancisco Rodriguez y Silva; Armando Gonzalez-Caban

    2011-01-01

    Most forestry property in Andalusia is privately held. One of the most important possibilities for economic development of rural areas is the use of pasture lands (dehesa in Spanish). During the spring–summer season, swine grazing takes advantage of grasses between the trees, and during winter (harsher times), they use Quercus tree fruit. Swine production has a direct...

  6. Oxygen radical-scavenging capacities of peptides from swine blood ...

    African Journals Online (AJOL)

    In China, about five hundred million swine are slaughtered yearly, which represents about 45% of the world´s production. Swine blood is generally discarded except for the small amount that is used in soybean curd and other food products. This not only wastes resources, but also contaminates the environment. In this study ...

  7. Seroprevalence of hepatitis E in swine abattoir workers. | Ukuli ...

    African Journals Online (AJOL)

    Background: Hepatitis E (HE) caused by Hepatitis E virus (HEV) is an emerging global public health threat. It has been identified as potentially zoonotic and swine act as main reservoirs. Objectives: The objective of this study was to determine the seroprevalence and risk factors associated with HEV in swine abattoir workers ...

  8. Close Relationship of Ruminant Pestiviruses and Classical Swine Fever Virus

    Science.gov (United States)

    Postel, Alexander; Schmeiser, Stefanie; Oguzoglu, Tuba Cigdem; Indenbirken, Daniela; Alawi, Malik; Fischer, Nicole; Grundhoff, Adam

    2015-01-01

    To determine why serum from small ruminants infected with ruminant pestiviruses reacted positively to classical swine fever virus (CSFV)–specific diagnostic tests, we analyzed 2 pestiviruses from Turkey. They differed genetically and antigenically from known Pestivirus species and were closely related to CSFV. Cross-reactions would interfere with classical swine fever diagnosis in pigs. PMID:25811683

  9. Seroprevalence and risk factors for swine influenza zoonotic transmission in swine workers from northwestern Mexico.

    Science.gov (United States)

    López-Robles, G; Montalvo-Corral, M; Caire-Juvera, G; Ayora-Talavera, G; Hernández, J

    2012-04-01

    A cross-sectional study was conducted to evaluate the transmission of swine influenza through occupational exposure and to assess some risk factors for zoonotic transmission in workers from commercial farms in Mexico. Seroprevalence to swine influenza subtypes was determined by hemagglutinin inhibition assay and was higher in exposed (E), in comparison with unexposed (UE) participants (Pinfluenza virus (SIV) H3N2 and the exposition to swine [OR 3.05, 95% (CI) 1.65-5.64] and to geographic location [OR 8.15, 95% (CI) 1.41-47.05] was found. Vaccination appeared as a protective factor [OR 0.05, 95% (CI) 0.01-0.52]. Farms with high number of breeding herd were associated with increased anti-SIV antibodies in the E group [OR 3.98, 95% (CI) 1.00-15.86]. These findings are relevant and support the evidence of zoonoses in swine farms and point out the need to implement preventive measures to diminish the occurrence of the disease and the potential emergence of pathogenic reassortant strains. © 2011 Blackwell Verlag GmbH.

  10. Simulating the epidemiological and economic effects of an African swine fever epidemic in industrialized swine populations

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Bøtner, Anette; Mortensen, Sten

    2016-01-01

    African swine fever (ASF) is a notifiable infectious disease with a considerable impact on animal health and is currently one of the most important emerging diseases of domestic pigs. ASF was introduced into Georgia in 2007 and subsequently spread to the Russian Federation and several Eastern Eur...

  11. Insulin stimulates mitochondrial fusion and function in cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 signaling pathway.

    Science.gov (United States)

    Parra, Valentina; Verdejo, Hugo E; Iglewski, Myriam; Del Campo, Andrea; Troncoso, Rodrigo; Jones, Deborah; Zhu, Yi; Kuzmicic, Jovan; Pennanen, Christian; Lopez-Crisosto, Camila; Jaña, Fabián; Ferreira, Jorge; Noguera, Eduard; Chiong, Mario; Bernlohr, David A; Klip, Amira; Hill, Joseph A; Rothermel, Beverly A; Abel, Evan Dale; Zorzano, Antonio; Lavandero, Sergio

    2014-01-01

    Insulin regulates heart metabolism through the regulation of insulin-stimulated glucose uptake. Studies have indicated that insulin can also regulate mitochondrial function. Relevant to this idea, mitochondrial function is impaired in diabetic individuals. Furthermore, the expression of Opa-1 and mitofusins, proteins of the mitochondrial fusion machinery, is dramatically altered in obese and insulin-resistant patients. Given the role of insulin in the control of cardiac energetics, the goal of this study was to investigate whether insulin affects mitochondrial dynamics in cardiomyocytes. Confocal microscopy and the mitochondrial dye MitoTracker Green were used to obtain three-dimensional images of the mitochondrial network in cardiomyocytes and L6 skeletal muscle cells in culture. Three hours of insulin treatment increased Opa-1 protein levels, promoted mitochondrial fusion, increased mitochondrial membrane potential, and elevated both intracellular ATP levels and oxygen consumption in cardiomyocytes in vitro and in vivo. Consequently, the silencing of Opa-1 or Mfn2 prevented all the metabolic effects triggered by insulin. We also provide evidence indicating that insulin increases mitochondrial function in cardiomyocytes through the Akt-mTOR-NFκB signaling pathway. These data demonstrate for the first time in our knowledge that insulin acutely regulates mitochondrial metabolism in cardiomyocytes through a mechanism that depends on increased mitochondrial fusion, Opa-1, and the Akt-mTOR-NFκB pathway.

  12. Heart transplant

    Science.gov (United States)

    ... hospital for 7 to 21 days after a heart transplant. The first 24 to 48 hours will likely be in ... follow your self-care instructions. Biopsies of the heart muscle are ... after transplant, and then less often after that. This helps ...

  13. Mitochondrial disease and endocrine dysfunction.

    Science.gov (United States)

    Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

    2017-02-01

    Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.

  14. Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

    Science.gov (United States)

    He, J; Cooper, H M; Reyes, A; Di Re, M; Sembongi, H; Litwin, T R; Gao, J; Neuman, K C; Fearnley, I M; Spinazzola, A; Walker, J E; Holt, I J

    2012-07-01

    Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

  15. Quantitative approach for the risk assessment of African swine fever and Classical swine fever introduction into the United States through legal imports of pigs and swine products.

    Science.gov (United States)

    Herrera-Ibatá, Diana María; Martínez-López, Beatriz; Quijada, Darla; Burton, Kenneth; Mur, Lina

    2017-01-01

    The US livestock safety strongly depends on its capacity to prevent the introduction of Transboundary Animal Diseases (TADs). Therefore, accurate and updated information on the location and origin of those potential TADs risks is essential, so preventive measures as market restrictions can be put on place. The objective of the present study was to evaluate the current risk of African swine fever (ASF) and Classical swine fever (CSF) introduction into the US through the legal importations of live pigs and swine products using a quantitative approach that could be later applied to other risks. Four quantitative stochastic risk assessment models were developed to estimate the monthly probabilities of ASF and CSF release into the US, and the exposure of susceptible populations (domestic and feral swine) to these introductions at state level. The results suggest a low annual probability of either ASF or CSF introduction into the US, by any of the analyzed pathways (5.5*10-3). Being the probability of introduction through legal imports of live pigs (1.8*10-3 for ASF, and 2.5*10-3 for CSF) higher than the risk of legally imported swine products (8.90*10-4 for ASF, and 1.56*10-3 for CSF). This could be caused due to the low probability of exposure associated with this type of commodity (products). The risk of feral pigs accessing to swine products discarded in landfills was slightly higher than the potential exposure of domestic pigs through swill feeding. The identification of the months at highest risk, the origin of the higher risk imports, and the location of the US states most vulnerable to those introductions (Iowa, Minnesota and Wisconsin for live swine and California, Florida and Texas for swine products), is valuable information that would help to design prevention, risk-mitigation and early-detection strategies that would help to minimize the catastrophic consequences of potential ASF/CSF introductions into the US.

  16. Cancer: Mitochondrial Origins

    OpenAIRE

    Stefano, George B.; Kream, Richard M.

    2015-01-01

    The primacy of glucose derived from photosynthesis as an existential source of chemical energy across plant and animal phyla is universally accepted as a core principle in the biological sciences. In mammalian cells, initial processing of glucose to triose phosphate intermediates takes place within the cytosolic glycolytic pathway and terminates with temporal transport of reducing equivalents derived from pyruvate metabolism by membrane-associated respiratory complexes in the mitochondrial ma...

  17. Irreversible electroporation in a Swine lung model.

    Science.gov (United States)

    Dupuy, Damian E; Aswad, Bassam; Ng, Thomas

    2011-04-01

    This study was designed to evaluate the safety and tissue effects of IRE in a swine lung model. This study was approved by the institutional animal care committee. Nine anesthetized domestic swine underwent 15 percutaneous irreversible electroporation (IRE) lesion creations (6 with bipolar and 3 with 3-4 monopolar electrodes) under fluoroscopic guidance and with pancuronium neuromuscular blockade and EKG gating. IRE electrodes were placed into the central and middle third of the right mid and lower lobes in all animals. Postprocedure PA and lateral chest radiographs were obtained to evaluate for pneumothorax. Three animals were sacrificed at 2 weeks and six at 4 weeks. Animals underwent high-resolution CT scanning and PA and lateral radiographs 1 h before sacrifice. The treated lungs were removed en bloc, perfused with formalin, and sectioned. Gross pathologic and microscopic changes after standard hematoxylin and eosin staining were analyzed within the areas of IRE lesion creation. No significant adverse events were identified. CT showed focal areas of spiculated high density ranging in greatest diameter from 1.1-2.2 cm. On gross inspection of the sectioned lung, focal areas of tan discoloration and increased density were palpated in the areas of IRE. Histological analysis revealed focal areas of diffuse alveolar damage with fibrosis and inflammatory infiltration that respected the boundaries of the interlobular septae. No pathological difference could be discerned between the 2- and 4-week time points. The bronchioles and blood vessels within the areas of IRE were intact and did not show signs of tissue injury. IRE creates focal areas of diffuse alveolar damage without creating damage to the bronchioles or blood vessels. Short-term safety in a swine model appears to be satisfactory.

  18. Human Mitochondrial DNA Replication

    Science.gov (United States)

    Holt, Ian J.; Reyes, Aurelio

    2012-01-01

    Elucidation of the process of DNA replication in mitochondria is in its infancy. For many years, maintenance of the mitochondrial genome was regarded as greatly simplified compared to the nucleus. Mammalian mitochondria were reported to lack all DNA repair systems, to eschew DNA recombination, and to possess but a single DNA polymerase, polymerase γ. Polγ was said to replicate mitochondrial DNA exclusively via one mechanism, involving only two priming events and a handful of proteins. In this “strand-displacement model,” leading strand DNA synthesis begins at a specific site and advances approximately two-thirds of the way around the molecule before DNA synthesis is initiated on the “lagging” strand. Although the displaced strand was long-held to be coated with protein, RNA has more recently been proposed in its place. Furthermore, mitochondrial DNA molecules with all the features of products of conventional bidirectional replication have been documented, suggesting that the process and regulation of replication in mitochondria is complex, as befits a genome that is a core factor in human health and longevity. PMID:23143808

  19. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney

    2013-01-01

    Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

  20. Prevalence of coronavirus antibodies in Iowa swine.

    OpenAIRE

    Wesley, R D; Woods, R D; McKean, J D; Senn, M K; Elazhary, Y

    1997-01-01

    Three hundred and forty-seven serum samples from 22 Iowa swine herds were screened for TGEV/PRCV neutralizing antibody. Ninety-one percent of the sera and all 22 herds were positive. These sera were then tested by the blocking ELISA test to distinguish TGEV and PRCV antibody. The ELISA test confirmed the high percentage of TGEV/PRCV positive sera. By the blocking ELISA test, 12 herds were PRCV positive, 6 herds were TGEV positive and 4 herds were mixed with sera either positive for TGEV or PR...

  1. Mitochondrial functionality in female reproduction

    Directory of Open Access Journals (Sweden)

    Łukasz Gąsior

    2017-01-01

    Full Text Available In most animal species female germ cells are the source of mitochondrial genome for the whole body of individuals. As a source of mitochondrial DNA for future generations the mitochondria in the female germ line undergo dynamic quantitative and qualitative changes. In addition to maintaining the intact template of mitochondrial genome from one generation to another, mitochondrial role in oocytes is much more complex and pleiotropic. The quality of mitochondria determines the ability of meiotic divisions, fertilization ability, and activation after fertilization or sustaining development of a new embryo. The presence of normal number of functional mitochondria is also crucial for proper implantation and pregnancy maintaining. This article addresses issues of mitochondrial role and function in mammalian oocyte and presents new approaches in studies of mitochondrial function in female germ cells.

  2. Molecular basis for mitochondrial signaling

    CERN Document Server

    2017-01-01

    This book covers recent advances in the study of structure, function, and regulation of metabolite, protein and ion translocating channels, and transporters in mitochondria. A wide array of cutting-edge methods are covered, ranging from electrophysiology and cell biology to bioinformatics, as well as structural, systems, and computational biology. At last, the molecular identity of two important channels in the mitochondrial inner membrane, the mitochondrial calcium uniporter and the mitochondrial permeability transition pore have been established. After years of work on the physiology and structure of VDAC channels in the mitochondrial outer membrane, there have been multiple discoveries on VDAC permeation and regulation by cytosolic proteins. Recent breakthroughs in structural studies of the mitochondrial cholesterol translocator reveal a set of novel unexpected features and provide essential clues for defining therapeutic strategies. Molecular Basis for Mitochondrial Signaling covers these and many more re...

  3. Vacuum pyrolysis of swine manure : biochar production and characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Verma, M. [Inst. de recherche et de developpement en agroenvironnement Inc., Quebec City, PQ (Canada); Centre de recherche industrielle du Quebec, Quebec City, PQ (Canada); Godbout, S.; Larouche, J.P.; Lemay, S.P.; Pelletier, F. [Inst. de recherche et de developpement en agroenvironnement Inc., Quebec City, PQ (Canada); Solomatnikova, O. [Centre de recherche industrielle du Quebec, Quebec City, PQ (Canada); Brar, S.K. [Inst. national de la recherche scientifique, eau, terre et environnement, Quebec City, PQ (Canada)

    2010-07-01

    Quebec accounts for nearly 25 per cent of swine production in Canada. The issue of swine manure is addressed through land spreading and conversion into fertilizer. However, current regulations restrict the use of swine manure as fertilizer on most farmlands due to the problem of surplus phosphorus and nitrogen. Although many technologies exist to separate phosphorus and nitrogen from the organic-rich dry matter in swine manure, about 40 per cent of the treated waste matter must still be disposed in an environmentally sound manner. This study investigated the technical feasibility of pretreating the swine manure solids into biofuels on a farm-scale basis using vacuum pyrolysis process. A custom built stainless steel pressure vessel was used to carry out pyrolysis reaction of swine manure biomass at a temperature range between 200 to 600 degrees C under vacuum. The pyrolytic vapour was condensed in 2 glass condensers in series. The biochar was collected directly from the pyrolysis vessel following completion of the pyrolysis batch. The non condensable vapour and gases were considered as losses. Biochar, bio-oil, an aqueous phase and a gas mixture were the 4 products of the pyrolysis process. A thermogravimetric analysis of the swine manure samples was conducted before the pyrolysis tests. The study showed that 238 degrees C is the optimal pyrolysis temperature for biochar production.

  4. In-situ pyrogenic production of biodiesel from swine fat.

    Science.gov (United States)

    Lee, Jechan; Tsang, Yiu Fai; Jung, Jong-Min; Oh, Jeong-Ik; Kim, Hyung-Wook; Kwon, Eilhann E

    2016-11-01

    In-situ production of fatty acid methyl esters from swine fat via thermally induced pseudo-catalytic transesterification on silica was investigated in this study. Instead of methanol, dimethyl carbonate (DMC) was used as acyl acceptor to achieve environmental benefits and economic viability. Thermo-gravimetric analysis of swine fat reveals that swine fat contains 19.57wt.% of water and impurities. Moreover, the fatty acid profiles obtained under various conditions (extracted swine oil+methanol+NaOH, extracted swine oil+DMC+pseudo-catalytic, and swine fat+DMC+pseudo-catalytic) were compared. These profiles were identical, showing that the introduced in-situ transesterification is technically feasible. This also suggests that in-situ pseudo-catalytic transesterification has a high tolerance against impurities. This study also shows that FAME yield via in-situ pseudo-catalytic transesterification of swine fat reached up to 97.2% at 380°C. Therefore, in-situ pseudo-catalytic transesterification can be applicable to biodiesel production of other oil-bearing biomass feedstocks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Prevalence of swine viral and bacterial pathogens in rodents and stray cats captured around pig farms in Korea.

    Science.gov (United States)

    Truong, Quang Lam; Seo, Tae Won; Yoon, Byung-Il; Kim, Hyeon-Cheol; Han, Jeong Hee; Hahn, Tae-Wook

    2013-12-30

    In 2008, 102 rodents and 24 stray cats from the areas around 9 pig farms in northeast South Korea were used to determine the prevalence of the following selected swine pathogens: ten viral pathogens [porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), rotavirus, classical swine fever virus (CSFV), porcine circovirus type 2 (PCV2), encephalomyocarditis virus (EMCV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), pseudorabies virus (PRV) and Japanese encephalitis virus (JEV)] and four bacterial pathogens (Brucella, Leptospira, Salmonella and Lawsonia intracellularis). In total, 1,260 tissue samples from 102 rodents and 24 stray cats were examined by specific PCR and RT-PCR assays, including tissue samples of the brain, tonsils, lungs, heart, liver, kidneys, spleen, small intestine, large intestine and mesenteric lymph nodes. The percentages of PCR-positive rodents for the porcine pathogens were as follows: 63.7% for Leptospira, 39.2% for Brucella, 6.8% for Salmonella, 15.7% for L. intracellularis, 14.7% for PCV2 and 3.9% for EMCV. The percentages of PCR-positive stray cats for the swine pathogens were as follows: 62.5% for Leptospira, 25% for Brucella, 12.5% for Salmonella, 12.5% for L. intracellularis and 4.2% for PEDV. These results may be helpful for developing control measures to prevent the spread of infectious diseases of pigs.

  6. Mitochondrial Genetics and Cancer

    Directory of Open Access Journals (Sweden)

    Safarina G. Malik

    2017-02-01

    Full Text Available The first modern human, the Mitochondrial Eve, was traced back to Africa about 200,000 years ago, based on the variation in the mitochondrial DNA (mtDNA. An eruption of a super volcano, Mount Toba, in Sumatra 70,000 years ago may have led to a 'nuclear winter', followed by a 1,000-year ice age. This cold snap would have made life difficult; genetic evidence indicated a sharp reduction in population size around this time, reaching approximately 10,000 individuals. Once the climate started to improve, our ancestors recovered from this near-extinction event. The population expanded, and some courageous explorers ventured beyond Africa. Around 50,000 years ago some of these brave ancestors had successfully crossed the globe to South East Asia and Australia. Some of them settled in the Indonesian archipelago, forming the first settlement of prehistoric Indonesia. The second migration happened around 10,000 years ago, where a group of hunter-gatherers followed the now-submerged river systems that once ran from mainland Asia between the modern islands of Sumatera, Java, and Borneo. Then, around 4,000 years ago the third group of ancestors arrived. This agricultural community brought along their culture of pottery, plant cultivation, and animal domestication, co-inciding with the vast spread of Austronesian languages. Therefore, it is likely that the Indonesian archipelago hosts a wide range of linguistic, ethnic and genetic diversity.1 Nowadays, the modern Indonesia is home to around 700 ethnic populations, each with distinct cultural and linguistic characteristics, representing vast genome diversity. Our ancestors’ decision to embark on a sea travel and take on its related lifestyle has influenced the development of susceptibility and resistance to various diseases observed today. During the prolonged travel, our ancestors were subjected to changes in global climate and geographic dynamic, which strongly influenced and shaped the genetic background

  7. Influence of mycotoxin zearalenone on the swine reproductive failure

    Directory of Open Access Journals (Sweden)

    Prodanov-Radulović Jasna Z.

    2013-01-01

    Full Text Available Reproductive failure in swine is often a difficult diagnostic problem. If diagnoses of infectious disease or management related problems are not obtained, feed quality and safety may be questioned. Mycotoxins are often present in swine feed in the amount that can have detrimental impact on production and reproduction. Problems are expressed only as alterations of the reproductive cycle, reduced feed intake, slow growth or impaired feed efficiency. In Serbia, generally speaking, high concentrations of mycotoxins were noticed, especially mycotoxin zearalenone. High presence of zearalenone in swine feed is probably due to climatic influence and should be monitored constantly. This paper includes field observations regarding the influence of moldy feed containing mycotoxin zearalenone on the occurrence of the reproductive failure in swine breeding categories (sows, gilts and boars. The material for this research was obtained from four swine farms where certain reproductive disorders and health problems in breeding animals were detected. Depending on the specificity of each evaluated case and available material, the applied research methods included: anamnestic and clinical evaluation, pathomorphological examination, standard laboratory testing for detection of aerobic and anaerobic bacteria, and microbiological feed testing, in order to examine the presence of fungi and mycotoxins by applying the method of thin layer chromatography. On the basis of the obtained results, it could be concluded that mycotoxin zearalenone was detected in all examined feed samples. The presence of mycotoxin in feed was directly related to the reproductive failures in the examined swine categories (vulvovaginitis, endometritis, rebreeding, infertility. Swine reproduction represents the base for intensive swine production. The presence of mycotoxins in swine feed have influence on the reproduction and health status of pigs and under certain conditions may significantly

  8. Coronary hyperperfusion and myocardial metabolism in isolated and intact hearts

    International Nuclear Information System (INIS)

    Miller, W.P.; Shimamoto, N.; Nellis, S.H.; Liedtke, A.J.

    1987-01-01

    The authors determined the independent influence of coronary hyperperfusion on myocardial metabolism in isolated and intact hearts. In an isovolumic blood-perfused rat heart preparation working against a left ventricular (LV) balloon, the effect of increasing coronary perfusion pressure from 100 to 150 mmHg was assessed. They concluded that coronary hyperperfusion was not an independent stimulus to myocardial VO 2 . To further test this, the effect of coronary hyperperfusion on myocardial metabolism was studied in an intact working swine heart preparation where the cardiac output was fixed with a right heart bypass circuit. Fatty acid oxidation in the left anterior descending bed was assessed by production of 14 CO 2 from [ 14 C(U)]palmitate. They conclude that coronary hyperperfusion is not an independent determinant of myocardial oxidation or fatty acid utilization, and enhancement of mechanical function by the garden-hose effect appears to be dependent on the parameters of LV performance that are controlled

  9. Deletions of the mitochondrial genome.

    Science.gov (United States)

    Harding, A E; Hammans, S R

    1992-01-01

    Single large deletions of mitochondrial DNA are found in the muscle of about 40% of patients with mitochondrial myopathies, and are detectable in both blood and muscle in Pearson syndrome. In mitochondrial myopathies, there is a close association between the presence of deletions and involvement of extra-ocular muscles, together with other features of the Kearns-Sayre syndrome. Deletions appear to arise as fresh mutations in the vast majority of patients and are often flanked by direct repeats up to 13 nucleotides in length. They should affect translation of all mitochondrially encoded components of the respiratory chain, but there is evidence to suggest that intramitochondrial complementation occurs in some cases.

  10. Heart MRI

    Science.gov (United States)

    ... Heart defibrillator or pacemaker Inner ear (cochlear) implants Kidney disease or dialysis (you may not be able to receive contrast) Recently placed artificial joints Certain types of vascular stents Worked with ...

  11. Heart Attack

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    ... pain Fatigue Heart attack Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  12. Heart Block

    Science.gov (United States)

    ... graph show each step of an electrical signal's journey through the heart. EKG The image shows the ... and Usage No FEAR Act Grants and Funding Customer Service/Center for Health Information Email Alerts Jobs ...

  13. Heart Truth

    Science.gov (United States)

    ... the stories that unite us in a shared journey toward better heart health. Hear from our new ... and Usage No FEAR Act Grants and Funding Customer Service/Center for Health Information Email Alerts Jobs ...

  14. Input and leaching potential of copper, zinc, and selenium in agricultural soil from swine slurry.

    Science.gov (United States)

    Comas, Jordi; Domínguez, Carmen; Salas-Vázquez, Dora I; Parera, Juan; Díez, Sergi; Bayona, Josep M

    2014-02-01

    Trace elements, such as copper, zinc, and selenium, used as feed additives were determined in samples of both fresh (N = 14) and anaerobically digested (N = 6) swine slurry collected on medium- to large-size farms in northeast Spain. Considering both fresh and anaerobically digested samples, mean concentrations of zinc (1,500 mg kg(-1) dry mass [dm]) were greater than those of copper (mean 239 mg kg(-1 )dm), and the selenium concentrations detected were even lower (mean 139 μg kg(-1) dm). Zinc concentrations were significantly greater in anaerobically digested samples, whereas no significant differences were found for copper or selenium. In addition, the leaching potential of zinc, copper, and selenium in cropped (lettuce heart) and uncropped experimental units subject to drip irrigation was assessed in a greenhouse experiment. Generally, the addition of swine slurry to soil (1.7 g kg(-1) dm) significantly increased zinc, copper, and selenium concentrations in leachates, which decreased in accordance with the volume of leachate eluted. Under the experimental conditions, the leaching potential of zinc and selenium was more strongly correlated with bulk parameters directly associated with the composition of the pig slurry (dissolved organic carbon, electrical conductivity, and ammonium), whereas copper mobility was more strongly associated with the crop root exudates. Although selenium has been shown to be mobile in soil, the selenium content found in the leachates did not pose any appreciable risk according to current drinking water standards.

  15. Skin Lesions in Swine with Decompression Sickness: Clinical Appearance and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Long Qing

    2017-07-01

    Full Text Available Skin lesions are visual clinical manifestations of decompression sickness (DCS. Comprehensive knowledge of skin lesions would give simple but strong clinical evidence to help diagnose DCS. The aim of this study was to systematically depict skin lesions and explore their pathophysiological basis in a swine DCS model. Thirteen Bama swine underwent simulated diving in a hyperbaric animal chamber with the profile of 40 msw-35 min exposure, followed by decompression in 11 min. After decompression, chronological changes in the appearance of skin lesions, skin ultrasound, temperature, tissue nitric oxide (NO levels, and histopathology were studied. Meanwhile bubbles and central nervous system (CNS function were monitored. All animals developed skin lesions and two died abruptly possibly due to cardiopulmonary failure. A staging approach was developed to divide the appearance into six consecutive stages, which could help diagnosing the progress of skin lesions. Bubbles were only seen in right but not left heart chambers. There were strong correlations between bubble load, lesion area, latency to lesion appearance and existence of cutaneous lesions (P = 0.007, P = 0.002, P = 0.004, respectively. Even though local skin temperature did not change significantly, skin thickness increased, NO elevated and histological changes were observed. Increased vessel echo-reflectors in lesion areas were detected ultrasonically. No CNS dysfunction was detected by treadmill walking and evoked potential. The present results suggest skin lesions mainly result from local bubbles and not CNS injuries or arterial bubbles.

  16. Swine manure digestate treatment using electrocoagulation

    Directory of Open Access Journals (Sweden)

    Rúbia Mores

    Full Text Available ABSTRACT Anaerobic biodigestion is an appropriate alternative for the treatment of swine wastewater due to its biogas generation properties and the possibility of its application as a source of energy for heating or electricity. However, digestate can still contain high levels of turbidity, organic carbon and nutrients and must be correctly managed as a biofertilizer, or treated to avoid any impact on the environment. Considering this, electrocoagulation (EC shows promise as a technology because of its ease of handling and high efficiency in effluent remediation. This study aimed to evaluate the performance of EC in a batch system in the treatment of swine wastewater digestate. The wastewater used in the treatment was sampled from a 10 m3 biodigestor effluent (digestate located at Concórdia, Santa Catarina, Brazil. A batch-scale experiment was carried out to evaluate the following two variables: electrode distance (ED and voltage applied (V. The removal efficiency levels (% for the best operational condition (2 cm, 5 V after 30 min were: 97 %, 98 %, 77 % and 10 % for color, turbidity, total organic carbon (TOC and total nitrogen (TN, respectively. The EC batch system produced efficient results, underlining its promise as an alternative to be applied in the treatment of digestate.

  17. Technical pearls for swine lung transplantation.

    Science.gov (United States)

    Karimi, Ashkan; Cobb, Jessica A; Staples, Edward D; Baz, Maher A; Beaver, Thomas M

    2011-11-01

    Since the advent of ex vivo lung perfusion (EVLP), there has been increased focus on swine models of lung transplantation; however, the anatomic differences between human and swine lungs and the technical challenges in performing porcine lung transplantation are not well described in the surgical literature. Surgically important anatomic variations are described, and the technical measures taken to address them during harvest and transplantation are introduced. There are three surgically important anatomic variations in pigs. First, the right cranial lobe bronchus arises directly from the trachea, which makes right lung transplantation technically challenging if not prohibitive. Second, the left hemi-azygos vein is fully developed and courses upward through the posterior mediastinum, where it crosses the left pulmonary hilum and drains directly into the coronary sinus. During transplantation, this vein is ligated and dissected away to expose the underlying left pulmonary hilar structures. Third, the right inferior pulmonary vein crosses the midline to drain into the left atrium immediately adjacent to the left inferior pulmonary vein. During donor lung preparation, the right inferior pulmonary vein is ligated distally from the left atrium, which leaves an adequate atrial cuff around the left sided pulmonary veins for later anastomosis. Experimental porcine lung transplantation is technically demanding. We have found recognition of the above described anatomical differences and technical nuances facilitate transplantation and provide reproducible results. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Coagulation in Treatment of Swine Slaughterhouse Wastewater

    Directory of Open Access Journals (Sweden)

    Ha Bui Manh

    2017-03-01

    Full Text Available In this study, wastewater taken from the Nam Phong swine slaughterhouse, Ho Chi Minh City, was used to evaluate the treatment efficiency of common coagulants, including Alum (Aluminum Sulfate - Al2(SO43.18H2O, Poly-Aluminum Chloride (PAC, and Ferrous Sulfate (FeSO4.7H2O, using a jar-test system. The experiments were conducted using the one-factor-at-a-time method to examine three variables which are pH, stirring speed, and coagulant dosage. The results showed that both Alum and PAC perform over 90% removal of colour, turbidity, COD, and total phosphorus (TP from slaughterhouse wastewater at pH 7 with a stirring speed of 75 revolutions per minute (RPM and average coagulant dosages of 450 mg/L for Alum and 550 mg/L for PAC. Meanwhile, under the appropriate conditions of pH equal to 10 and 75 RPM with a chemical dosage of 350 mg/L, COD and TP removal efficiencies by Ferrous Sulfate exceed 87%, but those of turbidity and colour only reach 25%. This finding could be a promising coagulation method as a pre-treatment for the swine slaughterhouse wastewater.

  19. Classical Swine Fever—An Updated Review

    Science.gov (United States)

    Blome, Sandra; Staubach, Christoph; Henke, Julia; Carlson, Jolene; Beer, Martin

    2017-01-01

    Classical swine fever (CSF) remains one of the most important transboundary viral diseases of swine worldwide. The causative agent is CSF virus, a small, enveloped RNA virus of the genus Pestivirus. Based on partial sequences, three genotypes can be distinguished that do not, however, directly correlate with virulence. Depending on both virus and host factors, a wide range of clinical syndromes can be observed and thus, laboratory confirmation is mandatory. To this means, both direct and indirect methods are utilized with an increasing degree of commercialization. Both infections in domestic pigs and wild boar are of great relevance; and wild boars are a reservoir host transmitting the virus sporadically also to pig farms. Control strategies for epidemic outbreaks in free countries are mainly based on classical intervention measures; i.e., quarantine and strict culling of affected herds. In these countries, vaccination is only an emergency option. However, live vaccines are used for controlling the disease in endemically infected regions in Asia, Eastern Europe, the Americas, and some African countries. Here, we will provide a concise, updated review on virus properties, clinical signs and pathology, epidemiology, pathogenesis and immune responses, diagnosis and vaccination possibilities. PMID:28430168

  20. Classical Swine Fever-An Updated Review.

    Science.gov (United States)

    Blome, Sandra; Staubach, Christoph; Henke, Julia; Carlson, Jolene; Beer, Martin

    2017-04-21

    Classical swine fever (CSF) remains one of the most important transboundary viral diseases of swine worldwide. The causative agent is CSF virus, a small, enveloped RNA virus of the genus Pestivirus. Based on partial sequences, three genotypes can be distinguished that do not, however, directly correlate with virulence. Depending on both virus and host factors, a wide range of clinical syndromes can be observed and thus, laboratory confirmation is mandatory. To this means, both direct and indirect methods are utilized with an increasing degree of commercialization. Both infections in domestic pigs and wild boar are of great relevance; and wild boars are a reservoir host transmitting the virus sporadically also to pig farms. Control strategies for epidemic outbreaks in free countries are mainly based on classical intervention measures; i.e., quarantine and strict culling of affected herds. In these countries, vaccination is only an emergency option. However, live vaccines are used for controlling the disease in endemically infected regions in Asia, Eastern Europe, the Americas, and some African countries. Here, we will provide a concise, updated review on virus properties, clinical signs and pathology, epidemiology, pathogenesis and immune responses, diagnosis and vaccination possibilities.

  1. Binding characteristics of swine erythrocyte insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Dieberg, G.; Bryan, G.S.; Sartin, J.L.; Williams, J.C.; Prince, T.J.; Kemppainen, R.J.

    1985-09-01

    Crossbred gilts had 8.8 +/- 1.1% maximum binding of ( SVI)insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows had a significant increase in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet and a low-fiber diet did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine.

  2. About Heart Attacks

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More About Heart Attacks Updated:Jan 11,2018 A heart attack is ... coronary artery damage leads to a heart attack . Heart Attack Questions and Answers What is a heart attack? ...

  3. Types of Heart Failure

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Types of Heart Failure Updated:May 8,2017 Left-sided heart failure ... This content was last reviewed May 2017. Heart Failure • Home • About Heart Failure Introduction Types of Heart ...

  4. Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine.

    Science.gov (United States)

    Madariaga, M L L; Spencer, P J; Michel, S G; La Muraglia, G M; O'Neil, M J; Mannon, E C; Leblang, C; Rosales, I A; Colvin, R B; Sachs, D H; Allan, J S; Madsen, J C

    2016-03-01

    A 12-day course of high-dose tacrolimus induces tolerance of major histocompatibility complex-mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart-lung cotransplantation using the same induction protocol. Hearts (n = 3), heart-kidneys (n = 3), lungs (n = 6), and hearts-lungs (n = 3) were transplanted into fully major histocompatibility complex-mismatched recipients treated with high-dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart-kidney recipients and five of six lung recipients demonstrated long-term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor-specific unresponsiveness by cell-mediated lympholysis/mixed-lymphocyte reaction. In contrast, heart-lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. Mitochondrial polymerase gamma dysfunction and aging cause cardiac nuclear DNA methylation changes.

    Science.gov (United States)

    Koczor, Christopher A; Ludlow, Ivan; Fields, Earl; Jiao, Zhe; Ludaway, Tomika; Russ, Rodney; Lewis, William

    2016-04-01

    Cardiomyopathy (CM) is an intrinsic weakening of myocardium with contractile dysfunction and congestive heart failure (CHF). CHF has been postulated to result from decreased mitochondrial energy production and oxidative stress. Effects of decreased mitochondrial oxygen consumption also can accelerate with aging. We previously showed DNA methylation changes in human hearts with CM. This was associated with mitochondrial DNA depletion, being another molecular marker of CM. We examined the relationship between mitochondrial dysfunction and cardiac epigenetic DNA methylation changes in both young and old mice. We used genetically engineered C57Bl/6 mice transgenic for a cardiac-specific mutant of the mitochondrial polymerase-γ (termed Y955C). Y955C mice undergo left ventricular hypertrophy (LVH) at a young age (∼ 94 days old), and LVH decompensated to CHF at old age (∼ 255 days old). Results found 95 genes differentially expressed as a result of Y955C expression, while 4,452 genes were differentially expressed as a result of aging hearts. Moreover, cardiac DNA methylation patterns differed between Y955C (4,506 peaks with 68.5% hypomethylation) and aged hearts (73,286 peaks with 80.2% hypomethylated). Correlatively, of the 95 Y955C-dependent differentially expressed genes, 30 genes (31.6%) also displayed differential DNA methylation; in the 4,452 age-dependent differentially expressed genes, 342 genes (7.7%) displayed associated DNA methylation changes. Both Y955C and aging demonstrated significant enrichment of CACGTG-associated E-box motifs in differentially methylated regions. Cardiac mitochondrial polymerase dysfunction alters nuclear DNA methylation. Furthermore, aging causes a robust change in cardiac DNA methylation that is partially associated with mitochondrial polymerase dysfunction. Copyright © 2016 the American Physiological Society.

  6. Mitochondrial Dysfunction Contributes to Hypertensive Target Organ Damage: Lessons from an Animal Model of Human Disease

    Directory of Open Access Journals (Sweden)

    Speranza Rubattu

    2016-01-01

    Full Text Available Mechanisms underlying hypertensive target organ damage (TOD are not completely understood. The pathophysiological role of mitochondrial oxidative stress, resulting from mitochondrial dysfunction, in development of TOD is unclear. The stroke-prone spontaneously hypertensive rat (SHRSP is a suitable model of human hypertension and of its vascular consequences. Pathogenesis of TOD in SHRSP is multifactorial, being determined by high blood pressure levels, high salt/low potassium diet, and genetic factors. Accumulating evidence points to a key role of mitochondrial dysfunction in increased susceptibility to TOD development of SHRSP. Mitochondrial abnormalities were described in both heart and brain of SHRSP. Pharmacological compounds able to protect mitochondrial function exerted a significant protective effect on TOD development, independently of blood pressure levels. Through our research efforts, we discovered that two genes encoding mitochondrial proteins, one (Ndufc2 involved in OXPHOS complex I assembly and activity and the second one (UCP2 involved in clearance of mitochondrial ROS, are responsible, when dysregulated, for vascular damage in SHRSP. The suitability of SHRSP as a model of human disease represents a promising background for future translation of the experimental findings to human hypertension. Novel therapeutic strategies toward mitochondrial molecular targets may become a valuable tool for prevention and treatment of TOD in human hypertension.

  7. Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics.

    Science.gov (United States)

    Marzetti, Emanuele; Csiszar, Anna; Dutta, Debapriya; Balagopal, Gauthami; Calvani, Riccardo; Leeuwenburgh, Christiaan

    2013-08-15

    Advanced age is associated with a disproportionate prevalence of cardiovascular disease (CVD). Intrinsic alterations in the heart and the vasculature occurring over the life course render the cardiovascular system more vulnerable to various stressors in late life, ultimately favoring the development of CVD. Several lines of evidence indicate mitochondrial dysfunction as a major contributor to cardiovascular senescence. Besides being less bioenergetically efficient, damaged mitochondria also produce increased amounts of reactive oxygen species, with detrimental structural and functional consequences for the cardiovascular system. The age-related accumulation of dysfunctional mitochondrial likely results from the combination of impaired clearance of damaged organelles by autophagy and inadequate replenishment of the cellular mitochondrial pool by mitochondriogenesis. In this review, we summarize the current knowledge about relevant mechanisms and consequences of age-related mitochondrial decay and alterations in mitochondrial quality control in the cardiovascular system. The involvement of mitochondrial dysfunction in the pathogenesis of cardiovascular conditions especially prevalent in late life and the emerging connections with neurodegeneration are also illustrated. Special emphasis is placed on recent discoveries on the role played by alterations in mitochondrial dynamics (fusion and fission), mitophagy, and their interconnections in the context of age-related CVD and endothelial dysfunction. Finally, we discuss pharmacological interventions targeting mitochondrial dysfunction to delay cardiovascular aging and manage CVD.

  8. Impaired in vivo mitochondrial Krebs cycle activity after myocardial infarction assessed using hyperpolarized magnetic resonance spectroscopy.

    Science.gov (United States)

    Dodd, Michael S; Atherton, Helen J; Carr, Carolyn A; Stuckey, Daniel J; West, James A; Griffin, Julian L; Radda, George K; Clarke, Kieran; Heather, Lisa C; Tyler, Damian J

    2014-11-01

    Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Using hyperpolarized carbon-13 ((13)C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased (13)C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates. The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment. © 2014 American Heart Association, Inc.

  9. [Observation on the best dose of methylprednisolone improving lung injury in swine with paraquat intoxication].

    Science.gov (United States)

    Lan, Chao; Li, Haina; Li, Li; Wang, Jinzhu; Pei, Hui; Li, Lu; Liu, Lanping; Di, Min

    2015-01-01

    To observe the best dose of methylprednisolone improving lung injury in swine with paraquat intoxication. Acute lung injury (ALI/ARDS) model was made by an intraperitoneal injection of a large dose of 20%PQ solution20 millilitres in swine. Then 24 swine were randomly divided into 4 groups: exposed PQ control group, 5 mg/kg of methylprednisolone group, 15 mg/kg of methylprednisolone group, 30 mg/kg of methylprednisolone group. All groups were based on the conventional rehydration for intervention, Arterial blood samples were collected before modeling and 0, 12, 24, 36 hours after different processing for blood gas analysis. At the same time heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were measured by using PICCO (pulse indicator continuous cardiac output), lung tissue was obtained by punctureneedle to produce lung biopsy, then observe the pathological changes of lung tissue in the microscope. 1. Comparison between groups: there is no significant difference about extravascular lung water index (EVLWI) and semi-quantitative score of lung tissue pathology in four groups (P > 0.05) before modeling, so is t0, there is significant difference at about extravascular lung water index and semi-quantitative score of lung tissue pathology 12 h, 24 h and 36 h after different processing (P Lung tissue pathology in four groups significantly increased when the model was made (P Lung tissue pathology in exposed PQ control group kept going up, in other three groups, EVLWI and semi-quantitative score of lung tissue pathology went down first and then went up, there is significant difference compared with t0 (P 0.05) before modeling, so is t0, there is significant difference about oxygenation at 12 h, 24 h and 36 h after different processing (P Lung tissue pathology (r = 0.903, P = 0.034). Methylprednisolone can obviously relieve lung injury caused by paraquat poisoning and improve oxygenation

  10. Accurate quantification of mouse mitochondrial DNA without co-amplification of nuclear mitochondrial insertion sequences.

    Science.gov (United States)

    Malik, Afshan N; Czajka, Anna; Cunningham, Phil

    2016-07-01

    Mitochondria contain an extra-nuclear genome in the form of mitochondrial DNA (MtDNA), damage to which can lead to inflammation and bioenergetic deficit. Changes in MtDNA levels are increasingly used as a biomarker of mitochondrial dysfunction. We previously reported that in humans, fragments in the nuclear genome known as nuclear mitochondrial insertion sequences (NumtS) affect accurate quantification of MtDNA. In the current paper our aim was to determine whether mouse NumtS affect the quantification of MtDNA and to establish a method designed to avoid this. The existence of NumtS in the mouse genome was confirmed using blast N, unique MtDNA regions were identified using FASTA, and MtDNA primers which do not co-amplify NumtS were designed and tested. MtDNA copy numbers were determined in a range of mouse tissues as the ratio of the mitochondrial and nuclear genome using real time qPCR and absolute quantification. Approximately 95% of mouse MtDNA was duplicated in the nuclear genome as NumtS which were located in 15 out of 21 chromosomes. A unique region was identified and primers flanking this region were used. MtDNA levels differed significantly in mouse tissues being the highest in the heart, with levels in descending order (highest to lowest) in kidney, liver, blood, brain, islets and lung. The presence of NumtS in the nuclear genome of mouse could lead to erroneous data when studying MtDNA content or mutation. The unique primers described here will allow accurate quantification of MtDNA content in mouse models without co-amplification of NumtS. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  11. The mitochondrial genome in aging and senescence.

    Science.gov (United States)

    Lauri, Andrea; Pompilio, Giulio; Capogrossi, Maurizio C

    2014-11-01

    Aging is characterized by a progressive decline in organism functions due to the impairment of all organs. The deterioration of both proliferative tissues in liver, skin and the vascular system, as well as of largely post-mitotic organs, such as the heart and brain could be attributed at least in part to cell senescence. In this review we examine the role of mitochondrial dysfunction and mtDNA mutations in cell aging and senescence. Specifically, we address how p53 and telomerase reverse transcriptase (TERT) activity switch their roles from cytoprotective to detrimental and also examine the role of microRNAs in cell aging. The proposed role of Reactive Oxygen Species (ROS), both as mutating agents and as signalling molecules, underlying these processes is also described. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Inheritance of the yeast mitochondrial genome

    DEFF Research Database (Denmark)

    Piskur, Jure

    1994-01-01

    Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast......Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast...

  13. Regulation of host translational machinery by African swine fever virus.

    Directory of Open Access Journals (Sweden)

    Alfredo Castelló

    2009-08-01

    Full Text Available African swine fever virus (ASFV, like other complex DNA viruses, deploys a variety of strategies to evade the host's defence systems, such as inflammatory and immune responses and cell death. Here, we analyse the modifications in the translational machinery induced by ASFV. During ASFV infection, eIF4G and eIF4E are phosphorylated (Ser1108 and Ser209, respectively, whereas 4E-BP1 is hyperphosphorylated at early times post infection and hypophosphorylated after 18 h. Indeed, a potent increase in eIF4F assembly is observed in ASFV-infected cells, which is prevented by rapamycin treatment. Phosphorylation of eIF4E, eIF4GI and 4E-BP1 is important to enhance viral protein production, but is not essential for ASFV infection as observed in rapamycin- or CGP57380-treated cells. Nevertheless, eIF4F components are indispensable for ASFV protein synthesis and virus spread, since eIF4E or eIF4G depletion in COS-7 or Vero cells strongly prevents accumulation of viral proteins and decreases virus titre. In addition, eIF4F is not only activated but also redistributed within the viral factories at early times of infection, while eIF4G and eIF4E are surrounding these areas at late times. In fact, other components of translational machinery such as eIF2alpha, eIF3b, eIF4E, eEF2 and ribosomal P protein are enriched in areas surrounding ASFV factories. Notably, the mitochondrial network is polarized in ASFV-infected cells co-localizing with ribosomes. Thus, translation and ATP synthesis seem to be coupled and compartmentalized at the periphery of viral factories. At later times after ASFV infection, polyadenylated mRNAs disappear from the cytoplasm of Vero cells, except within the viral factories. The distribution of these pools of mRNAs is similar to the localization of viral late mRNAs. Therefore, degradation of cellular polyadenylated mRNAs and recruitment of the translation machinery to viral factories may contribute to the inhibition of host protein synthesis

  14. Genetic diversity of Escherichia coli isolated from commercial swine ...

    African Journals Online (AJOL)

    PCR) for the analysis of genetic diversity among Escherichia coli strains isolated from commercial swine farms in Sichuan province of China. Thirty four strains of E. coli were selected by selective medium and conventional biochemical test from ...

  15. Controlled Cortical Impact in Swine: Pathophysiology and Biomechanics

    National Research Council Canada - National Science Library

    Manley, Geoffrey T; Rosenthal, Guy; Lam, Maggie; Morabito, Diane; Yan, Donghong; Derugin, Nikita; Bollen, Andrew; Knudson, M. M; Panter, S. S

    2005-01-01

    ...), and cerebral perfusion pressure (CPP) were collected for 10 hours after injury. Following injury, ICP and HR increased above baseline values in all swine with a more pronounced elevation in animals impacted to a depth of depression of 12 mm...

  16. Highly diverse posaviruses in swine faeces are aquatic in origin.

    Science.gov (United States)

    Hause, Ben M; Palinski, Rachel; Hesse, Richard; Anderson, Gary

    2016-06-01

    Posaviruses are a group of highly divergent viruses identified in swine faeces that are distantly related to other members of the order Picornavirales. Eighteen posavirus genomes were assembled from 10 out of 25 (40 %) faecal-swab pools collected from healthy adult swine. Phylogenetic analysis of the conserved RNA-dependent RNA polymerase (Pol) domain found that posaviruses form a large, highly diverse, monophyletic clade, which includes similar viruses identified in human (husavirus) and fish (fisavirus) faeces or intestinal contents, respectively. Quantitative reverse transcription PCR analysis of water samples collected from commercial swine barns identified four out of 19 (21 %) samples were positive using a 5'-nuclease assay targeting the Pol region of posavirus 1. ICPD (immunoprecipitation coupled to PCR detection) assays to explore serological evidence of posavirus infection found only a single positive sample, suggesting posaviruses do not commonly infect swine, and together these results suggests a likely aquatic host.

  17. Biochemical diagnosis of mitochondrial disorders

    NARCIS (Netherlands)

    Rodenburg, R.J.T.

    2011-01-01

    Establishing a diagnosis in patients with a suspected mitochondrial disorder is often a challenge. Both knowledge of the clinical spectrum of mitochondrial disorders and the number of identified disease-causing molecular genetic defects are continuously expanding. The diagnostic examination of

  18. Muscle regeneration in mitochondrial myopathies

    DEFF Research Database (Denmark)

    Krag, T O; Hauerslev, S; Jeppesen, T D

    2013-01-01

    myopathies. We investigated regeneration in muscle biopsies from 61 genetically well-defined patients affected by mitochondrial myopathy. Our results show that the perturbed energy metabolism in mitochondrial myopathies causes ongoing muscle regeneration in a majority of patients, and some were even affected...

  19. Hippo pathway deficiency reverses systolic heart failure after infarction.

    Science.gov (United States)

    Leach, John P; Heallen, Todd; Zhang, Min; Rahmani, Mahdis; Morikawa, Yuka; Hill, Matthew C; Segura, Ana; Willerson, James T; Martin, James F

    2017-10-12

    Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in mortality. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls. Using translating ribosomal affinity purification, we isolate cardiomyocyte-specific translating messenger RNA. Hippo-deficient cardiomyocytes have increased expression of proliferative genes and stress response genes, such as the mitochondrial quality control gene, Park2. Genetic studies indicate that Park2 is essential for heart repair, suggesting a requirement for mitochondrial quality control in regenerating myocardium. Gene therapy with a virus encoding Salv short hairpin RNA improves heart function when delivered at the time of infarct or after ischaemic heart failure following myocardial infarction was established. Our findings indicate that the failing heart has a previously unrecognized reparative capacity involving more than cardiomyocyte renewal.

  20. Swine farm wastewater and mineral fertilization in corn cultivation

    OpenAIRE

    Pereira, Pâmela A. M.; Sampaio, Silvio C.; Reis, Ralpho R. dos; Rosa, Danielle M.; Correa, Marcus M.

    2016-01-01

    ABSTRACT In the long run, swine wastewater can provide benefits to the soil-plant relationship, when its use is planned and the potential environmental impacts are monitored. The objective of this study was to investigate the effects of continuous application of swine wastewater, associated with mineral fertilization, after six years of management in no-tillage and crop rotation (14 production cycles), on the chemical conditions of the soil and the corn crop. The doses of wastewater were 0, 1...

  1. Recent advances in canola meal utilization in swine nutrition

    OpenAIRE

    Mejicanos, G.; Sanjayan, N.; Kim, I. H.; Nyachoti, C. M.

    2016-01-01

    Abstract Canola meal is derived from the crushing of canola seed for oil extraction. Although it has been used in swine diets for a long time, its inclusion levels have been limited due to concerns regarding its nutritive value primarily arising from results of early studies showing negative effects of dietary canola meal inclusion in swine diets. Such effects were attributable to the presence of anti-nutritional factors (ANF; notably glucosinolates) in canola meal. However, due to advances i...

  2. Experimental infection of pregnant gilts with swine hepatitis E virus

    OpenAIRE

    Kasorndorkbua, Chaiyan; Thacker, Brad J.; Halbur, Patrick G.; Guenette, Denis K.; Buitenwerf, Ryan M.; Royer, Ryan L.; Meng, Xiang-Jin

    2003-01-01

    To determine the effect of swine hepatitis E virus (HEV) infection on pregnant gilts, their fetuses, and offspring, 12 gilts were intravenously inoculated with swine HEV. Six gilts, who were not inoculated, served as controls. All inoculated gilts became actively infected and shed HEV in feces, but vertical transmission was not detected in the fetuses. There was no evidence of clinical disease in the gilts or their offspring. Mild multifocal lymphohistiocytic hepatitis was observed in 4 of 12...

  3. A Laparoscopic Swine Model of Noncompressible Torso Hemorrhage

    Science.gov (United States)

    2014-01-01

    swine for uncontrolled hemor- rhage has been the open (midline) laparotomy facilitating organ injury (most commonly a liver crush or spleen incision...Maryland; and Academic Department Military Surgery and Trauma (J.J.M.), Royal Centre for Defence Medicine, Birmingham; and Academic Unit of Surgery ...reapproximated using staples. Surgery The swine that did not receive a splenectomy underwent laparoscopic port placement using a Hassan technique, which

  4. What every Hepatologist should Know about Swine Flu?

    OpenAIRE

    Kamran Bagheri Lankarani

    2009-01-01

    As world is witnessing ever fastest growing pandemic, physicians with various specialties should adopt themselves to the new situation (1). Global death toll of swine flu by November 15, 2009, has raised to 6750. Many of those who died or were hospitalized suffered from comorbid conditions which increased either the severity or the risk of acquiring the disease (2). Swine flu may change the course of many chronic diseases. Thus, all physicians in different disciplines should realize and consi...

  5. Endocrine disorders in mitochondrial disease.

    Science.gov (United States)

    Schaefer, Andrew M; Walker, Mark; Turnbull, Douglass M; Taylor, Robert W

    2013-10-15

    Endocrine dysfunction in mitochondrial disease is commonplace, but predominantly restricted to disease of the endocrine pancreas resulting in diabetes mellitus. Other endocrine manifestations occur, but are relatively rare by comparison. In mitochondrial disease, neuromuscular symptoms often dominate the clinical phenotype, but it is of paramount importance to appreciate the multi-system nature of the disease, of which endocrine dysfunction may be a part. The numerous phenotypes attributable to pathogenic mutations in both the mitochondrial (mtDNA) and nuclear DNA creates a complex and heterogeneous catalogue of disease which can be difficult to navigate for novices and experts alike. In this article we provide an overview of the endocrine disorders associated with mitochondrial disease, the way in which the underlying mitochondrial disorder influences the clinical presentation, and how these factors influence subsequent management. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  6. Animal Mitochondrial DNA Replication

    Science.gov (United States)

    Ciesielski, Grzegorz L.; Oliveira, Marcos T.; Kaguni, Laurie S.

    2016-01-01

    Recent advances in the field of mitochondrial DNA (mtDNA) replication highlight the diversity of both the mechanisms utilized and the structural and functional organization of the proteins at mtDNA replication fork, despite the simplicity of the animal mtDNA genome. DNA polymerase γ, mtDNA helicase and mitochondrial single-stranded DNA-binding protein- the key replisome proteins, have evolved distinct structural features and biochemical properties. These appear to be correlated with mtDNA genomic features in different metazoan taxa and with their modes of DNA replication, although a substantial integrative research is warranted to establish firmly these links. To date, several modes of mtDNA replication have been described for animals: rolling circle, theta, strand-displacement, and RITOLS/bootlace. Resolution of a continuing controversy relevant to mtDNA replication in mammals/vertebrates will have a direct impact on the mechanistic interpretation of mtDNA-related human diseases. Here we review these subjects, integrating earlier and recent data to provide a perspective on the major challenges for future research. PMID:27241933

  7. Dynamic distribution and tissue tropism of classical swine fever virus in experimentally infected pigs

    Science.gov (United States)

    2011-01-01

    Background Classical swine fever (CSF), caused by the Classical swine fever virus (CSFV), is an Office International des Epizooties (OIE) notifiable disease. However, we are far from fully understand the distribution, tissue tropism, pathogenesis, replication and excretion of CSFV in pigs. In this report, we investigated the dynamic distribution and tissue tropism of the virus in internal organs of the experimentally infected pigs using real-time RT-PCR and immunohistochemistry (IHC). Results A relative quantification real-time PCR was established and used to detect the virus load in internal organs of the experimentally infected pigs. The study revealed that the virus was detected in all 21 of the internal organs and blood collected from pigs at day 1 to day 8 post infections, and had an increasing virus load from day 1 to day 8 post infections. However, there was irregular distribution virus load in most internal organs over the first 2 days post infection. Blood, lymphoid tissue, pancreas and ileum usually contain the highest viral loads, while heart, duodenum and brain show relatively low viral loads. Conclusions All the data suggest that CSFV had an increasing virus load from day 1 to day 8 post infections in experimentally infected pigs detected by real-time RT-PCR, which was in consistent with the result of the IHC staining. The data also show that CSFV was likely to reproduce in blood, lymphoid tissue, pancreas and the ileum, while unlikely to replicate in the heart, duodenum and brain. The results provide a foundation for further clarification of the pathogenic mechanism of CSFV in internal organs, and indicate that blood, lymphoid tissue, pancreas and ileum may be preferred sites of acute infection. PMID:21535885

  8. Occurrence of tylosin in swine wastewater in Mexico.

    Science.gov (United States)

    García-Sánchez, Liliana; Garzón-Zúñiga, Marco Antonio; Buelna, Gerardo; Moeller-Chávez, Gabriela Eleonora; Noyola, Adalberto; Avilez-Flores, Martha; Estrada-Arriaga, Edson B

    2013-01-01

    This study determined a tylosin concentration in swine wastewater located in a Mexican pig farm, during different stages of the pigs' growth. The detection of antibiotics in swine wastewater is complex due to its high concentration of solids. Analytical method was developed for detection of tylosin in swine wastewater and swine slurry. Average recoveries of tylosin in the liquid and solid phase were greater than 51 and 44%, respectively, with a greater total recovery of 95%. The results indicated the presence of tylosin in swine wastewater and slurry at concentrations greater than the ones reported in the literature. In grab samples of swine wastewater, the tylosin detected showed concentrations of 56, 72 and 8.6 μg L(-1), in breeding-gestation, nursery pigs, and grow-finishing area, respectively. In composite samples, the concentration of tylosin was 11.8 μg L(-1) for the breeding-gestation area and 2.4 μg L(-1) for the grow-finishing area. For slurry, the concentration of tylosin was 20.6 and 17.8 μg L(-1), for the breeding-gestation and grow-finishing area, respectively. This study presents the detection of a high concentration of tylosin in breeding-gestation and nursery pigs. Traces of tylosin in wastewater from grow-finishing stage were found although the animals were not receiving antibiotics.

  9. 9 CFR 93.504 - Import permits for swine and for swine specimens for diagnostic purposes; and reservation fees...

    Science.gov (United States)

    2010-01-01

    ... the origin, history, and health status of the swine; the lack of satisfactory information necessary to..., National Center for Import-Export, 4700 River Road Unit 38, Riverdale, Maryland 20737-1231. (B) The...

  10. Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics

    Science.gov (United States)

    Tan, Dun-Xian; Manchester, Lucien C.; Qin, Lilan; Reiter, Russel J.

    2016-01-01

    Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant. It accumulates in mitochondria with high concentration against a concentration gradient. This is probably achieved by an active transportation via mitochondrial melatonin transporter(s). Melatonin protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting the mitochondrial permeability transition pore (MPTP), and activating uncoupling proteins (UCPs). Thus, melatonin maintains the optimal mitochondrial membrane potential and preserves mitochondrial functions. In addition, mitochondrial biogenesis and dynamics is also regulated by melatonin. In most cases, melatonin reduces mitochondrial fission and elevates their fusion. Mitochondrial dynamics exhibit an oscillatory pattern which matches the melatonin circadian secretory rhythm in pinealeocytes and probably in other cells. Recently, melatonin has been found to promote mitophagy and improve homeostasis of mitochondria. PMID:27999288

  11. Fungal survival in ensiled swine faeces.

    Science.gov (United States)

    Serrano-García, E; Castrejón-Pineda, F; Herradora-Lozano, M A; Ramírez-Pérez, A H; Angeles-Campos, S; Buntinx, S E

    2008-06-01

    The survival of several genera of fungi was determined in the ensiled solid fraction of swine faeces after 0, 7, 14, 28 and 56 days of ensiling. The experiment had two treatments, un-ensiled and ensiled manure, in a split-plot design. The manure was distributed into 50 containers; samples, taken at the specified times, were cultured in agar potato dextrose medium, incubated, and colony forming units (CFU/g) were counted and log-transformed. The ensiling process decreased the number of CFU after 56 days. Five fungal genera were identified (Absidia spp., Aspergillus spp., Penicillium spp., Rhizopus spp. and non-fructiferous fungi), and their vulnerability to the ensiling conditions varied, although most of them slowed their growth or disappeared after 14 days of ensiling.

  12. Heart failure - tests

    Science.gov (United States)

    CHF - tests; Congestive heart failure - tests; Cardiomyopathy - tests; HF - tests ... best test to: Identify which type of heart failure (systolic, diastolic, valvular) Monitor your heart failure and ...

  13. Effect of Aging on Mitochondrial Energetics in the Human Atria.

    Science.gov (United States)

    Emelyanova, Larisa; Preston, Claudia; Gupta, Anu; Viqar, Maria; Negmadjanov, Ulugbek; Edwards, Stacie; Kraft, Kelsey; Devana, Kameswari; Holmuhamedov, Ekhson; O'Hair, Daniel; Tajik, A Jamil; Jahangir, Arshad

    2017-08-19

    Energy production in myocardial cells occurs mainly in the mitochondrion. Although alterations in mitochondrial functions in the senescent heart have been documented, the molecular bases for the aging-associated decline in energy metabolism in the human heart are not fully understood. In this study, we examined transcription profiles of genes coding for mitochondrial proteins in atrial tissue from aged (≥65 years old) and comorbidities-matched adult (energetic pathways. These changes were associated with a significant decrease in respiratory capacity of mitochondria oxidizing glutamate and malate and functional activity of complex I activity that correlated with the downregulation of NDUFA6, NDUFA9, NDUFB5, NDUFB8, and NDUFS2 genes coding for NADH dehydrogenase subunits. Thus, aging is associated with a decline in activity of OXPHOS within the broader transcriptional downregulation of genes regulating mitochondrial energetics, providing a substrate for reduced energetic efficiency in the senescent human atria. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Three-Dimensional Structure of Bovine NADH : Ubiquinone Oxidoreductase of the Mitochondrial Respiratory Chain

    NARCIS (Netherlands)

    Boekema, Egbert J.; Heel, Marin G. van; Bruggen, Ernst F.J. van

    1984-01-01

    We have studied the structure of bovine heart mitochondrial NADH:ubiquinone (Q) oxidoreductase (EC 1.6.99.3) by image analysis of electron micrographs. A three-dimensional reconstruction was calculated from a tilt-series of a two-dimensional crystal of the molecule. Our interpretation of the

  15. Is There a Link between Mitochondrial Reserve Respiratory Capacity and Aging?

    DEFF Research Database (Denmark)

    Hansen, Thomas Lau; Rasmussen, Lene Juel; Madsen, Claus Desler

    2012-01-01

    , and as a result of mitochondrial dysfunctions, the efficiency of oxidative phosphorylation declines. Based on examples from the energy requiring tissues such as brain, heart, and skeletal muscle, we propose that the age-related decline of oxidative phosphorylation decreases the reserve respiratory capacity...

  16. Heart failure in children - overview

    Science.gov (United States)

    Congestive heart failure - children; Cor pulmonale - children; Cardiomyopathy - children; CHF - children; Congenital heart defect - heart failure in children; Cyanotic heart disease - heart failure in children; Birth ...

  17. Molecular Characterization of Swine Manure Lagoon Microbial and Antibiotic Resistant Populations

    Science.gov (United States)

    Background: The differences in swine manure lagoon effluent based on differing management styles or approaches such as different stages of swine rearing determines the presence of variable antibiotic resistance determinants and functional microbial populations. These concerns determine the suitabil...

  18. Heart Attack

    Science.gov (United States)

    ... Pressure, tightness, pain, or a squeezing or aching sensation in your chest or arms that may spread to your neck, jaw or back Nausea, indigestion, heartburn or abdominal pain Shortness of breath Cold sweat Fatigue Lightheadedness or sudden dizziness Heart attack ...

  19. Heart Transplant

    Science.gov (United States)

    ... may need to have a pacemaker. Rarely, the tricuspid valve can become damaged by the endomyocardial biopsy procedure; if that happens it will need to be repaired or replaced. Patients with congenital heart disease who have had a coarctation repair or problems ...

  20. Lophotrochozoan mitochondrial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Valles, Yvonne; Boore, Jeffrey L.

    2005-10-01

    Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animals across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.

  1. Nitric oxide and mitochondrial respiration.

    Science.gov (United States)

    Brown, G C

    1999-05-05

    Nitric oxide (NO) and its derivative peroxynitrite (ONOO-) inhibit mitochondrial respiration by distinct mechanisms. Low (nanomolar) concentrations of NO specifically inhibit cytochrome oxidase in competition with oxygen, and this inhibition is fully reversible when NO is removed. Higher concentrations of NO can inhibit the other respiratory chain complexes, probably by nitrosylating or oxidising protein thiols and removing iron from the iron-sulphur centres. Peroxynitrite causes irreversible inhibition of mitochondrial respiration and damage to a variety of mitochondrial components via oxidising reactions. Thus peroxynitrite inhibits or damages mitochondrial complexes I, II, IV and V, aconitase, creatine kinase, the mitochondrial membrane, mitochondrial DNA, superoxide dismutase, and induces mitochondrial swelling, depolarisation, calcium release and permeability transition. The NO inhibition of cytochrome oxidase may be involved in the physiological regulation of respiration rate, as indicated by the finding that isolated cells producing NO can regulate cellular respiration by this means, and the finding that inhibition of NO synthase in vivo causes a stimulation of tissue and whole body oxygen consumption. The recent finding that mitochondria may contain a NO synthase and can produce significant amounts of NO to regulate their own respiration also suggests this regulation may be important for physiological regulation of energy metabolism. However, definitive evidence that NO regulation of mitochondrial respiration occurs in vivo is still missing, and interpretation is complicated by the fact that NO appears to affect tissue respiration by cGMP-dependent mechanisms. The NO inhibition of cytochrome oxidase may also be involved in the cytotoxicity of NO, and may cause increased oxygen radical production by mitochondria, which may in turn lead to the generation of peroxynitrite. Mitochondrial damage by peroxynitrite may mediate the cytotoxicity of NO, and may be

  2. Mitochondrial DNA Unwinding Enzyme Required for Liver Regeneration | Center for Cancer Research

    Science.gov (United States)

    The liver has an exceptional capacity to proliferate. This ability allows the liver to regenerate its mass after partial surgical removal or injury and is the key to successful partial liver transplants. Liver cells, called hepatocytes, are packed with mitochondria, and regulating mitochondrial DNA (mtDNA) copy number is crucial to mitochondrial function, including energy production, during proliferation. Yves Pommier, M.D., Ph.D., of CCR’s Developmental Therapeutics Branch, and his colleagues recently showed that the vertebrate mitochondrial topoisomerase, Top1mt, was critical in maintaining mitochondrial function in the heart after doxorubicin-induced damage. The group wondered whether Top1mt might play a similar role in liver regeneration.

  3. Heart Health: The Heart Truth Campaign 2009

    Science.gov (United States)

    ... Issues Cover Story Heart Health The Heart Truth Campaign 2009 Past Issues / Winter 2009 Table of Contents ... the celebrities supporting this year's The Heart Truth campaign. Both R&B singer Ashanti (center) and Allison ...

  4. Effect of desferrioxamine on reperfusion damage of rat heart ...

    African Journals Online (AJOL)

    Ischaemia of the myocardium leads to necrosis unless oxygen supply is restored but it has only recently been realised that reperfusion is not without danger. The greatest rate of myocardial damage, as measured by mitochondrial function, occurred during the first 5 minutes of reperfusion in rat hearts subjected to ...

  5. ROS-mediated PARP activity undermines mitochondrial function after permeability transition pore opening during myocardial ischemia-reperfusion.

    Science.gov (United States)

    Schriewer, Jacqueline M; Peek, Clara Bien; Bass, Joseph; Schumacker, Paul T

    2013-04-18

    Ischemia-reperfusion (I/R) studies have implicated oxidant stress, the mitochondrial permeability transition pore (mPTP), and poly(ADP-ribose) polymerase (PARP) as contributing factors in myocardial cell death. However, the interdependence of these factors in the intact, blood-perfused heart is not known. We therefore wanted to determine whether oxidant stress, mPTP opening, and PARP activity contribute to the same death pathway after myocardial I/R. A murine left anterior descending coronary artery (LAD) occlusion (30 minutes) and release (1 to 4 hours) model was employed. Experimental groups included controls and antioxidant-treated, mPTP-inhibited, or PARP-inhibited hearts. Antioxidant treatment prevented oxidative damage, mPTP opening, ATP depletion, and PARP activity, placing oxidant stress as the proximal death trigger. Genetic deletion of cyclophilin D (CypD(-/-)) prevented loss of total NAD(+) and PARP activity, and mPTP-mediated loss of mitochondrial function. Control hearts showed progressive mitochondrial depolarization and loss of ATP from 1.5 to 4 hours of reperfusion, but not outer mitochondrial membrane rupture. Neither genetic deletion of PARP-1 nor its pharmacological inhibition prevented the initial mPTP-mediated depolarization or loss of ATP, but PARP ablation did allow mitochondrial recovery by 4 hours of reperfusion. These results indicate that oxidant stress, the mPTP, and PARP activity contribute to a single death pathway after I/R in the heart. PARP activation undermines cell survival by preventing mitochondrial recovery after mPTP opening early in reperfusion. This suggests that PARP-mediated prolongation of mitochondrial depolarization contributes significantly to cell death via an energetic crisis rather than by mitochondrial outer membrane rupture.

  6. Mitochondrial DNA and primary mitochondrial dysfunction in Parkinson's disease.

    Science.gov (United States)

    Giannoccaro, Maria Pia; La Morgia, Chiara; Rizzo, Giovanni; Carelli, Valerio

    2017-03-01

    In 1979, it was observed that parkinsonism could be induced by a toxin inhibiting mitochondrial respiratory complex I. This initiated the long-standing hypothesis that mitochondrial dysfunction may play a key role in the pathogenesis of Parkinson's disease (PD). This hypothesis evolved, with accumulating evidence pointing to complex I dysfunction, which could be caused by environmental or genetic factors. Attention was focused on the mitochondrial DNA, considering the occurrence of mutations, polymorphic haplogroup-specific variants, and defective mitochondrial DNA maintenance with the accumulation of multiple deletions and a reduction of copy number. Genetically determined diseases of mitochondrial DNA maintenance frequently manifest with parkinsonism, but the age-related accumulation of somatic mitochondrial DNA errors also represents a major driving mechanism for PD. Recently, the discovery of the genetic cause of rare inherited forms of PD highlighted an extremely complex homeostatic control over mitochondria, involving their dynamic fission/fusion cycle, the balancing of mitobiogenesis and mitophagy, and consequently the quality control surveillance that corrects faulty mitochondrial DNA maintenance. Many genes came into play, including the PINK1/parkin axis, but also OPA1, as pieces of the same puzzle, together with mitochondrial DNA damage, complex I deficiency and increased oxidative stress. The search for answers will drive future research to reach the understanding necessary to provide therapeutic options directed not only at limiting the clinical evolution of symptoms but also finally addressing the pathogenic mechanisms of neurodegeneration in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  7. Determinants of adults' intention to vaccinate against pandemic swine flu

    Directory of Open Access Journals (Sweden)

    Goodwin Robin

    2011-01-01

    Full Text Available Abstract Background Vaccination is one of the cornerstones of controlling an influenza pandemic. To optimise vaccination rates in the general population, ways of identifying determinants that influence decisions to have or not to have a vaccination need to be understood. Therefore, this study aimed to predict intention to have a swine influenza vaccination in an adult population in the UK. An extension of the Theory of Planned Behaviour provided the theoretical framework for the study. Methods Three hundred and sixty two adults from the UK, who were not in vaccination priority groups, completed either an online (n = 306 or pen and paper (n = 56 questionnaire. Data were collected from 30th October 2009, just after swine flu vaccination became available in the UK, and concluded on 31st December 2009. The main outcome of interest was future swine flu vaccination intentions. Results The extended Theory of Planned Behaviour predicted 60% of adults' intention to have a swine flu vaccination with attitude, subjective norm, perceived control, anticipating feelings of regret (the impact of missing a vaccination opportunity, intention to have a seasonal vaccine this year, one perceived barrier: "I cannot be bothered to get a swine flu vaccination" and two perceived benefits: "vaccination decreases my chance of getting swine flu or its complications" and "if I get vaccinated for swine flu, I will decrease the frequency of having to consult my doctor," being significant predictors of intention. Black British were less likely to intend to have a vaccination compared to Asian or White respondents. Conclusions Theoretical frameworks which identify determinants that influence decisions to have a pandemic influenza vaccination are useful. The implications of this research are discussed with a view to maximising any future pandemic influenza vaccination uptake using theoretically-driven applications.

  8. Mitochondrial dynamics in the adult cardiomyocytes: which roles for a highly specialized cell?

    Directory of Open Access Journals (Sweden)

    Jerome ePiquereau

    2013-05-01

    Full Text Available Mitochondrial dynamics is a recent topic of research in the field of cardiac physiology. The study of mechanisms involved in the morphological changes and in the motility of mitochondria is legitimate since the adult cardiomyocytes possess numerous mitochondria which occupy at least 30% of cell volume. However, architectural constraints exist in the cardiomyocyte that limit mitochondrial movements and communication between adjacent mitochondria. Still, the proteins involved in mitochondrial fusion and fission are highly expressed in these cells and could be involved in different processes important for the cardiac function. For example, they are required for mitochondrial biogenesis to synthesize new mitochondria and for the quality-control of the organelles. They are also involved in inner membrane organization and may play a role in apoptosis. More generally, change in mitochondrial morphology can have consequences in the functioning of the respiratory chain, in the regulation of the mitochondrial permeability transition pore (MPTP, and in the interactions with other organelles. Furthermore, the proteins involved in fusion and fission of mitochondria are altered in cardiac pathologies such as ischemia/reperfusion or heart failure, and appear to be valuable targets for pharmacological therapies. Thus, mitochondrial dynamics deserves particular attention in cardiac research. The present review draws up a report of our knowledge on these phenomena.

  9. Mitochondrial miRNA (MitomiR): a new player in cardiovascular health.

    Science.gov (United States)

    Srinivasan, Hemalatha; Das, Samarjit

    2015-10-01

    Cardiovascular disease is one of the major causes of human morbidity and mortality in the world. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and are known to be involved in the pathogenesis of heart diseases, but the translocation phenomenon and the mode of action in mitochondria are largely unknown. Recent mitochondrial proteome analysis unveiled at least 2000 proteins, of which only 13 are made by the mitochondrial genome. There are numerous studies demonstrating the translocation of proteins into the mitochondria and also translocation of ribosomal RNA (viz., 5S rRNA) into mitochondria. Recent studies have suggested that miRNAs contain sequence elements that affect their subcellular localization, particularly nuclear localization. If there are sequence elements that direct miRNAs to the nucleus, it is also possible that similar sequence elements exist to direct miRNAs to the mitochondria. In this review we have summarized most of the miRNAs that have been shown to play an important role in mitochondrial function, either by regulating mitochondrial genes or by regulating nuclear genes that are known to influence mitochondrial function. While the focus of this review is cardiovascular diseases, we also illustrate the role of mitochondrial miRNA (MitomiR) in the initiation and progression of various diseases, including cardiovascular diseases, metabolic diseases, and cancer. Our goal here is to summarize the miRNAs that are localized to the mitochondrial fraction of cells, and how these miRNAs modulate cardiovascular health.

  10. Heart attack first aid

    Science.gov (United States)

    First aid - heart attack; First aid - cardiopulmonary arrest; First aid - cardiac arrest ... A heart attack occurs when the blood flow that carries oxygen to the heart is blocked. The heart muscle becomes ...

  11. What Is Heart Surgery?

    Science.gov (United States)

    ... which could relieve angina. Heart Valve Repair or Replacement For the heart to work well, blood must ... have blood flowing through it. Heart-Lung Bypass Machine The image shows how a heart-lung bypass ...

  12. Getting a New Heart

    Science.gov (United States)

    ... a procedure that opens clogged arteries. Repair the heart valve . This procedure can often make your heart function ... heart muscle. Ventricular assist devices (VAD) . These are mechanical pumps that surgeons insert to help the heart ...

  13. Pediatric heart surgery

    Science.gov (United States)

    Heart surgery - pediatric; Heart surgery for children; Acquired heart disease; Heart valve surgery - children ... Ginther RM, Forbess JM. Pediatric cardiopulmonary bypass. In: ... Care . 5th ed. Philadelphia, PA: Elsevier; 2017:chap 37. LeRoy S, ...

  14. Coronary heart disease

    Science.gov (United States)

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... more calcium, the higher your chance for CHD. Exercise stress test . Heart CT scan . Nuclear stress test .

  15. 9 CFR 166.3 - Separation of swine from the garbage handling and treatment areas.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Separation of swine from the garbage... Provisions § 166.3 Separation of swine from the garbage handling and treatment areas. (a) Access by swine to garbage handling and treatment areas shall be prevented by construction of facilities to exclude all ages...

  16. Farming styles and cooperatives disputes of swine farmers under economic pressure in southern France

    NARCIS (Netherlands)

    Commandeur, M.A.M.

    2010-01-01

    In Southern France, the regression of swine farms and swine is ongoing. It involves reorientation of socio-professional networks, especially the farmers’ cooperatives. For understanding the various ways of maintaining swine production under the regressive circumstances, we focus on the farmers’

  17. Changes in the use of antimicrobials and the effects on productivity of swine farms in Denmark

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Jensen, Vibeke Frøkjær; Emborg, Hanne-Dorthe

    2010-01-01

    Objective-To evaluate changes in antimicrobial consumption and productivity by Danish swine farms during 1992 to 2008. Sample Population-All Danish swine farms for antimicrobial consumption data and a representative sample of Danish swine herds for productivity data. Procedures-Antimicrobial cons...

  18. Swine flu-have we learnt any lesson from the past ? | Yadav | Pan ...

    African Journals Online (AJOL)

    Abstract. The world has suffered the pandemics due to swine flu in the past. The present epidemic in India has claimed many lives. Even, after the first outbreak of swine flu in 2009 no concrete efforts are done to prevent this infection. There is an urgent need to take radical steps to prevent such epidemics. Key words: Swine ...

  19. 9 CFR 309.5 - Swine; disposal because of hog cholera.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Swine; disposal because of hog cholera... INSPECTION AND CERTIFICATION ANTE-MORTEM INSPECTION § 309.5 Swine; disposal because of hog cholera. (a) All swine found by an inspector to be affected with hog cholera shall be identified as U.S. Condemned and...

  20. MOLECULAR GENETICS OF THE SWINE MAJOR HISTOCOMPATIBILITY COMPLEX, THE SLA COMPLEX

    Science.gov (United States)

    The swine major histocompatibility complex (MHC) or swine leukocyte antigen (SLA) complex is one of the most gene-dense regions in the swine genome. It consists of three major gene clusters, the SLA class I, class III and class II regions, that span ~1.1, 0.7 and 0.5 Mb, respectively, making the swi...

  1. Garlic activates SIRT-3 to prevent cardiac oxidative stress and mitochondrial dysfunction in diabetes.

    Science.gov (United States)

    Sultana, Md Razia; Bagul, Pankaj K; Katare, Parameshwar B; Anwar Mohammed, Soheb; Padiya, Raju; Banerjee, Sanjay K

    2016-11-01

    Cardiac complications are major contributor in the mortality of diabetic people. Mitochondrial dysfunctioning is a crucial contributor for the cardiac complications in diabetes, and SIRT-3 remains the major mitochondrial deacetylase. We hypothesized whether garlic has any role on SIRT-3 to prevent mitochondrial dysfunction in diabetic heart. Rats with developed hyperglycemia after STZ injection were divided into two groups; diabetic (Dia) and diabetic+garlic (Dia+Garl). Garlic was administered at a dose of 250mg/kg/day, orally for four weeks. An additional group was maintained to evaluate the effect of raw garlic administration on control rat heart. We have observed altered functioning of cardiac mitochondrial enzymes involved in metabolic pathways, and increased levels of cardiac ROS with decreased activity of catalase and SOD in diabetic rats. Cardiac mRNA expression of TFAM, PGC-1α, and CO1 was also altered in diabetes. In addition, reduced levels of electron transport chain complexes that observed in Dia group were normalized with garlic administration. This indicates the presence of increased oxidative stress with mitochondrial dysfunctioning in diabetic heart. We have observed reduced activity of SIRT3 and increased acetylation of MnSOD. Silencing SIRT-3 in cells also revealed the same. However, administration of garlic improved the SIRT-3 and MnSOD activity, by deacetylating MnSOD. Increased SOD activity was correlated with reduced levels of ROS in garlic-administered rat hearts. Collectively, our results provide an insight into garlic's protection to T1DM heart through activation of SIRT3-MnSOD pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Pathological Significance of Mitochondrial Glycation

    Directory of Open Access Journals (Sweden)

    Pamela Boon Li Pun

    2012-01-01

    Full Text Available Glycation, the nonenzymatic glycosylation of biomolecules, is commonly observed in diabetes and ageing. Reactive dicarbonyl species such as methylglyoxal and glyoxal are thought to be major physiological precursors of glycation. Because these dicarbonyls tend to be formed intracellularly, the levels of advanced glycation end products on cellular proteins are higher than on extracellular ones. The formation of glycation adducts within cells can have severe functional consequences such as inhibition of protein activity and promotion of DNA mutations. Although several lines of evidence suggest that there are specific mitochondrial targets of glycation, and mitochondrial dysfunction itself has been implicated in disease and ageing, it is unclear if glycation of biomolecules specifically within mitochondria induces dysfunction and contributes to disease pathology. We discuss here the possibility that mitochondrial glycation contributes to disease, focussing on diabetes, ageing, cancer, and neurodegeneration, and highlight the current limitations in our understanding of the pathological significance of mitochondrial glycation.

  3. Control of plant mitochondrial respiration.

    NARCIS (Netherlands)

    Affourtit, C.; Krab, K.; Moore, A.L.

    2001-01-01

    Plant mitochondria are characterised by the presence of both phosphorylating (cytochrome) and non-phosphorylating (alternative) respiratory pathways, the relative activities of which directly affect the efficiency of mitochondrial energy conservation. Different approaches to study the regulation of

  4. Mitochondrial contribution to lipofuscin formation

    Directory of Open Access Journals (Sweden)

    Jeannette König

    2017-04-01

    Moreover, we observed that Lon protease downregulation is linked to a higher lipofuscinogenesis whereas the application of the mitochondrial-targeted antioxidant mitoTEMPO is able to prevent the accumulation of this protein aggregate.

  5. The role of mitochondrial superoxide anion (O2(-)) on physiological aging in C57BL/6J mice.

    Science.gov (United States)

    Miyazawa, Masaki; Ishii, Takamasa; Yasuda, Kayo; Noda, Setsuko; Onouchi, Hiromi; Hartman, Philip S; Ishii, Naoaki

    2009-01-01

    Much attention has been focused on the mitochondrial superoxide anion (O2(-)), which is also a critical free radial produced by ionizing radiation. The specific role of the mitochondrial O2(-) on physiological aging in mammals is still unclear despite wide-spread evidence that oxidative stress is involved in aging and age-related diseases. The major endogenous source of O2(-) is generated as a byproduct of energy metabolism from mitochondria. In order to better understand how O2(-)relates to metazoan aging, we have comprehensively examined age-related changes in the levels of oxidative damage, mitochondrial O2(-) production, mitochondrial antioxidant enzyme activity and apoptosis induction in key organs of an inbred mouse strain (C57BL/6J). Oxidative damage accumulated and excess apoptosis occurred in the brain, oculus and kidney with aging, but comparatively little occurred in the heart and muscle. These rates are correlated with O2(-) levels. Mitochondrial O2(-) production levels increased with aging in the brain, oculus and kidney, and did not significantly increased in the heart and muscle. In contrast to O2(-) production, mitochondrial SOD activities increased in heart and muscle, and remained unchanged in the brain, oculus and kidney with aging. These results suggest that O2(-) production has high organ specificity, and oxidative damage by O2(-) from mitochondria mediated apoptosis can lead to organ atrophy and physiological dysfunction. In addition, O2(-) from mitochondria plays a core role in physiological aging.

  6. The role of mitochondrial superoxide anion (O2-) on physiological aging in C57BL/6J mice

    International Nuclear Information System (INIS)

    Miyazawa, Masaki; Ishii, Takamasa; Yasuda, Kayo; Onouchi, Hiromi; Ishii, Naoaki; Noda, Setsuko; Hartman, Philip S.

    2009-01-01

    Much attention has been focused on the mitochondrial superoxide anion (O 2 - ), which is also a critical free radical produced by ionizing radiation. The specific role of the mitochondrial O 2 - on physiological aging in mammals is still nuclear despite wide-spread evidence that oxidative stress is involved in aging and age-related diseases. The major endogenous source of O 2 - is generated as a byproduct of energy metabolism from mitochondria. In order to better understand how O 2 - relates to metazoan aging, we have comprehensively examined age-related changes in the levels of oxidative damage, mitochondrial O 2 - production, mitochondrial antioxidant enzyme activity and apoptosis induction in key organs of an inbred mouse strain (C57BL/6J). Oxidative damage accumulated and excess apoptosis occurred in the brain, oculus and kidney with aging, but comparatively little occurred in the heart and muscle. These rates are correlated with O 2 - levels. Mitochondrial O 2 - production levels increased with aging in the brain, oculus and kidney, and did not significantly increased in the heart and muscle. In contrast to O 2 - production, mitochondrial SOD activities increased in heart and muscle, and remained unchanged in the brain, oculus and kidney with aging. These results suggest that O 2 - production has high organ specificity, and oxidative damage by O 2 - from mitochondria mediated apoptosis can lead to organ atrophy and physiological dysfunction. In addition, O 2 - from mitochondria plays a core role in physiological aging. (author)

  7. Mitochondrial dysfunction and organophosphorus compounds

    International Nuclear Information System (INIS)

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2013-01-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP

  8. Mitochondrial dysfunction and organophosphorus compounds

    Energy Technology Data Exchange (ETDEWEB)

    Karami-Mohajeri, Somayyeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Kerman University of Medical Sciences, Kerman (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2013-07-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

  9. Mitochondrial PKA mediates sperm motility.

    Science.gov (United States)

    Mizrahi, Rashel; Breitbart, Haim

    2014-12-01

    Mitochondria are the major source of ATP to power sperm motility. Phosphorylation of mitochondrial proteins has been proposed as a major regulatory mechanism for mitochondrial bioenergetics. Sperm motility was measured by a computer-assisted analyzer, protein detection by western blotting, membrane potential by tetramethylrhodamine, cellular ATP by luciferase assay and localization of PKA by immuno-electron microscopy. Bicarbonate is essential for the creation of mitochondrial electro-chemical gradient, ATP synthesis and sperm motility. Bicarbonate stimulates PKA-dependent phosphorylation of two 60kDa proteins identified as Tektin and glucose-6-phosphate isomerase. This phosphorylation was inhibited by respiration inhibition and phosphorylation could be restored by glucose in the presence of bicarbonate. However, this effect of glucose cannot be seen when the mitochondrial ATP/ADP exchanger was inhibited indicating that glycolytic-produced ATP is transported into the mitochondria and allows PKA-dependent protein phosphorylation inside the mitochondria. Bicarbonate activates mitochondrial soluble adenylyl cyclase (sAC) which catalyzes cAMP production leading to the activation of mitochondrial PKA. Glucose can overcome the lack of ATP in the absence of bicarbonate but it cannot affect the mitochondrial sAC/PKA system, therefore the PKA-dependent phosphorylation of the 60kDa proteins does not occur in the absence of bicarbonate. Production of CO2 in Krebs cycle, which is converted to bicarbonate is essential for sAC/PKA activation leading to mitochondrial membrane potential creation and ATP synthesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Mitochondrial and cellular mechanisms for managing lipid excess

    Directory of Open Access Journals (Sweden)

    Miguel A Aon

    2014-07-01

    Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

  11. The novel in vitro reanimation of isolated human and large mammalian heart-lung blocs.

    Science.gov (United States)

    Goff, Ryan P; Howard, Brian T; Quallich, Stephen G; Iles, Tinen L; Iaizzo, Paul A

    2016-06-04

    In vitro isolated heart preparations are valuable tools for the study of cardiac anatomy and physiology, as well as for preclinical device testing. Such preparations afford investigators a high level of hemodynamic control, independent of host or systemic interactions. Here we hypothesize that recovered human and swine heart-lung blocs can be reanimated using a clear perfusate and elicit viable cardiodynamic and pulmonic function. Further, this approach will facilitate multimodal imaging, which is particularly valuable for the study of both functional anatomy and device-tissue interactions. Five human and 18 swine heart-lung preparations were procured using techniques analogous to those for cardiac transplant. Specimens were then rewarmed and reperfused using modifications of a closed circuit, isolated, beating and ventilated heart-lung preparation. Positive pressure mechanical ventilation was also employed, and epicardial defibrillation was applied to elicit native cardiac sinus rhythm. Videoscopy, fluoroscopy, ultrasound, and infrared imaging were performed for anatomical and experimental study. Systolic and diastolic left ventricular pressures observed for human and swine specimens were 68/2 ± 11/7 and 74/3 ± 17/5 mmHg, respectively, with associated native heart rates of 80 ± 7 and 96 ± 16 beats per minute. High-resolution imaging within functioning human pulmonary vasculature was obtained among other anatomies of interest. Note that one human specimen elicited poor cardiac performance post defibrillation. We report the first dynamic videoscopic images of the pulmonary vasculature during viable cardiopulmonary function in isolated reanimated heart-lung blocs. This experimental approach provides unique in vitro opportunities for the study of novel medical therapeutics applied to large mammalian, including human, heart-lung specimens.

  12. Effect of body size on organ-specific mitochondrial respiration rate of the largemouth bronze gudgeon.

    Science.gov (United States)

    Luo, Yiping; Wang, Wen; Zhang, Yurong; Huang, Qingda

    2013-06-01

    The effects of body size on the mitochondrial respiration rate were assessed in the heart, brain, gill, liver, and red muscle of largemouth bronze gudgeon, Coreius guichenoti, from the Yangtze River. Body mass had a significant influence on the state 3 oxygen consumption rate of the mitochondria from the heart, gill, and red muscle. The relationships between body mass (M, g) and state 3 oxygen consumption rate (V(state 3), nmol O min(-1) mg(-1)) of the mitochondria were represented by the following: V(state 3) = 3.56M(0.71) for heart, V(state 3) = 4.64M(0.50) for red muscle, and V(state 3) = 473.73M(-0.82) for gill. There was a significant difference in V(state 3), V(state 4), and respiratory control ratio among organs and all were highest in the heart. Our results suggest that the relationship between mitochondrial respiratory rate and body size varies among organs. The high mitochondrial respiratory rate in the heart of the largemouth gudgeon suggests that it has the highest oxidative capacity.

  13. Melatonin and human mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    Reza Sharafati-Chaleshtori

    2017-01-01

    Full Text Available Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function.

  14. CFTR activity and mitochondrial function

    Directory of Open Access Journals (Sweden)

    Angel Gabriel Valdivieso

    2013-01-01

    Full Text Available Cystic Fibrosis (CF is a frequent and lethal autosomal recessive disease, caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR. Before the discovery of the CFTR gene, several hypotheses attempted to explain the etiology of this disease, including the possible role of a chloride channel, diverse alterations in mitochondrial functions, the overexpression of the lysosomal enzyme α-glucosidase and a deficiency in the cytosolic enzyme glucose 6-phosphate dehydrogenase. Because of the diverse mitochondrial changes found, some authors proposed that the affected gene should codify for a mitochondrial protein. Later, the CFTR cloning and the demonstration of its chloride channel activity turned the mitochondrial, lysosomal and cytosolic hypotheses obsolete. However, in recent years, using new approaches, several investigators reported similar or new alterations of mitochondrial functions in Cystic Fibrosis, thus rediscovering a possible role of mitochondria in this disease. Here, we review these CFTR-driven mitochondrial defects, including differential gene expression, alterations in oxidative phosphorylation, calcium homeostasis, oxidative stress, apoptosis and innate immune response, which might explain some characteristics of the complex CF phenotype and reveals potential new targets for therapy.

  15. Influenza A Viruses of Human Origin in Swine, Brazil

    Science.gov (United States)

    Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-01-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759

  16. Swine farm wastewater and mineral fertilization in corn cultivation

    Directory of Open Access Journals (Sweden)

    Pâmela A. M. Pereira

    2016-01-01

    Full Text Available ABSTRACT In the long run, swine wastewater can provide benefits to the soil-plant relationship, when its use is planned and the potential environmental impacts are monitored. The objective of this study was to investigate the effects of continuous application of swine wastewater, associated with mineral fertilization, after six years of management in no-tillage and crop rotation (14 production cycles, on the chemical conditions of the soil and the corn crop. The doses of wastewater were 0, 100, 200, 300 m3 ha-1 during the cycle. The effects of the association between mineral fertilization at sowing and swine wastewater were evaluated simultaneously. Swine wastewater at the dose of 100 m3 ha-1 promoted availability and absorption of P, K+, Mg2+ and Zn2+ without causing toxicity to plants or damage to the soil, constituting a viable, low-cost alternative of water reuse and fertilization for farmers. The nutrients N, P, K+ and B must be complemented with mineral fertilization. Special attention should be directed to the accumulation of Zn2+ in the soil along the time of swine wastewater application.

  17. Molecular diagnostics of swine infection caused by Mycoplasma suis

    Directory of Open Access Journals (Sweden)

    Potkonjak Aleksandar

    2009-01-01

    Full Text Available The presence of two types of haemoplasm can be established in the swine population. Pathogenic haemoplasm, named Mycoplasma suis (previously called Eperythrozoon suis is the cause of swine eperythrozoonosis or swine ichtheroanaemia. The cause of this disease can also infect humans. The disease has spread all over the world. The most frequent form is latent infection of swine caused by M. suis. The disease is clinically manifest following action by the stress factor. The acute course of the disease is characterized by the occurrence of a febrile condition and ichtheroanaemia. The disease is usually diagnosed based on an epizootiological poll, a clinical examination, and a microscopic examination of a blood smear stained most often according to Giemsa. Contemporary methods of molecular biology have been developed, such as PCR, which are more sensitive and specific in making a diagnosis of swine infection caused by M. suis. In these investigations, the presence of M. suis on pig farms in the Republic of Serbia has been determined using the PCR test. .

  18. Mitofusin 2-containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca(2+) crosstalk.

    Science.gov (United States)

    Chen, Yun; Csordás, György; Jowdy, Casey; Schneider, Timothy G; Csordás, Norbert; Wang, Wei; Liu, Yingqiu; Kohlhaas, Michael; Meiser, Maxie; Bergem, Stefanie; Nerbonne, Jeanne M; Dorn, Gerald W; Maack, Christoph

    2012-09-14

    Mitochondrial Ca(2+) uptake is essential for the bioenergetic feedback response through stimulation of Krebs cycle dehydrogenases. Close association of mitochondria to the sarcoplasmic reticulum (SR) may explain efficient mitochondrial Ca(2+) uptake despite low Ca(2+) affinity of the mitochondrial Ca(2+) uniporter. However, the existence of such mitochondrial Ca(2+) microdomains and their functional role are presently unresolved. Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer membrane fusion, whereas Mfn2 but not Mfn1 tethers endoplasmic reticulum to mitochondria in noncardiac cells. To elucidate roles for Mfn1 and 2 in SR-mitochondrial tethering, Ca(2+) signaling, and bioenergetic regulation in cardiac myocytes. Fruit fly heart tubes deficient of the Drosophila Mfn ortholog MARF had increased contraction-associated and caffeine-sensitive Ca(2+) release, suggesting a role for Mfn in SR Ca(2+) handling. Whereas cardiac-specific Mfn1 ablation had no effects on murine heart function or Ca(2+) cycling, Mfn2 deficiency decreased cardiomyocyte SR-mitochondrial contact length by 30% and reduced the content of SR-associated proteins in mitochondria-associated membranes. This was associated with decreased mitochondrial Ca(2+) uptake (despite unchanged mitochondrial membrane potential) but increased steady-state and caffeine-induced SR Ca(2+) release. Accordingly, Ca(2+)-induced stimulation of Krebs cycle dehydrogenases during β-adrenergic stimulation was hampered in Mfn2-KO but not Mfn1-KO myocytes, evidenced by oxidation of the redox states of NAD(P)H/NAD(P)(+) and FADH(2)/FAD. Physical tethering of SR and mitochondria via Mfn2 is essential for normal interorganelle Ca(2+) signaling in the myocardium, consistent with a requirement for SR-mitochondrial Ca(2+) signaling through microdomains in the cardiomyocyte bioenergetic feedback response to physiological stress.

  19. Mitofusin 2-containing Mitochondrial-Reticular Microdomains Direct Rapid Cardiomyocyte Bioenergetic Responses via Inter-Organelle Ca2+ Crosstalk

    Science.gov (United States)

    Chen, Yun; Csordás, György; Jowdy, Casey; Schneider, Timothy G.; Csordás, Norbert; Wang, Wei; Liu, Yingqiu; Kohlhaas, Michael; Meiser, Maxie; Bergem, Stefanie; Nerbonne, Jeanne M.; Dorn, Gerald W.; Maack, Christoph

    2012-01-01

    Rationale Mitochondrial Ca2+ uptake is essential for the bioenergetic feedback response through stimulation of Krebs cycle dehydrogenases. Close association of mitochondria to the sarcoplasmic reticulum (SR) may explain efficient mitochondrial Ca2+ uptake despite low Ca2+ affinity of the mitochondrial Ca2+ uniporter. However, the existence of such mitochondrial Ca2+ microdomains and their functional role are presently unresolved. Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer membrane fusion, while Mfn2, but not Mfn1, tethers endoplasmic reticulum to mitochondria in non-cardiac cells. Objective To elucidate roles for Mfn1 and 2 in SR-mitochondrial tethering, Ca2+ signaling and bioenergetic regulation in cardiac myocytes. Methods and Results Fruit fly heart tubes deficient of the Drosophila Mfn ortholog, MARF, had increased contraction-associated and caffeine-sensitive Ca2+ release, suggesting a role for Mfn in SR Ca2+ handling. While cardiac-specific Mfn1 ablation had no effects on murine heart function or Ca2+ cycling, Mfn2 deficiency decreased cardiomyocyte SR-mitochondrial contact length by 30% and reduced the content of SR-associated proteins in mitochondria-associated membranes. This was associated with decreased mitochondrial Ca2+ uptake (despite unchanged mitochondrial membrane potential) but increased steady-state and caffeine-induced SR Ca2+ release. Accordingly, Ca2+-induced stimulation of Krebs cycle dehydrogenases during β-adrenergic stimulation was hampered in Mfn2-, but not Mfn1-KO myocytes, evidenced by oxidation of the redox states of NAD(P)H/NAD(P)+ and FADH2/FAD. Conclusions Physical tethering of SR and mitochondria via Mfn2 is essential for normal inter-organelle Ca2+ signaling in the myocardium, consistent with a requirement for SR-mitochondrial Ca2+ signaling through microdomains in the cardiomyocyte bioenergetic feedback response to physiological stress. PMID:22777004

  20. [Effects of resuscitation with different kinds of colloids on pulmonary edema in swine in shock stage of severe burn injury].

    Science.gov (United States)

    You, Xiao-en; Chen, Jiong; Zhou, Jian-jun; Xing, Nan; Shi, Jian-wu; Su, Guo-liang

    2013-06-01

    To observe and compare the effects of natural colloid and artificial colloid on pulmonary edema of swine during shock stage of severe burn injury. Twelve Guangxi Bama miniature swine were inflicted with 40% TBSA full-thickness burn on the back, and then they were divided into natural colloid group (N) and artificial colloid group (A) according to the random number table, with six swine in each group. At post injury hour (PIH) 2, fluid resuscitation was begun. The main part of electrolyte was lactic acid Ringer's solution. The colloids included swine plasma and hydroxyethyl starch 130/0.4. Before injury and at every hour within PIH 48, heart rate, blood pressure, urine volume, central venous pressure (CVP), and pulmonary arterial wedge pressure (PAWP) were recorded. The mean heart rate, blood pressure, urine volume per hour per kg of body weight, CVP, PAWP, resuscitation liquid volume, and the ratio of fluid intake to output during the first and second PIH 24 were calculated. At PIH 48, lung tissue was harvested for histopathological observation and calculation of lung water ratio. Data were processed with one-way analysis of variance, analysis of variance of repeated measurement, LSD test and independent sample t test. (1) There were no statistically significant differences between two groups in heart rate, blood pressure, and urine volume before injury and during the first and second PIH 24 (P values all above 0.05); during the first PIH 24, the CVP and PAWP of group A were significantly higher than those of group N (P values all below 0.05). Compared with those before injury, the heart rate, CVP and PAWP of two groups during the first and second PIH 24 were significantly higher (P 0.05); the urine volumes of two groups during the second PIH 24 were increased, while no statistically significant differences were observed (P values all above 0.05). There were no statistically significant differences in blood pressure of two groups between the first, second PIH 24

  1. African swine fever virus isolate, Georgia, 2007.

    Science.gov (United States)

    Rowlands, Rebecca J; Michaud, Vincent; Heath, Livio; Hutchings, Geoff; Oura, Chris; Vosloo, Wilna; Dwarka, Rahana; Onashvili, Tinatin; Albina, Emmanuel; Dixon, Linda K

    2008-12-01

    African swine fever (ASF) is widespread in Africa but is rarely introduced to other continents. In June 2007, ASF was confirmed in the Caucasus region of Georgia, and it has since spread to neighboring countries. DNA fragments amplified from the genome of the isolates from domestic pigs in Georgia in 2007 were sequenced and compared with other ASF virus (ASFV) isolates to establish the genotype of the virus. Sequences were obtained from 4 genome regions, including part of the gene B646L that encodes the p72 capsid protein, the complete E183L and CP204L genes, which encode the p54 and p30 proteins and the variable region of the B602L gene. Analysis of these sequences indicated that the Georgia 2007 isolate is closely related to isolates belonging to genotype II, which is circulating in Mozambique, Madagascar, and Zambia. One possibility for the spread of disease to Georgia is that pigs were fed ASFV-contaminated pork brought in on ships and, subsequently, the disease was disseminated throughout the region.

  2. Novel reassortant swine influenza viruses are circulating in Danish pigs

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

    of the reassortant viruses comprised a HA gene similar to H1 of H1N1 avian-like swine influenza virus (SIV) and a NA gene most closely related to N2 gene of human H3N2 influenza virus that circulated in humans in the mid 1990s. The internal genes of this reassortant virus with the subtype H1avN2hu all belonged...... to the H1N1 avian-like SIV lineages. Until now this novel virus H1avN2hu has only been detected in Danish swine. The other novel reassortant virus contained the HA gene from H1N1pdm09 virus and a NA gene similar to the N2 gene of H3N2 SIV that have been circulating in European swine since the mid 1980s...

  3. Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

    Directory of Open Access Journals (Sweden)

    Rabya Saraf

    Full Text Available Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome.Yorkshire swine (n = 8 per group were fed a normal diet (ND or a high-cholesterol (HCD for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD.There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002 and Bcl-xL (p = 0.05 and p = 0.01 in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01, pSmad1/5 (p = 0.03 and MMP-9 (p = 0.005 were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively. Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and-dp/dt (p = 0.05 and p = 0.007 respectively in the HCD group.Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

  4. Mitochondrial DNA Damage and its Consequences for Mitochondrial Gene Expression

    Science.gov (United States)

    Cline, Susan D.

    2012-01-01

    How mitochondria process DNA damage and whether a change in the steady-state level of mitochondrial DNA damage (mtDNA) contributes to mitochondrial dysfunction are questions that fuel burgeoning areas of research into aging and disease pathogenesis. Over the past decade, researchers have identified and measured various forms of endogenous and environmental mtDNA damage and have elucidated mtDNA repair pathways. Interestingly, mitochondria do not appear to contain the full range of DNA repair mechanisms that operate in the nucleus, although mtDNA contains types of damage that are targets of each nuclear DNA repair pathway. The reduced repair capacity may, in part, explain the high mutation frequency of the mitochondrial chromosome. Since mtDNA replication is dependent on transcription, mtDNA damage may alter mitochondrial gene expression at three levels: by causing DNA polymerase γ nucleotide incorporation errors leading to mutations, by interfering with the priming of mtDNA replication by the mitochondrial RNA polymerase, or by inducing transcriptional mutagenesis or premature transcript termination. This review summarizes our current knowledge of mtDNA damage, its repair, and its effects on mtDNA integrity and gene expression. PMID:22728831

  5. Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer

    Science.gov (United States)

    Kirches, E

    2009-01-01

    Although the observation of aerobic glycolysis of tumor cells by Otto v. Warburg had demonstrated abnormalities of mitochondrial energy metabolism in cancer decades ago, there was no clear evidence for a functional role of mutant mitochondrial proteins in cancer development until the early years of the 21st century. In the year 2000, a major breakthrough was achieved by the observation, that several genes coding for subunits of the respiratory chain (ETC) complex II, succinate dehydrogenase (SDH) are tumor suppressor genes in heritable paragangliomas, fulfilling Knudson’s classical two-hit hypothesis. A functional inactivation of both alleles by germline mutations and chromosomal losses in the tumor tissue was found in the patients. Later, SDH mutations were also identified in sporadic paragangliomas and pheochromocytomas. Genes of the mitochondrial ATP-synthase and of mitochondrial iron homeostasis have been implicated in cancer development at the level of cell culture and mouse experiments. In contrast to the well established role of some nuclear SDH genes, a functional impact of the mitochondrial genome itself (mtDNA) in cancer development remains unclear. Nevertheless, the extremely high frequency of mtDNA mutations in solid tumors raises the question, whether this small circular genome might be applicable to early cancer detection. This is a meaningful approach, especially in cancers, which tend to spread tumor cells early into bodily fluids or faeces, which can be screened by non-invasive methods. PMID:19949549

  6. Radiation-induced damage of the Wistar Rat heart

    International Nuclear Information System (INIS)

    Cilliers, G.D.; Lochner, A.

    1993-01-01

    A time sequence study was performed on Wistar rats to investigate the early effects of radiation on the mechanical function and energy metabolism of the heart. Two series of rats were exposed to 20 Gy electron irradiation to a field including the heart and approximately a third of the lungs. The hearts were excised at varying time intervals (8-180 days) post irradiation. In one series of hearts the mechanical function was measured using the isolated perfused working rat heart model. At the end of the perfusion the hearts were freeze-clamped for analysis of the high energy phosphate contents (ATP, ADP, AMP and creatine phosphate). In the second series, mitochondria were isolated and the oxidative phosphorylation function measured polarographically (substrate: glutamate). Maximal depression of mechanical function was observed at 60 days post irradiation. Thereafter the work performance of these hearts improved significantly, almost reaching control levels after 180 days. The mitochondrial oxidative phosphorylation function (as measured on the total mitochondrial population) was significantly depressed 30-120 days post irradiation. As in the case of the mechanical changes, the depression was transient and after 180 days post irradiation, values similar to those of controls were obtained. Myocardial high energy phosphates remained unaltered throughout the experiment. (author)

  7. Using probiotics to improve swine gut health and nutrient utilization

    Directory of Open Access Journals (Sweden)

    Shengfa F. Liao

    2017-12-01

    Full Text Available To maintain a healthy gut is definitely key for a pig to digest and absorb dietary nutrients efficiently. A balanced microbiota (i.e., a healthy micro-ecosystem is an indispensable constituent of a healthy gut. Probiotics, the live microorganisms which, when administered in adequate amounts, confer good health benefits onto the host, are a category of feed additives that can be used to replenish the gut microbial population while recuperating the host immune system. Besides their antitoxin and diarrhea reduction effects, dietary supplementation of probiotics can improve gut health, nutrient digestibilities and, therefore, benefit nutrient utilization and growth performance of pigs. Current knowledge in the literature pertinent to the beneficial effects of utilizing various probiotics for swine production has been comprehensively reviewed, and the safety and the risk issues related to probiotic usage have also been discussed in this paper. Considering that the foremost cost in a swine operation is feed cost, feed efficiency holds a very special, if not the paramount, significance in commercial swine production. Globally, the swine industry along with other animal industries is moving towards restricting and eventually a total ban on the usage of antibiotic growth promoters. Therefore, selection of an ideal alternative to the in-feed antibiotics to compensate for the lost benefits due to the ban on the antibiotic usage is urgently needed to support the industry for profitable and sustainable swine production. As is understood, a decision on this selection is not easy to make. Thus, this review paper aims to provide some much needed up-to-date knowledge and comprehensive references for swine nutritionists and producers to refer to before making prudent decisions and for scientists and researchers to develop better commercial products.

  8. Formation and Regulation of Mitochondrial Membranes

    Directory of Open Access Journals (Sweden)

    Laila Cigana Schenkel

    2014-01-01

    Full Text Available Mitochondrial membrane phospholipids are essential for the mitochondrial architecture, the activity of respiratory proteins, and the transport of proteins into the mitochondria. The accumulation of phospholipids within mitochondria depends on a coordinate synthesis, degradation, and trafficking of phospholipids between the endoplasmic reticulum (ER and mitochondria as well as intramitochondrial lipid trafficking. Several studies highlight the contribution of dietary fatty acids to the remodeling of phospholipids and mitochondrial membrane homeostasis. Understanding the role of phospholipids in the mitochondrial membrane and their metabolism will shed light on the molecular mechanisms involved in the regulation of mitochondrial function and in the mitochondrial-related diseases.

  9. Mitochondrial function in permeabilized cardiomyocytes is largely preserved in the senescent rat myocardium.

    Directory of Open Access Journals (Sweden)

    Martin Picard

    Full Text Available The aging heart is characterized by a progressive decline in contractile function and diastolic relaxation. Amongst the factors implicated in these changes is a progressive replacement fibrosis secondary to cardiomyocyte death, oxidative damage, and energetic deficit, each of which may be secondary to impaired mitochondrial function. Here, we performed an in-depth examination of mitochondrial function in saponin-permeabilized cardiomyocyte bundles, a preparation where all mitochondria are represented and their structure intact, from young adult (YA and senescent (SEN rats (n = 8 per group. When accounting for increased fibrosis (+19%, P<0.01 and proportional decrease in citrate synthase activity in the SEN myocardium (-23%, P<0.05, mitochondrial respiration and reactive oxygen species (H(2O(2 emission across a range of energized states was similar between age groups. Accordingly, the abundance of electron transport chain proteins was also unchanged. Likewise, except for CuZnSOD (-37%, P<0.05, the activity of antioxidant enzymes was unaltered with aging. Although time to mitochondrial permeability transition pore (mPTP opening was decreased (-25%, P<0.05 in the SEN heart, suggesting sensitization to apoptotic stimuli, this was not associated with a difference in apoptotic index measured by ELISA. Collectively, our results suggest that the function of existing cardiac ventricular mitochondria is relatively preserved in SEN rat heart when measured in permeabilized cells.

  10. Lumbricidae as transitory hosts in Metastrongylus infection in swine

    Directory of Open Access Journals (Sweden)

    Pavlović Ivan

    2005-01-01

    Full Text Available Metastrongylidosis or lungworm disease in swine is a disease caused by several types of nematodes of the genus Metastrongylus. Metastrongylidae are biohelminths whose causes use transitory hosts for their development and maintaining their biological cycle, and in this case they are numerous species of Lumbricidae (earthworms. Depending on the geographic environment, numerous representatives of Lumbricidae persist as transitory hosts. In our environment, these are dominant earthworm species of the genus Eisenia spp, Dandreobena spp, Allopbophora spp, Lubricus spp, Octoiasium spp, Bimastus spp, and rarely those from the genus Heledrillus spp. Swine are infected perorally with Metastrongylidae when they ingest infected earthworms.

  11. Functional analysis of replication determinantsin classical swine fever virus

    DEFF Research Database (Denmark)

    Hadsbjerg, Johanne

    and animal pathogens should facilitate finding new approaches for efficient disease control. The principal aim of this thesis is to characterise determinants involved in the replication of classical swine fever virus (CSFV). Classical swine fever is a highly contagious virus disease of domestic pigs and wild...... in cell culture. Knowledge of these sequence variations and putative long-range interactions will provide valuable insights into mechanisms underlying virustranslation and replication. In manuscript 3, a selection marker has been inserted into a CSFV-based replicon making it suitable for screening...

  12. Left Ventricular Remodeling after Myocardial Infarction: Characterization of a Swine Model on β-Blocker Therapy

    Science.gov (United States)

    Angeli, Franca S; Shapiro, Mia; Amabile, Nicolas; Orcino, Gina; Smith, Charles S; Tacy, Theresa; Boyle, Andrew J; Chatterjee, Kanu; Glantz, Stanton A; Grossman, William; Yeghiazarians, Yerem

    2009-01-01

    Current guidelines recommend β blockers for patients after myocardial infarction (MI). Novel therapies for heart failure should be tested in combination with this medication before entering clinical trials. In this methodologic study, we sought to describe the time course of systolic and diastolic parameters of cardiac performance over a 6-wk period in closed-chest model of swine MI treated with a β blocker. Myocardial infarction in pigs (n = 10) was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Echocardiography and pressure–volume data were collected before and at 1 and 6 wk after MI; histopathology was assessed at 6 wk. Left-ventricular (LV) volume increased significantly over 6 wk, with significant decreases in ejection fraction, wall motion index, stroke work, rate of pressure development (dP/dtmax), preload recruitable stroke work, and mechanical efficiency. Impairment of diastolic function was manifested by a significant increase in the exponential β coefficient of the LV end-diastolic pressure–volume relation and reduction of LV pressure decay. At 6 wk, histopathologic analysis showed that the size of the infarct area was 16.3% ± 4.4%, and the LV mass and myocyte cross-sectional area in both the infarct border and remote zones were increased compared with those of noninfarcted pigs (n = 5). These findings suggest a dynamic pattern of remodeling over time in a closed-chest ischemia–reperfusion swine model of acute MI on β-blocker therapy and may guide future studies. PMID:19619418

  13. Ventricular Effective Refraction Period and Ventricular Repolarization Analysis in Experimental Tachycardiomyopathy in Swine.

    Science.gov (United States)

    Noszczyk-Nowak, Agnieszka; Pasławska, Urszula; Gajek, Jacek; Janiszewski, Adrian; Pasławski, Robert; Zyśko, Dorota; Nicpoń, Józef

    2016-01-01

    Swine are recognized animal models of human cardiovascular diseases. However, little is known on the CHF-associated changes in the electrophysiological ventricular parameters of humans and animals. The aim of this study was to analyze changes in the durations of ventricular effective refraction period (VERP), QT and QTc intervals of pigs with chronic tachycardia-induced tachycardiomyopathy (TIC). The study was comprised of 28 adult pigs (8 females and 20 males) of the Polish Large White breed. A one-chamber pacemaker was implanted in each of the 28 pigs. Electrocardiographic, echocardiographic and electrophysiological studies were carried out prior to the pacemaker implantation and at subsequent 4-week intervals. All electrocardiographic, echocardiographic and short electrophysiological study measurements in all swine were done under general anesthesia (propofol) after premedication with midazolam, medetomidine, and ketamine. No significant changes in the duration of QT interval and corrected QT interval (QTc) were observed during consecutive weeks of the experiment. The duration of the QTc interval of female pigs was shown to be significantly longer than that of the males throughout the whole study period. Beginning from the 12th week of rapid ventricular pacing, a significant increase in duration of VERP was observed in both male and female pigs. Males and females did not differ significantly in terms of VERP duration determined throughout the whole study period. Ventricular pacing, stimulation with 2 and 3 premature impulses at progressively shorter coupling intervals and an imposed rhythm of 130 bpm or 150 bpm induced transient ventricular tachycardia in one female pig and four male pigs. One episode of permanent ventricular tachycardia was observed. The number of induced arrhythmias increased proportionally to the severity of heart failure and duration of the experiment. However, relatively aggressive protocols of stimulation were required in order to induce

  14. Differential differences in methylation status of putative imprinted genes among cloned swine genomes.

    Directory of Open Access Journals (Sweden)

    Chih-Jie Shen

    Full Text Available DNA methylation is a major epigenetic modification in the mammalian genome that regulates crucial aspects of gene function. Mammalian cloning by somatic cell nuclear transfer (SCNT often results in gestational or neonatal failure with only a small proportion of manipulated embryos producing live births. Many of the embryos that survive to term later succumb to a variety of abnormalities that are likely due to inappropriate epigenetic reprogramming. Aberrant methylation patterns of imprinted genes in cloned cattle and mice have been elucidated, but few reports have analyzed the cloned pig genome. Four surviving cloned sows that were created by ear fibroblast nuclear transfer, each with a different life span and multiple organ defects, such as heart defects and bone growth delay, were used as epigenetic study materials. First, we identified four putative differential methylation regions (DMR of imprinted genes in the wild-type pig genome, including two maternally imprinted loci (INS and IGF2 and two paternally imprinted loci (H19 and IGF2R. Aberrant DNA methylation, either hypermethylation or hypomethylation, commonly appeared in H19 (45% of imprinted loci hypermethylated vs. 30% hypomethylated, IGF2 (40% vs. 0%, INS (50% vs. 5%, and IGF2R (15% vs. 45% in multiple tissues from these four cloned sows compared with wild-type pigs. Our data suggest that aberrant epigenetic modifications occur frequently in the genome of cloned swine. Even with successful production of cloned swine that avoid prenatal or postnatal death, the perturbation of methylation in imprinted genes still exists, which may be one of reason for their adult pathologies and short life. Understanding the aberrant pattern of gene imprinting would permit improvements in future cloning techniques.

  15. The mitochondrial contact site complex, a determinant of mitochondrial architecture.

    Science.gov (United States)

    Harner, Max; Körner, Christian; Walther, Dirk; Mokranjac, Dejana; Kaesmacher, Johannes; Welsch, Ulrich; Griffith, Janice; Mann, Matthias; Reggiori, Fulvio; Neupert, Walter

    2011-10-18

    Mitochondria are organelles with a complex architecture. They are bounded by an envelope consisting of the outer membrane and the inner boundary membrane (IBM). Narrow crista junctions (CJs) link the IBM to the cristae. OMs and IBMs are firmly connected by contact sites (CS). The molecular nature of the CS remained unknown. Using quantitative high-resolution mass spectrometry we identified a novel complex, the mitochondrial contact site (MICOS) complex, formed by a set of mitochondrial membrane proteins that is essential for the formation of CS. MICOS is preferentially located at the CJs. Upon loss of one of the MICOS subunits, CJs disappear completely or are impaired, showing that CJs require the presence of CS to form a superstructure that links the IBM to the cristae. Loss of MICOS subunits results in loss of respiratory competence and altered inheritance of mitochondrial DNA.

  16. Pharmacologic modeling of primary mitochondrial respiratory chain dysfunction in zebrafish.

    Science.gov (United States)

    Byrnes, James; Ganetzky, Rebecca; Lightfoot, Richard; Tzeng, Michael; Nakamaru-Ogiso, Eiko; Seiler, Christoph; Falk, Marni J

    2017-07-18

    Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects as well as effects on mitochondrial biochemistry and physiology. Here, we characterize four pharmacologic inhibitor models of mitochondrial RC dysfunction in early larval zebrafish, including rotenone (complex I inhibitor), azide (complex IV inhibitor), oligomycin (complex V inhibitor), and chloramphenicol (mitochondrial translation inhibitor that leads to multiple RC complex dysfunction). A range of concentrations and exposure times of each RC inhibitor were systematically evaluated on early larval development, animal survival, integrated behaviors (touch and startle responses), organ physiology (brain death, neurologic tone, heart rate), and fluorescence-based analyses of mitochondrial physiology in zebrafish skeletal muscle. Pharmacologic RC inhibitor effects were validated by spectrophotometric analysis of Complex I, II and IV enzyme activities, or relative quantitation of ATP levels in larvae. Outcomes were prioritized that utilize in vivo animal imaging and quantitative behavioral assessments, as may optimally inform the translational potential of pre-clinical drug screens for future clinical study in human mitochondrial disease subjects. The RC complex inhibitors each delayed early embryo development, with short-term exposures of these three agents or chloramphenicol from 5 to 7 days

  17. What Is a Heart Attack?

    Science.gov (United States)

    ... to help prevent your first heart attack. Heart-Healthy Lifestyle Changes A heart-healthy lifestyle can help prevent ... blood to flow to the heart muscle. Heart-Healthy Lifestyle Changes Treatment for a heart attack usually includes ...

  18. Mitochondrial quality control pathways as determinants of metabolic health

    NARCIS (Netherlands)

    Held, Ntsiki M.; Houtkooper, Riekelt H.

    2015-01-01

    Mitochondrial function is key for maintaining cellular health, while mitochondrial failure is associated with various pathologies, including inherited metabolic disorders and age-related diseases. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have

  19. Mitochondrial Oxidative Stress Corrupts Coronary Collateral Growth by Activating Adenosine Monophosphate Activated Kinase-α Signaling

    Science.gov (United States)

    Pung, Yuh Fen; Sam, Wai Johnn; Stevanov, Kelly; Enrick, Molly; Chen, Chwen-Lih; Kolz, Christopher; Thakker, Prashanth; Hardwick, James P.; Chen, Yeong-Renn; Dyck, Jason R.B.; Yin, Liya; Chilian, William M.

    2015-01-01

    Objective Our goal was to determine the mechanism by which mitochondrial oxidative stress impairs collateral growth in the heart. Approach and Results Rats were treated with rotenone (mitochondrial complex I inhibitor that increases reactive oxygen species production) or sham-treated with vehicle and subjected to repetitive ischemia protocol for 10 days to induce coronary collateral growth. In control rats, repetitive ischemia increased flow to the collateral-dependent zone; however, rotenone treatment prevented this increase suggesting that mitochondrial oxidative stress compromises coronary collateral growth. In addition, rotenone also attenuated mitochondrial complex I activity and led to excessive mitochondrial aggregation. To further understand the mechanistic pathway(s) involved, human coronary artery endothelial cells were treated with 50 ng/ mL vascular endothelial growth factor, 1 µmol/L rotenone, and rotenone/vascular endothelial growth factor for 48 hours. Vascular endothelial growth factor induced robust tube formation; however, rotenone completely inhibited this effect (Pmediated by the activation of AMPK-α. Conversely, expression of a constitutively active AMPK-α blocked tube formation. Conclusions We conclude that activation of AMPK-α during mitochondrial oxidative stress inhibits mammalian target of rapamycin signaling, which impairs phenotypic switching necessary for the growth of blood vessels. PMID:23788766

  20. Sab mediates mitochondrial dysfunction involved in imatinib mesylate-induced cardiotoxicity.

    Science.gov (United States)

    Chambers, Tara P; Santiesteban, Luis; Gomez, David; Chambers, Jeremy W

    2017-05-01

    Imatinib mesylate is an effective treatment for chronic myelogenous leukemia and gastrointestinal stromal tumors. Although imatinib mesylate is highly tolerable, it has been implicated in severe congestive heart failure in mouse models and patients. A hallmark of imatinib mesylate-induced cardiotoxicity is mitochondrial dysfunction. The mitochondrial scaffold Sab has been implicated in facilitating signaling responsible for mitochondrial dysfunction in a c-Jun N-terminal Kinase (JNK)-dependent manner. We examined the impact of Sab-mediated signaling on imatinib mesylate cardiotoxicity in H9c2 rat cardiomyocyte-like cells. Silencing Sab increased the LD 50 of imatinib mesylate 4-fold in H9c2 cells. Disrupting Sab-mediated signaling prevented imatinib mesylate-induced apoptosis as well. Knockdown of Sab or inhibition with a small peptide prevented oxidative stress, which was indicated by decreased reactive oxygen species production, lipid peroxidation, and protein carbonylation. Further, inhibition of Sab-related signaling partially rescued deficits in mitochondrial respiration, ATP production, and membrane potential in imatinib mesylate-treated H9c2 cells. Conversely, over-expression of Sab in H9c2 cells increased the cardiotoxicity of imatinib mesylate in vitro decreasing the LD 50 over 4-fold. Sab expression was induced in H9c2 cells following cardiovascular-like stress in an AP-1 dependent manner. These data demonstrate that imatinib mesylate influences mitochondrial signaling leading to mitochondrial dysfunction and cardiotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Heart failure - surgeries and devices

    Science.gov (United States)

    CHF - surgery; Congestive heart failure - surgery; Cardiomyopathy - surgery; HF - surgery; Intra-aortic balloon pumps - heart failure; IABP - heart failure; Catheter based assist devices - heart failure

  2. Mitochondrial DNA and Cancer Epidemiology Workshop

    Science.gov (United States)

    A workshop to review the state-of-the science in the mitochondrial DNA field and its use in cancer epidemiology, and to develop a concept for a research initiative on mitochondrial DNA and cancer epidemiology.

  3. Microtubule-Dependent Mitochondria Alignment Regulates Calcium Release in Response to Nanomechanical Stimulus in Heart Myocytes

    Directory of Open Access Journals (Sweden)

    Michele Miragoli

    2016-01-01

    Full Text Available Arrhythmogenesis during heart failure is a major clinical problem. Regional electrical gradients produce arrhythmias, and cellular ionic transmembrane gradients are its originators. We investigated whether the nanoscale mechanosensitive properties of cardiomyocytes from failing hearts have a bearing upon the initiation of abnormal electrical activity. Hydrojets through a nanopipette indent specific locations on the sarcolemma and initiate intracellular calcium release in both healthy and heart failure cardiomyocytes, as well as in human failing cardiomyocytes. In healthy cells, calcium is locally confined, whereas in failing cardiomyocytes, calcium propagates. Heart failure progressively stiffens the membrane and displaces sub-sarcolemmal mitochondria. Colchicine in healthy cells mimics the failing condition by stiffening the cells, disrupting microtubules, shifting mitochondria, and causing calcium release. Uncoupling the mitochondrial proton gradient abolished calcium initiation in both failing and colchicine-treated cells. We propose the disruption of microtubule-dependent mitochondrial mechanosensor microdomains as a mechanism for abnormal calcium release in failing heart.

  4. Optical metabolic imaging of irradiated rat heart exposed to ischemia-reperfusion injury

    Science.gov (United States)

    la Cour, Mette Funding; Mehrvar, Shima; Heisner, James S.; Motlagh, Mohammad Masoudi; Medhora, Meetha; Ranji, Mahsa; Camara, Amadou K. S.

    2018-01-01

    Whole thoracic irradiation (WTI) is known to cause deterioration in cardiac function. Whether irradiation predisposes the heart to further ischemia and reperfusion (IR) injury is not well known. The aim of this study is to examine the susceptibility of rat hearts to IR injury following a single fraction of 15 Gy WTI and to investigate the role of mitochondrial metabolism in the differential susceptibility to IR injury. After day 35 of irradiation, ex vivo hearts from irradiated and nonirradiated rats (controls) were exposed to 25-min global ischemia followed by 60-min IR, or hearts were perfused without IR for the same protocol duration [time controls (TC)]. Online fluorometry of metabolic indices [redox state: reduced nicotinamide adenine dinucleotide (NADH), oxidized flavin adenine dinucleotide (FAD), and NADH/FAD redox ratio] and functional variables [systolic left ventricular pressure (LVP), diastolic LVP (diaLVP), coronary flow (CF), and heart rate were recorded in the beating heart; developed LVP (dLVP) and rate pressure product (RPP)] were derived. At the end of each experimental protocol, hearts were immediately snap frozen in liquid N2 for later three-dimensional imaging of the mitochondrial redox state using optical cryoimaging. Irradiation caused a delay in recovery of dLVP and RPP after IR when compared to nonirradiated hearts but recovered to the same level at the end of reperfusion. CF in the irradiated hearts recovered better than the control hearts after IR injury. Both fluorometry and 3-D cryoimaging showed that in WTI and control hearts, the redox ratio increased during ischemia (reduced) and decreased on reperfusion (oxidized) when compared to their respective TCs; however, there was no significant difference in the redox state between WTI and controls. In conclusion, our results show that although irradiation of rat hearts compromised baseline cardiovascular function, it did not alter cardiac mitochondrial redox state and induce greater

  5. GASTROINTESTINAL MANIFESTATIONS OF MITOCHONDRIAL DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    A. A. Ziganshina

    2016-01-01

    Full Text Available Objective: to highlight the current concepts of gastrointestinal manifestations of mitochondrial dysfunction. The data available in Russian and foreign literature on the gastrointestinal manifestations of mitochondrial dysfunction were analyzed. Functional digestive diseases are common in pediatric practice; however, their etiopathogenesis has not been adequately explored today. According to the literature, impaired cellular energy metabolism may underlie gastrointestinal motility disorders in cyclic vomiting syndrome, gastroesophageal reflux, gastric stasis, chronic diarrhea, constipation, intestinal pseudoobstruction, malabsorption syndrome, irritable bowel syndrome, as well as diseases of the liver and pancreas.

  6. Mitochondrial myopathy and myoclonic epilepsy

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1990-03-01

    Full Text Available The authors describe a family (mother, son and two daughters with mitochondrial myopathy. The mother was asymptomatic. Two daughters had lactic acidosis and myoclonic epilepsy, mild dementia, ataxia, weakness and sensory neuropathy. The son suffered one acute hemiplegic episode due to an ischemic infarct in the right temporal region. All the patients studied had hypertension. EEG disclosed photomyoclonic response in the proband patient. Muscle biopsy disclosed ragged-red fibers and abnormal mitochondria by electron microscopy. Biochemical analysis showed a defect of cytochrome C oxidase in mitochondria isolated from skeletal muscle. Several clinical and genetic aspects of the mitochondrial encephalomyopathies are discussed.

  7. Presence of gastrointestinal parasites in swine and human of four swine production farms in Cundinamarca- Colombia

    Directory of Open Access Journals (Sweden)

    María F Mendoza-Gómez

    2015-11-01

    Full Text Available Objectives. Determine the presence and the type of endoparasites with zoonotic potential in swine and human of two technified and two semi-technified farms in the department of Cundinamarca, Colombia. Materials and methods. Three serial samplings of feces were taken in a pen row within intervals of 15 days, in two technified and two semi-technified farms in different age groups distributed as follows: pregnant-sows, nursing-females, boars, weaners, suckling-piglets, and growing-pig. By means of informed consent thirty-three people agreed to enter the study. Thirty-three samples from men and women of different ages were received. The pool and individual samples of fecal were evaluated by direct analysis, qualitative flotation and sedimentation techniques and modified ZiehlNeelsen stain. Results. For the porcine population, on the average, the results obtained from both technified farms showed that Balantidium coli (42%, Endolimax nana (21.9% and Iodamoeba bütschlii (7.8% were the most common parasites. In semi-technified farms they were: Entamoeba coli (40%, Endolimax nana (35%, Iodamoeba bütschlii (25% and Balantidium coli (5%. By means of the test chi2 it is possible to conclude that there is a significant difference between the parasites species and the type of farm. The results obtained in human showed the presence of parasites as: E. coli (42.2%, Entamoeba hystolitica/dispar (12.1%, E. nana (9.1%, B. coli (9.1%, I. bütschlii (3.0% and Blastocystis hominis (3.0%. Conclusions. The presence of parasites such as Balantidium coli, Endolimax nana, Iodamoeba bütschlii and Entamoeba coli in swine and human suggests a possible rotation of parasitic species between hosts.

  8. Heat Stress Effects on Growing-Finishing Swine

    Science.gov (United States)

    Understanding the factors that create heat stress, the response of the animals while under heat stress, and the signs of heat-stressed swine are essential to making rational decisions for the selection, design, and management of their environments. Heat stressors include combinations of environment...

  9. Production system dynamism and parasitic interac- tion of swine in ...

    African Journals Online (AJOL)

    separate house without drainage) and poor (housed together with other live- stock in open barn with no shed). Statistical analysis. The Chi-square test was applied to ... owners release their swine to graze on the field along with other livestock. .... which 14 farms were having more than 30 pigs and 36 farms were having less.

  10. Diet modification as a mitigation tool for swine production

    Science.gov (United States)

    A series of experiments were conducted to evaluate air emission reductions from swine following implementation of diet strategies. In each study, the impact of these feeding strategies on pig performance and air emissions were compared to those of animals fed commercial diets. Groups of pigs were ho...

  11. Seroprevalence of hepatitis E in swine abattoir workers.

    African Journals Online (AJOL)

    This silent maintenance of HEV infection amongst swine abattoir workers is an occupational risk that could challenge .... HE Seroprevalence in different occupations ..... nary microbiology. 2011;149(1):236-41. 46. Aggarwal R, Krawczynski K. Hepatitis E: an overview and recent advances in clinical and laboratory research.

  12. Wet explosion og wheat straw and codigestion with swine manure

    DEFF Research Database (Denmark)

    Wang, Guangtao; Gavala, Hariklia N.; Skiadas, Ioannis V.

    2009-01-01

    compared to that from the raw biomas s. On the other hand, the results from the codigestion of raw (non-pretreated) wheat straw with swine manure were very promising, suggesting that 4.6 kg of straw added to 1 t of manure increase the methane production by 10%. Thus, wheat straw can be considered...

  13. Influenza A virus infections in swine: pathogenesis and diagnosis.

    Science.gov (United States)

    Janke, B H

    2014-03-01

    Influenza has been recognized as a respiratory disease in swine since its first appearance concurrent with the 1918 "Spanish flu" human pandemic. All influenza viruses of significance in swine are type A, subtype H1N1, H1N2, or H3N2 viruses. Influenza viruses infect epithelial cells lining the surface of the respiratory tract, inducing prominent necrotizing bronchitis and bronchiolitis and variable interstitial pneumonia. Cell death is due to direct virus infection and to insult directed by leukocytes and cytokines of the innate immune system. The most virulent viruses consistently express the following characteristics of infection: (1) higher or more prolonged virus replication, (2) excessive cytokine induction, and (3) replication in the lower respiratory tract. Nearly all the viral proteins contribute to virulence. Pigs are susceptible to infection with both human and avian viruses, which often results in gene reassortment between these viruses and endemic swine viruses. The receptors on the epithelial cells lining the respiratory tract are major determinants of infection by influenza viruses from other hosts. The polymerases, especially PB2, also influence cross-species infection. Methods of diagnosis and characterization of influenza viruses that infect swine have improved over the years, driven both by the availability of new technologies and by the necessity of keeping up with changes in the virus. Testing of oral fluids from pigs for virus and antibody is a recent development that allows efficient sampling of large numbers of animals.

  14. Classical Swine Fever and Avian Influenza epidemcis: Lessons learned

    NARCIS (Netherlands)

    Elbers, A.R.; Loeffen, W.L.A.; Koch, G.

    2012-01-01

    This publication is based on a talk which was held in the course of the spring symposium „Impfen statt Keulen“ of the Akademie für Tiergesundheit (AfT) 2011 in Wiesbaden-Naurod. Experience with recent large-scale epidemics of Classical Swine Fever and Avian Influenza – among others in the

  15. Enzymes in Poultry and Swine Nutrition | CRDI - Centre de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Book cover Enzymes in Poultry and Swine Nutrition. Auteur(s) : Ronald R. ... mechanisms. Such studies will enhance our understanding of the role of dietary enzymes in animal nutrition. ... Six équipes de chercheurs de classe mondiale étudieront comment surmonter la résistance au traitement des cancers les plus mortels.

  16. Soybean nutritional status and seed physiological quality with swine wastewater

    Directory of Open Access Journals (Sweden)

    Olga M. Passarin

    2016-01-01

    Full Text Available ABSTRACT Swine wastewater application is a practice that can become viable in agriculture, for minimizing fertilization costs and improving soil conditions. Therefore, it is essential to establish criteria that define appropriate application doses from the agronomic and environmental perspectives. The objective of this study was to evaluate the effects of swine wastewater doses associated with mineral fertilization on soybean nutritional status and physiological quality of seed. The experiment was conducted in the agricultural year of 2010/2011, using twenty-four drainage lysimeters in randomized block design in 4 x 2 factorial scheme, with four swine wastewater doses (0, 100, 200 and 300 m3 ha-1 applied before sowing, associated with presence and absence of mineral fertilization, in three replicates. Leaves at the flowering stage were collected for determinations of N, P, K+, Ca+2, Mg+2, Cu+2, Zn+2, Mn and Fe. Symptoms of toxicity and nutritional deficiency were observed in the crop. Furthermore, higher doses of swine wastewater caused lower physiological quality in soybean seeds.

  17. Detection of a Novel Porcine Parvovirus in Chinese Swine Herds

    Science.gov (United States)

    To determine whether the recently reported novel porcine parvovirus type 4 (PPV4) is prevalent in China, a set of PPV4 specific primers were designed and used for the molecular survey of PPV4 among clinical samples. The results indicated a positive detection for PPV4 in Chinese swine herds of 1.84% ...

  18. Field study of earth tempered swine ventilation systems

    Energy Technology Data Exchange (ETDEWEB)

    Goetsch, W.D.; Peterson, W.H.; Muehling, A.J.

    1981-01-01

    Four earth-tube heat exchanger systems for heating and cooling the ventilation air for swine farrowing and nursery buildings were studied. Results show appreciable winter heating and summer cooling from the earth tubes with minimal variation in the temperature of the discharge air. 5 refs.

  19. The future of influenza A virus vaccines for swine

    Science.gov (United States)

    Economic losses due to influenza A virus (IAV) infections are substantial and a global problem, ranking among the top three major health challenges in the swine industry. Currently, H1 and H3 subtypes circulate in pigs globally associated with different combinations of N1 and N2 subtypes; however, t...

  20. Comparative prevalence of immune evasion complex genes associated with beta-hemolysin converting bacteriophages in MRSA ST5 isolates from swine, swine facilities, humans with swine contact, and humans with no swine contact

    Science.gov (United States)

    Livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA) draws concern from the public health community because in some countries these organisms may represent the largest reservoir of MRSA outside hospital settings. Recent studies indicate LA-MRSA strains from swine are more genet...

  1. Nutrient management practices among swine operations of various sizes.

    Science.gov (United States)

    Hassinger, W J; Monahan, K A; Scanlon, T L; Parsons, T D

    2000-11-15

    To determine feeding, cropping, and manure-handling practices of swine operations of various sizes. Producer survey. 85 sow units and 132 finish floors. Swine producers were surveyed by mail and during farm visits for information regarding herd characteristics and management practices, with emphasis on the 3 components of the nutrient cycle: cropping, feeding and nutrition, and manure handling. Farms were categorized by operation type as sow units or finish floors and, subsequently, stratified by size as small sow units ( or = 600 head), small finish floors ( or = 2,000 head). Large sow units and large finish floors were approximately twice as likely to use environmentally sound nutrient management practices as small sow units or small finish floors. These large operations were more likely to use progressive feeding practices, to be aware of their nutrient flows, and to be capable of using these nutrients properly. There is a need for greater environmental awareness among all swine producers, especially among small producers. This provides a possible growth area for large-animal veterinary consultants. Economy of scale and increased governmental regulations allow large farms to use environmentally sound practices. Thus, large swine farms are not necessarily harmful to the environment.

  2. Composting swine manure from high rise finishing facilities

    Science.gov (United States)

    Over the last twenty years there have been considerable increases in the incidence of human infections with bacteria that are resistant to commonly used antibiotics. This has precipitated concerns about the use of antibiotics in livestock production. Composting of swine manure has several advantages...

  3. Cultivation of soybean with swine wastewater | Frigo | African ...

    African Journals Online (AJOL)

    This study evaluates the cultivation of soybean under the use of swine wastewater (SWW). The SWW used was diluted in water at 0, 25, 50 and 75%. At 15, 30 and 45 days after sowing, plant height, fresh weight, dry weight, leaf area, concentrations of NPK on leaf and productivity were determined. The results show that ...

  4. Persistent Classical Swine Fever infection in newborn piglets

    DEFF Research Database (Denmark)

    Uttenthal, Åse; Lohse, Louise; Rasmussen, Thomas Bruun

    Pestiviruses are unique in their ability to cause persistent infection (PI) in pigs infected in utero. In cattle, PI calves play an important role in maintenance of bovine viral diarrhoea virus infection in the herd. In pigs, the occurence of classical swine fever virus (CSFV) PI piglets...

  5. Treatment of swine wastewater with subsurface-flow constructed ...

    African Journals Online (AJOL)

    This study evaluates the capability of horizontal subsurface-flow constructed wetlands (SSF CWs) for treating pretreated swine wastewater as a function of contact time (CT) and type of macrophyte under the local conditions of Yucatán, Mexico. Experiments were conducted from July 2004 to November 2005 on a ...

  6. 9 CFR 52.3 - Appraisal of swine.

    Science.gov (United States)

    2010-01-01

    ... an APHIS employee alone. (b) The appraisal of swine will be based on the fair market value as determined by the meat or breeding value of the animals. Animals may be appraised in groups, provided that where appraisal is by the head, each animal in the group is the same value per head, and where appraisal...

  7. Optimal Resource Allocation In Swine Production For Rural ...

    African Journals Online (AJOL)

    The study investigated optimal resource allocation in swine production and its implication for rural development in Umuahia, Abia State, Nigeria. Data was collected with the aid of interview form 50 randomly selected respondents. The study revealed that pig production in Umuahia, Abia State is mainly carried out by young ...

  8. Genetic diversity of Escherichia coli isolated from commercial swine ...

    African Journals Online (AJOL)

    Administrator

    2011-09-07

    Sep 7, 2011 ... The infectious diseases caused by E. coli are very serious. Analysis of E. coli strains genetic diversity is important for epidemiology. The objective of this study was to use REP-PCR and ERIC-PCR for the analysis of genetic diversity among E. coli strains isolated from commercial swine farms in Sichuan ...

  9. Vaccinology of classical swine fever: from lab to field

    NARCIS (Netherlands)

    Oirschot, van J.T.

    2003-01-01

    There are two types of classical swine fever vaccines available: the classical live and the recently developed E2 subunit vaccines. The live Chinese strain vaccine is the most widely used. After a single vaccination, it confers solid immunity within a few days that appears to persist lifelong. The

  10. Odor control in swine buildings: recycle flush vs. automated scraper

    Science.gov (United States)

    A research project was conducted to compare odor concentrations in exhaust of traditional flush barns and barns equipped with automated scrapers. The study was conducted at commercial tunnel-ventilated swine barns in northwest Missouri. Odor samples were collected from the barn exhaust in polyvinyl ...

  11. Anaerobic digestion of swine manure: Inhibition by ammonia

    DEFF Research Database (Denmark)

    Hansen, Kaare Hvid; Angelidaki, Irini; Ahring, Birgitte Kiær

    1998-01-01

    A stable anaerobic degradation of swine manure with ammonia concentration of 6 g-N/litre was obtained in continuously stirred tank reactors with a hydraulic retention time of 15 days, at Four different temperatures. Methane yields of 188, 141, 67 and 22 ml-CH4/g-VS were obtained at 37, 45, 55...

  12. Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

    DEFF Research Database (Denmark)

    Friis, Martin Barfred; Rasmussen, Thomas Bruun; Belsham, Graham

    2012-01-01

    Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, cDNAs corresponding to the wild type (wt) or mutant forms of the IRES of CSFV strain Paderborn were...

  13. Modulation of Translation Initiation Efficiency in Classical Swine Fever Virus

    DEFF Research Database (Denmark)

    Friis, Martin Barfred; Rasmussen, Thomas Bruun; Belsham, Graham J.

    Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, the nucleotides 47 to 427, including the IRES region of the wt CSFV strain Paderborn, were amplified...

  14. African Swine Fever control in Ibadan, Nigeria: problems, needs and ...

    African Journals Online (AJOL)

    African swine fever (ASF) is a widely discussed disease in Ibadan, Nigeria, where high mortality losses occurred in outbreaks in the city between 2001-2006. To study the level to which ASF containment technologies were adopted and factors associated with adoption behavior, a sample of 60 pig farmers was selected from ...

  15. Hepatitis E Virus Genotype 3 in Humans and Swine, Bolivia

    Science.gov (United States)

    Cavallo, Annalisa; Gonzales, José Luis; Bonelli, Sara Irene; Valda, Ybar; Pieri, Angela; Segundo, Higinio; Ibañez, Ramón; Mantella, Antonia; Bartalesi, Filippo; Tolari, Francesco; Bartoloni, Alessandro

    2011-01-01

    We determined the seroprevalence of hepatitis E virus (HEV) in persons in 2 rural communities in southeastern Bolivia and the presence of HEV in human and swine fecal samples. HEV seroprevalence was 6.3%, and HEV genotype 3 strains with high sequence homology were detected. PMID:21801630

  16. Accelerating vaccine development for African swine fever virus ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2018-01-12

    Jan 12, 2018 ... Photo: IDRC / Bartay The challenge African swine fever (ASF) is a highly infectious hemorrhagic viral disease that wipes out entire herds of infected pigs. ASF is widespread in at least half of sub-Saharan Africa, and threatens food security due to devastating economic losses.

  17. A Review of Swine Influenza: An Emerging Pandemic | Adeola ...

    African Journals Online (AJOL)

    An unprecedented epizootic swine Influenza A (H1N1) virus that is highly pathogenic has crossed the species barrier in Mexico to cause many human fatalities and poses an increasing pandemic threat. This summary describes the aetiopathogenesis of human infection with Influenza A (H1N1) and reviews ...

  18. Deciphering the Swine-Flu Pandemics of 1918 and 2009

    Science.gov (United States)

    Goldstein, Richard; Dos Reis, Mario; Tamuri, Asif; Hay, Alan

    The devastating "Spanish flu" of 1918 killed an estimated 50 million people worldwide, ranking it as the deadliest pandemic in recorded human history. It is generally believed that the virus transferred from birds directly to humans shortly before the start of the pandemic, subsequently jumping from humans to swine. By developing 'non-homogeneous' substitution models that consider that substitution patterns may be different in human, avian, and swine hosts, we can determine the timing of the host shift to mammals. We find it likely that the Spanish flu of 1918, like the current 2009 pandemic, was a 'swine-origin' influenza virus. Now that we are faced with a new pandemic, can we understand how influenza is able to change hosts? Again by modelling the evolutionary process, considering the different selective constraints for viruses in the different hosts, we can identify locations that seem to be under different selective constraints in humans and avian hosts. This allows us to identify changes that may have facilitated the establishment of the 2009 swine-origin flu in humans.

  19. Screening of cellular proteins that interact with the classical swine ...

    Indian Academy of Sciences (India)

    In the current study, aiming to find more clues in understanding the molecular mechanisms of CSFV NS5A's function, the yeast two-hybrid (Y2H) system was adopted to screen for CSFV NS5A interactive proteins in the cDNA library of the swine umbilical vein endothelial cell (SUVEC). Alignment with the NCBI database ...

  20. Antibiotic Resistant Microbiota in the Swine Intestinal Tract

    Science.gov (United States)

    The healthy swine intestine is populated by upwards of 500 bacterial species, mainly obligate anaerobes. Our research focuses on the roles of these commensal bacteria in antimicrobial resistance and on interventions to reduce the prevalence of antibiotic resistant bacteria. In comparisons of intes...

  1. Quantification of underlying mechanisms of classical swine fever virus transmission

    NARCIS (Netherlands)

    Weesendorp, E.

    2010-01-01

    Classical swine fever (CSF) is an exotic viral disease in most European countries. Occasionally, outbreaks occur due to re-introduction of the virus. During these outbreaks, virus transmission between herds occurs via direct contact between infected and susceptible pigs, or via indirect transmission

  2. Production system dynamism and parasitic interaction of swine in ...

    African Journals Online (AJOL)

    The findings were Ascaris suum (13.9%), Eimeria species (5.6%), Oesophagostomum species (6.7%) and Sarcoptes scabiei (16.2%). Mixed infection was observed on 13 swine, among them 2% were positive for Ascaris suum and Eimeria species, where as 1.14% were positive for Ascaris suum and Oesophagostomum ...

  3. Evidence Suggesting Absence of Mitochondrial DNA Methylation

    DEFF Research Database (Denmark)

    Mechta, Mie; Ingerslev, Lars R; Fabre, Odile

    2017-01-01

    Methylation of nuclear genes encoding mitochondrial proteins participates in the regulation of mitochondria function. The existence of cytosine methylation in the mitochondrial genome is debated. To investigate whether mitochondrial DNA (mtDNA) is methylated, we used both targeted- and whole mito...

  4. Cyanotic heart disease

    Science.gov (United States)

    ... the aorta Ebstein anomaly Hypoplastic left heart syndrome Tetralogy of Fallot Total anomalous pulmonary venous return Transposition of the ... through the middle Cardiac catheterization Heart, front view Tetralogy of Fallot Clubbing Cyanotic heart disease References Bernstein D. Cyanotic ...

  5. Heart failure - home monitoring

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000113.htm Heart failure - home monitoring To use the sharing features on this page, please enable JavaScript. Heart failure is a condition in which the heart is ...

  6. Congenital heart disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001114.htm Congenital heart disease To use the sharing features on this page, please enable JavaScript. Congenital heart disease (CHD) is a problem with the heart's structure ...

  7. Heart Health Tests

    Science.gov (United States)

    ... is easier to treat. Blood tests and heart health tests can help find heart diseases or identify ... diseases. There are several different types of heart health tests. Your doctor will decide which test or ...

  8. Pediatric heart surgery - discharge

    Science.gov (United States)

    ... discharge; Heart valve surgery - children - discharge; Heart surgery - pediatric - discharge; Heart transplant - pediatric - discharge ... Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016:chap 434. ...

  9. Heart disease and depression

    Science.gov (United States)

    ... gov/ency/patientinstructions/000790.htm Heart disease and depression To use the sharing features on this page, ... a heart attack or heart surgery Signs of Depression It is pretty common to feel down or ...

  10. Left heart catheterization

    Science.gov (United States)

    Catheterization - left heart ... to help guide the catheters up into your heart and arteries. Dye (sometimes called "contrast") will be ... in the blood vessels that lead to your heart. The catheter is then moved through the aortic ...

  11. Heart Disease Risk Factors

    Science.gov (United States)

    ... About CDC.gov . Home About Heart Disease Coronary Artery Disease Heart Attack Heart Attack Signs and Symptoms ... Privacy FOIA No Fear Act OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO ( ...

  12. Transgenic overexpression of adenine nucleotide translocase 1 protects ischemic hearts against oxidative stress.

    Science.gov (United States)

    Klumpe, Inga; Savvatis, Konstantinos; Westermann, Dirk; Tschöpe, Carsten; Rauch, Ursula; Landmesser, Ulf; Schultheiss, Heinz-Peter; Dörner, Andrea

    2016-06-01

    Ischemia impairs the adenine nucleotide translocase (ANT), which transports ADP and ATP across the inner mitochondrial membrane. We investigated whether ANT1 overexpression has protective effects on ischemic hearts. Myocardial infarction was induced in wild-type (WT) and heart-specific ANT1-transgenic (ANT1-TG) rats, and hypoxia was set in isolated cardiomyocytes. ANT1 overexpression reduced the myocardial infarct area and increased the survival rate of infarcted rats. Reduced ANT1 expression and increased 4-hydroxynonenal modification of ANT paralleled to impaired ANT function in infarcted WT hearts. ANT1 overexpression improved ANT expression and function. This was accompanied by reduced mitochondrial cytochrome C release and caspase-3 activation. ANT1-TG hearts suffered less from oxidative stress, as shown by lower protein carbonylation and 4-hydroxynonenal modification of ANT. ANT1 overexpression also increased cell survival of hypoxic cardiomyocytes and attenuated reactive oxygen species (ROS) production. This was linked to higher stability of mitochondrial membrane potential and lower activity of ROS detoxifying catalase. ANT1-TG cardiomyocytes also showed higher resistance against H2O2 treatment, which was independent of catalase activity. In conclusion, ANT1 overexpression compensates impaired ANT activity under oxygen-restricted conditions. It reduces ROS production and oxidative stress, stabilizes mitochondrial integrity, and increases survival, making ANT1 a component in ROS management and heart protection during ischemia. ANT1 overexpression reduces infarct size and increases survival after infarction. ANT1 overexpression compensates restricted ANT expression and function in infarcted hearts. Increased ANT1 expression enhances mitochondrial integrity. ANT1-overexpressing hearts reduce oxidative stress by decreasing ROS generation. ANT1 is a component in ROS management and heart protection.

  13. Imported pigs may have introduced the first classical swine influenza viruses into Mainland China.

    Science.gov (United States)

    Zhu, Wenfei; Yang, Shuai; Guo, Yuanji; Yang, Lei; Bai, Tian; Yu, Zaijiang; Li, Xiaodan; Li, Ming; Guo, Junfeng; Wang, Dayan; Gao, Rongbao; Dong, Libo; Zou, Shumei; Li, Zi; Wang, Min; Shu, Yuelong

    2013-07-01

    The first classical swine influenza A H1N1 viruses were isolated in Mainland China in 1991. To aid surveillance of swine influenza viruses as part of pandemic preparedness, we sought to identify their origin. We sequenced and phylogenically analyzed 19 swine influenza viruses isolated in 1991 and 1992 in China and compared them with viruses isolated from other regions during the same period. All 19 swine influenza viruses analyzed in our study shared the highest similarity with the classical swine influenza virus A/Swine/Maryland/23239/1991 (H1N1). Phylogenetic trees of eight segmented genes exhibited similar topology, with all segments in the cluster of classical swine influenza viruses. In addition, antigenic analysis also indicated that the tested isolated were related to classical swine influenza isolates. Classical swine H1N1 influenza viruses were predominant in Beijing pig herds during this period. Since both antibody and virus detections did not indicate the presence of CS H1N1 before 1991 in Mainland China, we combined with the data on pigs imported to and exported from China and concluded that these viruses might spread to China via pigs imported from North America and that they could affect the genetic evolution and transmission dynamics of swine influenza viruses in Hong Kong. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Comparative Prevalence of Immune Evasion Complex Genes Associated with β-Hemolysin Converting Bacteriophages in MRSA ST5 Isolates from Swine, Swine Facilities, Humans with Swine Contact, and Humans with No Swine Contact.

    Directory of Open Access Journals (Sweden)

    Samantha J Hau

    Full Text Available Livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA draws concern from the public health community because in some countries these organisms may represent the largest reservoir of MRSA outside hospital settings. Recent studies indicate LA-MRSA strains from swine are more genetically diverse than the first reported sequence type ST398. In the US, a diverse population of LA-MRSA is found including organisms of the ST398, ST9, and ST5 lineages. Occurrence of ST5 MRSA in swine is of particular concern since ST5 is among the most prevalent lineages causing clinical infections in humans. The prominence of ST5 in clinical disease is believed to result from acquisition of bacteriophages containing virulence or host-adapted genes including the immune-evasion cluster (IEC genes carried by β-hemolysin converting bacteriophages, whose absence in LA-MRSA ST398 is thought to contribute to reduced rates of human infection and transmission associated with this lineage. The goal of this study was to investigate the prevalence of IEC genes associated with β-hemolysin converting bacteriophages in MRSA ST5 isolates obtained from agricultural sources, including swine, swine facilities, and humans with short- or long-term swine exposure. To gain a broader perspective, the prevalence of these genes in LA-MRSA ST5 strains was compared to the prevalence in clinical MRSA ST5 strains from humans with no known exposure to swine. IEC genes were not present in any of the tested MRSA ST5 strains from agricultural sources and the β-hemolysin gene was intact in these strains, indicating the bacteriophage's absence. In contrast, the prevalence of the β-hemolysin converting bacteriophage in MRSA ST5 strains from humans with no exposure to swine was 90.4%. The absence of β-hemolysin converting bacteriophage in LA-MRSA ST5 isolates is consistent with previous reports evaluating ST398 strains and provides genetic evidence indicating LA-MRSA ST5 isolates

  15. Comparative Prevalence of Immune Evasion Complex Genes Associated with β-Hemolysin Converting Bacteriophages in MRSA ST5 Isolates from Swine, Swine Facilities, Humans with Swine Contact, and Humans with No Swine Contact

    Science.gov (United States)

    Hau, Samantha J.; Sun, Jisun; Davies, Peter R.; Frana, Timothy S.; Nicholson, Tracy L.

    2015-01-01

    Livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA) draws concern from the public health community because in some countries these organisms may represent the largest reservoir of MRSA outside hospital settings. Recent studies indicate LA-MRSA strains from swine are more genetically diverse than the first reported sequence type ST398. In the US, a diverse population of LA-MRSA is found including organisms of the ST398, ST9, and ST5 lineages. Occurrence of ST5 MRSA in swine is of particular concern since ST5 is among the most prevalent lineages causing clinical infections in humans. The prominence of ST5 in clinical disease is believed to result from acquisition of bacteriophages containing virulence or host-adapted genes including the immune-evasion cluster (IEC) genes carried by β-hemolysin converting bacteriophages, whose absence in LA-MRSA ST398 is thought to contribute to reduced rates of human infection and transmission associated with this lineage. The goal of this study was to investigate the prevalence of IEC genes associated with β-hemolysin converting bacteriophages in MRSA ST5 isolates obtained from agricultural sources, including swine, swine facilities, and humans with short- or long-term swine exposure. To gain a broader perspective, the prevalence of these genes in LA-MRSA ST5 strains was compared to the prevalence in clinical MRSA ST5 strains from humans with no known exposure to swine. IEC genes were not present in any of the tested MRSA ST5 strains from agricultural sources and the β-hemolysin gene was intact in these strains, indicating the bacteriophage’s absence. In contrast, the prevalence of the β-hemolysin converting bacteriophage in MRSA ST5 strains from humans with no exposure to swine was 90.4%. The absence of β-hemolysin converting bacteriophage in LA-MRSA ST5 isolates is consistent with previous reports evaluating ST398 strains and provides genetic evidence indicating LA-MRSA ST5 isolates may harbor a

  16. Comparative Prevalence of Immune Evasion Complex Genes Associated with β-Hemolysin Converting Bacteriophages in MRSA ST5 Isolates from Swine, Swine Facilities, Humans with Swine Contact, and Humans with No Swine Contact.

    Science.gov (United States)

    Hau, Samantha J; Sun, Jisun; Davies, Peter R; Frana, Timothy S; Nicholson, Tracy L

    2015-01-01

    Livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA) draws concern from the public health community because in some countries these organisms may represent the largest reservoir of MRSA outside hospital settings. Recent studies indicate LA-MRSA strains from swine are more genetically diverse than the first reported sequence type ST398. In the US, a diverse population of LA-MRSA is found including organisms of the ST398, ST9, and ST5 lineages. Occurrence of ST5 MRSA in swine is of particular concern since ST5 is among the most prevalent lineages causing clinical infections in humans. The prominence of ST5 in clinical disease is believed to result from acquisition of bacteriophages containing virulence or host-adapted genes including the immune-evasion cluster (IEC) genes carried by β-hemolysin converting bacteriophages, whose absence in LA-MRSA ST398 is thought to contribute to reduced rates of human infection and transmission associated with this lineage. The goal of this study was to investigate the prevalence of IEC genes associated with β-hemolysin converting bacteriophages in MRSA ST5 isolates obtained from agricultural sources, including swine, swine facilities, and humans with short- or long-term swine exposure. To gain a broader perspective, the prevalence of these genes in LA-MRSA ST5 strains was compared to the prevalence in clinical MRSA ST5 strains from humans with no known exposure to swine. IEC genes were not present in any of the tested MRSA ST5 strains from agricultural sources and the β-hemolysin gene was intact in these strains, indicating the bacteriophage's absence. In contrast, the prevalence of the β-hemolysin converting bacteriophage in MRSA ST5 strains from humans with no exposure to swine was 90.4%. The absence of β-hemolysin converting bacteriophage in LA-MRSA ST5 isolates is consistent with previous reports evaluating ST398 strains and provides genetic evidence indicating LA-MRSA ST5 isolates may harbor a reduced

  17. Chicken muscle mitochondrial content appears co-ordinately regulated and is associated with performance phenotypes

    Directory of Open Access Journals (Sweden)

    Antonio Reverter

    2017-01-01

    Full Text Available Mitochondrial content is a fundamental cellular bioenergetic phenotype. Previous work has hypothesised possible links between variation in muscle mitochondrial content and animal performance. However, no population screens have been performed in any production species. Here, we have designed a high throughput molecular approach to estimate mitochondrial content in commercial broilers. Technical validity was established using several approaches, including its performance in monoclonal DF-1 cells, cross-tissue comparisons in tissues with differing metabolic demands (white fatheart muscle and, as a negative control, a near absence of mtDNA amplification from whole blood. We screened breast muscle and thigh muscle in 80 birds individually phenotyped for 11 growth and development traits. Substantial individual variation (fivefold was discovered in both breast and thigh muscle mitochondrial content. Interestingly, across birds we detected a very strong positive relationship between breast and thigh content (correlation coefficient 0.61; P<0.0001, consistent with coordinate regulatory control across the musculature. Further, breast muscle mitochondrial content is negatively correlated with breast muscle yield (−0.27; P=0.037, abdominal fat content (−0.31; P=0.017 and carcass yield (−0.26; P=0.045. Therefore, low breast muscle mitochondrial content is associated with more muscular birds possessing higher abdominal fat, the latter being in line with biomedical models of obesity. Finally, thigh mitochondrial content is negatively correlated with the bow out leg defect (−0.30; P=0.011. Overall, our data point to mitochondrial content as a promising consideration in predictive modelling of production traits.

  18. Disruption of Endothelial Cell Mitochondrial Bioenergetics in Lambs with Increased Pulmonary Blood Flow

    Science.gov (United States)

    Sharma, Shruti; Fratz, Sohrab; Kumar, Sanjiv; Rafikov, Ruslan; Aggarwal, Saurabh; Rafikova, Olga; Lu, Qing; Burns, Tantiana; Dasarathy, Sridevi; Wright, Johnny; Schreiber, Christian; Radman, Monique; Fineman, Jeffrey R.

    2013-01-01

    Abstract Aims: The mitochondrial dysfunction in our lamb model of congenital heart disease with increased pulmonary blood flow (PBF) (Shunt) is associated with disrupted carnitine metabolism. Our recent studies have also shown that asymmetric dimethylarginine (ADMA) levels are increased in Shunt lambs and ADMA increases the nitration of mitochondrial proteins in lamb pulmonary arterial endothelial cells (PAEC) in a nitric oxide synthase (NOS)-dependent manner. Thus, we determined whether there was a mechanistic link between endothelial nitric oxide synthase (eNOS), ADMA, and the disruption of carnitine homeostasis in PAEC. Results: Exposure of PAEC to ADMA induced the redistribution of eNOS to the mitochondria, resulting in an increase in carnitine acetyl transferase (CrAT) nitration and decreased CrAT activity. The resulting increase in acyl-carnitine levels resulted in mitochondrial dysfunction and the disruption of mitochondrial bioenergetics. Since the addition of l-arginine prevented these pathologic changes, we examined the effect of l-arginine supplementation on carnitine homeostasis, mitochondrial function, and nitric oxide (NO) signaling in Shunt lambs. We found that the treatment of Shunt lambs with l-arginine prevented the ADMA-mediated mitochondrial redistribution of eNOS, the nitration-mediated inhibition of CrAT, and maintained carnitine homeostasis. In turn, adenosine-5′-triphosphate levels and eNOS/heat shock protein 90 interactions were preserved, and this decreased NOS uncoupling and enhanced NO generation. Innovation: Our data link alterations in cellular l-arginine metabolism with the disruption of mitochondrial bioenergetics and implicate altered carnitine homeostasis as a key player in this process. Conclusion: l-arginine supplementation may be a useful therapy to prevent the mitochondrial dysfunction involved in the pulmonary vascular alterations secondary to increased PBF. Antioxid. Redox Signal. 18, 1739–1752. PMID:23244702

  19. Role of verocytotoxigenic Escherichia coli in the swine production chain

    Directory of Open Access Journals (Sweden)

    Laura Ercoli

    2015-06-01

    Full Text Available Shiga toxin-producing Escherichia coli (STEC can cause severe clinical diseases in humans, such as haemorrhagic colitis (HC and haemolytic-uremic syndrome (HUS. Although ruminants, primarily cattle, have been suggested as typical reservoirs of STEC, many food products of other origins, including pork products, have been confirmed as vehicles for STEC transmission. Only in rare cases, pork consumption is associated with severe clinical symptoms caused by high pathogenic STEC strains. However, in these outbreaks, it is unknown whether the contamination of food products occurs during swine processing or via cross-contamination from foodstuffs of different sources. In swine, STEC plays an important role in the pathogenesis of oedema disease. In particular a Shiga toxin subtype, named stx2e, it is considered as a key factor involved in the damage of swine endothelial cells. On the contrary, stx2e-producing Escherichia coli has rarely been isolated in humans, and usually only from asymptomatic carriers or from patients with mild symptoms, such as uncomplicated diarrhoea. In fact, the presence of gene stx2e, encoding for stx2e, has rarely been reported in STEC strains that cause HUS. Moreover, stx2e-producing STEC isolated from humans and pigs were found to differ in serogroup, their virulence profile and interaction with intestinal epithelial cells. Because of the limited epidemiologic data of STEC in swine and the increasing role of non-O157 STEC in human illnesses, the relationship between swine STEC and human disease needs to be further investigated.

  20. Effect of soy protein on swine intestinal lipoproteins

    International Nuclear Information System (INIS)

    Ho, H.T.

    1987-01-01

    Hypocholesterolemic effect of soy protein appears to be the result of reduced cholesterol absorption and enhanced cholesterol excretion. The objective of this study is to delineate the underlying mechanism of soy protein effect on cholesterol absorption. At the end of a 5-week soy-protein or casein diet, swine were subjected to cannulation of mesenteric lymph duct under halothane anesthesia. A single dose of 250 μCi [ 14 C]-cholesterol and 10 mCi [ 3 H]-leucine was infused into the upper jejunum two hours after one-fifth of daily food was given. Then lymph was collected hourly for three hours and the lipoprotein fractions were separated by ultracentrifugation. SDS-PAGE (5%) was used to measure the concentrations of individual apoproteins by densitometric scanning. The three-hour lymphatic transport of cholesterol in casein-fed swine was significantly higher than in those fed soy protein. Triglyceride transports were similar in two groups. The [ 3 H]-leucine incorporation study revealed that transport of apo B-48 bore a significant positive relationship to transport of cholesterol in both chylomicron and VLDL fractions of mesenteric lymph. A greater apo B-48 secretion with higher specific activity was probably responsible for the greater transport of cholesterol in chylomicrons in casein-fed swine. On the other hand, the lesser cholesterol transport in chylomicrons in soy protein-fed swine was probably caused by lower apo B-48 secretion. Similarly, the transport of lymph VLDL cholesterol in swine fed casein or soy protein paralleled the amount of accompanying apo B-48. Dietary proteins probably influence the intestinal synthesis of apo B-48 which in turn affects cholesterol transport into the lymphatics

  1. Antimicrobial use in Chinese swine and broiler poultry production.

    Science.gov (United States)

    Krishnasamy, Vikram; Otte, Joachim; Silbergeld, Ellen

    2015-01-01

    Antimicrobial use for growth promotion in food animal production is now widespread. A major concern is the rise of antimicrobial resistance and the subsequent impact on human health. The antimicrobials of concern are used in concentrated animal feeding operations (CAFOs) which are responsible for almost all meat production including swine and poultry in the US. With global meat consumption rising, the CAFO model has been adopted elsewhere to meet this demand. One such country where this has occurred is China, and evidence suggests 70% of poultry production now occurs outside of traditional small farms. Moreover, China is now the largest aggregate consumer of meat products in the world. With this rapid rise in consumption, the Chinese production model has changed along with the use of antimicrobials in feeds. However, the specific antibiotic use in the Chinese food animal production sector is unclear. Additionally, we are aware of high quantities of antimicrobial use because of reports of high concentrations of antimicrobials in animal waste and surface waters surrounding animal feeding operations. In this report, we estimate the volume of antibiotics used for swine and poultry production as these are the two meat sources with the highest levels of production and consumption in China. We adopt a model developed by Mellon et al. in the US for estimating drug use in feed for poultry and swine production to estimate overall antimicrobial use as well as antimicrobial use by class. We calculate that 38.5 million kg [84.9 million lbs] were used in 2012 in China's production of swine and poultry. By antibiotic class, the highest weights are tetracyclines in swine and coccidiostats in poultry. The volume of antimicrobial use is alarming. Although there are limitations to these data, we hope our report will stimulate further analysis and a sense of urgency in assessing the consequences of such high levels of utilization in terms of antibiotic resistance in the food supply

  2. Target Heart Rates

    Science.gov (United States)

    ... Check Recipe Certification Program Nutrition Requirements Heart-Check Professional Resources Contact the Heart-Check Certification Program Simple Cooking and Recipes Dining Out Choosing a Restaurant Deciphering ...

  3. Heart failure - medicines

    Science.gov (United States)

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... will need to take most of your heart failure medicines every day. Some medicines are taken once ...

  4. Aspirin and heart disease

    Science.gov (United States)

    ... fluids and diuretics Heart failure - home monitoring Heart failure - what to ask your ... of Cardiology, Harborview Medical Center, University of Washington Medical School, Seattle, WA. Also reviewed ...

  5. 76 FR 70037 - Importation of Live Swine, Swine Semen, Pork, and Pork Products From Liechtenstein and Switzerland

    Science.gov (United States)

    2011-11-10

    ... Liechtenstein and Switzerland AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Final rule... Liechtenstein and Switzerland to the region of Europe that we recognize as low risk for classical swine fever... Switzerland to the region of Europe that we recognize as low risk for CSF and to add Liechtenstein to the...

  6. 76 FR 7721 - Importation of Live Swine, Swine Semen, Pork, and Pork Products; Estonia, Hungary, Slovakia, and...

    Science.gov (United States)

    2011-02-11

    ... exception of semen collected from swine in Denmark, Finland, the Republic of Ireland, Sweden, or the United... CSF Region in the EU; History Before discussing our assessments of the animal health status of Estonia...,'' took into consideration the CSF history of the 10 Member States in the EC's request, the CSF history of...

  7. Quantitative assessment of the likelihood of the introduction of classical swine fever virus into the Danish swine population

    DEFF Research Database (Denmark)

    Bronsvoort, BMD; Alban, L.; Greiner, M.

    2008-01-01

    Classical swine fever virus (CSFV) is a major infectious-disease agent of livestock and causes production losses through increased morbidity and mortality, particularly of young pigs. We identified the pathways for introduction of CSFV into Denmark and assessed the annual probability...

  8. 77 FR 74555 - Importation of Live Swine, Swine Semen, Pork, and Pork Products; Estonia, Hungary, Slovakia, and...

    Science.gov (United States)

    2012-12-17

    ... semen collected from swine in Denmark, Finland, the Republic of Ireland, Sweden, or the United Kingdom.... This rule: (1) Preempts all State and local laws and regulations that are inconsistent with this rule..., Finland, the Republic of Ireland, Sweden, or the United Kingdom''. 0 b. By removing paragraph (h). 0 c. By...

  9. The potato tuber mitochondrial proteome

    DEFF Research Database (Denmark)

    Møller, Ian Max; Salvato, Fernanda; Havelund, Jesper

    We are testing the hypothesis that oxidized peptides are released from stressed mitochondria and contribute to retrograde signalling (Møller IM & Sweetlove LJ 2010 Trends Plant Sci 15, 370-374). However, there is a large gap between the number of experimentally verified mitochondrial proteins (~450...

  10. Insulin Resistance and Mitochondrial Dysfunction.

    Science.gov (United States)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

    Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

  11. Renal disease and mitochondrial genetics.

    Science.gov (United States)

    Rötig, Agnès

    2003-01-01

    Respiratory chain (RC) deficiencies have long been regarded as neuromuscular diseases mainly originating from mutations in the mitochondrial DNA. Oxidative phosphorylation, i.e. adenosine triphosphate (ATP) synthesis-coupled electron transfer from substrate to oxygen through the RC, does not occur only in the neuromuscular system. Therefore, a RC deficiency can theoretically give rise to any symptom, in any organ or tissue, at any age and with any mode of inheritance, owing to the dual genetic origin of RC enzymes (nuclear DNA and mitochondrial DNA). Mitochondrial diseases can give rise to various syndromes or association, namely, neurologic and neuromuscular diseases, cardiac, renal, hepatic, hematological and endocrin or dermatological presentations. The most frequent renal symptom is proximal tubular dysfunction with a more or less complete de Toni-Debre-Fanconi Syndrome. A few patients have been reported with tubular acidosis, Bartter Syndrome, chronic tubulointerstitial nephritis or nephrotic syndrome. The diagnosis of a RC deficiency is difficult when only renal symptoms are present, but should be easier when another, seemingly unrelated symptom is observed. Metabolic screening for abnormal oxidoreduction status in plasma, including lactate/pyruvate and ketone body molar ratios, can help to identify patients for further investigations. These include the measurement of oxygen consumption by mitochondria and the assessment of mitochondrial respiratory enzyme activities by spectrophotometric studies. Any mode of inheritance can be observed: sporadic, autosomal dominant or recessive, or maternal inheritance.

  12. Subunits Rip1 and Cox9p of the respiratory chain contribute to diclofenac-induced mitochondrial dysfunction

    NARCIS (Netherlands)

    van Leeuwen, J.S.; Orij, R.; Luttik, M.A.; Smits, G.J.; Vermeulen, N.P.E.; Vos, J.C.

    2010-01-01

    The widely used drug diclofenac can cause serious heart, liver and kidney injury, which may be related to its ability to cause mitochondrial dysfunction. Using Saccharomyces cerevisiae as a model system, we studied the mechanisms of diclofenac toxicity and the role of mitochondria therein. We found

  13. Subunits Rip1p and Cox9p of the respiratory chain contribute to diclofenac-induced mitochondrial dysfunction

    NARCIS (Netherlands)

    van Leeuwen, J.S.; Orij, R.; Luttik, M.A.H.; Smits, G.J.; Vermeulen, N.P.E.; Vos, J. C.

    2011-01-01

    The widely used drug diclofenac can cause serious heart, liver and kidney injury, which may be related to its ability to cause mitochondrial dysfunction. Using Saccharomyces cerevisiae as a model system, we studied the mechanisms of diclofenac toxicity and the role of mitochondria therein. We found

  14. Time-Dependent and Organ-Specific Changes in Mitochondrial Function, Mitochondrial DNA Integrity, Oxidative Stress and Mononuclear Cell Infiltration in a Mouse Model of Burn Injury.

    Directory of Open Access Journals (Sweden)

    Bartosz Szczesny

    Full Text Available Severe thermal injury induces a pathophysiological response that affects most of the organs within the body; liver, heart, lung, skeletal muscle among others, with inflammation and hyper-metabolism as a hallmark of the post-burn damage. Oxidative stress has been implicated as a key component in development of inflammatory and metabolic responses induced by burn. The goal of the current study was to evaluate several critical mitochondrial functions in a mouse model of severe burn injury. Mitochondrial bioenergetics, measured by Extracellular Flux Analyzer, showed a time dependent, post-burn decrease in basal respiration and ATP-turnover but enhanced maximal respiratory capacity in mitochondria isolated from the liver and lung of animals subjected to burn injury. Moreover, we detected a tissue-specific degree of DNA damage, particularly of the mitochondrial DNA, with the most profound effect detected in lungs and hearts of mice subjected to burn injury. Increased mitochondrial biogenesis in lung tissue in response to burn injury was also observed. Burn injury also induced time dependent increases in oxidative stress (measured by amount of malondialdehyde and neutrophil infiltration (measured by myeloperoxidase activity, particularly in lung and heart. Tissue mononuclear cell infiltration was also confirmed by immunohistochemistry. The amount of poly(ADP-ribose polymers decreased in the liver, but increased in the heart in later time points after burn. All of these biochemical changes were also associated with histological alterations in all three organs studied. Finally, we detected a significant increase in mitochondrial DNA fragments circulating in the blood immediately post-burn. There was no evidence of systemic bacteremia, or the presence of bacterial DNA fragments at any time after burn injury. The majority of the measured parameters demonstrated a sustained elevation even at 20-40 days post injury suggesting a long-lasting effect of thermal

  15. Mitochondrial rejuvenation after induced pluripotency.

    Directory of Open Access Journals (Sweden)

    Steven T Suhr

    2010-11-01

    Full Text Available As stem cells of the early embryo mature and differentiate into all tissues, the mitochondrial complement undergoes dramatic functional improvement. Mitochondrial activity is low to minimize generation of DNA-damaging reactive oxygen species during pre-implantation development and increases following implantation and differentiation to meet higher metabolic demands. It has recently been reported that when the stem cell type known as induced pluripotent stem cells (IPSCs are re-differentiated for several weeks in vitro, the mitochondrial complement progressively re-acquires properties approximating input fibroblasts, suggesting that despite the observation that IPSC conversion "resets" some parameters of cellular aging such as telomere length, it may have little impact on other age-affected cellular systems such as mitochondria in IPSC-derived cells.We have examined the properties of mitochondria in two fibroblast lines, corresponding IPSCs, and fibroblasts re-derived from IPSCs using biochemical methods and electron microscopy, and found a dramatic improvement in the quality and function of the mitochondrial complement of the re-derived fibroblasts compared to input fibroblasts. This observation likely stems from two aspects of our experimental design: 1 that the input cell lines used were of advanced cellular age and contained an inefficient mitochondrial complement, and 2 the re-derived fibroblasts were produced using an extensive differentiation regimen that may more closely mimic the degree of growth and maturation found in a developing mammal.These results - coupled with earlier data from our laboratory - suggest that IPSC conversion not only resets the "biological clock", but can also rejuvenate the energetic capacity of derived cells.

  16. Take heart!

    CERN Multimedia

    Alizée Dauvergne

    2010-01-01

    Recently, ten new semi-automatic defibrillators were installed at various locations around CERN. This is a preventive measure intended to provide cardiac arrest victims with the best possible response. The first responder could be you!   The Director-General has welcomed the initiative of the Medical Service and Fire Brigade for the installation of ten new semi-automatic defibrillators. You have probably seen them on your way to the restaurant, for example:  brand new semi-automatic defibrillators, ready for an emergency. Housed in a white wall-mounted case, the bright red defibrillators are marked with a white heart symbol crossed by a lightning bolt (see photo). The defibrillator is designed so that anyone can use it. “Anyone can use it, you don’t need to be a health professional,” says Dr Reymond from CERN's Medical Service. Together with the CERN Fire Brigade, he is behind the initiative to have these units put in place. And with good reason, as the unit...

  17. Reverse zoonosis of influenza to swine: new perspectives on the human-animal interface.

    Science.gov (United States)

    Nelson, Martha I; Vincent, Amy L

    2015-03-01

    The origins of the 2009 influenza A (H1N1) pandemic in swine are unknown, highlighting gaps in our understanding of influenza A virus (IAV) ecology and evolution. We review how recently strengthened influenza virus surveillance in pigs has revealed that influenza virus transmission from humans to swine is far more frequent than swine-to-human zoonosis, and is central in seeding swine globally with new viral diversity. The scale of global human-to-swine transmission represents the largest 'reverse zoonosis' of a pathogen documented to date. Overcoming the bias towards perceiving swine as sources of human viruses, rather than recipients, is key to understanding how the bidirectional nature of the human-animal interface produces influenza threats to both hosts. Published by Elsevier Ltd.

  18. Insulin upregulates GRIM-19 and protects cardiac mitochondrial morphology in type 1 diabetic rats partly through PI3K/AKT signaling pathway.

    Science.gov (United States)

    Li, Yong-Guang; Dong, Zhi-Feng; Chen, Kan-Kai; He, Ya-Ping; Dai, Xiao-Yan; Li, Shuai; Li, Jing-Bo; Zhu, Wei; Wei, Meng

    2017-11-04

    Insulin is involved in the development of diabetic heart disease and is important in the activities of mitochondrial complex I. However, the effect of insulin on cardiac mitochondrial nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 subunit of retinoic-interferon-induced mortality 19 (GRIM-19) has not been characterized. The aim of this study was to investigate the effect of insulin on the mitochondrial GRIM-19 in the hearts of rats with streptozotocin (STZ)-induced type 1 diabetes. Protein changes of GRIM-19 were evaluated by western blotting and reverse transcription-quantitative polymerase chain reaction. Furthermore, the effects of insulin on mitochondrial complex I were detected in HeLa cells and H9C2 cardiac myocytes. During the development of diabetic heart disease, the cardiac function did not change within the 8 weeks, but the mitochondrial morphology was altered. The hearts from the rats with STZ-induced diabetes exhibited reduced expression of GRIM-19. Prior to the overt cardiac dilatation, mitochondrial alterations were already present. Following subcutaneous insulin injection, it was demonstrated that GRIM-19 protein was altered, as well as the mitochondrial morphology. The phosphoinositide 3-kinase inhibitor LY294002 had an effect on insulin signaling in H9C2 cardiacmyocytes, and decreased the level of GRIM-19 by half compared with that in the insulin group. The results indicate that insulin is essential for the control of cardiac mitochondrial morphology and the GRIM-19 expression partly via PI3K/AKT signaling pathways. Copyright © 2017. Published by Elsevier Inc.

  19. A reaction-diffusion model of ROS-induced ROS release in a mitochondrial network.

    Directory of Open Access Journals (Sweden)

    Lufang Zhou

    2010-01-01

    Full Text Available Loss of mitochondrial function is a fundamental determinant of cell injury and death. In heart cells under metabolic stress, we have previously described how the abrupt collapse or oscillation of the mitochondrial energy state is synchronized across the mitochondrial network by local interactions dependent upon reactive oxygen species (ROS. Here, we develop a mathematical model of ROS-induced ROS release (RIRR based on reaction-diffusion (RD-RIRR in one- and two-dimensional mitochondrial networks. The nodes of the RD-RIRR network are comprised of models of individual mitochondria that include a mechanism of ROS-dependent oscillation based on the interplay between ROS production, transport, and scavenging; and incorporating the tricarboxylic acid (TCA cycle, oxidative phosphorylation, and Ca(2+ handling. Local mitochondrial interaction is mediated by superoxide (O2.- diffusion and the O2.(--dependent activation of an inner membrane anion channel (IMAC. In a 2D network composed of 500 mitochondria, model simulations reveal DeltaPsi(m depolarization waves similar to those observed when isolated guinea pig cardiomyocytes are subjected to a localized laser-flash or antioxidant depletion. The sensitivity of the propagation rate of the depolarization wave to O(2.- diffusion, production, and scavenging in the reaction-diffusion model is similar to that observed experimentally. In addition, we present novel experimental evidence, obtained in permeabilized cardiomyocytes, confirming that DeltaPsi(m depolarization is mediated specifically by O2.-. The present work demonstrates that the observed emergent macroscopic properties of the mitochondrial network can be reproduced in a reaction-diffusion model of RIRR. Moreover, the findings have uncovered a novel aspect of the synchronization mechanism, which is that clusters of mitochondria that are oscillating can entrain mitochondria that would otherwise display stable dynamics. The work identifies the

  20. [Antibodies against Toxoplasma gondii in swine in Costa Rica: epidemiologic importance].

    Science.gov (United States)

    Torres, A L; Chinchilla, M; Reyes, L

    1991-01-01

    On a three hundred swine sera sample collected from a Municipal Slaughter house and a Research Laboratory at the Ministerio de Agricultura y Ganadería a 26% of positivity against T. gondii was found using the carbon immunoassay. A relationship between the age and swine race are made. The epidemiological significance of this findings are discussed focused mainly on the role of swine meat as a source of human infection in Costa Rica.

  1. Hepatitis E virus and coliphages in waters proximal to swine concentrated animal feeding operations

    OpenAIRE

    Gentry-Shields, Jennifer; Myers, Kevin; Pisanic, Nora; Heaney, Christopher; Stewart, Jill

    2014-01-01

    North Carolina is the second leading state in pork production in the United States, with over 10 million swine. Swine manure in NC is typically collected and stored in open-pit lagoons before the liquid waste is sprayed onto agricultural fields for disposal. Components of this waste may be able to impact surface water quality with the potential for human exposure. This study examined viruses of public health concern in creeks adjacent to swine concentrated animal feeding operation (CAFO) spra...

  2. Efficacy of Influenza Vaccination and Tamiflu? Treatment ? Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

    OpenAIRE

    Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Th?ophile; Wutzler, Peter; Schmidtke, Michaela

    2013-01-01

    Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebu...

  3. Comparison of Hydroxocobalamin Versus Norepinephrine Versus Saline in a Swine Model of Servere Septic Shock

    Science.gov (United States)

    2016-05-20

    Versus Saline in a Swine Model of Severe Septic Shock presented at/published to SURF Conference, San Antonio, TX 20 May 2016 with MDWJ 41-108, and has...PRESENTED: Comparison of hydroxocobalamin versus norepinephrine versus saline in a Swine model of severe septic shock 7. FUNDING RECEIVED FOR THIS...Comparison of hydroxocbalamin versus norepinephrine versus saline in a swine model of severe septic shock . Background: Sepsis is associated with a mortality

  4. Comparison of Hydroxocobalamin Versus Norepinephrine Versus Saline in a Swine Model of Severe Septic Shock

    Science.gov (United States)

    2016-05-18

    Versus Saline in a Swine Model of Severe Septic Shock presented at/published to the Lightning Oral, SAEM Conference, New Orleans, LA 10-13 May 2016 with...PRESENTED: Comparison of hydroxocobalamin versus norepinephrine versus sal ine in a Swine model of severe septic shock 7. FUNDING RECEIVED FOR THIS...saline in a swine model of severe septic shock . Background: Sepsis is associated with a mortality of nearly 30%. Mortality is due, in part, to an

  5. Spatial Dynamics of Human-Origin H1 Influenza A Virus in North American Swine

    Science.gov (United States)

    Nelson, Martha I.; Lemey, Philippe; Tan, Yi; Vincent, Amy; Lam, Tommy Tsan-Yuk; Detmer, Susan; Viboud, Cécile; Suchard, Marc A.; Rambaut, Andrew; Holmes, Edward C.; Gramer, Marie

    2011-01-01

    The emergence and rapid global spread of the swine-origin H1N1/09 pandemic influenza A virus in humans underscores the importance of swine populations as reservoirs for genetically diverse influenza viruses with the potential to infect humans. However, despite their significance for animal and human health, relatively little is known about the phylogeography of swine influenza viruses in the United States. This study utilizes an expansive data set of hemagglutinin (HA1) sequences (n = 1516) from swine influenza viruses collected in North America during the period 2003–2010. With these data we investigate the spatial dissemination of a novel influenza virus of the H1 subtype that was introduced into the North American swine population via two separate human-to-swine transmission events around 2003. Bayesian phylogeographic analysis reveals that the spatial dissemination of this influenza virus in the US swine population follows long-distance swine movements from the Southern US to the Midwest, a corn-rich commercial center that imports millions of swine annually. Hence, multiple genetically diverse influenza viruses are introduced and co-circulate in the Midwest, providing the opportunity for genomic reassortment. Overall, the Midwest serves primarily as an ecological sink for swine influenza in the US, with sources of virus genetic diversity instead located in the Southeast (mainly North Carolina) and South-central (mainly Oklahoma) regions. Understanding the importance of long-distance pig transportation in the evolution and spatial dissemination of the influenza virus in swine may inform future strategies for the surveillance and control of influenza, and perhaps other swine pathogens. PMID:21695237

  6. Swine flu- a serious pandeMic threat | Rachna | IMTU Medical Journal

    African Journals Online (AJOL)

    Swine infl uenza (swine fl u) is a respiratory disease caused by type A infl uenza virus, the only pandemic strain. This new strain called swine-origin (H1N1) infl uenza A virus (SO-IAV), is transmitted to humans and spreads quickly from person to person. It emerged in Mexico and USA in April 2009. The 2009 outbreak of ...

  7. Inducible NO synthase is constitutively expressed in porcine myocardium and its level decreases along with tachycardia-induced heart failure.

    Science.gov (United States)

    Paslawska, Urszula; Kiczak, Liliana; Bania, Jacek; Paslawski, Robert; Janiszewski, Adrian; Dzięgiel, Piotr; Zacharski, Maciej; Tomaszek, Alicja; Michlik, Katarzyna

    2016-01-01

    The adverse effects of oxidative stress and the presence of proinflammatory factors in the heart have been widely demonstrated mainly on rodent models. However, larger clinical trials focusing on inflammation or oxidative stress in heart failure (HF) have not been carried out. This may be due to differences in the anatomy and physiology of the cardiovascular system between small rodents and large mammals. Thus, we investigated myocardial inflammatory factors, such as inducible NO synthase (iNOS) and oxidative stress indices in female pigs with chronic tachycardia-induced cardiomyopathy. Homogenous female siblings of Large White breed swine (n=15) underwent continuous right ventricular (RV) pacing at 170bpm, whereas five sham-operated subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were euthanized at subsequent stages of the disease: mild, moderate and severe HF. Left ventricle (LV) sections were examined with electron microscopy. The relative expression of iNOS in LV was determined by quantitative PCR. The protein level of iNOS was determined by Western blotting and immunohistochemistry. The level of the S-nitrosylated (S-NO) protein in LV was determined after S-NO moieties were substituted by biotin, followed by a colorimetrical detection with streptavidin. Malondialdehyde (MDA), a marker of lipid peroxidation, was evaluated in the LV and serum using thiobarbituric acid. The aconitase activity (based on measurement of the concomitant formation of NADPH from NADP(+)), a marker of oxidative stress, was analyzed in mitochondrial and cytosolic LV fractions. The concentration of interleukin-1β (IL-1β) was measured in LV homogenates using enzyme-linked immunosorbent assay. RV pacing resulted in an impairment of LV systolic function, LV dilatation and neurohormonal activation. The electron microscopy revealed abnormalities within the cardiomyocytes of failing hearts, i.e. swollen mitochondria and myofibril

  8. Advanced Heart Failure

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Advanced Heart Failure Updated:May 9,2017 When heart failure (HF) ... Making This content was last reviewed May 2017. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  9. African swine fever virus infection in Classical swine fever subclinically infected wild boars.

    Science.gov (United States)

    Cabezón, Oscar; Muñoz-González, Sara; Colom-Cadena, Andreu; Pérez-Simó, Marta; Rosell, Rosa; Lavín, Santiago; Marco, Ignasi; Fraile, Lorenzo; de la Riva, Paloma Martínez; Rodríguez, Fernando; Domínguez, Javier; Ganges, Llilianne

    2017-08-01

    Recently moderate-virulence classical swine fever virus (CSFV) strains have been proven capable of generating postnatal persistent infection (PI), defined by the maintenance of viremia and the inability to generate CSFV-specific immune responses in animals. These animals also showed a type I interferon blockade in the absence of clinical signs. In this study, we assessed the infection generated in 7-week-old CSFV PI wild boars after infection with the African swine fever virus (ASFV). The wild boars were divided in two groups and were infected with ASFV. Group A comprised boars who were CSFV PI in a subclinical form and Group B comprised pestivirus-free wild boars. Some relevant parameters related to CSFV replication and the immune response of CSFV PI animals were studied. Additionally, serum soluble factors such as IFN-α, TNF-α, IL-6, IL-10, IFN-γ and sCD163 were analysed before and after ASFV infection to assess their role in disease progression. After ASFV infection, only the CSFV PI wild boars showed progressive acute haemorrhagic disease; however, the survival rates following ASFV infection was similar in both experimental groups. Notwithstanding, the CSFV RNA load of CSFV PI animals remained unaltered over the study; likewise, the ASFV DNA load detected after infection was similar between groups. Interestingly, systemic type I FN-α and IL-10 levels in sera were almost undetectable in CSFV PI animals, yet detectable in Group B, while detectable levels of IFN-γ were found in both groups. Finally, the flow cytometry analysis showed an increase in myelomonocytic cells (CD172a + ) and a decrease in CD4 + T cells in the PBMCs from CSFV PI animals after ASFV infection. Our results showed that the immune response plays a role in the progression of disease in CSFV subclinically infected wild boars after ASFV infection, and the immune response comprised the systemic type I interferon blockade. ASFV does not produce any interference with CSFV replication, or vice

  10. EVIDENCE OF PSEUDORABIES VIRUS SHEDDING IN FERAL SWINE ( SUS SCROFA) POPULATIONS OF FLORIDA, USA.

    Science.gov (United States)

    Hernández, Felipe A; Sayler, Katherine A; Bounds, Courtney; Milleson, Michael P; Carr, Amanda N; Wisely, Samantha M

    2018-01-01

    :  Feral swine ( Sus scrofa) are a pathogen reservoir for pseudorabies virus (PrV). The virus can be fatal to wildlife and contributes to economic losses in the swine industry worldwide. National surveillance efforts in the US use serology to detect PrV-specific antibodies in feral swine populations, but PrV exposure is not a direct indicator of pathogen transmission among conspecifics or to non-suid wildlife species. We measured antibody production and the presence of PrV DNA in four tissue types from feral swine populations of Florida, US. We sampled blood, nasal, oral, and genital swabs from 551 individuals at 39 sites during 2014-16. Of the animals tested for antibody production, 224 of 436 (51%) feral swine were antibody positive while 38 of 549 feral swine (7%) tested for viral shedding were quantitative polymerase chain reaction (qPCR)-positive for PrV. The detection of PrV DNA across all the collected sample types (blood, nasal, oral, and genital [vaginal] swabs) suggested viral shedding via direct (oronasal or venereal), and potentially indirect (through carcass consumption), routes of transmission among infected and susceptible animals. Fourteen of 212 seronegative feral swine were qPCR-positive, indicating 7% false negatives in the serologic assay. Our findings suggest that serology may underestimate the actual infection risk posed by feral swine to other species and that feral swine populations in Florida are capable of shedding the virus through multiple routes.

  11. Caffeine Enhances the Calcium-Dependent Cardiac Mitochondrial Permeability Transition: Relevance for Caffeine Toxicity

    OpenAIRE

    Sardão, Vilma A.; Oliveira, Paulo J.; Moreno, António J. M.

    2002-01-01

    Caffeine (1,3,7-trimethylxanthine), a compound present in beverages such as tea and coffee, is known to be toxic at high concentrations. Some of the observed clinical conditions include cardiovascular disease and reproductive disorders, among others. The possible toxic effects of caffeine on heart mitochondria are still poorly understood. The influence of caffeine on the mitochondrial permeability transition has not been clarified so far. The objective of this study was to investigate whether...

  12. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.

    Science.gov (United States)

    Xu, Wenjing; Barrientos, Tomasa; Mao, Lan; Rockman, Howard A; Sauve, Anthony A; Andrews, Nancy C

    2015-10-20

    Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1) might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart

    Directory of Open Access Journals (Sweden)

    Wenjing Xu

    2015-10-01

    Full Text Available Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1 might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure.

  14. The Genetic Challenges and Opportunities in Advanced Heart Failure.

    Science.gov (United States)

    Hannah-Shmouni, Fady; Seidelmann, Sara B; Sirrs, Sandra; Mani, Arya; Jacoby, Daniel

    2015-11-01

    The causes of heart failure are diverse. Inherited causes represent an important clinical entity and can be divided into 2 major categories: familial and metabolic cardiomyopathies. The distinct features that might be present in early disease states can become broadly overlapping with other diseases, such as in the case of inherited cardiomyopathies (ie, familial hypertrophic cardiomyopathy or mitochondrial diseases). In this review article, we focus on genetic issues related to advanced heart failure. Because of the emerging importance of this topic and its breadth, we sought to focus our discussion on the known genetic forms of heart failure syndromes, genetic testing, and newer data on pharmacogenetics and therapeutics in the treatment of heart failure, to primarily encourage clinicians to place a priority on the diagnosis and treatment of these potentially treatable conditions. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  15. Hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction.

    Science.gov (United States)

    Hall, A R; Burke, N; Dongworth, R K; Kalkhoran, S B; Dyson, A; Vicencio, J M; Dorn, G W; Yellon, D M; Hausenloy, D J

    2016-05-26

    Mitochondria alter their shape by undergoing cycles of fusion and fission. Changes in mitochondrial morphology impact on the cellular response to stress, and their interactions with other organelles such as the sarcoplasmic reticulum (SR). Inhibiting mitochondrial fission can protect the heart against acute ischemia/reperfusion (I/R) injury. However, the role of the mitochondrial fusion proteins, Mfn1 and Mfn2, in the response of the adult heart to acute I/R injury is not clear, and is investigated in this study. To determine the effect of combined Mfn1/Mfn2 ablation on the susceptibility to acute myocardial I/R injury, cardiac-specific ablation of both Mfn1 and Mfn2 (DKO) was initiated in mice aged 4-6 weeks, leading to knockout of both these proteins in 8-10-week-old animals. This resulted in fragmented mitochondria (electron microscopy), decreased mitochondrial respiratory function (respirometry), and impaired myocardial contractile function (echocardiography). In DKO mice subjected to in vivo regional myocardial ischemia (30 min) followed by 24 h reperfusion, myocardial infarct size (IS, expressed as a % of the area-at-risk) was reduced by 46% compared with wild-type (WT) hearts. In addition, mitochondria from DKO animals had decreased MPTP opening susceptibility (assessed by Ca(2+)-induced mitochondrial swelling), compared with WT hearts. Mfn2 is a key mediator of mitochondrial/SR tethering, and accordingly, the loss of Mfn2 in DKO hearts reduced the number of interactions measured between these organelles (quantified by proximal ligation assay), attenuated mitochondrial calcium overload (Rhod2 confocal microscopy), and decreased reactive oxygen species production (DCF confocal microscopy) in response to acute I/R injury. No differences in isolated mitochondrial ROS emissions (Amplex Red) were detected in response to Ca(2+) and Antimycin A, further implicating disruption of mitochondria/SR tethering as the protective mechanism. In summary, despite apparent

  16. H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.

    Directory of Open Access Journals (Sweden)

    Marion Russier

    2017-03-01

    Full Text Available A pandemic-capable influenza virus requires a hemagglutinin (HA surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5.1 to 5.9 for H1 viruses and pH 5.3 to 5.8 for H3 viruses. Thus, contemporary swine isolates vary widely in HA stability, having values favored by both avian (pH >5.5 and human and ferret (pH ≤5.5 species. Using an early 2009 pandemic H1N1 (pH1N1 virus backbone, we generated three viruses differing by one HA residue that only altered HA stability: WT (pH 5.5, HA1-Y17H (pH 6.0, and HA2-R106K (pH 5.3. All three replicated in pigs and transmitted from pig-to-pig and pig-to-ferret. WT and R106 viruses maintained HA genotype and phenotype after transmission. Y17H (pH 6.0 acquired HA mutations that stabilized the HA protein to pH 5.8 after transmission to pigs and 5.5 after transmission to ferrets. Overall, we found swine support a broad range of HA activation pH for contact transmission and many recent swine H1N1 and H3N2 isolates have stabilized (human-like HA proteins. This constitutes a heightened pandemic risk and underscores the importance of ongoing surveillance and control efforts for swine viruses.

  17. The Bordetella Bps polysaccharide is required for biofilm formation and persistence in the lower respiratory tract of swine

    Science.gov (United States)

    Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Additionally, B. bronchiseptica is capable of establishing long-term or chronic infections in swine. Bacterial biofilms are increasingly recognized as important contributors to chronic bacter...

  18. Fate and transport of antibiotic resistant bacteria and resistance genes in artificially drained agricultural fields receiving swine manure application

    Science.gov (United States)

    While previous studies have examined the occurrence of antibiotic resistant bacteria and antibiotic resistant genes around confined swine feeding operations, little information is known about their release and transport from artificially drained fields receiving swine manure application. Much of the...

  19. Transcriptional immunoresponse of tissue-specific macrophages in swine after infection with African swine fever virus

    Directory of Open Access Journals (Sweden)

    Kowalczyk Andrzej

    2015-12-01

    Full Text Available Macrophages and cytokines are important in the control of inflammation and regulation of the immune response. However, they can also contribute to immunopathology in the host after viral infection and the regulatory network can be subverted by infectious agents, including viruses, some of which produce cytokine analogues or have mechanisms that inhibit cytokine function. African swine fever virus (ASFV encodes a number of proteins which modulate cytokine and chemokine induction, host transcription factor activation, stress responses, and apoptosis. The aim of this review is to elucidate the mechanisms of immune responses to ASFV in different subpopulations of porcine macrophages. A transcriptional immune response in different resident tissue macrophages following ASFV infection was presented in many publications. ASFV-susceptible porcine macrophages can be of several origins, such as peripheral blood, lungs, bone marrow, etc. blood monocytes, blood macrophages, and lung macrophages have demonstrated a modulation of phenotype. Monocyte-derived macrophages could express surface markers not found on their monocyte precursors. Moreover, they can undergo further differentiation after infection and during inflammation. When viruses infect such cells, immunological activity can be seriously impaired or modified.

  20. A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Houman Ashrafian

    2010-06-01

    Full Text Available Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM. However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease.

  1. Mitochondrial Respiration and Oxygen Tension.

    Science.gov (United States)

    Shaw, Daniel S; Meitha, Karlia; Considine, Michael J; Foyer, Christine H

    2017-01-01

    Measurements of respiration and oxygen tension in plant organs allow a precise understanding of mitochondrial capacity and function within the context of cellular oxygen metabolism. Here we describe methods that can be routinely used for the isolation of intact mitochondria, and the determination of respiratory electron transport, together with techniques for in vivo determination of oxygen tension and measurement of respiration by both CO 2 production and O 2 consumption that enables calculation of the respiratory quotient [CO 2 ]/[O 2 ].

  2. Mitochondrial disorders in congenital myopathies

    Directory of Open Access Journals (Sweden)

    D. A. Kharlamov

    2014-01-01

    Full Text Available The literature review gives data on the role of mitochondrial disorders in the pathogenesis of congenital myopathies: congenital muscular dystrophies and congenital structural myopathies. It describes changes in congenital muscular dystrophies with type VI collagen, in myodystrophy with giant mitochondria, in congenital central core myopathies, myotubular myopathy, etc. Clinical and experimental findings are presented. Approaches to therapy for energy disorders in congenital myopathies are depicted.

  3. Zeolite and swine inoculum effect on poultry manure biomethanation

    DEFF Research Database (Denmark)

    Kougias, Panagiotis; Fotidis, Ioannis; Zaganas, I.D.

    2013-01-01

    Poultry manure is an ammonia-rich substrate that inhibits methanogenesis, causing severe problems to the anaerobic digestion process. In this study, the effect of different natural zeolite concentrations on the mesophilic anaerobic digestion of poultry waste inoculated with well-digested swine...... manure was investigated. A significant increase in methane production was observed in treatments where zeolite was added, compared to the treatment without zeolite.Methane production in the treatment with 10 g dm-3 of natural zeolite was found to be 109.75% higher compared to the treatment without...... zeolite addition. The results appear to be influenced by the addition of zeolite, which reduces ammonia toxicity in anaerobic digestion and by the ammonia-tolerant swine inoculum....

  4. Swine Influenza Viruses – Evolution and Zoonotic Potential

    DEFF Research Database (Denmark)

    Fobian, Kristina

    the establishment of a reverse genetics system based on a backbone from the Danish H1N2 SIV, which is one of the two most prevalent subtypes in Denmark. Recently, a variant of a North American swine H3N2 virus containing a pandemic M gene was transmitted to humans in the US and on few occasions human......-to-human transmission was observed. These events underline the need for a reverse genetics system to be used for an analysis of the behavior of a pandemic M gene in a Danish SIV.......Influenza A virus (IAV) is an important respiratory pathogen with a broad host range. The natural reservoir for IAV is waterfowls, but both human and swine are considered natural hosts. During the past century IAV has caused severe pandemics as well as seasonal epidemics in the human population...

  5. Creation of transcatheter aortopulmonary and cavopulmonary shunts using magnetic catheters: feasibility study in swine.

    Science.gov (United States)

    Levi, Daniel S; Danon, Saar; Gordon, Brent; Virdone, Nicky; Vinuela, Fernando; Shah, Sanjay; Carman, Greg; Moore, John W

    2009-05-01

    Surgical shunts are the basic form of palliation for many types of congenital heart disease. The Glenn shunt (superior cavopulmonary connection) and central shunt (aortopulmonary connection) represent surgical interventions that could potentially be accomplished by transcatheter techniques. We sought to investigate the efficacy of using neodymium iron boron (NdFeB) magnetic catheters to create transcatheter cavopulmonary and aortopulmonary shunts. NdFeB magnets were machined and integrated into catheters. "Target" catheters were placed in the pulmonary arteries (PAs), and radiofrequency "perforation" catheters were placed in either the descending aorta (DAo) for central shunts or the superior vena cava (SVC) for Glenn shunts. The magnet technique or "balloon target" method was used to pass wires from the DAo or the SVC into the PA. Aortopulmonary and cavopulmonary connections were then created using Atrium iCAST covered stents. Magnet catheters were used to perforate the left pulmonary artery from the DAo, thereby establishing a transcatheter central shunt. Given the orientation of the vasculature, magnetic catheters could not be used for SVC-to-PA connections; however, perforation from the SVC to the right pulmonary artery was accomplished with a trans-septal needle and balloon target. Transcatheter Glenn or central shunts were successfully created in four swine.

  6. Desmin and αB-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival.

    Science.gov (United States)

    Diokmetzidou, Antigoni; Soumaka, Elisavet; Kloukina, Ismini; Tsikitis, Mary; Makridakis, Manousos; Varela, Aimilia; Davos, Constantinos H; Georgopoulos, Spiros; Anesti, Vasiliki; Vlahou, Antonia; Capetanaki, Yassemi

    2016-10-15

    The association of desmin with the α-crystallin Β-chain (αΒ-crystallin; encoded by CRYAB), and the fact that mutations in either one of them leads to heart failure in humans and mice, suggests a potential compensatory interplay between the two in cardioprotection. To address this hypothesis, we investigated the consequences of αΒ-crystallin overexpression in the desmin-deficient (Des -/- ) mouse model, which possesses a combination of the pathologies found in most cardiomyopathies, with mitochondrial defects as a hallmark. We demonstrated that cardiac-specific αΒ-crystallin overexpression ameliorates all these defects and improves cardiac function to almost wild-type levels. Protection by αΒ-crystallin overexpression is linked to maintenance of proper mitochondrial protein levels, inhibition of abnormal mitochondrial permeability transition pore activation and maintenance of mitochondrial membrane potential (Δψ m ). Furthermore, we found that both desmin and αΒ-crystallin are localized at sarcoplasmic reticulum (SR)-mitochondria-associated membranes (MAMs), where they interact with VDAC, Mic60 - the core component of mitochondrial contact site and cristae organizing system (MICOS) complex - and ATP synthase, suggesting that these associations could be crucial in mitoprotection at different levels. © 2016. Published by The Company of Biologists Ltd.

  7. VDAC-Targeted Drugs Affecting Cytoprotection and Mitochondrial Physiology in Cerebrovascular and Cardiovascular Diseases.

    Science.gov (United States)

    Karachitos, Andonis; Jordan, Joaquin; Kmita, Hanna

    2017-01-01

    Cerebrovascular and cardiovascular diseases are caused by impairment of the brain and/or heart circulation. Insufficient blood flow results in decreased oxygen delivery (ischemia), which affects mitochondrial functioning and consequently leads to insufficient ATP production. The predominant mitochondrial outer membrane protein, the voltage dependent anion selective channel (VDAC), is considered to be crucial for mitochondrial functioning. In human mitochondria, as in other vertebrates, three isoforms of VDAC (VDAC1-VDAC3) are present, and they likely play different roles. In this review, we summarize the available data concerning VDAC involvement in cardiovascular and cerebrovascular diseases with regard to VDAC isoforms and discuss the use of possible VDAC-related intervention targets as well as known VDAC-interacting and cytoprotection- conferring molecules in the treatment of cerebrovascular and cardiovascular diseases. The suitable references on disorders defined as cerebrovascular and cardiovascular diseases as well as VDAC contribution to these conditions were searched using PubMed and ClinicalTrials.gov databases. The review is based on the 138 carefully selected articles. Mitochondrial dysfunction triggered by changes in VDAC properties undoubtedly contributes to cell death and related diseases, including cerebrovascular and cardiovascular diseases. Thus, beside diagnostic application, modulation of VDAC activity, including its isoforms, is thus of great importance for the development of efficient therapeutic interventions. Moreover, identification of VDAC-interacting molecules that protect against mitochondrial dysfunction and cell death seems to be of great importance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Polymerase discordance in novel swine influenza H3N2v constellations is tolerated in swine but not human respiratory epithelial cells.

    Science.gov (United States)

    Powell, Joshua D; Dlugolenski, Daniel; Nagy, Tamas; Gabbard, Jon; Lee, Christopher; Tompkins, Stephen M; Tripp, Ralph A

    2014-01-01

    Swine-origin H3N2v, a variant of H3N2 influenza virus, is a concern for novel reassortment with circulating pandemic H1N1 influenza virus (H1N1pdm09) in swine because this can lead to the emergence of a novel pandemic virus. In this study, the reassortment prevalence of H3N2v with H1N1pdm09 was determined in swine cells. Reassortants evaluated showed that the H1N1pdm09 polymerase (PA) segment occurred within swine H3N2 with ∼ 80% frequency. The swine H3N2-human H1N1pdm09 PA reassortant (swH3N2-huPA) showed enhanced replication in swine cells, and was the dominant gene constellation. Ferrets infected with swH3N2-huPA had increased lung pathogenicity compared to parent viruses; however, swH3N2-huPA replication in normal human bronchoepithelial cells was attenuated - a feature linked to expression of IFN-β and IFN-λ genes in human but not swine cells. These findings indicate that emergence of novel H3N2v influenza constellations require more than changes in the viral polymerase complex to overcome barriers to cross-species transmission. Additionally, these findings reveal that while the ferret model is highly informative for influenza studies, slight differences in pathogenicity may not necessarily be indicative of human outcomes after infection.

  9. Impact of production systems on swine confinement buildings bioaerosols.

    Science.gov (United States)

    Létourneau, Valérie; Nehmé, Benjamin; Mériaux, Anne; Massé, Daniel; Duchaine, Caroline

    2010-02-01

    Hog production has been substantially intensified in Eastern Canada. Hogs are now fattened in swine confinement buildings with controlled ventilation systems and high animal densities. Newly designed buildings are equipped with conventional manure handling and management systems, shallow or deep litter systems, or source separation systems to manage the large volumes of waste. However, the impacts of those alternative production systems on bioaerosol concentrations within the barns have never been evaluated. Bioaerosols were characterized in 18 modern swine confinement buildings, and the differences in bioaerosol composition in the three different production systems were evaluated. Total dust, endotoxins, culturable actinomycetes, fungi, and bacteria were collected with various apparatuses. The total DNA of the air samples was extracted, and quantitative polymerase chain reaction (PCR) was used to assess the total number of bacterial genomes, as a total (culturable and nonculturable) bacterial assessment. The measured total dust and endotoxin concentrations were not statistically different in the three studied production systems. In buildings with sawdust beds, actinomycetes and molds were found in higher concentrations than in the conventional barns. Aspergillus, Cladosporium, Penicillium, and Scopulariopsis species were identified in all the studied swine confinement buildings. A. flavus, A. terreus, and A. versicolor were abundantly present in the facilities with sawdust beds. Thermotolerant A. fumigatus and Mucor were usually found in all the buildings. The culturable bacteria concentrations were higher in the barns with litters than in the conventional buildings, while real-time PCR revealed nonstatistically different concentrations of total bacteria in all the studied swine confinement buildings. In terms of workers' respiratory health, barns equipped with a solid/liquid separation system may offer better air quality than conventional buildings or barns with

  10. Investigations of eugenol efficacy in treatment of mange in swine

    Directory of Open Access Journals (Sweden)

    Jezdimirović Milanka

    2006-01-01

    Full Text Available The acaricide efficacy, tolerability and safety of the active ingredient of the etheric oil of cloves eugenol was investigated in the treatment of mange in swine, and the obtained results were compared with the results of acaricide efficacy of the synthetic acaricide permethrin, which has been in use for quite a some time. A single application of permethrin in the form of a 1% solution showed maximum efficacy of 62.5%, and after three applications of 75.0% in the treatment of sarcoptes in swine mange. A single application of eugenol in the form of a 10% solution had maximum efficacy of 75.0%, and applied three times an efficacy of 100% in curbing Sarcoptes scabiei var. suis. A single administration of 20% eugenol solution showed maximum efficacy of 87.5%, and applied three times it was 100% efficient in curbing Sarcoptes scabeiei var. suis. The best efficacy in the treatment of sarcoptes mange in swine was achieved with three applications of eugenol in a concentration of 20%. This maximum effect (100% was obtained already after the second treatment. Eugenol in a concentration of 10% was safe for local application on skin because it does not cause any undesired reactions, while a 20% concentration caused irritation followed by a passing redness and disquiet in a smaller number of treated animals. The results of comparative investigations of acaricide efficacy of permethrin and eugenol demonstrate that there is resistence in Sarcoptes scabiei var. suis to permethrin. The biocide eugenol can safely be recommended for the treatment of sarcoptes mange in swine.

  11. Reduction of STAT3 expression induces mitochondrial dysfunction and autophagy in cardiac HL-1 cells.

    Science.gov (United States)

    Elschami, Myriam; Scherr, Michaela; Philippens, Brigitte; Gerardy-Schahn, Rita

    2013-01-01

    Signal transducer and activator of transcription 3 (STAT3) is an important mediator of cardiac survival pathways. Reduced levels of STAT3 in patients with end-stage heart failure suggest a clinical relevance of STAT3 deficiency for cardiac disease. The recent identification of STAT3 as a mitochondrial protein which is important for full activity of mitochondrial complex I has opened a new field for the investigation of how STAT3 functions in cardioprotection. The goal of this study was to establish a cell culture model with a reduced STAT3 expression, and to use this model for the investigation of mitochondrial and mitochondrial-associated functions under STAT3 deficiency. In the murine cardiomyogenic cell line HL-1, the expression of STAT3 was silenced by lentiviral transduction with anti-STAT3 shRNA (STAT3 KD cells). STAT3 mRNA and protein levels were significantly reduced in HL-1 STAT3 KD cells compared to HL-1 cells transduced with a control shRNA. Spectrophotometric and polarographic assays with mitochondrial enriched fractions and intact cells showed reduced activities of respiratory chain complexes I, II, III and IV in HL-1 STAT3 KD cells. At ultrastructural level, a severe damage of mitochondrial integrity was observed, combined with a significant increase in autophagolysosomes in STAT3-deficient HL-1 cells. Our results demonstrate that the HL-1 STAT3 KD cell line is a good model to study cellular consequences of STAT3 deficiency. Moreover, this is the first study to show that STAT3 deficiency leads to a disruption of mitochondrial ultrastructure and increased autophagy. Copyright © 2012 Elsevier GmbH. All rights reserved.

  12. Humanin exerts cardioprotection against cardiac ischemia/reperfusion injury through attenuation of mitochondrial dysfunction.

    Science.gov (United States)

    Thummasorn, Savitree; Apaijai, Nattayaporn; Kerdphoo, Sasiwan; Shinlapawittayatorn, Krekwit; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-12-01

    Myocardial reperfusion via the re-canalization of occluded coronary arteries is gold standard for the treatment of acute myocardial infarction. However, reperfusion itself can cause myocardial damage due to increased reactive oxygen species (ROS) production, a process known as ischemia/reperfusion (I/R) injury. Cardiac mitochondria are the major organelle of ROS production in the heart. Cardiac mitochondrial dysfunction caused by an increased ROS production can increase cardiac arrhythmia incidence, myocardial infarct size, and cardiac dysfunction. Thus, preservation of cardiac mitochondrial function is a promising pharmacological approach to reduce cardiac I/R injury. Humanin (HN), a newly discovered 24-amino acid polypeptide, has been shown to exert antioxidative stress and antiapoptotic effects. Although the cardioprotective effects of HN against I/R injury has been reported, the effect of HN on cardiac mitochondrial function has not yet been investigated. Thus, we tested the hypothesis that HN exerts its cardioprotective effects against I/R injury through the attenuation of cardiac mitochondrial dysfunction. I/R protocol was carried out using a 30-minutes occlusion of a left anterior descending coronary artery followed by a 120-minutes of reperfusion. The plasma HN level, infarct size, arrhythmia incidence, left ventricular function, and cardiac mitochondrial function were determined. Endogenous HN level before I/R injury showed no difference between groups, but was markedly decreased after I/R injury. HN analogue pretreatment decreased arrhythmia incidence and infarct size, improved cardiac mitochondrial function, and attenuated cardiac dysfunction. Humanin analogue pretreatment exerted cardioprotective effects against I/R injury through the attenuation of cardiac mitochondrial dysfunction. © 2016 John Wiley & Sons Ltd.

  13. Assessing Hemorrhage Severity with Continuous Automatic Heart-Rate-Complexity Monitoring in Swine

    Science.gov (United States)

    2014-12-02

    diately after ECMO initiation (median AST 482[345-1802] UI/L and median ALT 401 [177-1215] UI/L. There was a significant increase in PT and...in survivors (n=32) than non-survivors (n=37. Among the 28 patients with ELE, 9 had a further elevation in AST / ALT and 6 eventually died with...multiple organ failure. Of the 19 patients with reduction of AST / ALT , only 7 normalized their levels within 3 days since ECMO initiation. The reduction in

  14. Accelerating Coagulation in Traumatic Injuries Using Inorganic Polyphosphate-Coated Silica Nanoparticles in a Swine (Sus scrofa) Model

    Science.gov (United States)

    2018-03-13

    blood loss in a swine in a swine model. Methods : 9 male and 4 female pigs weighing 65±8 kg were anesthetized and instrumented . After abdominal...nanoparticles (PLNP) will decrease blood loss in a swine in a swine model. Methods : Pigs were anesthetized and instrumented and randomized to receive...study/training models in this protocol? No. REDUCTION: Since the last IACUC approval, have any methods been identified to reduce the number of live

  15. Characterization of the withdrawal phase in a swine controlled intestinal donation after circulatory death model.

    Science.gov (United States)

    Guo, Mingxiao; Li, Linlin; Lu, Chunlei

    2014-10-04

    Transplantation of donation after cardiac death (DCD) intestine has higher rates of organ failure and complications. Fortunately, this is less grievous in a subclass of DCD called controlled (CDCD), those with irreversible but incomplete brain injury. The aim of the paper is to establish a CDCD porcine model which is closely mimicking human CDCD scenario, and investigate the physiologic changes from withdrawal of ventilatory support to circulatory arrest. Ten domestic crossbred pigs were anesthetized and ventilated with room air. Once all baseline data was taken, atracurium besilate (0.9 mg/kg, 3×ED95) was administered and the ventilator was discontinued while the animal was under deep anesthesia to establish the porcine CDCD model. Meanwhile, heparin (150~200 U/kg) was administered after discontinuation of the ventilator. The time to death and the changes of arterial blood gases and hemodynamic parameters were monitored every 5 minutes until circulatory arrest. In addition, histopathology, ultrastructures (via electron microscope) and expression of tight junction proteins of intestinal mucosa were observed at the baseline and the time of death. The mean time to death was approximately (21.8±3.12 min. Within 5 minutes of removal of the ventilator, there was a hyperdynamic period. Systolic blood pressure and heart rate quickly increased to 118.5±10.4 mmHg and 108.2±4.94 bpm, respectively. Blood pressure and heart rate then reduced rapidly until circulatory arrest. Moreover, the PaO2 quickly dropped to 17.4±3.13 mmHg, the blood gases throughout the apneic time showed a rapid hypercapnia and acidosis. In addition, warm ischemia damaged intestinal mucosa and reduced TJ proteins expression. A new swine CDCD model, simulating three stages of "withdrawal of ventilation, systemic anticoagulation and determination of death", which closely mimics the human DCD scenario and can thus be used in studies related to organ transplantation, was successfully established.

  16. Decellularized Swine Dental Pulp as a Bioscaffold for Pulp Regeneration

    Directory of Open Access Journals (Sweden)

    Lei Hu

    2017-01-01

    Full Text Available Endodontic regeneration shows promise in treating dental pulp diseases; however, no suitable scaffolds exist for pulp regeneration. Acellular natural extracellular matrix (ECM is a favorable scaffold for tissue regeneration since the anatomical structure and ECM of the natural tissues or organs are well-preserved. Xenogeneic ECM is superior to autologous or allogeneic ECM in tissue engineering for its unlimited resources. This study investigated the characteristics of decellularized dental pulp ECM from swine and evaluated whether it could mediate pulp regeneration. Dental pulps were acquired from the mandible anterior teeth of swine 12 months of age and decellularized with 10% sodium dodecyl sulfate (SDS combined with Triton X-100. Pulp regeneration was conducted by seeding human dental pulp stem cells into decellularized pulp and transplanted subcutaneously into nude mice for 8 weeks. The decellularized pulp demonstrated preserved natural shape and structure without any cellular components. Histological analysis showed excellent ECM preservation and pulp-like tissue, and newly formed mineralized tissues were regenerated after being transplanted in vivo. In conclusion, decellularized swine dental pulp maintains ECM components favoring stem cell proliferation and differentiation, thus representing a suitable scaffold for improving clinical outcomes and functions of teeth with dental pulp diseases.

  17. Swine manure composting by means of experimental turning equipment.

    Science.gov (United States)

    Chiumenti, A; Da Borso, F; Rodar, T; Chiumenti, R

    2007-01-01

    The purpose of research was to test the effectiveness of a prototype of a turning machine and to evaluate the feasability of a farm-scale composting process of the solid fraction of swine manure. A qualitative evaluation of the process and final product was made by monitoring the following parameters: process temperature, oxygen concentration inside the biomass, gaseous emissions (CH4, CO2, NH3, N2O), respiration index, humification index, total and volatile solids, carbon and nitrogen, pH and microbial load. The prototype proved to be very effective from a technical-operational point of view. The composting process exhibited a typical time-history, characterised by a thermophilic phase followed by a curing phase [Chiumenti, A., Chiumenti, R., Diaz, L.F., Savage, G.M., Eggerth, L.L., Goldstein, N., 2005. Modern Composting Technologies. BioCycle-JG Press, Emmaus, PA, USA]. Gas emissions from compost the windrow were more intense during the active phase of the process and showed a decreasing trend from the thermophilic to the curing phase. The final compost was characterized by good qualitative characteristics, a significant level of humification [Rossi, L., Piccinini, S., 1999. La qualità agronomica dei compost derivanti da liquami suinicoli. (Agronomic quality of swine manure compost). L'informatore Agrario 38, 29-31] and no odor emissions. This method of managing manure represents an effective, low cost approach that could be an interesting opportunity for swine farms.

  18. Acute infection of swine by various Salmonella serovars.

    Science.gov (United States)

    Loynachan, A T; Nugent, J M; Erdman, M M; Harris, D L

    2004-07-01

    The objective of this study was to evaluate the ability of various serovars of Salmonella enterica subsp. enterica to infect alimentary and nonalimentary tissues of swine within 3 h of inoculation. Fourteen wild-type S. enterica serovars (4,12:imonophasic, 6,7 nonmotile, Agona, Brandenburg, Bredeney, Derby, Heidelberg, Infantis, Muenchen, Thompson, Typhimurium, Typhimurium variant Copenhagen, untypeable, and Worthington), two known virulent S. enterica serovars (Choleraesuis strain SC-38 and Typhimurium strain chi4232), and two avirulent S. enterica Choleraesuis vaccine strains (Argus and SC-54) were inoculated intranasally (approximately 5 x 10(9) cells) into swine (four animals per Salmonella isolate). Three hours after inoculation, animals were euthanized, and both alimentary tissues (tonsil, colon contents, and cecum contents) and nonalimentary tissues (mandibular lymph node, thymus, lung, liver, spleen, ileocecal lymph node, and blood) were collected for Salmonella isolation. All Salmonella serovars evaluated except Salmonella Choleraesuis SC-54 acutely infected both alimentary and nonalimentary tissues. These results indicate that Salmonella isolates commonly found in swine are capable of acutely infecting both alimentary and nonalimentary tissues in a time frame consistent with that in which animals are transported and held in lairage prior to slaughter.

  19. Ankistrodesmus gracilis (Chlorophyta fertilized in swine manure in the laboratory

    Directory of Open Access Journals (Sweden)

    Lúcia Helena Sipaúba-Tavares

    2008-03-01

    Full Text Available The objective of the present work was to investigate the influence of swine manure media on the growth, total length, dry weight, and nutritional value of Ankistrodesmus gracilis microalgae. Two media were measured: “in natura” and biodigested. The growth rate peak for A. gracilis was highest with biodigester treatment (6.2 x 107 cells.mL-1 on the 5th day, at a volume of 2L. The highest percentage of lipids was verifi ed for “in natura” media. Protein was highest (p > 0.05 for the biodigested media at 2L. Biovolume, ash rate, and total length were different (p 0.05. Light demand was also different between media, with lesser intensity being required for biodigested media (13.5μE.cm-2.s-1. In fact, the biodigested media proved to be cheaper in terms of cost and benefit. Generally, the medium containing swine manure, both “in natura” and biodigested, showed better results in A. gracilis development, with water quality adequate for culture systems. Swine manure in both forms may also be used in high-density cultures in the laboratory.

  20. Decellularized Swine Dental Pulp as a Bioscaffold for Pulp Regeneration.

    Science.gov (United States)

    Hu, Lei; Gao, Zhenhua; Xu, Junji; Zhu, Zhao; Fan, Zhipeng; Zhang, Chunmei; Wang, Jinsong; Wang, Songlin

    2017-01-01

    Endodontic regeneration shows promise in treating dental pulp diseases; however, no suitable scaffolds exist for pulp regeneration. Acellular natural extracellular matrix (ECM) is a favorable scaffold for tissue regeneration since the anatomical structure and ECM of the natural tissues or organs are well-preserved. Xenogeneic ECM is superior to autologous or allogeneic ECM in tissue engineering for its unlimited resources. This study investigated the characteristics of decellularized dental pulp ECM from swine and evaluated whether it could mediate pulp regeneration. Dental pulps were acquired from the mandible anterior teeth of swine 12 months of age and decellularized with 10% sodium dodecyl sulfate (SDS) combined with Triton X-100. Pulp regeneration was conducted by seeding human dental pulp stem cells into decellularized pulp and transplanted subcutaneously into nude mice for 8 weeks. The decellularized pulp demonstrated preserved natural shape and structure without any cellular components. Histological analysis showed excellent ECM preservation and pulp-like tissue, and newly formed mineralized tissues were regenerated after being transplanted in vivo. In conclusion, decellularized swine dental pulp maintains ECM components favoring stem cell proliferation and differentiation, thus representing a suitable scaffold for improving clinical outcomes and functions of teeth with dental pulp diseases.