Direct and transgenerational effects of low doses of perinatal di-(2-ethylhexyl phthalate (DEHP on social behaviors in mice.

Directory of Open Access Journals (Sweden)

Kayla M Quinnies

Full Text Available Di-(2-ethylhexyl phthalate (DEHP is an endocrine disrupting chemical commonly used as a plasticizer in medical equipment, food packaging, flooring, and children's toys. DEHP exposure during early development has been associated with adverse neurobehavioral outcomes in children. In animal models, early exposure to DEHP results in abnormal development of the reproductive system as well as altered behavior and neurodevelopment. Based on these data, we hypothesized that developmental exposure to DEHP would decrease social interactions and increase anxiety-like behaviors in mice in a dose-dependent manner, and that the effects would persist over generations. C57BL/6J mice consumed one of three DEHP doses (0, 5, 40, and 400 μg/kg body weight throughout pregnancy and during the first ten days of lactation. The two higher doses yielded detectable levels of DEHP metabolites in serum. Pairs of mice from control, low, and high DEHP doses were bred to create three dose lineages in the third generation (F3. Average anogenital index (AGI: anogenital distance/body weight was decreased in F1 males exposed to the low dose of DEHP and in F1 females exposed to the highest dose. In F1 mice, juvenile pairs from the two highest DEHP dose groups displayed fewer socially investigative behaviors and more exploratory behaviors as compared with control mice. The effect of DEHP on these behaviors was reversed in F3 mice as compared with F1 mice. F1 mice exposed to low and medium DEHP doses spent more time in the closed arms of the elevated plus maze than controls, indicating increased anxiety-like behavior. The generation-dependent effects on behavior and AGI suggest complex mechanisms by which DEHP directly impacts reproductive and neurobehavioral development and influences germline-inherited traits.

Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice

International Nuclear Information System (INIS)

Nakashima, Ryosuke; Hayashi, Yumi; Khalequzzaman, Md.; Jia, Xiaofang; Wang, Dong; Naito, Hisao; Ito, Yuki; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

2013-01-01

Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPARα), peroxisome proliferator-activated receptor α-null (Pparα-null) and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, α-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARa mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPARα mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, α-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPARα mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPARα mice, similarly to triglyceride levels

Comparative exposure to DEHP from food contact materials: application of the product intake fraction

DEFF Research Database (Denmark)

Ernstoff, Alexi; Jolliet, Olivier; Fantke, Peter

Quantitative Sustainability Assessment Food contact materials (FCM), e.g. bottles and food handling gloves, can contain potentially endocrine disrupting chemicals, such as di-2-ethylhexyl phthalate(DEHP, CAS: 117-81-7). To investigate the contribution of FCM to dietary DEHP exposure we apply...... thresholds. A hypothetical average PiF for the FCM sector was calculated via production volume and oral exposure doses estimated from NHANES data. In both cases the indication was gloves may contribute more to DEHP exposure when used with certain food items than bottled water. DEHP content in gloves greater...... than 5% would cause exceedance of US EPA threshold when used with certain food items,e.g. radishes based on PiF calculated here. The PiF used in thís context has applications for regulations related to FCM and exposure assessments on a per unit kilo basis....

Degradation kinetics of di-(2-ethylhexyl) phthalate (DEHP) and organic matter of sewage sludge during composting

International Nuclear Information System (INIS)

Cheng, H.-F.; Kumar, Mathava; Lin, J.-G.

2008-01-01

The potential degradation of di-(2-ethylhexyl) phthalate (DEHP) and organic matter of sewage sludge by composting was investigated using laboratory reactor at different operating conditions (E-1, E-2 and E-3). In all conditions, single stage thermophilic phase was observed within 2 days and almost, 60% of DEHP was degraded under this phase. At the end of composting, total DEHP degradation of more than 85% was observed in all conditions and total carbon reduction was 11.8% in E-1, 7.6% in E-2 and 10.8% in E-3. Similar trend was observed in the degradation of total nitrogen. The reduction of volatile solids (VS) in the composting reactors was 5.4% in E-1 (18 days), 5.5% in E-2 (12 days) and 4.3% in E-3 (18 days). The degradation kinetics of DEHP in thermophilic phase (including initial mesophilic phase) and the phase there after were determined by first order and fractional power kinetics, respectively. The significance of experimental parameters in DEHP degradation was assessed by Pearson correlation approach. Elevated temperature produced during composting was effective for the rapid degradation of DEHP from sewage sludge compared to mesophilic treatment

Uncoupling Marriages.

Science.gov (United States)

Kane, Barbara

1979-01-01

In counseling groups, uncoupling partners learn to say their good-byes and accept the death of the marriage. They complete their unfinished business with each other. An organizational strategy is necessary. Skill in helping partners uncouple is a vital function of a marriage counselor, who must be proficient in group counseling. (Author)

The Inflammation Response to DEHP through PPARγ in Endometrial Cells

Directory of Open Access Journals (Sweden)

Qiansheng Huang

2016-03-01

Full Text Available Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa were recruited to investigate the effects of di-(2-ethylhexyl phthalate (DEHP at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction.

Di(2-ethylhexyl)phthalate (DEHP) and di-n-butylphthalate (DBP) exposure through diet in hospital patients.

Science.gov (United States)

Cirillo, Teresa; Fasano, Evelina; Esposito, Francesco; Montuori, Paolo; Amodio Cocchieri, Renata

2013-01-01

Ready-to-eat packed meals intended to hospital patients were studied over a two-weeks period to measure the contents of di-(2-ethylhexyl) phthalate (DEHP) and di-n-butylphthalate (DBP) and to evaluate their daily intake by total diet. The packaging consisted of polyethylene terephthalate (PET) dishes sealed with polypropylene (PP) foil. The DEHP mean concentrations in total meals varied from 0.061±0.028 to 0.307±0.138μg/gwetweight (wet wt.); the DBP mean levels varied from 0.025±0.018 to 0.174±0.091μg/gwetwt. Highest levels of concentration for DEHP and DBP were found in bread with mean values of 0.307±0.138μg/gwetwt. and 0.174±0.091μg/gwetwt. for DEHP and DBP, respectively. The daily intake for DEHP was 3.1±0.9μg/kgbw and 1.5±0.5μg/kgbw for DBP. The mean±sd incidence of DEHP and DBP intake via hospital meals on the respective EFSA TDI was 6±2% (range 4-11%), and 15±5% (range 8-24%), respectively. Even if for hospital patients the major route of exposure may be represented by medical devices, the influence of the diet could have a significant value on TDI. Copyright © 2012 Elsevier Ltd. All rights reserved.

Designed biocompatible nano-inhibitor based on poly(β-cyclodextrin-ester) for reduction of the DEHP migration from plasticized PVC.

Science.gov (United States)

Raeisi, Ahmad; Faghihi, Khalil; Shabanian, Meisam

2017-10-15

The easy migration of di(2-ethylhexyl) phthalate (DEHP) from the plasticized PVC (P-PVC) poses a serious threat to human health and the ecosystems. Thus, its control migration from the P-PVC products is very important. In this work, a poly(β-cyclodextrin-ester) network (β-CDP) was synthesized via reaction of β-cyclodextrin with 3,3',4,4'-benzophenone tetracarboxylic dianhydride. As a potential inhibitor for reduction of the DEHP migration, the β-CDP was grafted to Fe 3 O 4 nanoparticles. Poly(β-cyclodextrin-ester) functionalized Fe 3 O 4 nanoparticles (MNP-CDP) has been used in PVC/DEHP system as a reactive nano-inhibitor to reduce DEHP migration. Thermal stability and mechanical properties of obtained films were investigated. DEHP migration tests of the P-PVC films were also carried out by using Gas chromatography. It was found that by incorporating the small amounts of nano-inhibitor in PVC/DEHP system, the migration of DEHP effectively reduced from the P-PVC samples about 65% without any serious changes in mechanical and thermal properties of the P-PVC films. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of di(2-ethylhexyl) phthalate (DEHP)-induced endocrine disruption by co-treatment of vitamins C and E and their mechanism of action.

Science.gov (United States)

Choi, Seul Min; Lim, Duck Soo; Kim, Min Kook; Yoon, Sungpil; Kacew, Sam; Kim, Hyung Sik; Lee, Byung-Mu

2018-05-29

The endocrine disrupting actions of di(2-ethylhexyl) phthalate (DEHP) on testicular functions are postulated to involve excess free radical generation. Thus the aim of this study was to examine the ability of antioxidant vitamins C and E to prevent DEHP-induced testicular disruption in male Sprague-Dawley (SD) rats. SD male rats were administered DEHP alone or DEHP with vitamin C and/or vitamin E for 30 days. DEHP alone increased the levels of testosterone (T) and reduced estradiol (E 2 ) concentrations. Supplementation with antioxidant vitamins diminished or restored serum T levels noted in DEHP-treated rats to control values. In contrast vitamins C and E increased E 2 levels to control in rats administered DEHP. Antioxidants significantly improved the decreased testicular levels of reduced glutathione and activity of superoxide dismutase compared to DEHP-treatment alone. Co-treatment of vitamins C and E also markedly improved the reduced epididymal sperm head counts and elevated levels of malondialdehyde (MDA) or 8-hydroxydeoxyguanosine (8-OHdG) induced by DEHP treatment. These results support the concept that the adverse actions of DEHP may be related to increased free radical generation while co-treatment with vitamins C and E significantly blocked the actions of DEHP on male testicular functions.

Development and characterization of a synthetic PVC/DEHP myocardial tissue analogue material for CT imaging applications.

Science.gov (United States)

Ramadan, Sherif; Paul, Narinder; Naguib, Hani E

2018-04-01

A simple myocardial analogue material has great potential to help researchers in the creation of medical CT Imaging phantoms. This work aims to outline a Bis(2-ethylhexyl) phthalate (DEHP) plasticizer/PVC material to achieve this. DEHP-PVC was manufactured in three ratios, 75, 80, and 85% DEHP by heating at 110 °C for 10 min to promote DEHP-PVC binding followed by heating at 150 °C to melt the blend. The material was then tested utilizing FTIR, tensile testing, dynamic mechanical analysis and imaged with computed tomography. The FTIR testing finds the presence of C-CL and carbonyl bonds that demonstrate the binding required in this plasticized material. The tensile testing finds a modulus of 180-20 kPa that increases with the proportion of plasticizer. The dynamic mechanical analysis finds a linear increase in viscoelastic properties with a storage/loss modulus of 6/.5-120/18 kPa. Finally, the CT number of the material increases with higher PVC content from 55 to 144HU. The 80% DEHP-PVC ratio meets the mechanical and CT properties necessary to function as a myocardial tissue analogue.

Mitochondrial uncouplers with an extraordinary dynamic range.

Science.gov (United States)

Lou, Phing-How; Hansen, Birgit S; Olsen, Preben H; Tullin, Søren; Murphy, Michael P; Brand, Martin D

2007-10-01

We have discovered that some weak uncouplers (typified by butylated hydroxytoluene) have a dynamic range of more than 10(6) in vitro: the concentration giving measurable uncoupling is less than one millionth of the concentration causing full uncoupling. They achieve this through a high-affinity interaction with the mitochondrial adenine nucleotide translocase that causes significant but limited uncoupling at extremely low uncoupler concentrations, together with more conventional uncoupling at much higher concentrations. Uncoupling at the translocase is not by a conventional weak acid/anion cycling mechanism since it is also caused by substituted triphenylphosphonium molecules, which are not anionic and cannot protonate. Covalent attachment of the uncoupler to a mitochondrially targeted hydrophobic cation sensitizes it to membrane potential, giving a small additional effect. The wide dynamic range of these uncouplers in isolated mitochondria and intact cells reveals a novel allosteric activation of proton transport through the adenine nucleotide translocase and provides a promising starting point for designing safer uncouplers for obesity therapy.

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

Energy Technology Data Exchange (ETDEWEB)

Shin, In-Sik; Lee, Mee-Young [Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, 483 Expo-ro, Yusung-gu, Daejeon 305-811 (Korea, Republic of); Cho, Eun-Sang [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Choi, Eun-young [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of); Son, Hwa-Young [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Lee, Kyoung-Youl, E-mail: youl10@hanmail.net [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of)

2014-02-01

Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue.

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

International Nuclear Information System (INIS)

Shin, In-Sik; Lee, Mee-Young; Cho, Eun-Sang; Choi, Eun-young; Son, Hwa-Young; Lee, Kyoung-Youl

2014-01-01

Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue

Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach

International Nuclear Information System (INIS)

Eveillard, Alexandre; Lasserre, Frederic; Tayrac, Marie de; Polizzi, Arnaud; Claus, Sandrine; Canlet, Cecile; Mselli-Lakhal, Laila; Gotardi, Gaelle; Paris, Alain; Guillou, Herve; Martin, Pascal G.P.; Pineau, Thierry

2009-01-01

Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPARα targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erbα pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erbα target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erbα pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.

Untersuchung der Di-(2-ethylhexyl)phthalat (DEHP)-Belastung der Allgemeinbevölkerung – Durchführung eines Human-Biomonitorings

OpenAIRE

Koch, Holger Martin

2007-01-01

i-(2-ethylhexyl)phthalat (DEHP) ist einer der bedeutendsten Weichmacher für PVC-Polymere mit Produktionszahlen im Bereich um 1 Million Tonnen pro Jahr weltweit. Als sog. äußerer Weichmacher ist DEHP nicht kovalent an den Kunststoff gebunden und blutet so mehr oder weniger schnell aus diesem aus und kann so die Umwelt, Nahrungsmittel oder den Menschen belasten. DEHP steht unter dringendem Verdacht, als Endokriner Disruptor/Modulator ins menschliche Hormonsystem einzugreifen und so eine Vielzah...

Influence of temperature on the emission of di-(2-ethylhexyl)phthalate (DEHP) from PVC flooring in the emission cell FLEC.

Science.gov (United States)

Clausen, Per Axel; Liu, Zhe; Kofoed-Sørensen, Vivi; Little, John; Wolkoff, Peder

2012-01-17

Emissions of di-(2-ethylhexyl) phthalate (DEHP) from one type of polyvinylchloride (PVC) flooring with approximately 13% (w/w) DEHP as plasticizer were measured in the Field and Laboratory Emission Cell (FLEC). The gas-phase concentrations of DEHP versus time were measured at air flow rate of 450 mL·min(-1) and five different temperatures: 23 °C, 35 °C, 47 °C, 55 °C, and 61 °C. The experiments were terminated two weeks to three months after steady-state was reached and the interior surface of the FLECs was rinsed with methanol to determine the surface concentration of DEHP. The most important findings are (1) DEHP steady-state concentrations increased greatly with increasing temperature (0.9 ± 0.1 μg·m(-3), 10 ± 1 μg·m(-3), 38 ± 1 μg·m(-3), 91 ± 4 μg·m(-3), and 198 ± 5 μg·m(-3), respectively), (2) adsorption to the chamber walls decreased greatly with increasing temperature (measured partition coefficient between FLEC air and interior surface are: 640 ± 146 m, 97 ± 20 m, 21 ± 5 m, 11 ± 2 m, and 2 ± 1 m, respectively), (3) gas-phase DEHP concentration in equilibrium with the vinyl flooring surface is close to the vapor pressure of pure DEHP, and (4) with an increase of temperature in a home from 23 to 35 °C, the amount of DEHP in the gas- and particle-phase combined is predicted to increase almost 10-fold. The amount in the gas-phase increases by a factor of 24 with a corresponding decrease in the amount on the airborne particles.

Synchronizing noisy nonidentical oscillators by transient uncoupling

Energy Technology Data Exchange (ETDEWEB)

Tandon, Aditya, E-mail: adityat@iitk.ac.in; Mannattil, Manu, E-mail: mmanu@iitk.ac.in [Department of Physics, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016 (India); Schröder, Malte, E-mail: malte@nld.ds.mpg.de [Network Dynamics, Max Planck Institute for Dynamics and Self-Organization (MPIDS), 37077 Göttingen (Germany); Timme, Marc, E-mail: timme@nld.ds.mpg.de [Network Dynamics, Max Planck Institute for Dynamics and Self-Organization (MPIDS), 37077 Göttingen (Germany); Department of Physics, Technical University of Darmstadt, 64289 Darmstadt (Germany); Chakraborty, Sagar, E-mail: sagarc@iitk.ac.in [Department of Physics, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016 (India); Mechanics and Applied Mathematics Group, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016 (India)

2016-09-15

Synchronization is the process of achieving identical dynamics among coupled identical units. If the units are different from each other, their dynamics cannot become identical; yet, after transients, there may emerge a functional relationship between them—a phenomenon termed “generalized synchronization.” Here, we show that the concept of transient uncoupling, recently introduced for synchronizing identical units, also supports generalized synchronization among nonidentical chaotic units. Generalized synchronization can be achieved by transient uncoupling even when it is impossible by regular coupling. We furthermore demonstrate that transient uncoupling stabilizes synchronization in the presence of common noise. Transient uncoupling works best if the units stay uncoupled whenever the driven orbit visits regions that are locally diverging in its phase space. Thus, to select a favorable uncoupling region, we propose an intuitive method that measures the local divergence at the phase points of the driven unit's trajectory by linearizing the flow and subsequently suppresses the divergence by uncoupling.

Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining neuronal death

International Nuclear Information System (INIS)

Guida, Natascia; Laudati, Giusy; Galgani, Mario; Santopaolo, Marianna; Montuori, Paolo; Triassi, Maria; Di Renzo, Gianfranco; Canzoniero, Lorella M.T.; Formisano, Luigi

2014-01-01

Phthalates, phthalic acid esters, are widely used as plasticizers to produce polymeric materials in industrial production of plastics and daily consumable products. Animal studies have shown that di(2-ethylhexyl)phthalate (DEHP) may cause toxic effects in the rat brain. In the present study, chronic exposure to DEHP (0.1–100 μM) caused dose-dependent cell death via the activation of caspase-3 in neuroblastoma cells. Intriguingly, this harmful effect was prevented by the pan-histone deacetylase (HDAC) inhibitor trichostatin A, by the class II HDAC inhibitor MC-1568, but not by the class I HDAC inhibitor MS-275. Furthermore, DEHP reduced specificity protein 3 (Sp3) gene expression, but not Sp3 mRNA, after 24 and 48 h exposures. However, Sp3 protein reduction was prevented by pre-treatment with MC-1568, suggesting the involvement of class II HDACs in causing this effect. Then, we investigated the possible relationship between DEHP-induced neuronal death and the post-translational mechanisms responsible for the down-regulation of Sp3. Interestingly, DEHP-induced Sp3 reduction was associated to its deacetylation and polyubiquitination. Co-immunoprecipitation studies showed that Sp3 physically interacted with HDAC4 after DEHP exposure, while HDAC4 inhibition by antisense oligodeoxynucleotide reverted the DEHP-induced degradation of Sp3. Notably, Sp3 overexpression was able to counteract the detrimental effect induced by DEHP. Taken together, these results suggest that DEHP exerts its toxic effect by inducing deacetylation of Sp3 via HDAC4, and afterwards, Sp3-polyubiquitination. - Highlights: • Di(2-ethylhexyl)phthalate (DEHP) is cytotoxic to SH-SY5Y cells and cortical neurons. • DEHP-induced cytotoxicity is mediated by apoptosis. • DEHP-induced apoptotic cell death is inhibited by class II HDAC MC-1568. • DEHP neurotoxicity is caused by HDAC4-mediated Sp3 degradation by ubiquitin

Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining neuronal death

Energy Technology Data Exchange (ETDEWEB)

Guida, Natascia; Laudati, Giusy [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Galgani, Mario; Santopaolo, Marianna [Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Napoli (Italy); Montuori, Paolo; Triassi, Maria [Department of Preventive Medical Sciences, University Federico II, Via Pansini 5, 80131 Naples (Italy); Di Renzo, Gianfranco [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Canzoniero, Lorella M.T., E-mail: canzon@unisannio.it [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Division of Pharmacology, Department of Science and Technology, University of Sannio, Via Port' Arsa 11, 82100 Benevento (Italy); Formisano, Luigi, E-mail: cformisa@unisannio.it [Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, “Federico II” University of Naples, Via Pansini 5, 80131 Naples (Italy); Division of Pharmacology, Department of Science and Technology, University of Sannio, Via Port' Arsa 11, 82100 Benevento (Italy)

2014-10-01

Phthalates, phthalic acid esters, are widely used as plasticizers to produce polymeric materials in industrial production of plastics and daily consumable products. Animal studies have shown that di(2-ethylhexyl)phthalate (DEHP) may cause toxic effects in the rat brain. In the present study, chronic exposure to DEHP (0.1–100 μM) caused dose-dependent cell death via the activation of caspase-3 in neuroblastoma cells. Intriguingly, this harmful effect was prevented by the pan-histone deacetylase (HDAC) inhibitor trichostatin A, by the class II HDAC inhibitor MC-1568, but not by the class I HDAC inhibitor MS-275. Furthermore, DEHP reduced specificity protein 3 (Sp3) gene expression, but not Sp3 mRNA, after 24 and 48 h exposures. However, Sp3 protein reduction was prevented by pre-treatment with MC-1568, suggesting the involvement of class II HDACs in causing this effect. Then, we investigated the possible relationship between DEHP-induced neuronal death and the post-translational mechanisms responsible for the down-regulation of Sp3. Interestingly, DEHP-induced Sp3 reduction was associated to its deacetylation and polyubiquitination. Co-immunoprecipitation studies showed that Sp3 physically interacted with HDAC4 after DEHP exposure, while HDAC4 inhibition by antisense oligodeoxynucleotide reverted the DEHP-induced degradation of Sp3. Notably, Sp3 overexpression was able to counteract the detrimental effect induced by DEHP. Taken together, these results suggest that DEHP exerts its toxic effect by inducing deacetylation of Sp3 via HDAC4, and afterwards, Sp3-polyubiquitination. - Highlights: • Di(2-ethylhexyl)phthalate (DEHP) is cytotoxic to SH-SY5Y cells and cortical neurons. • DEHP-induced cytotoxicity is mediated by apoptosis. • DEHP-induced apoptotic cell death is inhibited by class II HDAC MC-1568. • DEHP neurotoxicity is caused by HDAC4-mediated Sp3 degradation by ubiquitin.

In vitro acute exposure to DEHP affects oocyte meiotic maturation, energy and oxidative stress parameters in a large animal model.

Directory of Open Access Journals (Sweden)

Barbara Ambruosi

Full Text Available Phthalates are ubiquitous environmental contaminants because of their use in plastics and other common consumer products. Di-(2-ethylhexyl phthalate (DEHP is the most abundant phthalate and it impairs fertility by acting as an endocrine disruptor. The aim of the present study was to analyze the effects of in vitro acute exposure to DEHP on oocyte maturation, energy and oxidative status in the horse, a large animal model. Cumulus cell (CC apoptosis and oxidative status were also investigated. Cumulus-oocyte complexes from the ovaries of slaughtered mares were cultured in vitro in presence of 0.12, 12 and 1200 µM DEHP. After in vitro maturation (IVM, CCs were removed and evaluated for apoptosis (cytological assessment and TUNEL and intracellular reactive oxygen species (ROS levels. Oocytes were evaluated for nuclear chromatin configuration. Matured (Metaphase II stage; MII oocytes were further evaluated for cytoplasmic energy and oxidative parameters. DEHP significantly inhibited oocyte maturation when added at low doses (0.12 µM; P<0.05. This effect was related to increased CC apoptosis (P<0.001 and reduced ROS levels (P<0.0001. At higher doses (12 and 1200 µM, DEHP induced apoptosis (P<0.0001 and ROS increase (P<0.0001 in CCs without affecting oocyte maturation. In DEHP-exposed MII oocytes, mitochondrial distribution patterns, apparent energy status (MitoTracker fluorescence intensity, intracellular ROS localization and levels, mt/ROS colocalization and total SOD activity did not vary, whereas increased ATP content (P<0.05, possibly of glycolytic origin, was found. Co-treatment with N-Acetyl-Cysteine reversed apoptosis and efficiently scavenged excessive ROS in DEHP-treated CCs without enhancing oocyte maturation. In conclusion, acute in vitro exposure to DEHP inhibits equine oocyte maturation without altering ooplasmic energy and oxidative stress parameters in matured oocytes which retain the potential to be fertilized and develop into

In vitro acute exposure to DEHP affects oocyte meiotic maturation, energy and oxidative stress parameters in a large animal model.

Science.gov (United States)

Ambruosi, Barbara; Uranio, Manuel Filioli; Sardanelli, Anna Maria; Pocar, Paola; Martino, Nicola Antonio; Paternoster, Maria Stefania; Amati, Francesca; Dell'Aquila, Maria Elena

2011-01-01

Phthalates are ubiquitous environmental contaminants because of their use in plastics and other common consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is the most abundant phthalate and it impairs fertility by acting as an endocrine disruptor. The aim of the present study was to analyze the effects of in vitro acute exposure to DEHP on oocyte maturation, energy and oxidative status in the horse, a large animal model. Cumulus cell (CC) apoptosis and oxidative status were also investigated. Cumulus-oocyte complexes from the ovaries of slaughtered mares were cultured in vitro in presence of 0.12, 12 and 1200 µM DEHP. After in vitro maturation (IVM), CCs were removed and evaluated for apoptosis (cytological assessment and TUNEL) and intracellular reactive oxygen species (ROS) levels. Oocytes were evaluated for nuclear chromatin configuration. Matured (Metaphase II stage; MII) oocytes were further evaluated for cytoplasmic energy and oxidative parameters. DEHP significantly inhibited oocyte maturation when added at low doses (0.12 µM; P<0.05). This effect was related to increased CC apoptosis (P<0.001) and reduced ROS levels (P<0.0001). At higher doses (12 and 1200 µM), DEHP induced apoptosis (P<0.0001) and ROS increase (P<0.0001) in CCs without affecting oocyte maturation. In DEHP-exposed MII oocytes, mitochondrial distribution patterns, apparent energy status (MitoTracker fluorescence intensity), intracellular ROS localization and levels, mt/ROS colocalization and total SOD activity did not vary, whereas increased ATP content (P<0.05), possibly of glycolytic origin, was found. Co-treatment with N-Acetyl-Cysteine reversed apoptosis and efficiently scavenged excessive ROS in DEHP-treated CCs without enhancing oocyte maturation. In conclusion, acute in vitro exposure to DEHP inhibits equine oocyte maturation without altering ooplasmic energy and oxidative stress parameters in matured oocytes which retain the potential to be fertilized and develop into embryos

Development of electrochemical impedance spectroscopy based sensing system for DEHP detection

KAUST Repository

Zia, Asif I.; Mohd. Syaifudin, A. R.; Mukhopadhyay, Subhas Chandra; Al-Bahadly, Ibrahim H.; Yu, Paklam; Gooneratne, Chinthaka Pasan; Kosel, Jü rgen

2011-01-01

This research work presents a real time and non invasive technique to detect Di(2-ethylhexyl) phthalate (DEHP)content in purified water and quantify its concentration by Electrochemical Impedance Spectroscopy(E.I.S.). Planar Inter-digital capacitive

The mitochondrial uncoupling proteins

OpenAIRE

Ledesma, Amalia; de Lacoba, Mario García; Rial, Eduardo

2002-01-01

The uncoupling proteins (UCPs) are transporters, present in the mitochondrial inner membrane, that mediate a regulated discharge of the proton gradient that is generated by the respiratory chain. This energy-dissipatory mechanism can serve functions such as thermogenesis, maintenance of the redox balance, or reduction in the production of reactive oxygen species. Some UCP homologs may not act as true uncouplers, however, and their activity has yet to be defined. The UCPs are integral membrane...

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

International Nuclear Information System (INIS)

Pocar, Paola; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano

2017-01-01

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice

Energy Technology Data Exchange (ETDEWEB)

Pocar, Paola, E-mail: paola.pocar@unimi.it; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano

2017-05-01

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP

Boule gene expression underpins the meiotic arrest in spermatogenesis in male rainbow trout (Oncorhynchus mykiss) exposed to DEHP and butachlor.

Science.gov (United States)

Ahmadivand, Sohrab; Farahmand, Hamid; Teimoori-Toolabi, Ladan; Mirvaghefi, Alireza; Eagderi, Soheil; Geerinckx, Tom; Shokrpoor, Sara; Rahmati-Holasoo, Hooman

2016-01-01

Boule, the ancestor of the DAZ (Deleted in AZoospermia) gene family, in most organisms is mainly involved in male meiosis. The present study investigates the effects of the plasticizer DEHP (50mg/kg body weight) and herbicide butachlor (0.39mg/L) on male rainbow trout (Oncorhynchus mykiss) for a 10-day period in two independent experiments. The results showed that plasma testosterone (T) concentrations were significantly lower in fish exposed to either DEHP or butachlor compared to the control fish (P0.05). In addition, no significant differences were found in the gonadosomatic index (GSI) in both DEHP and butachlor treatments (P>0.05). Histologically, testes of male trout in the control groups were well differentiated and filled with large numbers of cystic structures containing spermatozoa. In contrast, the testes of male trout contained mostly spermatocytes with few spermatozoa in both treated group, suggesting that DEHP and butachlor may inhibit the progression of meiosis. Also, boule gene expression was significantly lower in the testes of male trout affected by DEHP and butachlor in comparison with their control groups (Ptrout. Based on the results, the present study demonstrated that DEHP and butachlor can inhibit the progression of spermatogenesis in male trout, potentially by causing an arrest of meiosis, maybe due to down-regulation of boule gene expression through T and/or IGF1 via ERK1/2 signaling in T-independent pathways. In addition, these results confirmed that boule can be considered as a predictive marker to assess meiotic efficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

Childhood exposure to DEHP, DBP and BBP in Denmark and Korea

DEFF Research Database (Denmark)

Lee, Jihyun; Lee, Jong-Hyun; Kim, Chan-Kook

Since early 20th century, phthalates have been used as plasticizers and among these, Di(2-ethylhexyl) phthalate (DEHP), Benzyl-butyl phthalate (BBP) and Di-n-butyl phthalate (DBP) have been widely used. However, as adverse health effects such as endocrine disrupting effects were reported, these c...

Exercise on-transition uncoupling of ventilatory, gas exchange and cardiac hemodynamic kinetics accompany pulmonary oxygen stores depletion to impact exercise intolerance in human heart failure.

Science.gov (United States)

Van Iterson, E H; Smith, J R; Olson, T P

2018-03-25

In contrast to knowledge that heart failure (HF) patients demonstrate peak exercise uncoupling across ventilation, gas exchange and cardiac haemodynamics, whether this dyssynchrony follows that at the exercise on-transition is unclear. This study tested whether exercise on-transition temporal lag for ventilation relative to gas exchange and oxygen pulse (O 2 pulse) couples with effects from abnormal pulmonary gaseous oxygen store (O 2store ) contributions to V˙O 2 to interdependently precipitate persistently elevated ventilatory demand and low oxidative metabolic capacity in HF. Beat-to-beat HR and breath-to-breath ventilation and gas exchange were continuously acquired in HF (N = 9, ejection fraction = 30 ± 9%) and matched controls (N = 10) during square-wave ergometry at 60% V˙O 2peak (46 ± 14 vs 125 ± 54-W, P < .001). Temporal responses across V˙ E , V˙O 2 and O 2 pulse were assessed for the exercise on-transition using single exponential model Phase II on-kinetic time constants (τ = time to reach 63% steady-state rise). Breath-to-breath gas fractions and respiratory flows were used to determine O 2stores . HF vs controls: τ for V˙ E (137 ± 93 vs 74 ± 40-seconds, P = .03), V˙O 2 (60 ± 40 vs 23 ± 5-seconds, P = .03) and O 2 pulse (28 ± 18 vs 23 ± 15-seconds, P = .59). Within HF, τ for V˙ E differed from O 2 pulse (P < .02), but not V˙O 2 . Exercise V˙ E rise (workload indexed) differed in HF vs controls (545 ± 139 vs 309 ± 88-mL min -1 W -1 , P < .001). Exercise on-transition O 2store depletion in HF exceeded controls, generally persisting to end-exercise. These data suggest HF demonstrated exercise on-transition O 2store depletion (high O 2store contribution to V˙O 2 ) coupled with dyssynchronous V˙ E , V˙O 2 and O 2 pulse kinetics-not attributable to prolonged cardiac haemodynamics. Persistent high ventilatory demand and low oxidative metabolic capacity in HF may be precipitated by physiological uncoupling occurring within the exercise

Certain aspects of uncoupling due to mitochondrial uncoupling proteins in vitro and in vivo

Czech Academy of Sciences Publication Activity Database

Dlasková, Andrea; Špaček, Tomáš; Škobisová, Eva; Šantorová, Jitka; Ježek, Petr

2006-01-01

Roč. 1757, č. 5-6 (2006), s. 467-473 ISSN 0005-2728 R&D Projects: GA MŠk(CZ) 1P05ME794; GA ČR(CZ) GA521/02/0183; GA AV ČR(CZ) IAA5011106 Institutional research plan: CEZ:AV0Z50110509 Keywords : fatty acid-induced uncoupling * uncoupling protein-1 * carnitine cycle Subject RIV: CE - Biochemistry Impact factor: 4.237, year: 2006

30 CFR 56.14215 - Coupling or uncoupling cars.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at minimum...

Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency.

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Fallahi, Ali Asghar; Shekarfroush, Shahnaz; Rahimi, Mostafa; Jalali, Amirhossain; Khoshbaten, Ali

2016-03-01

High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. Wistar rats were divided into five groups: control group (n=12), HIIT for an acute bout (AT1), short term HIIT for 3 and 5 sessions (ST3 and ST5), long-term training for 8 weeks (LT) (6 in each group). The rats of the training groups were made to run on a treadmill for 60 min in three stages: 6 min running for warm-up, 7 intervals of 7 min running on treadmill with a slope of 5° to 20° (4 min with an intensity of 80-110% VO2max and 3 min at 50-60% VO2max), and 5-min running for cool-down. The control group did not participate in any exercise program. Rats were sacrificed and the hearts were extracted to analyze the levels of UCP2, UCP3 and eNOS mRNA by RT-PCR. UCP3 expression was increased significantly following an acute training bout. Repeated HIIT for 8 weeks resulted in a significant decrease in UCPs mRNA and a significant increase in eNOS expression in cardiac muscle. This study indicates that Long term HIIT through decreasing UCPs mRNA and increasing eNOS mRNA expression may enhance energy efficiency and physical performance.

Investigating the role of uncoupling of Troponin I phosphorylation from changes in myofibrillar Ca2+-sensitivity in the pathogenesis of Cardiomyopathy

Directory of Open Access Journals (Sweden)

Andrew Easton Messer

2014-08-01

Full Text Available Contraction in the mammalian heart is controlled by the intracellular Ca2+ concentration as it is in all striated muscle, but the heart has an additional signalling system that comes into play to increase heart rate and cardiac output during exercise or stress. β-adrenergic stimulation of heart muscle cells leads to release of cyclic-AMP and the activation of protein kinase A which phosphorylates key proteins in the sarcolemma, sarcoplasmic reticulum and contractile apparatus. Troponin I (TnI and Myosin Binding Protein C (MyBP-C are the prime targets in the myofilaments. TnI phosphorylation lowers myofibrillar Ca2+-sensitivity and increases the speed of Ca2+-dissociation and relaxation (lusitropic effect.Recent studies have shown that this relationship between Ca2+-sensitivity and TnI phosphorylation may be unstable. In familial cardiomyopathies, both dilated and hypertrophic (DCM and HCM, a mutation in one of the proteins of the thin filament often results in the loss of the relationship (uncoupling and blunting of the lusitropic response. For familial dilated cardiomyopathy in thin filament proteins it has been proposed that this uncoupling is causative of the phenotype. Uncoupling has also been found in human heart tissue from patients with hypertrophic obstructive cardiomyopathy as a secondary effect. Recently, it has been found that Ca2+-sensitizing drugs can promote uncoupling, whilst one Ca2+-desensitising drug Epigallocatechin 3-Gallate (EGCG can reverse uncoupling.We will discuss recent findings about the role of uncoupling in the development of cardiomyopathies and the molecular mechanism of the process.

Mitochondrial uncoupling proteins and energy metabolism

Directory of Open Access Journals (Sweden)

Rosa Anna Busiello

2015-02-01

Full Text Available Understanding the metabolic factors that contribute to energy metabolism (EM is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1, which was the first in this family to be discovered, the reactions catalyzed by its homologue UCP3 and the physiological role remain under debate.This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus.

A procedure for noise uncoupling in laser interferometry

CERN Document Server

Barone, F; Rosa, R D; Eleuteri, A; Milano, L; Qipiani, K

2002-01-01

A numerical procedure for noise recognition and uncoupling is described. The procedure is applied to a Michelson interferometer and is effective in seismic and acoustic noise uncoupling from the output signal of the interferometer. Due to the low data flow coming from the instrumentation this uncoupling can be performed in real time and it is useful as a data quality procedure for interferometer data output.

An investigation of red blood cell concentrate quality during storage in paediatric-sized polyvinylchloride bags plasticized with alternatives to di-2-ethylhexyl phthalate (DEHP).

Science.gov (United States)

Serrano, K; Levin, E; Chen, D; Hansen, A; Turner, T R; Kurach, J; Reidel, A; Boecker, W F; Acker, J P; Devine, D V

2016-04-01

Di-2-ethylhexyl phthalate (DEHP) is a blood bag plasticizer. It is also a toxin, raising concerns for vulnerable populations, for example, neonates and infants. Here, the in vitro quality of red cell concentrates (RCC) stored in paediatric bags formulated with alternative plasticizers to DEHP was compared. RCC were pooled and split into polyvinylchloride (PVC)/DEHP, PVC/1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) or PVC/butyryl trihexyl citrate (BTHC) bags. Quality was assessed on storage days 5, 21, 35 and 43. Metabolism differed among the bags: pCO2 levels were lowest and pO2 were highest in BTHC bags. Glucose consumption and lactate production suggested higher metabolic rates in BTHC bags. ATP levels were best maintained in DINCH bags (day 43 mean level: 2·86 ± 0·29 μmol/g Hb). RCC in BTHC bags had the greatest potassium release (54·6 ± 3·0 mm on day 43). From day 21, haemolysis was higher in BTHC bags (P bags showed more microparticle formation than RCC in DEHP or DINCH bags. The results suggest that the BTHC formulation used was detrimental to RBC quality. DINCH bags could be a viable alternative to DEHP: they outperformed DEHP bags energetically, with better maintenance of ATP levels. © 2015 International Society of Blood Transfusion.

A SPME-based method for rapidly and accurately measuring the characteristic parameter for DEHP emitted from PVC floorings.

Science.gov (United States)

Cao, J; Zhang, X; Little, J C; Zhang, Y

2017-03-01

Semivolatile organic compounds (SVOCs) are present in many indoor materials. SVOC emissions can be characterized with a critical parameter, y 0 , the gas-phase SVOC concentration in equilibrium with the source material. To reduce the required time and improve the accuracy of existing methods for measuring y 0 , we developed a new method which uses solid-phase microextraction (SPME) to measure the concentration of an SVOC emitted by source material placed in a sealed chamber. Taking one typical indoor SVOC, di-(2-ethylhexyl) phthalate (DEHP), as the example, the experimental time was shortened from several days (even several months) to about 1 day, with relative errors of less than 5%. The measured y 0 values agree well with the results obtained by independent methods. The saturated gas-phase concentration (y sat ) of DEHP was also measured. Based on the Clausius-Clapeyron equation, a correlation that reveals the effects of temperature, the mass fraction of DEHP in the source material, and y sat on y 0 was established. The proposed method together with the correlation should be useful in estimating and controlling human exposure to indoor DEHP. The applicability of the present approach for other SVOCs and other SVOC source materials requires further study. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins

Directory of Open Access Journals (Sweden)

Angélica Ruiz-Ramírez

2016-01-01

Full Text Available Metabolic diseases such as obesity, metabolic syndrome, and type II diabetes are often characterized by increased reactive oxygen species (ROS generation in mitochondrial respiratory complexes, associated with fat accumulation in cardiomyocytes, skeletal muscle, and hepatocytes. Several rodents studies showed that lipid accumulation in cardiac myocytes produces lipotoxicity that causes apoptosis and leads to heart failure, a dynamic pathological process. Meanwhile, several tissues including cardiac tissue develop an adaptive mechanism against oxidative stress and lipotoxicity by overexpressing uncoupling proteins (UCPs, specific mitochondrial membrane proteins. In heart from rodent and human with obesity, UCP2 and UCP3 may protect cardiomyocytes from death and from a state progressing to heart failure by downregulating programmed cell death. UCP activation may affect cytochrome c and proapoptotic protein release from mitochondria by reducing ROS generation and apoptotic cell death. Therefore the aim of this review is to discuss recent findings regarding the role that UCPs play in cardiomyocyte survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote heart protection.

EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS

Science.gov (United States)

DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue wei...

UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction

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Hongmei Lang

2018-04-01

Full Text Available Background/Aims: Excessive salt intake and left ventricular hypertrophy (LVH are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3 plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. Methods: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5% or a high-salt (HS, 8% diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Results: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. Conclusion: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.

Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system

Energy Technology Data Exchange (ETDEWEB)

Chen, Kun [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Sun, Guoxun [Department of Hematology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001 (China); Lv, Zhiyuan; Wang, Chen [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Jiang, Xueyuan, E-mail: xueyuanjiang@yahoo.com.cn [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Li, Donghai, E-mail: lidonghai@gmail.com [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China); Zhang, Chenyu, E-mail: cyzhang@nju.edu.cn [Jiangsu Diabetes Research Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu (China)

2010-10-01

Research highlights: {yields} Invertebrates, for example amphioxus, do express uncoupling proteins. {yields} Both the sequence and the uncoupling activity of amphioxus UCP resemble UCP2. {yields} UCP1 is the only UCP that can form dimer on yeast mitochondria. -- Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system

International Nuclear Information System (INIS)

Chen, Kun; Sun, Guoxun; Lv, Zhiyuan; Wang, Chen; Jiang, Xueyuan; Li, Donghai; Zhang, Chenyu

2010-01-01

Research highlights: → Invertebrates, for example amphioxus, do express uncoupling proteins. → Both the sequence and the uncoupling activity of amphioxus UCP resemble UCP2. → UCP1 is the only UCP that can form dimer on yeast mitochondria. -- Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

Triclosan is a Mitochondrial Uncoupler in Live Zebrafish

Science.gov (United States)

Shim, Juyoung; Weatherly, Lisa M.; Luc, Richard H.; Dorman, Maxwell T.; Neilson, Andy; Ng, Ryan; Kim, Carol H.; Millard, Paul J.; Gosse, Julie A.

2016-01-01

Triclosan (TCS) is a synthetic antimicrobial agent used in many consumer goods at millimolar concentrations. As a result of exposure, TCS has been detected widely in humans. We have recently discovered that TCS is a proton ionophore mitochondrial uncoupler in multiple types of living cells. Here we present novel data indicating that TCS is also a mitochondrial uncoupler in a living organism: 24 hour post fertilization zebrafish embryos. These experiments were conducted using a Seahorse Bioscience XFe 96 Extracellular Flux Analyzer modified for bidirectional temperature control, using the XF96 spheroid plate to position and measure one zebrafish embryo per well. Using this method, following acute exposure to TCS, basal oxygen consumption rate (OCR) increases, without a decrease in survival or heartbeat rate. TCS also decreases ATP-linked respiration and spare respiratory capacity and increases proton leak: all indicators of mitochondrial uncoupling. Our data indicate, that TCS is a mitochondrial uncoupler in vivo, which should be taken into consideration when assessing the toxicity and/or pharmaceutical uses of TCS. This is the first example of usage of a Seahorse Extracellular Flux Analyzer to measure bioenergetic flux of a single zebrafish embryo per well in a 96 well assay format. The method developed in this study provides a high-throughput tool to identify previously-unknown mitochondrial uncouplers in a living organism. PMID:27111768

Urinary metabolomic profiling in rats exposed to dietary di(2-ethylhexyl) phthalate (DEHP) using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS).

Science.gov (United States)

Dong, Xinwen; Zhang, Yunbo; Dong, Jin; Zhao, Yue; Guo, Jipeng; Wang, Zhanju; Liu, Mingqi; Na, Xiaolin; Wang, Cheng

2017-07-01

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental chemical with widespread nonoccupational human exposure through multiple ways. Although considerable efforts have been invested to investigate mechanisms of DEHP toxicity, the key metabolic biomarkers of DEHP toxicity remain to be identified. The aim of this study was to assess the urinary metabonomics of dietary DEHP in rats using the technique of ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). Fourteen female Wistar rats were divided into two groups and given increasing dietary doses of DEHP for 30 consecutive days. The urinary metabolite profile was studied using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) enabled clusters to be clearly separated. Eleven principal urinary metabolites were identified as contributing to the clusters. The clusters in the positive electrospray ionization (ESI) mode were xanthurenic acid, kynurenic acid, nonate, N6-methyladenosine, and L-isoleucyl-L-proline. The clusters in the negative ESI mode were hippuric acid, tetrahydrocortisol, citric acid, phenylpropionylglycine, cPA(18:2(9Z, 12Z)/0:0), and LysoPC(14:1(9Z)). The urinary metabonomic changes indicated that exposure to dietary DEHP can affect energy-related metabolism, liver and renal function, fatty acid metabolism, and cause DNA damage in rats. The findings of this study on the urinary metabolites and metabolic pathways of DEHP may form the basis for future studies on the mechanisms of toxicity of this commonly found environmental chemical.

Role of Uncoupling Proteins in Cancer

Directory of Open Access Journals (Sweden)

Adamo Valle

2010-04-01

Full Text Available Uncoupling proteins (UCPs are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS. Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance.

Role of Uncoupling Proteins in Cancer

International Nuclear Information System (INIS)

Valle, Adamo; Oliver, Jordi; Roca, Pilar

2010-01-01

Uncoupling proteins (UCPs) are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, by dissipating the proton gradient and, subsequently, decreasing membrane potential and production of reactive oxygen species (ROS). Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer. In this review we compile the latest evidence showing a link between uncoupling and the carcinogenic process, paying special attention to their involvement in cancer initiation, progression and drug chemoresistance

Mitochondrial uncoupling proteins and phylogenesis - UCP4 as the ancestral uncoupling protein

Czech Academy of Sciences Publication Activity Database

Hanák, Petr; Ježek, Petr

2001-01-01

Roč. 495, č. 3 (2001), s. 137-141 ISSN 0014-5793 R&D Projects: GA ČR GA301/98/0568; GA AV ČR IAA5011106 Institutional research plan: CEZ:AV0Z5011922 Keywords : phylogenesis of mitochondrial uncoupling protein * specific sequence motif Subject RIV: CE - Biochemistry Impact factor: 3.644, year: 2001

Degradation of brown adipocyte purine nucleotides regulates uncoupling protein 1 activity

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Tobias Fromme

2018-02-01

Full Text Available Objective: Non-shivering thermogenesis in mammalian brown adipose tissue depends on thermogenic uncoupling protein 1. Its activity is triggered by free fatty acids while purine nucleotides mediate inhibition. During activation, it is thought that free fatty acids overcome purine-mediated inhibition. We measured the cellular concentration and the release of purine nucleotide metabolites to uncover a possible role of purine nucleotide degradation in uncoupling protein 1 activation. Methods: With mass spectrometry, purine nucleotide metabolites were quantified in cellular homogenates and supernatants of cultured primary brown adipocytes. We also determined oxygen consumption in response to a β-adrenergic agonist. Results: Upon adrenergic activation, brown adipocytes decreased the intracellular concentration of inhibitory nucleotides (ATP, ADP, GTP and GDP and released the respective degradation products. At the same time, an increase in cellular calcium occurred. None of these phenomena occurred in white adipocytes or myotubes. The brown adipocyte expression of enzymes implicated in purine metabolic remodeling is altered upon cold exposure. Pharmacological and genetic interference of purine metabolism altered uncoupling protein 1 mediated uncoupled respiration. Conclusion: Adrenergic stimulation of brown adipocytes lowers the intracellular concentration of purine nucleotides, thereby contributing to uncoupling protein 1 activation. Keywords: Purine nucleotides, Uncoupling protein 1, Brown adipose tissue, Non-shivering thermogenesis, HILIC-MS/MS, Guanosine monophosphate reductase

Cardiac tissue slices: preparation, handling, and successful optical mapping.

Science.gov (United States)

Wang, Ken; Lee, Peter; Mirams, Gary R; Sarathchandra, Padmini; Borg, Thomas K; Gavaghan, David J; Kohl, Peter; Bollensdorff, Christian

2015-05-01

Cardiac tissue slices are becoming increasingly popular as a model system for cardiac electrophysiology and pharmacology research and development. Here, we describe in detail the preparation, handling, and optical mapping of transmembrane potential and intracellular free calcium concentration transients (CaT) in ventricular tissue slices from guinea pigs and rabbits. Slices cut in the epicardium-tangential plane contained well-aligned in-slice myocardial cell strands ("fibers") in subepicardial and midmyocardial sections. Cut with a high-precision slow-advancing microtome at a thickness of 350 to 400 μm, tissue slices preserved essential action potential (AP) properties of the precutting Langendorff-perfused heart. We identified the need for a postcutting recovery period of 36 min (guinea pig) and 63 min (rabbit) to reach 97.5% of final steady-state values for AP duration (APD) (identified by exponential fitting). There was no significant difference between the postcutting recovery dynamics in slices obtained using 2,3-butanedione 2-monoxime or blebistatin as electromechanical uncouplers during the cutting process. A rapid increase in APD, seen after cutting, was caused by exposure to ice-cold solution during the slicing procedure, not by tissue injury, differences in uncouplers, or pH-buffers (bicarbonate; HEPES). To characterize intrinsic patterns of CaT, AP, and conduction, a combination of multipoint and field stimulation should be used to avoid misinterpretation based on source-sink effects. In summary, we describe in detail the preparation, mapping, and data analysis approaches for reproducible cardiac tissue slice-based investigations into AP and CaT dynamics. Copyright © 2015 the American Physiological Society.

Protective Effect of Peroxisome Proliferator-Activated Receptor α Activation against Cardiac Ischemia-Reperfusion Injury Is Related to Upregulation of Uncoupling Protein-3

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Jong Wook Song

2016-01-01

Full Text Available Activation of peroxisome proliferator-activated receptor α (PPARα confers cardioprotection, while its mechanism remains elusive. We investigated the protective effect of PPARα activation against cardiac ischemia-reperfusion injury in terms of the expression of uncoupling protein (UCP. Myocardial infarct size and UCP expression were measured in rats treated with WY-14643 20 mg/kg, a PPARα ligand, or vehicle. WY-14643 increased UCP3 expression in vivo. Myocardial infarct size was decreased in the WY-14643 group (76 ± 8% versus 42 ± 12%, P<0.05. During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY-14643 group (9/10 versus 3/10, P<0.05. H9c2 cells were incubated for 24 h with WY-14643 or vehicle. WY-14643 increased UCP3 expression in H9c2 cells. WY-14643 decreased hypoxia-stimulated ROS production. Cells treated with WY-14643 were more resistant to hypoxia-reoxygenation than the untreated cells. Knocking-down UCP3 by siRNA prevented WY-14643 from attenuating the production of ROS. UCP3 siRNA abolished the effect of WY-14643 on cell viability against hypoxia-reoxygenation. In summary, administration of PPARα agonist WY-14643 mitigated the extent of myocardial infarction and incidence of reperfusion-induced arrhythmia. PPARα activation conferred cytoprotective effect against hypoxia-reoxygenation. Associated mechanisms involved increased UCP3 expression and resultant attenuation of ROS production.

Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

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Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

2004-01-01

Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion.

Uncoupled and coupled analysis of a large HDR pipe

International Nuclear Information System (INIS)

Muller, W.C.

1987-01-01

The main differences are in the structural response. There is no clear tendency that a coupled calculation will result in lower amplitudes of the structural response, but it can be seen from the results that there is a typical difference between coupled and uncoupled analysis which increases with time. This increase is mainly due to the fact that in a coupled analysis the speed of sound of the fluid and the eigenmodes of the piping system structure are lower than in the uncoupled analysis. Coupled and uncoupled piping transient analyses show similar results for the fluiddynamic data. The differences are less than 10% and as long as the fluid is in the two phase domain they can almost be neglected

Metallothionein Abrogates GTP Cyclohydrolase I inhibition-Induced Cardiac Contractile and Morphological Defect: Role of Mitochondrial Biogenesis

OpenAIRE

Ceylan-Isik, Asli F.; Guo, Kelly K.; Carlson, Edward C.; Privratsky, Jamie R.; Liao, Song-Jie; Cai, Lu; Chen, Alex F.; Ren, Jun

2009-01-01

One key mechanism for endothelial dysfunction is eNOS uncoupling, whereby eNOS generates O2•− rather than NO, due to deficient eNOS cofactor tetrahydrobiopterin (BH4). This study was designed to examine the effect of BH4 deficiency on cardiac morphology and function as well as the impact of metallothionein (MT) on BH4 deficiency-induced abnormalities, if any. FVB and cardiac-specific MT transgenic mice were exposed to 2,4-diamino-6-hydroxy-pyrimidine (DAHP, 10 mmol/l, 3 wks), an inhibitor of ...

DETERMINATION OF DIBUTYL PHTHALATE (DBP, BENZYL BUTYL PHTHALATE (BBP AND BIS (2-ETHYLHEXYL PHTHALATE (DEHP IN SOFT PLASTIC TOYS AND THE FIRST SURVEY OF THE BULGARIAN MARKET

Directory of Open Access Journals (Sweden)

Valentina CHRISTOVA-BAGDASSARIAN

2017-12-01

Full Text Available Phthalates are a large group of compounds with similar chemical structure widely used as plasticizers for plastics. They can easily be released from the polymer during usage and in this way enter the human body. Their adverse effect on health is known as "phthalate syndrome" and can impact children and adults alike. For children in particular, there is an additional potential risk of exposure to phthalates via toys intended for oral use. The Regulation (EC No 1907/2006 (REACH prohibits the use of bis (2-ethylhexyl phthalate (DEHP, di butyl phthalate (DBP and benzyl butyl phthalate (BBP as a substance or constituent of preparations at concentrations higher than 0.1 % in the plasticized material meant to toys and childcare items. The aim of this article is to quantify the content of DEHP, DBP and BBP in soft toys intended for children up to 3 years of age, including toys designed to be placed in the mouth. A method consisting of an extraction procedure of phthalates from polymers, purification of the extract, followed by GC/MS identification and quantification was validated. Three different techniques for phthalates’ extraction (Soxhlet, ultrasonic and vibrator were compared and the most effective one was chosen.This method was applied to the analysis of DEHP, DBP and BBP in soft toys from the Bulgarian market to establish their compliance with REACH requirements. All the tested toys contained at least one phthalate. Exceedence of the permitted content for DEHP, DBP and BBP (as sume, mainly due to the high levels of DEHP, was observed in several toys from retail.

The mechanism of uncoupling by picrate in Escherichia coli K-12 membrane systems.

Science.gov (United States)

Michels, M; Bakker, E P

1981-06-01

The mechanism of action of the uncoupler picrate on intact cells and everted membrane vesicles of Escherichia coli K-12 was investigated. Like in mitochondria [Hanstein, W. G. and Hatefi, Y. (1974) Proc. Natl Acad. Sci. USA, 71, 288-292], it was observed that picrate uncoupled energy-linked functions only in everted, but not in intact membrane systems. In the vesicles picrate also decreased the magnitude of the transmembrane proton-motive force at concentrations similar to those at which it caused uncoupling. Experiments with 14C-labelled picrate showed that this compound bound both to deenergized intact cells and everted vesicles. However, upon energization of the membrane, picrate was extruded from the intact cell and taken up to a larger extent by the vesicles. These energy-dependent changes in picrate uptake correlated with the magnitude of the transmembrane electrical potential, delta psi. It is therefore proposed that picrate is a permeant uncoupler, that delta psi is the driving force for picrate movement across biological membranes, and that the uncoupling activity of picrate in everted membrane systems is due to its protonophoric action.

Concentration of rat brown adipose tissue uncoupling protein may not be correlated with 3H-GDP binding

International Nuclear Information System (INIS)

Henningfield, M.F.; Swick, A.G.; Swick, R.W.

1986-01-01

Rats fed diets low in protein or exposed to cold show an increase in brown adipose tissue (BAT) mitochondrial 3 H-GDP binding. To investigate this phenomenon further, the uncoupling protein associated with BAT function was measured immunochemically on nitrocellulose blots. Quantitation of uncoupling protein was achieved by densitometer scanning with a BioRad densitometer. Peaks were integrated with Chromatochart software and an Apple IIe computer. A standard curve of purified uncoupling protein (50 to 500 ng) was used to calculate uncoupling protein concentration. There is a 1.5-fold increase in uncoupling protein per mg of protein in BAT mitochondria from rats exposed to cold for 15 days. There was no decrease in uncoupling protein from rats exposed to the cold followed by 24 h at 27 0 C although 3 H-GDP binding had decreased by half. Rats fed diets containing either 5 or 15% lactalbumin for 3 weeks did not show differences in uncoupling protein concentration although 3 H-GDP binding was 1.5-fold greater in BAT mitochondria from the low protein group. These results indicate that GDP binding does not necessarily reflect the concentration of uncoupling protein in BAT mitochondria

3-OST-7 regulates BMP-dependent cardiac contraction.

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Shiela C Samson

2013-12-01

Full Text Available The 3-O-sulfotransferase (3-OST family catalyzes rare modifications of glycosaminoglycan chains on heparan sulfate proteoglycans, yet their biological functions are largely unknown. Knockdown of 3-OST-7 in zebrafish uncouples cardiac ventricular contraction from normal calcium cycling and electrophysiology by reducing tropomyosin4 (tpm4 expression. Normal 3-OST-7 activity prevents the expansion of BMP signaling into ventricular myocytes, and ectopic activation of BMP mimics the ventricular noncontraction phenotype seen in 3-OST-7 depleted embryos. In 3-OST-7 morphants, ventricular contraction can be rescued by overexpression of tropomyosin tpm4 but not by troponin tnnt2, indicating that tpm4 serves as a lynchpin for ventricular sarcomere organization downstream of 3-OST-7. Contraction can be rescued by expression of 3-OST-7 in endocardium, or by genetic loss of bmp4. Strikingly, BMP misregulation seen in 3-OST-7 morphants also occurs in multiple cardiac noncontraction models, including potassium voltage-gated channel gene, kcnh2, affected in Romano-Ward syndrome and long-QT syndrome, and cardiac troponin T gene, tnnt2, affected in human cardiomyopathies. Together these results reveal 3-OST-7 as a key component of a novel pathway that constrains BMP signaling from ventricular myocytes, coordinates sarcomere assembly, and promotes cardiac contractile function.

PERINATAL EXPOSURE TO THE PHTHALATES DEHP, BBP AND DINP, BUT NOT DEP, DMP OR DOTP ALTERS SEXUAL DIFFERENTIATION OF THE MALE RAT

Science.gov (United States)

In mammals, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of AR antagonists like vinclozolin and procymidone or chemicals like di (2-bis) ethylhexyl phthalate (DEHP), that inhibit ...

Intrinsic uncoupling of mitochondrial proton pumps. 2. Modeling studies.

Science.gov (United States)

Pietrobon, D; Zoratti, M; Azzone, G F; Caplan, S R

1986-02-25

The thermodynamic and kinetic properties associated with intrinsic uncoupling in a six-state model of a redox proton pump have been studied by computing the flow-force relations for different degrees of coupling. Analysis of these relations shows the regulatory influence of the thermodynamic forces on the extent and relative contributions of redox slip and proton slip. Inhibition has been introduced into the model in two different ways, corresponding to possible modes of action of experimental inhibitors. Experiments relating the rate of electron transfer to delta microH at static head upon progressive inhibition of the pumps have been simulated considering (1) the limiting case that the nonzero rate of electron transfer at static head is only due to intrinsic uncoupling (no leaks) and (2) the experimentally observed case that about 30% of the nonzero rate of electron transfer at static head is due to a constant proton leakage conductance in parallel with the pumps, the rest being due to intrinsic uncoupling. The same simulations have been performed for experiments in which the rate of electron transfer is varied by varying the substrate concentration rather than by using an inhibitor. The corresponding experimental results obtained by measuring delta microH and the rate of electron transfer at different succinate concentrations in rat liver mitochondria are presented. Comparison between simulated behavior and experimental results leads to the general conclusion that the typical relationship between rate of electron transfer and delta microH found in mitochondria at static head could certainly be a manifestation of some degree of intrinsic uncoupling in the redox proton pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

30 CFR 57.14215 - Coupling or uncoupling cars.

Science.gov (United States)

2010-07-01

... NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Machinery... uncoupling shall not be attempted from the inside of curves unless the railroad and cars are designed to...

Uncoupling in Secondary Transport Proteins. A Mechanistic Explanation for Mutants of lac Permease with an Uncoupled Phenotype

NARCIS (Netherlands)

Lolkema, J.S.; Poolman, B.

1995-01-01

The kinetic behavior of a H+-substrate symporter has been studied in which in addition to the unloaded (E) and fully loaded states (E.S.H) of the carrier also one of the binary complexes (E.S or E.H) may reorient its binding sites. This results in two types of uncoupled mutants, the ES leak and the

Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

Energy Technology Data Exchange (ETDEWEB)

Lim, Han Wern; Lim, Hwee Ying [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore); Wong, Kim Ping, E-mail: bchsitkp@nus.edu.sg [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore)

2009-11-06

Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F{sub 0}F{sub 1}-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 {mu}M, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F{sub 0}F{sub 1}-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

International Nuclear Information System (INIS)

Lim, Han Wern; Lim, Hwee Ying; Wong, Kim Ping

2009-01-01

Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F 0 F 1 -ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F 0 F 1 -ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

Uncoupler resistance in E. coli Tuv and Cuv is due to the exclusion of uncoupler by the outer membrane

DEFF Research Database (Denmark)

Haworth, Robert S.; Jensen, Peter Ruhdal; Michelsen, Ole

1990-01-01

The uncoupler resistant bacterial strains E. coli Tuv and Cuv share the high deoxycholate sensitivity of the parent strain, Doc S. However, both Tuv and Cuv show greater resistance than Doc S to other detergents. Measurement of the periplasmic volume indicates that the outer membrane of Doc S is ...

Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants.

Science.gov (United States)

Echtay, Karim S; Murphy, Michael P; Smith, Robin A J; Talbot, Darren A; Brand, Martin D

2002-12-06

Superoxide activates nucleotide-sensitive mitochondrial proton transport through the uncoupling proteins UCP1, UCP2, and UCP3 (Echtay, K. S., et al. (2002) Nature 415, 1482-1486). Two possible mechanisms were proposed: direct activation of the UCP proton transport mechanism by superoxide or its products and a cycle of hydroperoxyl radical entry coupled to UCP-catalyzed superoxide anion export. Here we provide evidence for the first mechanism and show that superoxide activates UCP2 in rat kidney mitochondria from the matrix side of the mitochondrial inner membrane: (i) Exogenous superoxide inhibited matrix aconitase, showing that external superoxide entered the matrix. (ii) Superoxide-induced uncoupling was abolished by low concentrations of the mitochondrially targeted antioxidants 10-(6'-ubiquinonyl)decyltriphenylphosphonium (mitoQ) or 2-[2-(triphenylphosphonio)ethyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol bromide (mitoVit E), which are ubiquinone (Q) or tocopherol derivatives targeted to the matrix by covalent attachment to triphenylphosphonium cation. However, superoxide-induced uncoupling was not affected by similar concentrations of the nontargeted antioxidants Q(o), Q(1), decylubiquinone, vitamin E, or 6-hydroxy-2,5,7,8-tetramethylchroman 2-carboxylic acid (TROLOX) or of the mitochondrially targeted but redox-inactive analogs decyltriphenylphosphonium or 4-chlorobutyltriphenylphosphonium. Thus matrix superoxide appears to be necessary for activation of UCP2 by exogenous superoxide. (iii) When the reduced to oxidized ratio of mitoQ accumulated by mitochondria was increased by inhibiting cytochrome oxidase, it induced nucleotide-sensitive uncoupling that was not inhibited by external superoxide dismutase. Under these conditions quinols are known to produce superoxide, and because mitoQ is localized within the mitochondrial matrix this suggests that production of superoxide in the matrix was sufficient to activate UCP2. Furthermore, the superoxide

Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds.

Science.gov (United States)

Stier, Antoine; Massemin, Sylvie; Criscuolo, François

2014-12-01

Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.

Pubertal administration of DEHP delays puberty, suppresses testosterone production and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans Rats

Science.gov (United States)

While is clear that exposure to high dosage levels of some phthalates delays the onset of puberty in the male rat it has been hypothesized that low levels of DEHP accelerate puberty by enhancing testicular androgen synthesis. The current study was designed to determine if the do...

p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-uncoupling in obesity.

Science.gov (United States)

Yu, Yi; Rajapakse, Angana G; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

2014-07-18

Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk with signal transduction pathways, and that p38 mitogen-activated protein kinase (p38mapk) is involved in eNOS-uncoupling, we investigated here whether p38mapk is involved in Arg-II-mediated eNOS-uncoupling in a high fat diet (HFD)-induced obesity mouse model. Obesity was induced in wild type (WT) and Arg-II-deficient (Arg-II(-/-)) mice on C57BL/6 J background by high-fat diet (HFD, 55% fat) for 14 weeks starting from age of 7 weeks. The entire aortas were isolated and subjected to 1) immunoblotting analysis of the protein level of eNOS, Arg-II and p38mapk activation; 2) arginase activity assay; 3) endothelium-dependent and independent vasomotor responses; 4) en face staining of superoxide anion and NO production with Dihydroethidium and 4,5-Diaminofluorescein Diacetate, respectively, to assess eNOS-uncoupling. To evaluate the role of p38mapk, isolated aortas were treated with p38mapk inhibitor SB203580 (10 μmol/L, 1 h) prior to the analysis. In addition, the role of p38mapk in Arg-II-induced eNOS-uncoupling was investigated in cultured human endothelial cells overexpressing Arg-II in the absence or presence of shRNA against p38mapk. HFD enhanced Arg-II expression/activity and p38mapk activity, which was associated with eNOS-uncoupling as revealed by decreased NO and enhanced L-NAME-inhibitable superoxide in aortas of WT obese mice. In accordance, WT obese mice revealed decreased endothelium-dependent relaxations to acetylcholine despite of higher eNOS protein level, whereas Arg-II(-/-) obese mice were protected from HFD-induced eNOS-uncoupling and endothelial dysfunction, which

Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation.

Science.gov (United States)

Zhang, Jun-Xia; Qu, Xin-Liang; Chu, Peng; Xie, Du-Jiang; Zhu, Lin-Lin; Chao, Yue-Lin; Li, Li; Zhang, Jun-Jie; Chen, Shao-Liang

2018-05-01

Uncoupled endothelial nitric oxide synthase (eNOS) produces O 2 - instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O 2 - production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O 2 - burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O 2 - releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Derivatives of Rhodamine 19 as Mild Mitochondria-targeted Cationic Uncouplers*

Science.gov (United States)

Antonenko, Yuri N.; Avetisyan, Armine V.; Cherepanov, Dmitry A.; Knorre, Dmitry A.; Korshunova, Galina A.; Markova, Olga V.; Ojovan, Silvia M.; Perevoshchikova, Irina V.; Pustovidko, Antonina V.; Rokitskaya, Tatyana I.; Severina, Inna I.; Simonyan, Ruben A.; Smirnova, Ekaterina A.; Sobko, Alexander A.; Sumbatyan, Natalia V.; Severin, Fedor F.; Skulachev, Vladimir P.

2011-01-01

A limited decrease in mitochondrial membrane potential can be beneficial for cells, especially under some pathological conditions, suggesting that mild uncouplers (protonophores) causing such an effect are promising candidates for therapeutic uses. The great majority of protonophores are weak acids capable of permeating across membranes in their neutral and anionic forms. In the present study, protonophorous activity of a series of derivatives of cationic rhodamine 19, including dodecylrhodamine (C12R1) and its conjugate with plastoquinone (SkQR1), was revealed using a variety of assays. Derivatives of rhodamine B, lacking dissociable protons, showed no protonophorous properties. In planar bilayer lipid membranes, separating two compartments differing in pH, diffusion potential of H+ ions was generated in the presence of C12R1 and SkQR1. These compounds induced pH equilibration in liposomes loaded with the pH probe pyranine. C12R1 and SkQR1 partially stimulated respiration of rat liver mitochondria in State 4 and decreased their membrane potential. Also, C12R1 partially stimulated respiration of yeast cells but, unlike the anionic protonophore FCCP, did not suppress their growth. Loss of function of mitochondrial DNA in yeast (grande-petite transformation) is known to cause a major decrease in the mitochondrial membrane potential. We found that petite yeast cells are relatively more sensitive to the anionic uncouplers than to C12R1 compared with grande cells. Together, our data suggest that rhodamine 19-based cationic protonophores are self-limiting; their uncoupling activity is maximal at high membrane potential, but the activity decreases membrane potentials, which causes partial efflux of the uncouplers from mitochondria and, hence, prevents further membrane potential decrease. PMID:21454507

Modelling of the protonophoric uncoupling by phenoxyacetic acid of the plasma membrane of Penicillium chrysogenum

DEFF Research Database (Denmark)

Henriksen, Claus Maxel; Nielsen, Jens Bredal; Villadsen, John

1998-01-01

negligible influence on the growth energetics due to protonophoric uncoupling of membrane potentials by passive diffusive uptake. On the other hand, when the extracellular pH is lowered to 5.00, a severe maintenance-related uncoupling effect of phenoxyacetic acid is calculated. These findings were confirmed...

Use the Protonmotive Force: Mitochondrial Uncoupling and Reactive Oxygen Species.

Science.gov (United States)

Berry, Brandon J; Trewin, Adam J; Amitrano, Andrea M; Kim, Minsoo; Wojtovich, Andrew P

2018-04-04

Mitochondrial respiration results in an electrochemical proton gradient, or protonmotive force (pmf), across the mitochondrial inner membrane. The pmf is a form of potential energy consisting of charge (∆ψ m ) and chemical (∆pH) components, that together drive ATP production. In a process called uncoupling, proton leak into the mitochondrial matrix independent of ATP production dissipates the pmf and energy is lost as heat. Other events can directly dissipate the pmf independent of ATP production as well, such as chemical exposure or mechanisms involving regulated mitochondrial membrane electrolyte transport. Uncoupling has defined roles in metabolic plasticity and can be linked through signal transduction to physiologic events. In the latter case, the pmf impacts mitochondrial reactive oxygen species (ROS) production. Although capable of molecular damage, ROS also have signaling properties that depend on the timing, location, and quantity of their production. In this review, we provide a general overview of mitochondrial ROS production, mechanisms of uncoupling, and how these work in tandem to affect physiology and pathologies, including obesity, cardiovascular disease, and immunity. Overall, we highlight that isolated bioenergetic models-mitochondria and cells-only partially recapitulate the complex link between the pmf and ROS signaling that occurs in vivo. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cardiac sarcoplasmic reticulum

International Nuclear Information System (INIS)

Jacobson, M.S.; Ambudkar, I.S.; Young, E.P.; Naseem, S.M.; Heald, F.P.; Shamoo, A.E.

1985-01-01

The effect on the cardiac sarcoplasmic reticulum of an atherogenic (1% cholesterol) diet fed during the neonatal vs the juvenile period of life was studied in Yorkshire swine. Male piglets were randomly assigned at birth to 1 of 4 groups: group I (control), group II (lactation feeding), group III (juvenile period feeding) and group IV (lactation and juvenile feeding). All animals were killed at 55 weeks of age and cardiac sarcoplasmic reticulum (SR) isolated for assay of calcium uptake, Ca 2+ -Mg 2+ ATPase activity, and lipid analysis by thin-layer chromatography and gas chromatography. The amount of cholesterol/mg SR protein and the cholesterol/phospholipid ratio were higher in the animals fed during lactation (groups II and IV) and lower in those fed only during the juvenile period (group III). Phospholipid fatty acid patterns as measured by gas chromatography were unaltered in any group. Calcium uptake was markedly diminished in all experimental conditions: group II 47%, group III 65% and group IV 96%. Compared to the observed changes in calcium transport, the ATP hydrolytic activity was relatively less affected. Only in group IV a significant decrease (41%) was seen. Groups II and III show no change in ATP hydrolytic activity. The decrease in calcium uptake and altered cholesterol/phospholipid ratio without effect on ATP hydrolytic activity is consistent with an uncoupling of calcium transport related to the atherogenic diet in early life. (author)

Uncoupling of Vascular Nitric Oxide Synthase Caused by Intermittent Hypoxia

Directory of Open Access Journals (Sweden)

Mohammad Badran

2016-01-01

Full Text Available Objective. Obstructive sleep apnea (OSA, characterized by chronic intermittent hypoxia (CIH, is often present in diabetic (DB patients. Both conditions are associated with endothelial dysfunction and cardiovascular disease. We hypothesized that diabetic endothelial dysfunction is further compromised by CIH. Methods. Adult male diabetic (BKS.Cg-Dock7m +/+ Leprdb/J (db/db mice (10 weeks old and their heterozygote littermates were subjected to CIH or intermittent air (IA for 8 weeks. Mice were separated into 4 groups: IA (intermittent air nondiabetic, IH (intermittent hypoxia nondiabetic, IADB (intermittent air diabetic, and IHDB (intermittent hypoxia diabetic groups. Endothelium-dependent and endothelium-independent relaxation and modulation by basal nitric oxide (NO were analyzed using wire myograph. Plasma 8-isoprostane, interleukin-6 (IL-6, and asymmetric dimethylarginine (ADMA were measured using ELISA. Uncoupling of eNOS was measured using dihydroethidium (DHE staining. Results. Endothelium-dependent vasodilation and basal NO production were significantly impaired in the IH and IADB group compared to IA group but was more pronounced in IHDB group. Levels of 8-isoprostane, IL-6, ADMA, and eNOS uncoupling were ≈2-fold higher in IH and IADB groups and were further increased in the IHDB group. Conclusion. Endothelial dysfunction is more pronounced in diabetic mice subjected to CIH compared to diabetic or CIH mice alone. Oxidative stress, ADMA, and eNOS uncoupling were exacerbated by CIH in diabetic mice.

Arsenate uncoupling of oxidative phosphorylation in isolated plant mitochondria

Energy Technology Data Exchange (ETDEWEB)

Wickes, W A; Wiskich, J T

1976-01-01

The uncoupling by arsenate of beetroot and cauliflower bud mitochondria showed the following characteristics: arsenate stimulation of respiration above the rate found with phosphate; inhibition of arsenate-stimulated respiration by phosphate; enhancement of arsenate-stimulated respiration by ADP; only partial prevention of this ADP-enhanced respiration by atractyloside; inhibition by oligomycin of the arsenate-stimulated respiration back to the phosphate rate; and the absence of any stimulatory effect of ADP in the presence of oligomycin. These results are qualitatively analogous to those reported for arsenate uncoupling in rat liver mitochondria. Arsenate stimulated malate oxidation, presumably by stimulating malate entry, in both beetroot and cauliflower bud mitochondria; however, high rates of oxidation, and presumably entry, were only sustained with arsenate in beetroot mitochondria. NADH was oxidized rapidly in cauliflower bud mitochondria in the presence of arsenate, showing that arsenate did not inhibit electron transfer processes.

Possible physiological roles of mitochondrial uncoupling proteins-UCPn

Czech Academy of Sciences Publication Activity Database

Ježek, Petr

2002-01-01

Roč. 34, č. 10 (2002), s. 1190-1206 ISSN 1357-2725 R&D Projects: GA AV ČR IAA5011106; GA ČR GA301/02/1215; GA MŠk ME 389 Institutional research plan: CEZ:AV0Z5011922 Keywords : uncoupling proteins * diabetes * obesity Subject RIV: ED - Physiology Impact factor: 3.044, year: 2002

Kidney transplantation restored uncoupled bone turnover in end-stage renal disease.

Science.gov (United States)

Kawarazaki, Hiroo; Shibagaki, Yugo; Kido, Ryo; Nakajima, Ichiro; Fuchinoue, Shohei; Ando, Katsuyuki; Fujita, Toshiro; Fukagawa, Masafumi; Teraoka, Satoshi; Fukumoto, Seiji

2012-07-01

While kidney transplantation (KTx) reverses many disorders associated with end-stage renal disease (ESRD), patients who have received KTx often have chronic kidney disease and bone and mineral disorder (CKD-MBD). However, it is unknown how bone metabolism changes by KTx. Living donor-KTx recipients (n = 34) at Tokyo Women's Medical University were prospectively recruited and the levels of bone-specific alkaline phosphatase (BAP) and serum cross-linked N-telopeptides of Type 1 collagen (NTX) were measured before, 6 and 12 months after transplantation. Before KTx, serum BAP was within the reference range in more than half of patients while NTX was high in most patients. Serum NTX was higher in patients with longer dialysis durations compared to that with shorter durations before KTx. However, there was no difference in serum BAP between these patients. After KTx, BAP increased while NTX decreased along with the decline of PTH. In addition, the numbers of patients who showed high BAP and NTX were comparable after KTx. These results suggest that bone formation is suppressed and uncoupled with bone resorption in patients with ESRD and this uncoupling is restored by KTx. Further studies are necessary to clarify the mechanism of bone uncoupling in patients with ESRD.

Childhood exposure to DEHP, DBP and BBP under the existing chemical management systems

DEFF Research Database (Denmark)

Lee, Jihyun; Lee, Jong-Hyeon; Kim, Chan-Kook

with a median RCR of 0.91 (DK) vs. 0.62 (KR) (unpublished results). The present study aims to assess the aggregated exposure from consumer products assuming that every single product’s regulatory standard is respected. Total exposure to the three phthalates will be estimated taking into account different...... consumption patterns and life styles of children in Denmark and Korea. The estimated exposure from products will be added to the exposure via the environment and foods and total exposure will be compared to biomonitoring data. The result will verify the appropriateness of current product regulations for DEHP......-butyl phthalate (BBP) have been gradually under regulations. Despite the similar adverse health effects, no harmonized regulations exist for these substances. Varying regulations are focused on single/multiple substances in separate product categories, e.g. toys, childcare articles, cosmetics and food packaging...

Muscle Mitochondrial Uncoupling Dismantles Neuromuscular Junction and Triggers Distal Degeneration of Motor Neurons

Science.gov (United States)

Dupuis, Luc; Gonzalez de Aguilar, Jose-Luis; Echaniz-Laguna, Andoni; Eschbach, Judith; Rene, Frédérique; Oudart, Hugues; Halter, Benoit; Huze, Caroline; Schaeffer, Laurent; Bouillaud, Frédéric; Loeffler, Jean-Philippe

2009-01-01

Background Amyotrophic lateral sclerosis (ALS), the most frequent adult onset motor neuron disease, is associated with hypermetabolism linked to defects in muscle mitochondrial energy metabolism such as ATP depletion and increased oxygen consumption. It remains unknown whether muscle abnormalities in energy metabolism are causally involved in the destruction of neuromuscular junction (NMJ) and subsequent motor neuron degeneration during ALS. Methodology/Principal Findings We studied transgenic mice with muscular overexpression of uncoupling protein 1 (UCP1), a potent mitochondrial uncoupler, as a model of muscle restricted hypermetabolism. These animals displayed age-dependent deterioration of the NMJ that correlated with progressive signs of denervation and a mild late-onset motor neuron pathology. NMJ regeneration and functional recovery were profoundly delayed following injury of the sciatic nerve and muscle mitochondrial uncoupling exacerbated the pathology of an ALS animal model. Conclusions/Significance These findings provide the proof of principle that a muscle restricted mitochondrial defect is sufficient to generate motor neuron degeneration and suggest that therapeutic strategies targeted at muscle metabolism might prove useful for motor neuron diseases. PMID:19404401

Comparative effects of butyl benzyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP) on the aquatic larvae of Chironomus riparius based on gene expression assays related to the endocrine system, the stress response and ribosomes.

Science.gov (United States)

Planelló, Rosario; Herrero, Oscar; Martínez-Guitarte, José Luis; Morcillo, Gloria

2011-09-01

In this work, the effects of butyl benzyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP), two of the most extensively used phthalates, were studied in Chironomus riparius under acute short-term treatments, to compare their relative toxicities and identify genes sensitive to exposure. The ecotoxicity of these phthalates was assessed by analysis of the alterations in gene expression profiles of selected inducible and constitutive genes related to the endocrine system, the cellular stress response and the ribosomal machinery. Fourth instar larvae, a model system in aquatic toxicology, were experimentally exposed to five increasing concentrations (0.01, 0.1, 1, 10, and 100mg/L) of DEHP and BBP for 24h. Gene expression was analysed by the changes in levels of transcripts, using RT-PCR techniques with specific gene probes. The exposures to DEHP or BBP were able to rapidly induce the hsp70 gene in a concentration-dependent manner, whereas the cognate form hsc70 was not altered by either of these chemicals. Transcription of ribosomal RNA as a measure of cell viability, quantified by the levels of ITS2, was not affected by DEHP, but was slightly, yet significantly, downregulated by BBP at the highest concentrations tested. Finally, as these phthalates are classified as endocrine disruptor chemicals (EDCs), their potential effect on the ecdysone endocrine system was studied by analysing the two genes, EcR and usp, of the heterodimeric ecdysone receptor complex. It was found that BBP provoked the overexpression of the EcR gene, with significant increases from exposures of 0.1mg/L and above, while DEHP significantly decreased the activity of this gene at the highest concentration. These data are relevant as they show for the first time the ability of phthalates to interfere with endocrine marker genes in invertebrates, demonstrating their potential capacity to alter the ecdysone signalling pathway. Overall, the study clearly shows a differential gene-toxin interaction

Childhood exposure to DEHP, DBP and BBP under existing chemical management systems: A comparative study of sources of childhood exposure in Korea and in Denmark

DEFF Research Database (Denmark)

Lee, Jihyun; Lee, Jong-Hyeon; Kim, Chan-Kook

2014-01-01

In this paper, the cumulative risks of Di(2-ethylhexyl) phthalate (DEHP), Di-n-butyl phthalate (DBP), and Benzylbutyl phthalate (BBP) to 2-year-old children in two countries: one European (Denmark) and one Asian (South Korea) were compared. Denmark does not produce phthalates as a raw material, w...

Mitochondrial uncoupling proteins in unicellular eukaryotes.

Science.gov (United States)

Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Antos-Krzeminska, Nina; Sluse, Francis E

2010-01-01

Uncoupling proteins (UCPs) are members of the mitochondrial anion carrier protein family that are present in the mitochondrial inner membrane and mediate free fatty acid (FFA)-activated, purine nucleotide (PN)-inhibited proton conductance. Since 1999, the presence of UCPs has been demonstrated in some non-photosynthesising unicellular eukaryotes, including amoeboid and parasite protists, as well as in non-fermentative yeast and filamentous fungi. In the mitochondria of these organisms, UCP activity is revealed upon FFA-induced, PN-inhibited stimulation of resting respiration and a decrease in membrane potential, which are accompanied by a decrease in membranous ubiquinone (Q) reduction level. UCPs in unicellular eukaryotes are able to divert energy from oxidative phosphorylation and thus compete for a proton electrochemical gradient with ATP synthase. Our recent work indicates that membranous Q is a metabolic sensor that might utilise its redox state to release the PN inhibition of UCP-mediated mitochondrial uncoupling under conditions of phosphorylation and resting respiration. The action of reduced Q (QH2) could allow higher or complete activation of UCP. As this regulatory feature was demonstrated for microorganism UCPs (A. castellanii UCP), plant and mammalian UCP1 analogues, and UCP1 in brown adipose tissue, the process could involve all UCPs. Here, we discuss the functional connection and physiological role of UCP and alternative oxidase, two main energy-dissipating systems in the plant-type mitochondrial respiratory chain of unicellular eukaryotes, including the control of cellular energy balance as well as preventive action against the production of reactive oxygen species. Copyright © 2009 Elsevier B.V. All rights reserved.

Alkylsulfonates as probes of uncoupling protein transport mechanism. Ion pair transport demonstrates that direct H(+) translocation by UCP1 is not necessary for uncoupling

Czech Academy of Sciences Publication Activity Database

Jabůrek, M.; Vařecha, M.; Ježek, Petr; Garlid, K. D.

2001-01-01

Roč. 276, č. 34 (2001), s. 31897-31905 ISSN 0021-9258 R&D Projects: GA AV ČR IAA5011106 Grant - others:NIH(US) DK56273 Institutional research plan: CEZ:AV0Z5011922 Keywords : mitochondrial uncoupling proteins * alkylsulfonates * ion pair transport Subject RIV: CE - Biochemistry Impact factor: 7.258, year: 2001

eNOS-uncoupling in age-related erectile dysfunction

OpenAIRE

Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

2011-01-01

Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ...

Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

DEFF Research Database (Denmark)

Dhamrait, Sukhbir S.; Maubaret, Cecilia; Pedersen-bjergaard, Ulrik

2016-01-01

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial...... amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P 

Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression

DEFF Research Database (Denmark)

Dhamrait, Sukhbir S.; Maubaret, Cecilia; Pedersen-Bjergaard, Ulrik

2016-01-01

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial...... amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P 

Classical-processing and quantum-processing signal separation methods for qubit uncoupling

Science.gov (United States)

Deville, Yannick; Deville, Alain

2012-12-01

The Blind Source Separation problem consists in estimating a set of unknown source signals from their measured combinations. It was only investigated in a non-quantum framework up to now. We propose its first quantum extensions. We thus introduce the Quantum Source Separation field, investigating both its blind and non-blind configurations. More precisely, we show how to retrieve individual quantum bits (qubits) only from the global state resulting from their undesired coupling. We consider cylindrical-symmetry Heisenberg coupling, which e.g. occurs when two electron spins interact through exchange. We first propose several qubit uncoupling methods which typically measure repeatedly the coupled quantum states resulting from individual qubits preparations, and which then statistically process the classical data provided by these measurements. Numerical tests prove the effectiveness of these methods. We then derive a combination of quantum gates for performing qubit uncoupling, thus avoiding repeated qubit preparations and irreversible measurements.

Metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) in rats: in vivo and in vitro dose and time dependency of metabolism

International Nuclear Information System (INIS)

Lhuguenot, J.C.; Mitchell, A.M.; Milner, G.; Lock, E.A.; Elcombe, C.R.

1985-01-01

This study investigated the in vivo metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in rats after multiple dosing, the metabolism of MEHP in primary rat hepatocyte cultures for periods of up to 3 days, and the biotransformation of some major metabolites of MEHP. Rats were orally administered [ 14 C]DEHP or [ 14 C]MEHP at doses of 50 and 500 mg/kg body wt for three consecutive days. Urine was collected at 24-hr intervals, and metabolite profiles were determined. After a single dose of either compound, urinary metabolite profiles were similar to those previously reported. However, after multiple administration of both DEHP and MEHP at 500 mg/kg, increases in omega-/beta-oxidation products [metabolites I and V, mono(3-carboxy-2-ethylpropyl) phthalate and mono(5-carboxy-2-ethylpentyl) phthalate, respectively] and decreases in omega - 1-oxidation products [metabolites VI and IX, mono(2-ethyl-5-oxohexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate, respectively] were seen. At the low dose of 50 mg/kg little or no alteration in urinary metabolite profiles was observed. At 500 mg/kg of MEHP a 4-fold stimulation of CN- -insensitive palmitoyl-CoA oxidation (a peroxisomal beta-oxidation marker) was seen after three consecutive daily doses. At the low dose of 50 mg/kg only a 1.8-fold increase was noted. Similar observations were made with rat hepatocyte cultures. MEHP at concentrations of 50 and 500 microM was extensively metabolized in the rat hepatocyte cultures. Similar metabolic profiles to those seen after in vivo administration of MEHP were observed. At the high (500 microM) concentration of MEHP, changes in the relative proportions of omega- and omega- 1-oxidized metabolites were seen

Uncoupling proteins of invertebrates: A review.

Science.gov (United States)

Slocinska, Malgorzata; Barylski, Jakub; Jarmuszkiewicz, Wieslawa

2016-09-01

Uncoupling proteins (UCPs) mediate inducible proton conductance in the mitochondrial inner membrane. Herein, we summarize our knowledge regarding UCPs in invertebrates. Since 2001, the presence of UCPs has been demonstrated in nematodes, mollusks, amphioxi, and insects. We discuss the following important issues concerning invertebrate UCPs: their evolutionary relationships, molecular and functional properties, and physiological impact. Evolutionary analysis indicates that the branch of vertebrate and invertebrate UCP4-5 diverged early in the evolutionary process prior to the divergence of the animal groups. Several proposed physiological roles of invertebrate UCPs are energy control, metabolic balance, and preventive action against oxidative stress. © 2016 IUBMB Life, 68(9):691-699, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Uncoupling of sarcoplasmic reticulum Ca²⁺-ATPase by N-arachidonoyl dopamine. Members of the endocannabinoid family as thermogenic drugs

DEFF Research Database (Denmark)

Mahmmoud, Yasser Ahmed; Gaster, Michel

2013-01-01

BACKGROUND AND PURPOSE: The sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) plays a role in thermogenesis. The exogenous compound capsaicin increased SERCA-mediated ATP hydrolysis not coupled to Ca²⁺ transport. Here, we have sought to identify endogenous compounds that may function as SERCA uncoupling...... agents. EXPERIMENTAL APPROACH: Using isolated SR vesicles from rabbits, we have screened for endogenous compounds that uncouple SERCA. We have also studied their ability to deplete cytoplasmic ATP from human skeletal muscle cells in culture. KEY RESULTS: Studies on SR vesicles showed that the endogenous......, regardless of the presence of glucose. CONCLUSIONS AND IMPLICATIONS: NADA is an endogenous molecule that may function as SERCA uncoupling agent in vivo. Members of the endocannabinoid family exert concerted actions on several Ca²⁺-handling proteins. Uncoupling of SERCA by exogenous compounds could be a novel...

Mitochondrial Complex I superoxide production is attenuated by uncoupling

Czech Academy of Sciences Publication Activity Database

Dlasková, Andrea; Hlavatá, Lydie; Ježek, Jan; Ježek, Petr

2008-01-01

Roč. 40, č. 10 (2008), s. 2098-2109 ISSN 1357-2725 R&D Projects: GA ČR GP303/05/P100; GA AV ČR IAA500110701; GA MŠk(CZ) 1P05ME794 Institutional research plan: CEZ:AV0Z50110509 Keywords : mitochondrial H2O2 production * mitochondrial Complex I proton pumping * uncoupling Subject RIV: CE - Biochemistry Impact factor: 4.178, year: 2008

Optimal parameters uncoupling vibration modes of oscillators

Science.gov (United States)

Le, K. C.; Pieper, A.

2017-07-01

This paper proposes a novel optimization concept for an oscillator with two degrees of freedom. By using specially defined motion ratios, we control the action of springs to each degree of freedom of the oscillator. We aim at showing that, if the potential action of the springs in one period of vibration, used as the payoff function for the conservative oscillator, is maximized among all admissible parameters and motions satisfying Lagrange's equations, then the optimal motion ratios uncouple vibration modes. A similar result holds true for the dissipative oscillator having dampers. The application to optimal design of vehicle suspension is discussed.

Triglyceride-lowering effect of respiratory uncoupling in white adipose tissue

Czech Academy of Sciences Publication Activity Database

Rossmeisl, Martin; Kovář, J.; Syrový, Ivo; Flachs, Pavel; Bobková, D.; Kolář, František; Poledne, R.; Kopecký, Jan

2005-01-01

Roč. 13, č. 5 (2005), s. 835-844 ISSN 1071-7323 R&D Projects: GA ČR(CZ) GP303/03/P127; GA ČR(CZ) GA303/02/1220 Institutional research plan: CEZ:AV0Z5011922 Keywords : adipose tissue * uncoupling protein * lipoprotein lipase Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.972, year: 2005

Comparison of coupled and uncoupled load simulations on a jacket support structure

DEFF Research Database (Denmark)

Haselbach, Philipp Ulrich; Natarajan, Anand; Jiwinangun, Randi Gusto

2013-01-01

In this article, a comparison of the moments and forces at the joints of a jacket structure is made between fully coupled aerohydroelastic simulations in HAWC2 and uncoupled load predictions in the finite element software Abaqus. The jacket sub structure is modelled in moderate deep waters of 50m...... structure similar to the Upwind reference jacket is developed in the Abaqus environment, to which is added the transition piece and tower. The aeroelastic loads determined in normal operating conditions of the turbine is integrated and centralized as nodal forces and moments acting at the tower top...... in Abaqus. The fully coupled simulation is implemented and performed in HAWC2. In the uncoupled case, the loads (wave loads and tower base loads) are analysed by an implicit structural Finite Element Analysis (Abaqus 6.11-1). A subroutine is used as a preprocessor generating a beam element model and linking...

Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

Science.gov (United States)

Berghella, Libera; Ferraro, Elisabetta

2012-01-01

Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

Zinc Potentiates an Uncoupled Anion Conductance Associated with the Dopamine Transporter

DEFF Research Database (Denmark)

Meinild, Anne-Kristine; Sitte, Harald H; Gether, Ulrik

2004-01-01

but by a marked increase in the charge/DA flux coupling ratio as assessed from concomitant measurements of [(3)H]DA uptake and currents in voltage-clamped oocytes. These data suggest that Zn(2+) facilitates an uncoupled ion conductance mediated by DAT. Whereas this required substrate in the wild type (WT), we...

Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle

DEFF Research Database (Denmark)

Fernström, Maria; Tonkonogi, Michail; Sahlin, Kent

2004-01-01

Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting...... respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training, .VO2peak, citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P ... mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored....

PSD-95 uncoupling from NMDA receptors by Tat-N-dimer ameliorates neuronal depolarisation in cortical spreading depression

DEFF Research Database (Denmark)

Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders

2017-01-01

during the first hour after i.v. injection. The Tat-N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat-N-dimer reduced the average amplitude...... depression on cortical blood flow and CMRO2 We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarisation wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling...

The β3 Adrenergic Receptor Agonist BRL37344 Exacerbates Atrial Structural Remodeling Through iNOS Uncoupling in Canine Models of Atrial Fibrillation.

Science.gov (United States)

Wang, Xiaobing; Wang, Ruifeng; Liu, Guangzhong; Dong, Jingmei; Zhao, Guanqi; Tian, Jingpu; Sun, Jiayu; Jia, Xiuyue; Wei, Lin; Wang, Yuping; Li, Weimin

2016-01-01

The role of the β3-adrenergic receptor (β3-AR) agonist BRL37344 in atrial fibrillation (AF) structural remodeling and the underlying mechanisms as a therapeutic target were investigated. Four groups of dogs were evaluated: sham, pacing, β3-AR agonist BRL37344 (β3-AGO), and β3-AR antagonist L748337 (β3-ANT) groups. Dogs in the pacing, β3-AGO and β3-ANT groups were subjected to rapid atrial pacing for four weeks. Atrial structure and function, AF inducibility and duration, atrial myocyte apoptosis and interstitial fibrosis were assessed. Atrial superoxide anions were evaluated by fluorescence microscopy and colorimetric assays. Cardiac nitrate+nitrite levels were used to assess nitric oxide (NO) production. Protein and mRNA expression of β3-AR, neuronal NO synthase (nNOS), inducible NO synthase (iNOS), endothelial NO synthase (eNOS) and guanosine triphosphate cyclohydrolase-1 (GCH-1) as well as tetrahydrobiopterin (BH4) levels were measured. β3-AR was up-regulated in AF. Stimulation of β3-AR significantly increased atrial myocyte apoptosis, fibrosis and atrial dilatation, resulting in increased AF induction and prolonged duration. These effects were attenuated by β3-ANT. Moreover, β3-AGO reduced BH4 and NO production and increased superoxide production, which was inhibited by the specific iNOS inhibitor, 1400w β3-AGO also increased iNOS but decreased eNOS and had no effect on nNOS expression in AF. β3-AR stimulation resulted in atrial structural remodeling by increasing iNOS uncoupling and related oxidative stress. β3-AR up-regulation and iNOS uncoupling might be underlying AF therapeutic targets. © 2016 The Author(s) Published by S. Karger AG, Basel.

Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells.

Science.gov (United States)

Shikata, Yuki; Kiga, Masaki; Futamura, Yushi; Aono, Harumi; Inoue, Hiroyuki; Kawada, Manabu; Osada, Hiroyuki; Imoto, Masaya

2017-04-01

The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound. Nonactin, as well as other mitochondrial uncouplers, induced apoptosis selectively in β-catenin mutated tumor cells. Significant tumor regression was observed in the β-catenin mutant HCT 116 xenograft model, but not in the β-catenin wild type A375 xenograft model, in response to daily administration of nonactin in vivo. Furthermore, we found that expression of an active mutant form of β-catenin induced a decrease in the glycolysis rate. Taken together, our results demonstrate that tumor cells with mutated β-catenin depend on mitochondrial oxidative phosphorylation for survival. Therefore, they undergo apoptosis in response to mitochondrial dysfunction following the addition of mitochondrial uncouplers, such as nonactin. These results suggest that targeting mitochondria is a potential chemotherapeutic strategy for tumor cells that harbor β-catenin mutations. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Recruitment of mitochondrial uncoupling protein UCP2 after lipopolysaccharide induction

Czech Academy of Sciences Publication Activity Database

Růžička, Michal; Škobisová, Eva; Dlasková, Andrea; Šantorová, Jitka; Smolková, Katarína; Špaček, Tomáš; Žáčková, Markéta; Modrianský, M.; Ježek, Petr

2005-01-01

Roč. 37, č. 4 (2005), s. 809-821 ISSN 1357-2725 R&D Projects: GA ČR(CZ) GA301/02/1215; GA ČR(CZ) GP301/01/P084; GA AV ČR(CZ) IAA5011106 Grant - others:NIH(US) TW01487 Institutional research plan: CEZ:AV0Z5011922 Keywords : lipopolysaccharide * oxidative stress in liver * mitochondrial uncoupling protein UCP2 Subject RIV: CE - Biochemistry Impact factor: 3.871, year: 2005

CAPSAICIN SUPPLEMENTATION FAILS TO MODULATE AUTONOMIC AND CARDIAC ELECTROPHYSIOLOGIC ACTIVITY DURING EXERCISE IN THE OBESE: WITH VARIANTS OF UCP2 AND UCP3 POLYMORPHISM

Directory of Open Access Journals (Sweden)

Ki Ok Shin

2008-09-01

Full Text Available We investigated the effects of capsaicin supplementation (150mg on alterations of autonomic nervous system (ANS activity associated with adverse effects of cardiac depolarization-repolarization intervals during aerobic exercise in obese humans. Nine obese males (26.1 ± 1.5 yrs volunteered between study designed. The cardiac ANS activities evaluated by means of heart rate variability of power spectral analysis and cardiac QT interval were continuously measured during 5-min rest and 30-min exercise at 50% of maximal ventilation threshold (50%VTmax on stationary ergometer with placebo (CON or capsaicin (CAP oral administration chosen at random. The uncoupling protein (UCP 2 and UCP 3 genetic variants of the subjects were analyzed by noninvasive genotyping method from collecting buccal mucosa cells. The results indicated that there were no significant differences in cardiac ANS activities during rest and exercise between CON and CAP trials. Although no significant difference, A/A allele of UCP2 polymorphism showed a reduced sympathetic nervous system (SNS index activity compared to G/G + G/A allele during exercise intervention in our subjects. On the other hand, the data on cardiac QT interval showed no significant difference, indicating that oral administration of capsaicin did not cause any adverse effect on cardiac depolarization-repolarization. In conclusion, our results suggest that capsaicin supplementation 1 h before exercise intervention has no effect on cardiac ANS activities and cardiac electrical stability during exercise in obese individuals. Further studies should also consider genetic variants for exercise efficacy against obesity

Excitation contraction uncoupling by high intracellular [Ca2+] in frog skeletal muscle: a voltage clamp study.

Science.gov (United States)

Olivera, J Fernando; Pizarro, Gonzalo

2016-10-01

Raising the intracellular [Ca 2+ ] ([Ca 2+ ] i ) was previously found to produce uncoupling between the electrical depolarization of the transverse tubules and contraction in skinned muscle fibers. Here we study the effect of elevated [Ca 2+ ] i in voltage clamped cut fibers of frog skeletal muscle to establish how the charge movement, a measure of the activation of the dihydropyridine receptors (DHPR)-voltage sensors, and Ca 2+ release, a consequence of the opening of the ryanodine receptor (RyR)-release channels, were affected. [Ca 2+ ] i was raised by various procedures (pharmacological release from the sarcoplasmic reticulum, application of high [Ca 2+ ] i intracellular solution, permeabilization of the plasma membrane by a Ca 2+ ionophore) all of which produced impairment of excitation-contraction coupling. The charge movement was reduced from 20.2 ± 1.24 to 9.9 ± 0.94 nC/μF meanwhile the Ca 2+ release flux was reduced from 13.5 + 0.7 to 2.2 ± 0.3 μM/ms (n = 33). This suggests that a significant fraction of the DHPRs that remained functional, could not activate RyRs, and were therefore presumably disconnected. These results are broadly consistent with the original reports in skinned fibers. Uncoupling was prevented by the addition to the intracellular solution of the protease inhibitor leupeptin. In approximately 40 % of the uncoupled cells we observed that the [Ca 2+ ] i transient continued to rise after the voltage clamp pulse was turned off. This loss of control by membrane voltage suggests that the uncoupled release channels might have another mechanism of activation, likely by Ca 2+ .

Co-factor engineering in lactobacilli: Effects of uncoupled ATPase activity on metabolic fluxes in Lactobacillus (L.) plantarum and L. sakei

DEFF Research Database (Denmark)

Rud, Ida; Solem, Christian; Jensen, Peter Ruhdal

2008-01-01

The hydrolytic F-1-part of the F1F0-ATPase was over-expressed in Lactobacillus (L.) plantarum NC8 and L. sakei Lb790x during fermentation of glucose or ribose, in order to study how changes in the intracellular levels of ATP and ADP affect the metabolic fluxes. The uncoupled ATPase activity...... resulted in a decrease in intracellular energy level (ATP/ADP ratio), biomass yield and growth rate. Interestingly, the glycolytic and ribolytic flux increased in L. plantarum with uncoupled ATPase activity compared to the reference strain by up to 20% and 50%, respectively. The ATP demand was estimated...... to have approximately 80% control on both the glycolytic and ribolytic flux in L. plantarum under these conditions. In contrast, the glycolytic and ribolytic flux decreased in L. sakei with uncoupled ATPase activity. (C) 2008 Elsevier Inc. All rights reserved....

Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

Energy Technology Data Exchange (ETDEWEB)

Pardo Andreu, G.L. [Centro de Quimica Farmaceutica, Departamento de Investigaciones Biomedicas, Ciudad de La Habana (Cuba); Inada, N.M.; Vercesi, A.E. [Universidade Estadual de Campinas, Departamento de Patologia Clinica, Faculdade de Ciencias Medicas, Campinas, SP (Brazil); Curti, C. [Universidade de Sao Paulo, Departamento de Fisica e Quimica, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, SP (Brazil)

2009-01-15

One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21{+-}4 to 130{+-}7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H{sup +} leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria. (orig.)

Circulating microparticles from patients with valvular heart disease and cardiac surgery inhibit endothelium-dependent vasodilation.

Science.gov (United States)

Fu, Li; Hu, Xiao-Xia; Lin, Ze-Bang; Chang, Feng-Jun; Ou, Zhi-Jun; Wang, Zhi-Ping; Ou, Jing-Song

2015-09-01

Vascular function is very important for maintaining circulation after cardiac surgery. Circulating microparticles (MPs) generated in various diseases play important roles in causing inflammation, coagulation, and vascular injury. However, the impact of MPs generated from patients who have valvular heart disease (VHD), before and after cardiac surgery, on vascular function remains unknown. This study is designed to investigate the impact of such MPs on vasodilation. Microparticles were isolated from age-matched healthy subjects and patients who had VHD, before cardiac surgery, and at 12 hours and 72 hours afterward. The number of MPs was measured and compared. Effects evaluated were of the impact of MPs on: vasodilation of mice aorta; the phosphorylation and expression of Akt, endothelial nitric oxide synthase (eNOS), protein kinase C-βII (PKC-βII), and p70 ribosomal protein S6 kinase (p70S6K); expression of caveolin-1; the association of eNOS with heat shock protein 90 (HSP90); and generation of nitric oxide and superoxide anion of human umbilical vein endothelial cells. Compared with the healthy subjects, VHD patients had significantly higher levels of circulating MPs and those MPs before cardiac surgery can: impair endothelium-dependent vasodilation; inhibit phosphorylation of Akt and eNOS; increase activation of PKC-βII and p70S6K; enhance expression of caveolin-1; reduce the association of HSP90 with eNOS; decrease nitric oxide production, and increase superoxide anion generation. These deleterious effects were even stronger in postoperative MPs. Our data demonstrate that MPs generated from VHD patients before and after cardiac surgery contributed to endothelial dysfunction, by uncoupling and inhibiting eNOS. Circulating MPs are potential therapeutic targets for the maintenance of vascular function postoperatively. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Potential roles for uncoupling proteins in HIV lipodystrophy.

Science.gov (United States)

Nolan, David; Pace, Craig

2004-07-01

The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.

Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension

NARCIS (Netherlands)

Papazova, Diana A.; Friederich-Persson, Malou; Joles, Jaap A.; Verhaar, Marianne C.

2015-01-01

Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (PO2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney

Comparative study on the migration of di-2-ethylhexyl phthalate (DEHP) and tri-2-ethylhexyl trimellitate (TOTM) into blood from PVC tubing material of a heart-lung machine.

Science.gov (United States)

Eckert, Elisabeth; Münch, Frank; Göen, Thomas; Purbojo, Ariawan; Müller, Johannes; Cesnjevar, Robert

2016-02-01

Medical devices like blood tubing often consist of PVC material that requires the addition of plasticizers. These plasticizers may migrate into the blood leading to an exposure of the patients. In this study the migration behavior of three different blood tubing sets (PVC material with two different plasticizers and silicone as control material) applied on a heart-lung machine standardly used for cardiopulmonary bypass (CPB) in children was studied. We analyzed the total plasticizer migration by analysis of both, the parent compounds as well as their primary degradation products in blood. Additionally, the total mass loss of the tubing over perfusion time was examined. The PVC tubing plasticized with DEHP (di-2-ethylhexyl phthalate) was found to have the highest mass loss over time and showed a high plasticizer migration rate. In comparison, the migration of TOTM (tri-2-ethylhexyl trimellitate) and its primary degradation products was found to be distinctly lower (by a factor of approx. 350). Moreover, it was observed that the storage time of the tubing affects the plasticizer migration rates. In conclusion, the DEHP substitute TOTM promises to be an effective alternative plasticizer for PVC medical devices particularly regarding the decreased migration rate during medical procedures. Copyright © 2015 Elsevier Ltd. All rights reserved.

A novel amino acid and metabolomics signature in mice overexpressing muscle uncoupling protein 3

Science.gov (United States)

Uncoupling protein 3 (UCP3) is highly expressed in skeletal muscle and is known to lower mitochondrial reactive oxygen species and promote fatty acid oxidation; however, the global impact of UCP3 activity on skeletal muscle and whole body metabolism has not been extensively studied. We utilized unt...

Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria.

Science.gov (United States)

Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Koziel, Agnieszka; Majerczak, Joanna; Zoladz, Jerzy A

2015-06-01

Mitochondrial respiratory and phosphorylation activities, mitochondrial uncoupling, and hydrogen peroxide formation were studied in isolated rat skeletal muscle mitochondria during experimentally induced hypothermia (25 °C) and hyperthermia (42 °C) compared to the physiological temperature of resting muscle (35 °C). For nonphosphorylating mitochondria, increasing the temperature from 25 to 42 °C led to a decrease in membrane potential, hydrogen peroxide production, and quinone reduction levels. For phosphorylating mitochondria, no temperature-dependent changes in these mitochondrial functions were observed. However, the efficiency of oxidative phosphorylation decreased, whereas the oxidation and phosphorylation rates and oxidative capacities of the mitochondria increased, with increasing assay temperature. An increase in proton leak, including uncoupling protein-mediated proton leak, was observed with increasing assay temperature, which could explain the reduced oxidative phosphorylation efficiency and reactive oxygen species production. Copyright © 2015 Elsevier Inc. All rights reserved.

Considering common sources of exposure in association studies - Urinary benzophenone-3 and DEHP metabolites are associated with altered thyroid hormone balance in the NHANES 2007-2008.

Science.gov (United States)

Kim, Sujin; Kim, Sunmi; Won, Sungho; Choi, Kyungho

2017-10-01

Epidemiological studies have shown that thyroid hormone balances can be disrupted by chemical exposure. However, many association studies have often failed to consider multiple chemicals with possible common sources of exposure, rendering their conclusions less reliable. In the 2007-2008 National Health and Nutrition Examination Survey (NHANES) from the U.S.A., urinary levels of environmental phenols, parabens, and phthalate metabolites as well as serum thyroid hormones were measured in a general U.S. population (≥12years old, n=1829). Employing these data, first, the chemicals or their metabolites associated with thyroid hormone measures were identified. Then, the chemicals/metabolites with possible common exposure sources were included in the analytical model to test the sensitivities of their association with thyroid hormone levels. Benzophenone-3 (BP-3), bisphenol A (BPA), and a metabolite of di(2-ethylhexyl) phthalate (DEHP) were identified as significant determinants of decreased serum thyroid hormones. However, significant positive correlations were detected (p-value<0.05, r=0.23 to 0.45) between these chemicals/metabolites, which suggests that they might share similar exposure sources. In the subsequent sensitivity analysis, which included the chemicals/metabolite with potentially similar exposure sources in the model, we found that urinary BP-3 and DEHP exposure were associated with decreased thyroid hormones among the general population but BPA exposure was not. In association studies, the presence of possible common exposure sources should be considered to circumvent possible false-positive conclusions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design of an achromatic and uncoupled medical gantry for radiation therapy

International Nuclear Information System (INIS)

Tsoupas, N.; Kayran, D.; Litvinenko, V.; MacKay, W.W.

2011-01-01

We are presenting the layout and the optics of a beam line to be used as a medical gantry in radiation therapy. The optical properties of the gantry's beam line are such as to make the beam line achromatic and uncoupled. These two properties make the beam spot size, which is delivered and focused by the gantry, on the tumor of the patient, independent of the angular orientation of the gantry. In this paper we present the layout of the magnetic elements of the gantry, and also present the theoretical basis for the optics design of such a gantry. A medical gantry, as it is used in the radiation treatment of cancer patients, is the last part of the beam optical system, of the accelerator complex, which delivers and focuses the beam on the tumor. The curved line shown in figure 1 is a schematic diagram of a gantry which can rotate about a horizontal axis. The particle beam (green arrow in fig. 1) enters the gantry, and is guided by the gantry on the tumor (red spot in fig. 1). As the gantry rotates about the axis shown in figure 1, the beam exiting the gantry always lies on a plane normal to the rotation axis at the point of the icocenter. Thus the gantry facilitates the ability of the beam delivery system, to deliver the beam at the tumor, which is placed at the icocenter, from any angle on this vertical plane, which is normal to the rotation angle of the gantry as stated earlier. The gantry consists of dipoles and quadrupoles elements whose median symmetry plane lies on a plane which contains the rotation axis of the gantry. In this paper we define this plane as the 'plane of the gantry'. As the beam is transported along the axis of rotation of the gantry and before it enters the gantry, it is focused by 'normal' quadrupoles and experiences no linear beam coupling. Subsequently the beam enters the gantry, and is transported by the gantry to the delivery point which is the tumor. The transported beam at the tumor is still linearly uncoupled as long as the plane of the

Astrocyte uncoupling as a cause of human temporal lobe epilepsy.

Science.gov (United States)

Bedner, Peter; Dupper, Alexander; Hüttmann, Kerstin; Müller, Julia; Herde, Michel K; Dublin, Pavel; Deshpande, Tushar; Schramm, Johannes; Häussler, Ute; Haas, Carola A; Henneberger, Christian; Theis, Martin; Steinhäuser, Christian

2015-05-01

Glial cells are now recognized as active communication partners in the central nervous system, and this new perspective has rekindled the question of their role in pathology. In the present study we analysed functional properties of astrocytes in hippocampal specimens from patients with mesial temporal lobe epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp recording, K(+) concentration analysis, electroencephalography/video-monitoring, and fate mapping analysis. We found that the hippocampus of patients with mesial temporal lobe epilepsy with sclerosis is completely devoid of bona fide astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly present in non-sclerotic specimens. To decide whether these glial changes represent cause or effect of mesial temporal lobe epilepsy with sclerosis, we developed a mouse model that reproduced key features of human mesial temporal lobe epilepsy with sclerosis. In this model, uncoupling impaired K(+) buffering and temporally preceded apoptotic neuronal death and the generation of spontaneous seizures. Uncoupling was induced through intraperitoneal injection of lipopolysaccharide, prevented in Toll-like receptor4 knockout mice and reproduced in situ through acute cytokine or lipopolysaccharide incubation. Fate mapping confirmed that in the course of mesial temporal lobe epilepsy with sclerosis, astrocytes acquire an atypical functional phenotype and lose coupling. These data suggest that astrocyte dysfunction might be a prime cause of mesial temporal lobe epilepsy with sclerosis and identify novel targets for anti-epileptogenic therapeutic intervention. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Uncoupling Protein 3 Content Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes

NARCIS (Netherlands)

Keizer; E.E. Blaak; P. Schrauwen; G. Schaart; dr. Lars B. Borghouts; Saris; M.K.C. Hesselink

2001-01-01

Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin

Mitochondrial Hormesis in Pancreatic β Cells: Does Uncoupling Protein 2 Play a Role?

Directory of Open Access Journals (Sweden)

Ning Li

2012-01-01

Full Text Available In pancreatic β cells, mitochondrial metabolism translates glucose sensing into signals regulating insulin secretion. Chronic exposure of β cells to excessive nutrients, namely, glucolipotoxicity, impairs β-cell function. This is associated with elevated ROS production from overstimulated mitochondria. Mitochondria are not only the major source of cellular ROS, they are also the primary target of ROS attacks. The mitochondrial uncoupling protein UCP2, even though its uncoupling properties are debated, has been associated with protective functions against ROS toxicity. Hormesis, an adaptive response to cellular stresses, might contribute to the protection against β-cell death, possibly limiting the development of type 2 diabetes. Mitochondrial hormesis, or mitohormesis, is a defense mechanism observed in ROS-induced stress-responses by mitochondria. In β cells, mitochondrial damages induced by sublethal exogenous H2O2 can induce secondary repair and defense mechanisms. In this context, UCP2 is a marker of mitohormesis, being upregulated following stress conditions. When overexpressed in nonstressed naïve cells, UCP2 confers resistance to oxidative stress. Whether treatment with mitohormetic inducers is sufficient to restore or ameliorate secretory function of β cells remains to be determined.

Explicit thin-lens solution for an arbitrary four by four uncoupled beam transfer matrix

Energy Technology Data Exchange (ETDEWEB)

Balandin, V. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Orlov, S. [Moscow State Univ. (Russian Federation). Faculty of Computational Mathematics and Cybernetics

2011-10-15

In the design of beam transport lines one often meets the problem of constructing a quadrupole lens system that will produce desired transfer matrices in both the horizontal and vertical planes. Nowadays this problem is typically approached with the help of computer routines, but searching for the numerical solution one has to remember that it is not proven yet that an arbitrary four by four uncoupled beam transfer matrix can be represented by using a finite number of drifts and quadrupoles (representation problem) and the answer to this questions is not known not only for more or less realistic quadrupole field models but also for the both most commonly used approximations of quadrupole focusing, namely thick and thin quadrupole lenses. In this paper we make a step forward in resolving the representation problem and, by giving an explicit solution, we prove that an arbitrary four by four uncoupled beam transfer matrix actually can be obtained as a product of a finite number of thin-lenses and drifts. (orig.)

Understanding uncoupling in the multiredox centre P450 3A4-BMR model system.

Science.gov (United States)

Degregorio, Danilo; Sadeghi, Sheila J; Di Nardo, Giovanna; Gilardi, Gianfranco; Solinas, Sandro P

2011-01-01

Understanding the uncoupling at the haem active site and/or at the level of multidomain electron transfer is an important element in cytochrome P450 chemistry. Here a chimeric model system consisting of human cytochrome P450 3A4 and the soluble reductase domain of CYP102A1 from Bacillus megaterium (BMR) is used to study the relationship between electron transfer and the coupling efficiency in substrate monoxygenation. Several regulatory features were considered. FAD and FMN added to apoenzyme in oversaturating concentrations influence neither formaldehyde production nor coupling efficiency. The optimal conditions of coupling efficiency depended only on the NADPH concentration. The pH (8.0) and ionic strength (50 mM potassium phosphate) were found to modulate the level of coupling, indicating an influence over the formation of a productive interaction between the BMR and the haem domain. Overall, uncoupling is found to be an intrinsic property of the haem domain, and the covalent linkage of the reductase in a single polypeptide chain has little influence over the activity coupled to product formation.

Hydroperoxy fatty acid cycling mediated by mitochondrial uncoupling protein UCP2

Czech Academy of Sciences Publication Activity Database

Jabůrek, Martin; Miyamoto, S.; Di Mascio, P.; Garlid, K. D.; Ježek, Petr

2004-01-01

Roč. 279, č. 51 (2004), s. 53097-53102 ISSN 0021-9258 R&D Projects: GA AV ČR IAA5011106; GA MŠk LZ1K03002; GA ČR GA204/04/0495 Grant - others:NIH(US) TW01487; NIH(US) DK 56273; FAPESP(BR) CHPq; Programa de Apoio aos Nucleos de Excelencia(BR) PRONEX/FINEP Institutional research plan: CEZ:AV0Z5011922 Keywords : uncoupling protein * fatty acid hydroperoxides * reactive oxygen species Subject RIV: CE - Biochemistry Impact factor: 6.355, year: 2004

Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase

Czech Academy of Sciences Publication Activity Database

Klaus, S.; Keipert, S.; Rossmeisl, Martin; Kopecký, Jan

2012-01-01

Roč. 7, č. 3 (2012), s. 369-386 ISSN 1555-8932 R&D Projects: GA MZd(CZ) NS10528; GA MŠk(CZ) 7E10059; GA MŠk(CZ) OC08008 Institutional research plan: CEZ:AV0Z50110509 Keywords : adipose tissue * skeletal muscle * uncoupling protein * transgenic mice * insulin sensitivity Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.329, year: 2012

Examination of the requirement for ucp-4, a putative homolog of mammalian uncoupling proteins, for stress tolerance and longevity in C. elegans.

Science.gov (United States)

Iser, Wendy B; Kim, Daemyung; Bachman, Eric; Wolkow, Catherine

2005-10-01

Reactive oxygen species (ROS) are generated by mitochondrial respiration and can react with and damage cellular components. According to the free radical theory of aging, oxidative damage from mitochondrial ROS is a major cause of cellular decline during aging. Mitochondrial uncoupling proteins (UCPs) uncouple ATP production from electron transport and can be stimulated by free radicals, suggesting UCPs may perform a cytoprotective function. The nematode, Caenorhabditis elegans, contains one UCP-like protein, encoded by the ucp-4 gene. We have investigated the genetic requirement for ucp-4 in normal aging and stress resistance. Consistent with the hypothesis that ucp-4 encodes a putative uncoupling protein, animals lacking ucp-4 function contained elevated ATP levels. However, the absence of ucp-4 function did not affect adult lifespan or survival in the presence of thermal or oxidative stress. Together, these results demonstrate that ucp-4 is a negative regulator of ATP production in C. elegans, but is not required for normal lifespan.

Small structural changes on a hydroquinone scaffold determine the complex I inhibition or uncoupling of tumoral oxidative phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Urra, Félix A., E-mail: felix.urra@qf.uchile.cl [Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Casilla 7, Santiago (Chile); Córdova-Delgado, Miguel [Departamento de Química Orgánica y Físico-Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1 (Chile); Lapier, Michel; Orellana-Manzano, Andrea [Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Casilla 7, Santiago (Chile); Acevedo-Arévalo, Luis; Pessoa-Mahana, Hernán; González-Vivanco, Jaime M. [Departamento de Química Orgánica y Físico-Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1 (Chile); Martínez-Cifuentes, Maximiliano [Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca (Chile); and others

2016-01-15

Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cell line. Our results indicate that these structural changes modify the effect on OXPHOS, obtaining compounds with three alternative actions: inhibitors of complex I-dependent respiration, uncoupler of OXPHOS and compounds with both actions. To confirm this, the effect of a bicyclic hydroquinone (9) was evaluated in isolated mitochondria. Hydroquinone 9 increased mitochondrial respiration in state 4o without effects on the ADP-stimulated respiration (state 3{sub ADP}), decreasing the complexes I and II-dependent respiratory control ratio. The effect on mitochondrial respiration was reversed by 6-ketocholestanol addition, indicating that this hydroquinone is a protonophoric uncoupling agent. In intact TA3/Ha cells, hydroquinone 9 caused mitochondrial depolarization, decreasing intracellular ATP and NAD(P)H levels and GSH/GSSG ratio, and slightly increasing the ROS levels. Moreover, it exhibited selective NAD(P)H availability-dependent anti-proliferative effect on cancer cells. Therefore, our results indicate that the ortho-carbonyl hydroquinone scaffold offers the possibility to design compounds with specific actions on OXPHOS of cancer cells. - Highlights: • Small changes on a hydroquinone scaffold modify the action on OXPHOS of cancer

Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

International Nuclear Information System (INIS)

Fox, P.T.; Raichle, M.E.

1986-01-01

Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

Type I Diabetic Akita Mouse Model is Characterized by Abnormal Cardiac Deformation During Early Stages of Diabetic Cardiomyopathy with Speckle-Tracking Based Strain Imaging.

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Zhou, Yingchao; Xiao, Hong; Wu, Jianfei; Zha, Lingfeng; Zhou, Mengchen; Li, Qianqian; Wang, Mengru; Shi, Shumei; Li, Yanze; Lyu, Liangkun; Wang, Qing; Tu, Xin; Lu, Qiulun

2018-01-01

Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages. Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses. With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled. We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice. © 2018 The Author(s). Published by S. Karger AG, Basel.

Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2

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Quadros Edward V

2009-05-01

Full Text Available Abstract Background Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. Methods Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM, or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. Results There was a high correlation of cell growth with ATP concentration (r = 0.948 in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p Conclusion Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies.

Uncoupling effect of palmitate is exacerbated in skeletal muscle mitochondria of sea-acclimatized king penguins (Aptenodytes patagonicus).

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Rey, Benjamin; Duchamp, Claude; Roussel, Damien

2017-09-01

In king penguin juveniles, the environmental transition from a terrestrial to a marine habitat, occurring at fledging, drastically stimulates lipid catabolism and the remodelling of muscle mitochondria to sustain extensive swimming activity and thermoregulation in the cold circumpolar oceans. However, the exact nature of these mechanisms remains only partially resolved. Here we investigated, in vitro, the uncoupling effect of increasing doses of fatty acids in pectoralis muscle intermyofibrillar mitochondria isolated, either from terrestrial never-immersed or experimentally cold water immersed pre-fledging king penguins or from sea-acclimatized fledged penguins. Mitochondria exhibited much greater palmitate-induced uncoupling respiration and higher maximal oxidative capacity after acclimatization to marine life. Such effects were not reproduced experimentally after repeated immersions in cold water, suggesting that the plasticity of mitochondrial characteristics may not be primarily driven by cold exposure per se but by other aspects of sea acclimatization. Copyright © 2017. Published by Elsevier Inc.

Ursolic Acid-enriched herba cynomorii extract induces mitochondrial uncoupling and glutathione redox cycling through mitochondrial reactive oxygen species generation: protection against menadione cytotoxicity in h9c2 cells.

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Chen, Jihang; Wong, Hoi Shan; Ko, Kam Ming

2014-01-27

Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used 'Yang-invigorating' tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP generation capacity (ATP-GC) and induced mitochondrial uncoupling as well as a cellular glutathione response, thereby protecting against oxidant injury in H9c2 cells. In this study, we demonstrated that pre-incubation of H9c2 cells with HCY2 increased mitochondrial reactive oxygen species (ROS) generation in these cells, which is likely an event secondary to the stimulation of the mitochondrial electron transport chain. The suppression of mitochondrial ROS by the antioxidant dimethylthiourea abrogated the HCY2-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, and also protected against menadione-induced cytotoxicity. Studies using specific inhibitors of uncoupling protein and GR suggested that the HCY2-induced mitochondrial uncoupling and glutathione redox cycling play a determining role in the cytoprotection against menadione-induced oxidant injury in H9c2 cells. Experimental evidence obtained thus far supports the causal role of HCY2-induced mitochondrial ROS production in eliciting mitochondrial uncoupling and glutathione antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.

Cardiac regeneration therapy: connections to cardiac physiology.

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Takehara, Naofumi; Matsubara, Hiroaki

2011-12-01

Without heart transplantation, a large number of patients with failing hearts worldwide face poor outcomes. By means of cardiomyocyte regeneration, cardiac regeneration therapy is emerging with great promise as a means for restoring loss of cardiac function. However, the limited success of clinical trials using bone marrow-derived cells and myoblasts with heterogeneous constituents, transplanted at a wide range of cell doses, has led to disagreement on the efficacy of cell therapy. It is therefore essential to reevaluate the evidence for the efficacy of cell-based cardiac regeneration therapy, focusing on targets, materials, and methodologies. Meanwhile, the revolutionary innovation of cardiac regeneration therapy is sorely needed to help the millions of people who suffer heart failure from acquired loss of cardiomyocytes. Cardiac regeneration has been used only in limited species or as a developing process in the rodent heart; now, the possibility of cardiomyocyte turnover in the human heart is being revisited. In the pursuit of this concept, the use of cardiac stem/progenitor stem cells in the cardiac niche must be focused to usher in a second era of cardiac regeneration therapy for the severely injured heart. In addition, tissue engineering and cellular reprogramming will advance the next era of treatment that will enable current cell-based therapy to progress to "real" cardiac regeneration therapy. Although many barriers remain, the prevention of refractory heart failure through cardiac regeneration is now becoming a realistic possibility.

Chimera states in a multilayer network of coupled and uncoupled neurons

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Majhi, Soumen; Perc, Matjaž; Ghosh, Dibakar

2017-07-01

We study the emergence of chimera states in a multilayer neuronal network, where one layer is composed of coupled and the other layer of uncoupled neurons. Through the multilayer structure, the layer with coupled neurons acts as the medium by means of which neurons in the uncoupled layer share information in spite of the absence of physical connections among them. Neurons in the coupled layer are connected with electrical synapses, while across the two layers, neurons are connected through chemical synapses. In both layers, the dynamics of each neuron is described by the Hindmarsh-Rose square wave bursting dynamics. We show that the presence of two different types of connecting synapses within and between the two layers, together with the multilayer network structure, plays a key role in the emergence of between-layer synchronous chimera states and patterns of synchronous clusters. In particular, we find that these chimera states can emerge in the coupled layer regardless of the range of electrical synapses. Even in all-to-all and nearest-neighbor coupling within the coupled layer, we observe qualitatively identical between-layer chimera states. Moreover, we show that the role of information transmission delay between the two layers must not be neglected, and we obtain precise parameter bounds at which chimera states can be observed. The expansion of the chimera region and annihilation of cluster and fully coherent states in the parameter plane for increasing values of inter-layer chemical synaptic time delay are illustrated using effective range measurements. These results are discussed in the light of neuronal evolution, where the coexistence of coherent and incoherent dynamics during the developmental stage is particularly likely.

Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases

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Giorgia Pierelli

2017-01-01

Full Text Available Uncoupling protein 2 (UCP2 is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension. The deletion of the UCP2 gene contributes to atherosclerosis lesion development in the knockout mice, also showing significantly shorter lifespan. The UCP2 gene downregulation is a key determinant of higher predisposition to renal and cerebrovascular damage in an animal model of spontaneous hypertension and stroke. In contrast, UCP2 overexpression improves both hyperglycemia- and high-salt diet-induced endothelial dysfunction and ameliorates hypertensive target organ damage in SHRSP. Moreover, drugs (fenofibrate and sitagliptin and several vegetable compounds (extracts from Brassicaceae, berberine, curcumin, and capsaicin are able to induce UCP2 expression level and to exert beneficial effects on the occurrence of vascular damage. As a consequence, UCP2 becomes an interesting therapeutic target for the treatment of common human vascular diseases.

Fatty Acids are Key in 4-Hydroxy-2-Nonenal-Mediated Activation of Uncoupling Proteins 1 and 2

Czech Academy of Sciences Publication Activity Database

Malingriaux, E. A.; Rupprecht, A.; Gille, L.; Jovanovic, O.; Ježek, Petr; Jabůrek, Martin; Pohl, E. E.

2013-01-01

Roč. 8, č. 10 (2013), e77786 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP302/10/0346 Institutional support: RVO:67985823 Keywords : mitochondrial uncoupling proteins * 4-hydroxy-2-nonenal * fatty acids Subject RIV: EA - Cell Biology Impact factor: 3.534, year: 2013

Increased platelet mitochondrial respiration after cardiac arrest and resuscitation as a potential peripheral biosignature of cerebral bioenergetic dysfunction.

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Ferguson, Michael A; Sutton, Robert M; Karlsson, Michael; Sjövall, Fredrik; Becker, Lance B; Berg, Robert A; Margulies, Susan S; Kilbaugh, Todd J

2016-06-01

Cardiac arrest (CA) results in a sepsis-like syndrome with activation of the innate immune system and increased mitochondrial bioenergetics. To determine if platelet mitochondrial respiration increases following CA in a porcine pediatric model of asphyxia-associated ventricular fibrillation (VF) CA, and if this readily obtained biomarker is associated with decreased brain mitochondrial respiration. CA protocol: 7 min of asphyxia, followed by VF, protocolized titration of compression depth to systolic blood pressure of 90 mmHg and vasopressor administration to a coronary perfusion pressure greater than 20 mmHg. platelet integrated mitochondrial electron transport system (ETS) function evaluated pre- and post-CA/ROSC four hours after return of spontaneous circulation (ROSC). Secondary outcome: correlation of platelet mitochondrial bioenergetics to cerebral bioenergetic function. Platelet maximal oxidative phosphorylation (OXPHOSCI+CII), P respiration through Complex II (OXPHOSCII, P respiration was not due to uncoupling, as the LEAKCI + CII respiration (mitochondrial respiration independent of ATP-production) was unchanged after CA/ROSC. Larger increases in platelet mitochondrial respiratory control ratio (RCR) compared to pre-CA RCR were significantly correlated with lower RCRs in the cortex (P respiration. Platelet mitochondrial respiration is significantly increased four hours after ROSC. Future studies will identify mechanistic relationships between this serum biomarker and altered cerebral bioenergetics function following cardiac arrest.

Synchronization of uncoupled excitable systems induced by white and coloured noise

International Nuclear Information System (INIS)

Zambrano, Samuel; Marino, Ines P; Seoane, Jesus M; Sanjuan, Miguel A F; Euzzor, Stefano; Geltrude, Andrea; Meucci, Riccardo; Arecchi, Fortunato T

2010-01-01

We study, both numerically and experimentally, the synchronization of uncoupled excitable systems due to a common noise. We consider two identical FitzHugh-Nagumo systems, which display both spiking and non-spiking behaviours in chaotic or periodic regimes. An electronic circuit provides a laboratory implementation of these dynamics. Synchronization is tested with both white and coloured noise, showing that coloured noise is more effective in inducing synchronization of the systems. We also study the effects on the synchronization of parameter mismatch and of the presence of intrinsic (not common) noise, and we conclude that the best performance of coloured noise is robust under these distortions.

Halogenated anaesthetics and cardiac protection in cardiac and non-cardiac anaesthesia

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Landoni Giovanni

2009-01-01

Full Text Available Volatile anaesthetic agents have direct protective properties against ischemic myocardial damage. The implementation of these properties during clinical anaesthesia can provide an additional tool in the treatment or prevention, or both, of ischemic cardiac dysfunction in the perioperative period. A recent meta-analysis showed that desflurane and sevoflurane reduce postoperative mortality and incidence of myocardial infarction following cardiac surgery, with significant advantages in terms of postoperative cardiac troponin release, need for inotrope support, time on mechanical ventilation, intensive care unit and overall hospital stay. Multicentre, randomised clinical trials had previously demonstrated that the use of desflurane can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalisation following coronary artery bypass graft surgery either with and without cardiopulmonary bypass. The American College of Cardiology/American Heart Association Guidelines recommend volatile anaesthetic agents during non-cardiac surgery for the maintenance of general anaesthesia in patients at risk for myocardial infarction. Nonetheless, e vidence in non-coronary surgical settings is contradictory and will be reviewed in this paper together with the mechanisms of cardiac protection by volatile agents.

Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan.

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Wolkow, Catherine A; Iser, Wendy B

2006-05-01

Uncoupling proteins (UCPs), which dissipate the mitochondrial proton gradient, have the ability to decouple mitochodrial respiration from ATP production. Since mitochondrial electron transport is a major source of free radical production, it is possible that UCP activity might impact free radical production. Free radicals can react with and damage cellular proteins, DNA and lipids. Accumulated damage from oxidative stress is believed to be a major contributor to cellular decline during aging. If UCP function were to impact mitochondrial free radical production, then one would expect to find a link between UCP activity and aging. This theory has recently been tested in a handful of organisms whose genomes contain UCP1 homologs. Interestingly, these experiments indicate that UCP homologs can affect lifespan, although they do not support a simple relationship between UCP activity and aging. Instead, UCP-like proteins appear to have a variety of effects on lifespan, and on pathways implicated in lifespan regulation. One possible explanation for this complex picture is that UCP homologs may have tissue-specific effects that complicate their effects on aging. Furthermore, the functional analysis of UCP1 homologs is incomplete. Thus, these proteins may perform functions in addition to, or instead of, mitochondrial uncoupling. Although these studies have not revealed a clear picture of UCP effects on aging, they have contributed to the growing knowledge base for these interesting proteins. Future biochemical and genetic investigation of UCP-like proteins will do much to clarify their functions and to identify the regulatory networks in which they are involved.

Cardiac sarcoplasmic reticulum. Effects of an atherogenic diet during the neonatal and juvenile period

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Jacobson, M S; Ambudkar, I S; Young, E P; Naseem, S M; Heald, F P; Shamoo, A E [Maryland Univ., College Park (USA). School of Medicine

1985-04-01

The effect on the cardiac sarcoplasmic reticulum of an atherogenic (1% cholesterol) diet fed during the neonatal vs the juvenile period of life was studied in Yorkshire swine. Male piglets were randomly assigned at birth to 1 of 4 groups: group I (control), group II (lactation feeding), group III (juvenile period feeding) and group IV (lactation and juvenile feeding). All animals were killed at 55 weeks of age and cardiac sarcoplasmic reticulum (SR) isolated for assay of calcium uptake, Ca/sup 2 +/-Mg/sup 2 +/ ATPase activity, and lipid analysis by thin-layer chromatography and gas chromatography. The amount of cholesterol/mg SR protein and the cholesterol/phospholipid ratio were higher in the animals fed during lactation (groups II and IV) and lower in those fed only during the juvenile period (group III). Phospholipid fatty acid patterns as measured by gas chromatography were unaltered in any group. Calcium uptake was markedly diminished in all experimental conditions: group II 47%, group III 65% and group IV 96%. Compared to the observed changes in calcium transport, the ATP hydrolytic activity was relatively less affected. Only in group IV a significant decrease (41%) was seen. Groups II and III show no change in ATP hydrolytic activity. The decrease in calcium uptake and altered cholesterol/phospholipid ratio without effect on ATP hydrolytic activity is consistent with an uncoupling of calcium transport related to the atherogenic diet in early life.

Cardiac fusion and complex congenital cardiac defects in thoracopagus twins: diagnostic value of cardiac CT

Energy Technology Data Exchange (ETDEWEB)

Goo, Hyun Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Park, Jeong-Jun [University of Ulsan College of Medicine, Asan Medical Center, Department of Pediatric Cardiac Surgery, Seoul (Korea, Republic of); Kim, Ellen Ai-Rhan [University of Ulsan College of Medicine, Asan Medical Center, Division of Neonatology, Department of Pediatrics, Seoul (Korea, Republic of); Won, Hye-Sung [University of Ulsan College of Medicine, Asan Medical Center, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of)

2014-09-15

Most thoracopagus twins present with cardiac fusion and associated congenital cardiac defects, and assessment of this anatomy is of critical importance in determining patient care and outcome. Cardiac CT with electrocardiographic triggering provides an accurate and quick morphological assessment of both intracardiac and extracardiac structures in newborns, making it the best imaging modality to assess thoracopagus twins during the neonatal period. In this case report, we highlight the diagnostic value of cardiac CT in thoracopagus twins with an interatrial channel and complex congenital cardiac defects. (orig.)

Antioxidant and regulatory role of mitochondrial uncoupling protein UCP2 in pancreatic beta-cells

Czech Academy of Sciences Publication Activity Database

Ježek, Petr; Olejár, Tomáš; Smolková, Katarína; Ježek, Jan; Dlasková, Andrea; Plecitá-Hlavatá, Lydie; Zelenka, Jaroslav; Špaček, Tomáš; Engstová, Hana; Reguera Pajuelo, David; Jabůrek, Martin

2014-01-01

Roč. 63, Suppl.1 (2014), S73-S91 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GAP305/12/1247; GA ČR(CZ) GPP304/10/P204; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : mitochondria * uncoupling protein UCP2 * pancreatic beta-cells * reactive oxygen species * glucose-stimulated insulin secretion Subject RIV: EA - Cell Biology Impact factor: 1.293, year: 2014

β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade.

Science.gov (United States)

Karimi Galougahi, Keyvan; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A; Hamilton, Elisha J; Figtree, Gemma A; Rasmussen, Helge H

2015-09-01

Dysregulated nitric oxide (NO)- and superoxide (O2 (·-))-dependent signaling contributes to the pathobiology of diabetes-induced cardiovascular complications. We examined if stimulation of β3-adrenergic receptors (β3-ARs), coupled to endothelial NO synthase (eNOS) activation, relieves oxidative inhibition of eNOS and the Na(+)-K(+) pump induced by hyperglycemia. Hyperglycemia was established in male New Zealand White rabbits by infusion of the insulin receptor antagonist S961 for 7 days. Hyperglycemia increased tissue and blood indexes of oxidative stress. It induced glutathionylation of the Na(+)-K(+) pump β1-subunit in cardiac myocytes, an oxidative modification causing pump inhibition, and reduced the electrogenic pump current in voltage-clamped myocytes. Hyperglycemia also increased glutathionylation of eNOS, which causes its uncoupling, and increased coimmunoprecipitation of cytosolic p47(phox) and membranous p22(phox) NADPH oxidase subunits, consistent with NADPH oxidase activation. Blocking translocation of p47(phox) to p22(phox) with the gp91ds-tat peptide in cardiac myocytes ex vivo abolished the hyperglycemia-induced increase in glutathionylation of the Na(+)-K(+) pump β1-subunit and decrease in pump current. In vivo treatment with the β3-AR agonist CL316243 for 3 days eliminated the increase in indexes of oxidative stress, decreased coimmunoprecipitation of p22(phox) with p47(phox), abolished the hyperglycemia-induced increase in glutathionylation of eNOS and the Na(+)-K(+) pump β1-subunit, and abolished the decrease in pump current. CL316243 also increased coimmunoprecipitation of glutaredoxin-1 with the Na(+)-K(+) pump β1-subunit, which may reflect facilitation of deglutathionylation. In vivo β3-AR activation relieves oxidative inhibition of key cardiac myocyte proteins in hyperglycemia and may be effective in targeting the deleterious cardiac effects of diabetes. Copyright © 2015 the American Physiological Society.

Effect of RNAi p21 gene on uncoupling of EL-4 cells induced by X-irradiation

International Nuclear Information System (INIS)

Ju Guizhi; Yan Fengqin; Fu Shibo; Shen Bo; Sun Shilong; Yang Ying; Li Pengwu

2008-01-01

Objective: To investigate the effect of RNAi p21 gene on uncoupling of EL-4 cells induced by X-irradiation. Methods: Construction of RNAi p21 plasmid of pSileneer3.1-H1 neo-p21 was performed. Lipofectamine transfection assay was used to transfer the p21siBNA into EL-4 cells. Fluorescent staining and flow cytometry (FCM) analysis were employed for measurement of protein expression. Fluorescent staining of propidium iodide (PI) and FCM were used for measurement of potyploid cells. Results: In dose-effect experiment it was found that the expression of P21 protein of EL-4 cells increased significantly 24 h after X- irradiation with different doses compared with sham-inadiated control. In time course experiment it was found that the expression of P21 protein of EL-4 cells increased significantly at 8 h to 72 h after 4.0 Gy X-irradiation compared with sham-irradiated control. The results showed that the number of polyploid cells in EL-4 cells was not changed markedly after X-irradiation with doses of 0.5-6.0 Gy. After RNA interference with p21 gene, the expression of P21 protein of EL-4 cells decreased significantly 24 h and 48 h after 4.0 Gy X-irradiation in transfection of plasmid of pSilencer3.1-H1 neo-p21 compared with transfection of plasmid of pSilencer3.1-H1 nco control. And at the same time, the number of polyploid cells in EL-4 cells was increased significantly in transfection of plasmid of pSilencer3.1-H1 neo-p21 compared with transfection of plasmid of pSilencer3.1-H1 nco control. Conclusions: Uncoupling could be induced by X-irradiation in EL-4 cells following BNAi p21 gene, suggesting that P21 protein may play an important role in uncoupling induced by X-rays. (authors)

Acceptably aware during general anaesthesia: 'dysanaesthesia'--the uncoupling of perception from sensory inputs.

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Pandit, Jaideep J

2014-07-01

This review makes the case for 'dysanaesthesia', a term encompassing states of mind that can arise in the course of anaesthesia during surgery, characterised by an uncoupling of sensation and perceptual experience. This is reflected in a macroscopic, functional model of anaesthetically-relevant consciousness. Patients in this state can be aware of events but in a neutral way, not in pain, sometimes personally dissociated from the experiences. This makes events associated with surgery peripheral to their whole experience, such that recall is less likely and if it exists, makes any spontaneous report of awareness unlikely. This state of perception-sensation uncoupling is therefore broadly acceptable (a minimum requirement for acceptable anaesthesia) but since it is likely a dose-related phenomenon, may also represent a precursor for awareness with adverse recall. This hypothesis uniquely explains the often inconsistent responses seen during the experimental paradigm of the 'isolated forearm technique', wherein apparently anaesthetised patients exhibit a positive motor response to verbal command, but no spontaneous movement to surgery. The hypothesis can also explain the relatively high incidence of positive response to relatively direct questions for recall (e.g., using the Brice questionnaire; ∼1:500; the vast majority of these being neutral reports) versus the very low incidence of spontaneous reports of awareness (∼1:15,000; a higher proportion of these being adverse recollections). The hypothesis is consistent with relevant notions from philosophical discussions of consciousness, and neuroscientific evidence. Dysanaesthesia has important implications for research and also for the development of appropriate monitoring. Copyright © 2014 Elsevier Inc. All rights reserved.

Undecanesulfonate does not allosterically activate H+ uniport mediated by uncoupling protein-1 in brown adipose tissue mitochondria

Czech Academy of Sciences Publication Activity Database

Ježek, Petr; Špaček, Tomáš; Garlid, K.; Jabůrek, Martin

2006-01-01

Roč. 38, č. 11 (2006), s. 1965-1974 ISSN 1357-2725 R&D Projects: GA AV ČR(CZ) IAA5011106; GA MŠk(CZ) 1P05ME794 Grant - others:NIH(US) TW01487 Institutional research plan: CEZ:AV0Z50110509 Keywords : uncoupling protein–1 * mitochondria * fatty acid Subject RIV: ED - Physiology Impact factor: 4.804, year: 2006

Hypoxia-induced decrease of UCP3 gene expression in rat heart parallels metabolic gene switching but fails to affect mitochondrial respiratory coupling.

Science.gov (United States)

Essop, M Faadiel; Razeghi, Peter; McLeod, Chris; Young, Martin E; Taegtmeyer, Heinrich; Sack, Michael N

2004-02-06

Mitochondrial uncoupling proteins 2 and 3 (UCP2 and UCP3) are postulated to contribute to antioxidant defense, nutrient partitioning, and energy efficiency in the heart. To distinguish isotype function in response to metabolic stress we measured cardiac mitochondrial function and cardiac UCP gene expression following chronic hypobaric hypoxia. Isolated mitochondrial O(2) consumption and ATP synthesis rate were reduced but respiratory coupling was unchanged compared to normoxic groups. Concurrently, left ventricular UCP3 mRNA levels were significantly decreased with hypoxia (pheart as opposed to uncoupling of mitochondria. Moreover, the divergent hypoxia-induced regulation of UCP2 and UCP3 supports distinct mitochondrial regulatory functions of these inner mitochondrial membrane proteins in the heart in response to metabolic stress.

Thyroid hormone affects secretory activity and uncoupling protein-3 expression in rat harderian gland.

Science.gov (United States)

Chieffi Baccari, Gabriella; Monteforte, Rossella; de Lange, Pieter; Raucci, Franca; Farina, Paola; Lanni, Antonia

2004-07-01

The effects of T(3) administration on the rat Harderian gland were examined at morphological, biochemical, and molecular levels. T(3) induced hypertrophy of the two cell types (A and B) present in the glandular epithelium. In type A cells, the hypertrophy was mainly due to an increase in the size of the lipid compartment. The acinar lumina were filled with lipoproteic substances, and the cells often showed an olocrine secretory pattern. In type B cells, the hypertrophy largely consisted of a marked proliferation of mitochondria endowed with tightly packed cristae, the mitochondrial number being nearly doubled (from 62 to 101/100 microm(2)). Although the average area of individual mitochondria decreased by about 50%, the total area of the mitochondrial compartment increased by about 80% (from 11 to 19/100 microm(2)). This could be ascribed to T(3)-induced mitochondrial proliferation. The morphological and morphometric data correlated well with our biochemical results, which indicated that mitochondrial respiratory activity is increased in hyperthyroid rats. T(3), by influencing the metabolic function of the mitochondrial compartment, induces lipogenesis and the release of secretory product by type A cells. Mitochondrial uncoupling proteins 2 and 3 were expressed at both mRNA and protein levels in the euthyroid rat Harderian gland. T(3) treatment increased the mRNA levels of both uncoupling protein 2 (UCP2) and UCP3, but the protein level only of UCP3. A possible role for these proteins in the Harderian gland is discussed.

Cardiac tamponade: contrast reflux as an indicator of cardiac chamber equalization

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Nauta Foeke Jacob

2012-05-01

Full Text Available Abstract Background Traumatic hemopericardium remains a rare entity; it does however commonly cause cardiac tamponade which remains a major cause of death in traumatic blunt cardiac injury. Objectives We present a case of blunt chest trauma complicated by cardiac tamponade causing cardiac chamber equalization revealed by reflux of contrast. Case report A 29-year-old unidentified male suffered blunt chest trauma in a motor vehicle collision. Computed tomography (CT demonstrated a periaortic hematoma and hemopericardium. Significant contrast reflux was seen in the inferior vena cava and hepatic veins suggesting a change in cardiac chamber pressures. After intensive treatment including cardiac massage this patient expired of cardiac arrest. Conclusion Reflux of contrast on CT imaging can be an indicator of traumatic cardiac tamponade.

Living cardiac patch: the elixir for cardiac regeneration.

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Lakshmanan, Rajesh; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

2012-12-01

A thorough understanding of the cellular and muscle fiber orientation in left ventricular cardiac tissue is of paramount importance for the generation of artificial cardiac patches to treat the ischemic myocardium. The major challenge faced during cardiac patch engineering is to choose a perfect combination of three entities; cells, scaffolds and signaling molecules comprising the tissue engineering triad for repair and regeneration. This review provides an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering. Stem cell therapies in clinical trials and the commercially available cardiac patch materials were summarized in an attempt to provide a recent perspective in the treatment of heart failure. Various tissue engineering strategies employed thus far to construct viable thick cardiac patches is schematically illustrated. Though many strategies have been proposed for fabrication of various cardiac scaffold materials, the stage and severity of the disease condition demands the incorporation of additional cues in a suitable scaffold material. The scaffold may be nanofibrous patch, hydrogel or custom designed films. Integration of stem cells and biomolecular cues along with the scaffold may provide the right microenvironment for the repair of unhealthy left ventricular tissue as well as promote its regeneration.

Regulation of cardiac remodeling by cardiac Na/K-ATPase isoforms

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Lijun Catherine Liu

2016-09-01

Full Text Available Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na+/K+-ATPase has multiple α isoforms (1-3. The expression of the α subunit of the Na+/K+-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na+/K+-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The α1 isoform of the Na+/K+-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The α2 isoform of the Na+/K+-ATPase regulates intracellular Ca2+ signaling, contractility and pathological hypertrophy. The α3 isoform of the Na+/K+-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na+/K+-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1 the distribution and function of isoform specific Na+/K+-ATPase in the cardiomyocytes. (2 the role of cardiac Na+/K+-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na+/K+-ATPase isoform may offer a new target for the prevention of cardiac remodeling.

Dissociation Between Brown Adipose Tissue 18F-FDG Uptake and Thermogenesis in Uncoupling Protein 1-Deficient Mice.

Science.gov (United States)

Hankir, Mohammed K; Kranz, Mathias; Keipert, Susanne; Weiner, Juliane; Andreasen, Sille G; Kern, Matthias; Patt, Marianne; Klöting, Nora; Heiker, John T; Brust, Peter; Hesse, Swen; Jastroch, Martin; Fenske, Wiebke K

2017-07-01

18 F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis, which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain, however, whether BAT 18 F-FDG uptake is a reliable surrogate measure of UCP1-mediated heat production. Methods: UCP1 knockout (KO) and wild-type (WT) mice housed at thermoneutrality were treated with the selective β3 adrenergic receptor agonist CL 316, 243 and underwent metabolic cage, infrared thermal imaging and 18 F-FDG PET/MRI experiments. Primary brown adipocytes were additionally examined for their bioenergetics by extracellular flux analysis as well as their uptake of 2-deoxy- 3 H-glucose. Results: In response to CL 316, 243 treatments, oxygen consumption, and BAT thermogenesis were diminished in UCP1 KO mice, but BAT 18 F-FDG uptake was fully retained. Isolated UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy- 3 H-glucose uptake rates were largely unaffected. Conclusion: Adrenergic stimulation can increase BAT 18 F-FDG uptake independently of UCP1 thermogenic function. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5

Directory of Open Access Journals (Sweden)

Viggiano E

2016-07-01

Full Text Available Emanuela Viggiano,1,2 Vincenzo Monda,1 Antonietta Messina,1 Fiorenzo Moscatelli,3 Anna Valenzano,3 Domenico Tafuri,4 Giuseppe Cibelli,3 Bruno De Luca,1 Giovanni Messina,1,3 Marcellino Monda1 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Second University of Naples, Naples, 2Department of Medicine, University of Padua, Padua, 3Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 4Department of Motor Sciences and Wellness, University of Naples “Parthenope”, Naples, Italy Abstract: Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD, which is probably related to the pathophysiology of stroke, epilepsy, and migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2 hours, 4 hours, 6 hours, and 24 hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24 hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect. Keywords: cortical spreading depression, neuroprotective effect, uncoupling protein-5

Initial Efficacy of a Cardiac Rehabilitation Transition Program: Cardiac TRUST

Science.gov (United States)

Zullo, Melissa; Boxer, Rebecca; Moore, Shirley M.

2012-01-01

Patients recovering from cardiac events are increasingly using postacute care, such as home health care and skilled nursing facility services. The purpose of this pilot study was to test the initial efficacy, feasibility, and safety of a specially designed postacute care transitional rehabilitation intervention for cardiac patients. Cardiac Transitional Rehabilitation Using Self- Management Techniques (Cardiac TRUST) is a family-focused intervention that includes progressive low-intensity walking and education in self-management skills to facilitate recovery following a cardiac event. Using a randomized two-group design, exercise self-efficacy, steps walked, and participation in an outpatient cardiac rehabilitation program were compared in a sample of 38 older adults; 17 who received the Cardiac TRUST program and 21 who received usual care only. At discharge from postacute care, the intervention group had a trend for higher levels of self-efficacy for exercise outcomes (X=39.1, SD=7.4) than the usual care group (X=34.5; SD=7.0) (t-test 1.9, p=.06). During the 6 weeks following discharge, compared with the usual care group, the intervention group had more attendance in out-patient cardiac rehabilitation (33% compared to 11.8%, F=7.1, p=.03) and a trend toward more steps walked during the first week (X=1,307, SD=652 compared to X=782, SD=544, t-test 1.8, p=.07). The feasibility of the intervention was better for the home health participants than for those in the skilled nursing facility and there were no safety concerns. The provision of cardiac-focused rehabilitation during postacute care has the potential to bridge the gap in transitional services from hospitalization to outpatient cardiac rehabilitation for these patients at high risk for future cardiac events. Further evidence of the efficacy of Cardiac TRUST is warranted. PMID:22084960

Kinetics of oxygen uncoupling of a copper based oxygen carrier

International Nuclear Information System (INIS)

Hu, Wenting; Donat, Felix; Scott, S.A.; Dennis, J.S.

2016-01-01

Highlights: • The kinetics of a Cu-based oxygen carrier was determined using a TGA. • A diffusion model was applied to remove mass transfer effects from rate parameters. • Thermodynamics are separated from kinetics, usually difficult for the CLOU reaction. • The rate parameters correctly described the behaviour in a fluidised bed. • The rate parameters can be used to predict performance of large CLOU systems. - Abstract: Here, an oxygen carrier consisting of 60 wt% CuO supported on a mixture of Al_2O_3 and CaO (23 wt% and 17 wt% respectively) was synthesised by wet-mixing powdered CuO, Al(OH)_3 and Ca(OH)_2, followed by calcination at 1000 °C. Its suitability for chemical looping with oxygen uncoupling (CLOU) was investigated. After 25 repeated redox cycles in either a thermogravimetric analyser (TGA) or a laboratory-scale fluidised bed, (with 5 vol% H_2 in N_2 as the fuel, and air as the oxidant) no significant change in either the oxygen uncoupling capacity or the overall oxygen availability of the carrier was found. In the TGA, it was found that the rate of oxygen release from the material was controlled by intrinsic chemical kinetics and external transfer of mass from the surface of the particles to the bulk gas. By modelling the various resistances, values of the rate constant for the decomposition were obtained. The activation energy of the reaction was found to be 59.7 kJ/mol (with a standard error of 5.6 kJ/mol) and the corresponding pre-exponential factor was 632 m"3/mol/s. The local rate of conversion within a particle was assumed to occur either (i) by homogeneous chemical reaction, or (ii) in uniform, non-porous grains, each reacting as a kinetically-controlled shrinking core. Upon cross validation against a batch fluidised bed experiment, the homogeneous reaction model was found to be more plausible. By accurately accounting for the various artefacts (e.g. mass transfer resistances) present in both TGA and fluidised bed experiments, it was

Cardiac tumors: optimal cardiac MR sequences and spectrum of imaging appearances.

LENUS (Irish Health Repository)

O'Donnell, David H

2012-02-01

OBJECTIVE: This article reviews the optimal cardiac MRI sequences for and the spectrum of imaging appearances of cardiac tumors. CONCLUSION: Recent technologic advances in cardiac MRI have resulted in the rapid acquisition of images of the heart with high spatial and temporal resolution and excellent myocardial tissue characterization. Cardiac MRI provides optimal assessment of the location, functional characteristics, and soft-tissue features of cardiac tumors, allowing accurate differentiation of benign and malignant lesions.

Cardiac gated ventilation

International Nuclear Information System (INIS)

Hanson, C.W. III; Hoffman, E.A.

1995-01-01

There are several theoretic advantages to synchronizing positive pressure breaths with the cardiac cycle, including the potential for improving distribution of pulmonary and myocardial blood flow and enhancing cardiac output. The authors evaluated the effects of synchronizing respiration to the cardiac cycle using a programmable ventilator and electron beam CT (EBCT) scanning. The hearts of anesthetized dogs were imaged during cardiac gated respiration with a 50 msec scan aperture. Multi slice, short axis, dynamic image data sets spanning the apex to base of the left ventricle were evaluated to determine the volume of the left ventricular chamber at end-diastole and end-systole during apnea, systolic and diastolic cardiac gating. The authors observed an increase in cardiac output of up to 30% with inspiration gated to the systolic phase of the cardiac cycle in a non-failing model of the heart

Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

KAUST Repository

Lambert, Hélène Perreten

2014-09-18

Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.

Cardiac function and cognition in older community-dwelling cardiac patients.

Science.gov (United States)

Eggermont, Laura H P; Aly, Mohamed F A; Vuijk, Pieter J; de Boer, Karin; Kamp, Otto; van Rossum, Albert C; Scherder, Erik J A

2017-11-01

Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour-word test. Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures. None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies. © 2017 Japanese Psychogeriatric Society.

Oxidase uncoupling in heme monooxygenases: Human cytochrome P450 CYP3A4 in Nanodiscs

Energy Technology Data Exchange (ETDEWEB)

Grinkova, Yelena V.; Denisov, Ilia G.; McLean, Mark A. [Departments of Biochemistry and Chemistry, University of Illinois, 505 South Goodwin Avenue (United States); Sligar, Stephen G., E-mail: s-sligar@illinois.edu [Departments of Biochemistry and Chemistry, University of Illinois, 505 South Goodwin Avenue (United States)

2013-01-25

Highlights: ► Substantial reducing equivalents are lost in human P450 CYP3A4 via an oxidase channel. ► Substrate binding has a pronounced effect on uncoupling in cytochrome P450. ► Anionic phospholipids improve the overall coupling in CYP3A4 Nanodiscs. -- Abstract: The normal reaction mechanism of cytochrome P450 operates by utilizing two reducing equivalents to reduce atmospheric dioxygen, producing one molecule of water and an oxygenated product in an overall stoichiometry of 2 electrons:1 dioxygen:1 product. However, three alternate unproductive pathways exist where the intermediate iron–oxygen states in the catalytic cycle can yield reduced oxygen products without substrate metabolism. The first involves release of superoxide from the oxygenated intermediate while the second occurs after input of the second reducing equivalent. Superoxide rapidly dismutates and hence both processes produce hydrogen peroxide that can be cytotoxic to the organism. In both cases, the formation of hydrogen peroxide involves the same overall stoichiometry as oxygenases catalysis. The key step in the catalytic cycle of cytochrome P450 involves scission of the oxygen–oxygen bond of atmospheric dioxygen to produce a higher valent iron-oxo state termed “Compound I”. This intermediate initiates a radical reaction in the oxygenase pathway but also can uptake two additional reducing equivalents from reduced pyridine nucleotide (NADPH) and the flavoprotein reductase to produce a second molecule of water. This non-productive decay of Compound I thus yields an overall oxygen to NADPH ratio of 1:2 and does not produce hydrocarbon oxidation. This water uncoupling reaction provides one of a limited means to study the reactivity of the critical Compound I intermediate in P450 catalysis. We measured simultaneously the rates of NADPH and oxygen consumption as a function of substrate concentration during the steady-state hydroxylation of testosterone catalyzed by human P450 CYP3A4

Cardiac function and cognition in older community-dwelling cardiac patients

NARCIS (Netherlands)

Eggermont, Laura H.P.; Aly, Mohamed F.A.; Vuijk, Pieter J.; de Boer, Karin; Kamp, Otto; van Rossum, Albert C.; Scherder, Erik J.A.

2017-01-01

Background: Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older

Uncoupling protein and ATP/ADP carrier increase mitochondrial proton conductance after cold adaptation of king penguins.

Science.gov (United States)

Talbot, Darren A; Duchamp, Claude; Rey, Benjamin; Hanuise, Nicolas; Rouanet, Jean Louis; Sibille, Brigitte; Brand, Martin D

2004-07-01

Juvenile king penguins develop adaptive thermogenesis after repeated immersion in cold water. However, the mechanisms of such metabolic adaptation in birds are unknown, as they lack brown adipose tissue and uncoupling protein-1 (UCP1), which mediate adaptive non-shivering thermogenesis in mammals. We used three different groups of juvenile king penguins to investigate the mitochondrial basis of avian adaptive thermogenesis in vitro. Skeletal muscle mitochondria isolated from penguins that had never been immersed in cold water showed no superoxide-stimulated proton conductance, indicating no functional avian UCP. Skeletal muscle mitochondria from penguins that had been either experimentally immersed or naturally adapted to cold water did possess functional avian UCP, demonstrated by a superoxide-stimulated, GDP-inhibitable proton conductance across their inner membrane. This was associated with a markedly greater abundance of avian UCP mRNA. In the presence (but not the absence) of fatty acids, these mitochondria also showed a greater adenine nucleotide translocase-catalysed proton conductance than those from never-immersed penguins. This was due to an increase in the amount of adenine nucleotide translocase. Therefore, adaptive thermogenesis in juvenile king penguins is linked to two separate mechanisms of uncoupling of oxidative phosphorylation in skeletal muscle mitochondria: increased proton transport activity of avian UCP (dependent on superoxide and inhibited by GDP) and increased proton transport activity of the adenine nucleotide translocase (dependent on fatty acids and inhibited by carboxyatractylate).

Detecting early cardiac dysfunction with radionuclide cardiac blood-pool imaging

International Nuclear Information System (INIS)

Wu Kegui; Chen Daguang; Lin Haoxue

1992-01-01

Cardiac function was measured by radionuclide cardiac blood-pool imaging in 15 normal persons, 19 cases of hypertension, 32 cases of coronary heart disease, 35 cases of coronary heart disease combined with hypertension and 44 cases of myocardial infarction. Significant differences have been found in indices of cardiac function between normal subjects and patients with coronary heart disease and coronary heart disease combined with hypertension, even though the patients were without any clinical sin of cardiac failure. Lowered regional EF and decreased ventricular was motion were found in 38.8% of patients, while 65.7%of patients revealed marked abnormality in MFR. The results indicate that latent cardiac dysfunction is common in patients with coronary heart disease. The earliest change is diastolic function abnormalities

Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

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Peter Moritz Becher

2017-01-01

Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

Current role of cardiac and extra-cardiac pathologies in clinically indicated cardiac computed tomography with emphasis on status before pulmonary vein isolation

Energy Technology Data Exchange (ETDEWEB)

Sohns, J.M.; Lotz, J. [Goettingen University Medical Center (Germany). Inst. for Diagnostic and Interventional Radiology; German Center for Cardiovascular Research (DZHK), Goettingen (Germany); Menke, J.; Staab, W.; Fasshauer, M.; Kowallick, J.T.; Zwaka, P.A.; Schwarz, A. [Goettingen University Medical Center (Germany). Inst. for Diagnostic and Interventional Radiology; Spiro, J. [Koeln University Hospital (Germany). Radiology; Bergau, L.; Unterberg-Buchwald, C. [Goettingen University Medical Center (Germany). Cardiology and Pneumology

2014-09-15

Purpose: The aim of this study was to assess the incidence of cardiac and significant extra-cardiac findings in clinical computed tomography of the heart in patients with atrial fibrillation before pulmonary vein isolation (PVI). Materials and Methods: 224 patients (64 ± 10 years; male 63%) with atrial fibrillation were examined by cardiac 64-slice multidetector CT before PVI. Extra-cardiac findings were classified as 'significant' if they were recommended to additional diagnostics or therapy, and otherwise as 'non-significant'. Additionally, cardiac findings were documented in detail. Results: A total of 724 cardiac findings were identified in 203 patients (91% of patients). Additionally, a total of 619 extra-cardiac findings were identified in 179 patients (80% of patients). Among these extra-cardiac findings 196 (32%) were 'significant', and 423 (68%) were 'non-significant'. In 2 patients (1%) a previously unknown malignancy was detected (esophageal cancer and lung cancer, local stage, no metastasis). 203 additional imaging diagnostics followed to clarify the 'significant' findings (124 additional CT, costs 38,314.69 US dollars). Overall, there were 3.2 cardiac and 2.8 extra-cardiac findings per patient. Extra-cardiac findings appear significantly more frequently in patients over 60 years old, in smokers and in patients with a history of cardiac findings (p < 0.05). Conclusion: Cardiac CT scans before PVI should be screened for extracardiac incidental findings that could have important clinical implications for each patient. (orig.)

Epidemiology and Outcomes After In-Hospital Cardiac Arrest After Pediatric Cardiac Surgery

Science.gov (United States)

Gupta, Punkaj; Jacobs, Jeffrey P.; Pasquali, Sara K.; Hill, Kevin D.; Gaynor, J. William; O’Brien, Sean M.; He, Max; Sheng, Shubin; Schexnayder, Stephen M.; Berg, Robert A.; Nadkarni, Vinay M.; Imamura, Michiaki; Jacobs, Marshall L.

2014-01-01

Background Multicenter data regarding cardiac arrest in children undergoing heart operations are limited. We describe epidemiology and outcomes associated with postoperative cardiac arrest in a large multiinstitutional cohort. Methods Patients younger than 18 years in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2007 through 2012) were included. Patient factors, operative characteristics, and outcomes were described for patients with and without postoperative cardiac arrest. Multivariable models were used to evaluate the association of center volume with cardiac arrest rate and mortality after cardiac arrest, adjusting for patient and procedural factors. Results Of 70,270 patients (97 centers), 1,843 (2.6%) had postoperative cardiac arrest. Younger age, lower weight, and presence of preoperative morbidities (all p < 0.0001) were associated with cardiac arrest. Arrest rate increased with procedural complexity across common benchmark operations, ranging from 0.7% (ventricular septal defect repair) to 12.7% (Norwood operation). Cardiac arrest was associated with significant mortality risk across procedures, ranging from 15.4% to 62.3% (all p < 0.0001). In multivariable analysis, arrest rate was not associated with center volume (odds ratio, 1.06; 95% confidence interval, 0.71 to 1.57 in low- versus high-volume centers). However, mortality after cardiac arrest was higher in low-volume centers (odds ratio, 2.00; 95% confidence interval, 1.52 to 2.63). This association was present for both high- and low-complexity operations. Conclusions Cardiac arrest carries a significant mortality risk across the stratum of procedural complexity. Although arrest rates are not associated with center volume, lower-volume centers have increased mortality after cardiac arrest. Further study of mechanisms to prevent cardiac arrest and to reduce mortality in those with an arrest is warranted. PMID:25443018

Inhibition of electron transfer and uncoupling effects by emodin and emodinanthrone in Escherichia coli.

Science.gov (United States)

Ubbink-Kok, T; Anderson, J A; Konings, W N

1986-07-01

The anthraquinones emodin (1,3,delta-trihydroxy-6-methylanthraquinone) and emodinanthrone (1,3,8-trihydroxy-6-methylanthrone) inhibited respiration-driven solute transport at micromolar concentrations in membrane vesicles of Escherichia coli. This inhibition was enhanced by Ca ions. The inhibitory action on solute transport is caused by inhibition of electron flow in the respiratory chain, most likely at the level between ubiquinone and cytochrome b, and by dissipation of the proton motive force. The uncoupling action was confirmed by studies on the proton motive force in beef heart cytochrome oxidase proteoliposomes. These two effects on energy transduction in cytoplasmic membranes explain the antibiotic properties of emodin and emodinanthrone.

Variable ATP yields and uncoupling of oxygen consumption in human brain

DEFF Research Database (Denmark)

Gjedde, Albert; Aanerud, Joel; Peterson, Ericka

2011-01-01

normalized the metabolic rate to the population average of that region. Coefficients of variation ranged from 10 to 15% in the different regions of the human brain and the normalized regional metabolic rates ranged from 70% to 140% of the population average for each region, equal to a two-fold variation......The distribution of brain oxidative metabolism values among healthy humans is astoundingly wide for a measure that reflects normal brain function and is known to change very little with most changes of brain function. It is possible that the part of the oxygen consumption rate that is coupled...... to ATP turnover is the same in all healthy human brains, with different degrees of uncoupling explaining the variability of total oxygen consumption among people. To test the hypothesis that about 75% of the average total oxygen consumption of human brains is common to all individuals, we determined...

Stimulating endogenous cardiac regeneration

Directory of Open Access Journals (Sweden)

Amanda eFinan

2015-09-01

Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

Expression of uncoupling protein 1 in bovine muscle cells.

Science.gov (United States)

Abd Eldaim, M A; Hashimoto, O; Ohtsuki, H; Yamada, T; Murakami, M; Onda, K; Sato, R; Kanamori, Y; Qiao, Y; Tomonaga, S; Matsui, T; Funaba, M

2016-12-01

Uncoupling protein 1 (Ucp1) is predominantly expressed in brown/beige adipocytes in mammals. Although myogenic cells have been suggested to commit to a brown adipocyte lineage through the induction of Prdm16 expression, Prdm16 is also expressed in skeletal muscle. Thus, we examined expression of Ucp1 in bovine myogenic cells. Considering that Ucp1 is a principle molecule that induces energy expenditure in brown/beige adipocytes, expression of Ucp1 is not preferable in beef cattle because of potential decrease in energy (fattening) efficiency. The RT-PCR analyses revealed the expression of Ucp1 in the skeletal muscle of cattle; expression levels were markedly lower than those in the brown fat of calves. Immunohistochemical analyses showed that Ucp1 surrounded muscle fibers, but not adipocytes residing in skeletal muscle. Myosatellite cells cultured in myogenic medium showed an increase in the expression levels of myogenic regulatory factors ( levels were greater in cells after myogenic culture for 12 d than in those after myogenic culture for 6 d ( bovine skeletal muscle, which suggests the necessity for further studies on Ucp1-mediated energy expenditure in bovine skeletal muscle.

Use of source term uncoupled in radionuclide migration equations

International Nuclear Information System (INIS)

Silveira, Claudia Siqueira da; Lima, Zelmo Rodrigues de; Alvim, Antonio Carlos Marques

2008-01-01

Final repositories of high-level radioactive waste have been considered in deep, low permeability and stable geological formations. A common problem found is the migration modeling of radionuclides in a fractured rock. In this work, the physical system adopted consists of the rock matrix containing a single planar fracture situated in water saturated porous rock. The partial differential equations that describe the radionuclide transport were discretized using finite differences techniques, of which the following methods were adopted: Explicit Euler, Implicit Euler and Crank-Nicholson. For each one of these methods, the advective term was discretized with the following numerical schemes: backward differences, centered differences and forward differences. We make a comparison to determine which temporal and space discretization has the best result in relation to a reference solution. The obtained results show that the Explicit Euler Method with forward discretization in the advective term has a good accuracy. Next, with the objective of improving the answer of the Implicit Euler and Crank-Nicholson Methods it was accomplished a source term uncouplement, the diffusive flux. The obtained results were considered satisfactory by comparison with previous studies. (author)

Cardiac rehabilitation

Science.gov (United States)

... rehab; Heart failure - cardiac rehab References Anderson L, Taylor RS. Cardiac rehabilitation for people with heart disease: ... of Medicine, Division of Cardiology, Harborview Medical Center, University of Washington Medical School, Seattle, WA. Also reviewed ...

Defining the Intrinsic Cardiac Risks of Operations to Improve Preoperative Cardiac Risk Assessments.

Science.gov (United States)

Liu, Jason B; Liu, Yaoming; Cohen, Mark E; Ko, Clifford Y; Sweitzer, Bobbie J

2018-02-01

Current preoperative cardiac risk stratification practices group operations into broad categories, which might inadequately consider the intrinsic cardiac risks of individual operations. We sought to define the intrinsic cardiac risks of individual operations and to demonstrate how grouping operations might lead to imprecise estimates of perioperative cardiac risk. Elective operations (based on Common Procedural Terminology codes) performed from January 1, 2010 to December 31, 2015 at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program were studied. A composite measure of perioperative adverse cardiac events was defined as either cardiac arrest requiring cardiopulmonary resuscitation or acute myocardial infarction. Operations' intrinsic cardiac risks were derived from mixed-effects models while controlling for patient mix. Resultant risks were sorted into low-, intermediate-, and high-risk categories, and the most commonly performed operations within each category were identified. Intrinsic operative risks were also examined using a representative grouping of operations to portray within-group variation. Sixty-six low, 30 intermediate, and 106 high intrinsic cardiac risk operations were identified. Excisional breast biopsy had the lowest intrinsic cardiac risk (overall rate, 0.01%; odds ratio, 0.11; 95% CI, 0.02 to 0.25) relative to the average, whereas aorto-bifemoral bypass grafting had the highest (overall rate, 4.1%; odds ratio, 6.61; 95% CI, 5.54 to 7.90). There was wide variation in the intrinsic cardiac risks of operations within the representative grouping (median odds ratio, 1.40; interquartile range, 0.88 to 2.17). A continuum of intrinsic cardiac risk exists among operations. Grouping operations into broad categories inadequately accounts for the intrinsic cardiac risk of individual operations.

Mathematical cardiac electrophysiology

CERN Document Server

Colli Franzone, Piero; Scacchi, Simone

2014-01-01

This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

Science.gov (United States)

Cerqueira, Fernanda M; Laurindo, Francisco R M; Kowaltowski, Alicia J

2011-03-31

Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

Effects of sewage sludge on Di-(2-ethylhexyl) phthalate uptake by plants

International Nuclear Information System (INIS)

Aranda, J.M.; O'Connor, G.A.; Eiceman, G.A.

1989-01-01

Di-(2-ethylhexyl) phthalate (DEHP) is a priority organic pollutant frequently found in municipal sludges. A greenhouse study was conducted to determine the effect of sludge on plant uptake of 14 C-DEHP (carbonyl labeled). Plants grown included three food chain crops, lettuce (Lactuca sativa L.), carrot (Daucus carota L.) and chile pepper (Capsicum annuum L.) and tall fescue (Festuca arundinacea Schreb.). Net 14 C concentration in plants grown in soil amended with 14 C-DEHP-contaminated sludge was independent of sludge rate (at the same DEHP loading) for lettuce, chile fruit, and carrot roots. Net 14 C concentration, however, was inversely related to sludge rate in carrot tops, fescue, and chile plants. Intact DEHP was not detected in plants by gas chromatography/mass spectrometry analysis. Calculated plant DEHP concentrations (based on measured net 14 C concentrations and DEHP specific activities) were generally correlated better with DEHP soil solution concentrations than with total DEHP soil concentrations. Net 14 C-DEHP bioconcentration factors were calculated from initial soil DEHP concentration and plant fresh weights. Bioconcentration factors ranged from 0.01 to 0.03 for fescue, lettuce, carrots, and chile, suggesting little DEHP uptake. Additionally, because intact DEHP was not detected in any plants, DEHP uptake by plants was of minor importance and would not limit sludge additions to soils used to grow these crops

Association between dental caries and out-of-hospital cardiac arrests of cardiac origin in Japan.

Science.gov (United States)

Suematsu, Yasunori; Miura, Shin-Ichiro; Zhang, Bo; Uehara, Yoshinari; Ogawa, Masahiro; Yonemoto, Naohiro; Nonogi, Hiroshi; Nagao, Ken; Kimura, Takeshi; Saku, Keijiro

2016-04-01

Oral infection contributes to atherosclerosis and coronary heart disease. We hypothesized that dental caries may be associated with out-of-hospital cardiac arrests (OHCA) of cardiac origin, but not non-cardiac origin. We compared the age-adjusted incidence of OHCA (785,591 cases of OHCA: 55.4% of cardiac origin and 44.6% of non-cardiac origin) to the age-adjusted prevalence of dental caries between 2005 and 2011 in the 47 prefectures of Japan. In both the total population and males over 65 years, the number of cases of dental caries was significantly associated with the number of OHCA of total and cardiac origin from 2005 to 2011, but not those of non-cardiac origin. In the total population, the age-adjusted prevalence of dental caries was not significantly associated with the age-adjusted incidence of OHCA (total OHCA: r correlation coefficient=0.22, p=0.14; OHCA of cardiac origin: r=0.25, p=0.09; OHCA of non-cardiac origin: r=-0.002, p=0.99). Among male patients over 65 years, the age-adjusted prevalence of dental caries was significantly associated with OHCA of total and cardiac origin, but not non-cardiac origin (total OHCA: r=0.47, p<0.001; OHCA of cardiac origin: r=0.37, p=0.01; OHCA of non-cardiac origin: r=0.28, p=0.054). While oral hygiene is important in all age groups, it may be particularly associated with OHCAs of cardiac origin in males over 65 years. Copyright © 2015. Published by Elsevier Ltd.

Exercise-related cardiac arrest in cardiac rehabilitation - The ...

African Journals Online (AJOL)

Prescribed physical activity plays a major role in the rehabilitation of patients with coronary artery disease, and as with any other form of treatment its benefits must be weighed against its possible risks. This study attempted to establish the safety of cardiac rehabilitation as a medical intervention at the Johannesburg Cardiac ...

A novel high-throughput assay for islet respiration reveals uncoupling of rodent and human islets.

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Jakob D Wikstrom

Full Text Available The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this study was to develop such an assay and to examine bioenergetic efficiency of rodent and human islets.The XF24 respirometer platform was adapted to islets by the development of a 24-well plate specifically designed to confine islets. The islet plate generated data with low inter-well variability and enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase blocker oligomycin was used to assess uncoupling while rotenone together with myxothiazol/antimycin was used to measure the level of non-mitochondrial respiration. The use of oligomycin in islets was validated by reversing its effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59% and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to 38% and 23% respectively. Islets from a cohort of human donors showed a respiratory leak of 38%, significantly lower than mouse islets.The assay for islet respiration presented here provides a novel tool that can be used to study islet mitochondrial function in a relatively high-throughput manner. The data obtained in this study shows that rodent islets are less bioenergetically efficient than human islets as well as INS1 cells.

Degradation of di(2-ethyl hexyl) phthalate by Fusarium culmorum: Kinetics, enzymatic activities and biodegradation pathway based on quantum chemical modelingpathway based on quantum chemical modeling

International Nuclear Information System (INIS)

Ahuactzin-Pérez, Miriam; Tlecuitl-Beristain, Saúl; García-Dávila, Jorge; González-Pérez, Manuel; Gutiérrez-Ruíz, María Concepción; Sánchez, Carmen

2016-01-01

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in the manufacture of plastics, and it is an environmental contaminant. The specific growth rate (μ), maximum biomass (X_m_a_x), biodegradation constant of DEHP (k), half-life (t_1_/_2) of DEHP biodegradation and removal efficiency of DEHP, esterase and laccase specific activities, and enzymatic yield parameters were evaluated for Fusarium culmorum grown on media containing glucose and different concentrations of DEHP (0, 500 and 1000 mg/L). The greatest μ and the largest X_m_a_x occurred in media supplemented with 1000 mg of DEHP/L. F. culmorum degraded 95% of the highest amount of DEHP tested (1000 mg/L) within 60 h of growth. The k and t_1_/_2 were 0.024 h"−"1 and 28 h, respectively, for both DEHP concentrations. The removal efficiency of DEHP was 99.8% and 99.9% for 1000 and 500 mg/L, respectively. Much higher specific esterase activity than specific laccase activity was observed in all media tested. The compounds of biodegradation of DEHP were identified by GC–MS. A DEHP biodegradation pathway by F. culmorum was proposed on the basis of the intermolecular flow of electrons of the identified intermediate compounds using quantum chemical modeling. DEHP was fully metabolized by F. culmorum with butanediol as the final product. This fungus offers great potential in bioremediation of environments polluted with DEHP. - Highlights: • F. culmorum degraded 95% of DEHP (1000 mg/L) within 60 h. • Removal efficiency of DEHP was 99.8% and 99.9% for 1000 and 500 mg/L, respectively. • DEHP was fully metabolized by F. culmorum, with butanediol as the final product. • A DEHP biodegradation pathway was proposed using on quantum chemical modeling.

Degradation of di(2-ethyl hexyl) phthalate by Fusarium culmorum: Kinetics, enzymatic activities and biodegradation pathway based on quantum chemical modelingpathway based on quantum chemical modeling

Energy Technology Data Exchange (ETDEWEB)

Ahuactzin-Pérez, Miriam [Doctorado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa (UAM-I) (Mexico); Facultad de Agrobiología, Universidad Autónoma de Tlaxcala, Ixtacuixtla, Tlaxcala (Mexico); Tlecuitl-Beristain, Saúl; García-Dávila, Jorge [Universidad Politécnica de Tlaxcala, San Pedro Xalcatzinco, Tepeyanco, Tlaxcala CP 90180 (Mexico); González-Pérez, Manuel [Universidad Popular Autónoma del Estado de Puebla, Puebla CP 72410 (Mexico); Gutiérrez-Ruíz, María Concepción [Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, D.F (Mexico); Sánchez, Carmen, E-mail: sanher6@hotmail.com [Laboratory of Biotechnology, Research Centre for Biological Sciences, Universidad Autónoma de Tlaxcala, Ixtacuixtla, Tlaxcala CP. 90062 (Mexico)

2016-10-01

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in the manufacture of plastics, and it is an environmental contaminant. The specific growth rate (μ), maximum biomass (X{sub max}), biodegradation constant of DEHP (k), half-life (t{sub 1/2}) of DEHP biodegradation and removal efficiency of DEHP, esterase and laccase specific activities, and enzymatic yield parameters were evaluated for Fusarium culmorum grown on media containing glucose and different concentrations of DEHP (0, 500 and 1000 mg/L). The greatest μ and the largest X{sub max} occurred in media supplemented with 1000 mg of DEHP/L. F. culmorum degraded 95% of the highest amount of DEHP tested (1000 mg/L) within 60 h of growth. The k and t{sub 1/2} were 0.024 h{sup −1} and 28 h, respectively, for both DEHP concentrations. The removal efficiency of DEHP was 99.8% and 99.9% for 1000 and 500 mg/L, respectively. Much higher specific esterase activity than specific laccase activity was observed in all media tested. The compounds of biodegradation of DEHP were identified by GC–MS. A DEHP biodegradation pathway by F. culmorum was proposed on the basis of the intermolecular flow of electrons of the identified intermediate compounds using quantum chemical modeling. DEHP was fully metabolized by F. culmorum with butanediol as the final product. This fungus offers great potential in bioremediation of environments polluted with DEHP. - Highlights: • F. culmorum degraded 95% of DEHP (1000 mg/L) within 60 h. • Removal efficiency of DEHP was 99.8% and 99.9% for 1000 and 500 mg/L, respectively. • DEHP was fully metabolized by F. culmorum, with butanediol as the final product. • A DEHP biodegradation pathway was proposed using on quantum chemical modeling.

Sudden cardiac death

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Neeraj Parakh

2015-01-01

Full Text Available Sudden cardiac death is one of the most common cause of mortality worldwide. Despite significant advances in the medical science, there is little improvement in the sudden cardiac death related mortality. Coronary artery disease is the most common etiology behind sudden cardiac death, in the above 40 years population. Even in the apparently healthy population, there is a small percentage of patients dying from sudden cardiac death. Given the large denominator, this small percentage contributes to the largest burden of sudden cardiac death. Identification of this at risk group among the apparently healthy individual is a great challenge for the medical fraternity. This article looks into the causes and methods of preventing SCD and at some of the Indian data. Details of Brugada syndrome, Long QT syndrome, Genetics of SCD are discussed. Recent guidelines on many of these causes are summarised.

Activation of AMPKα2 is not crucial for mitochondrial uncoupling-induced metabolic effects but required to maintain skeletal muscle integrity.

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Mario Ost

Full Text Available Transgenic (UCP1-TG mice with ectopic expression of UCP1 in skeletal muscle (SM show a phenotype of increased energy expenditure, improved glucose tolerance and increase substrate metabolism in SM. To investigate the potential role of skeletal muscle AMPKα2 activation in the metabolic phenotype of UCP1-TG mice we generated double transgenic (DTG mice, by crossing of UCP1-TG mice with DN-AMPKα2 mice overexpressing a dominant negative α2 subunit of AMPK in SM which resulted in an impaired AMPKα2 activity by 90±9% in SM of DTG mice. Biometric analysis of young male mice showed decreased body weight, lean and fat mass for both UCP1-TG and DTG compared to WT and DN-AMPKα2 mice. Energy intake and weight-specific total energy expenditure were increased, both in UCP1-TG and DTG mice. Moreover, glucose tolerance, insulin sensitivity and fatty acid oxidation were not altered in DTG compared to UCP1-TG. Also uncoupling induced induction and secretion of fibroblast growth factor 21 (FGF21 from SM was preserved in DTG mice. However, voluntary physical cage activity as well as ad libitum running wheel access during night uncovered a severe activity intolerance of DTG mice. Histological analysis showed a progressive degenerative morphology in SM of DTG mice which was not observed in SM of UCP1-TG mice. Moreover, ATP-depletion related cellular stress response via heat shock protein 70 was highly induced, whereas capillarization regulator VEGF was suppressed in DTG muscle. In addition, AMPKα2-mediated induction of mitophagy regulator ULK1 was suppressed in DTG mice, as well as mitochondrial respiratory capacity and content. In conclusion, we demonstrate that AMPKα2 is dispensable for SM mitochondrial uncoupling induced metabolic effects on whole body energy balance, glucose homeostasis and insulin sensitivity. But strikingly, activation of AMPKα2 seems crucial for maintaining SM function, integrity and the ability to compensate chronic metabolic stress

ZmPUMP encodes a fully functional monocot plant uncoupling mitochondrial protein whose affinity to fatty acid is increased with the introduction of a His pair at the second matrix loop

International Nuclear Information System (INIS)

Favaro, Regiane Degan; Borecky, Jiri; Colombi, Debora; Maia, Ivan G.

2006-01-01

Uncoupling proteins (UCPs) are specialized mitochondrial transporter proteins that uncouple respiration from ATP synthesis. In this study, cDNA encoding maize uncoupling protein (ZmPUMP) was expressed in Escherichia coli and recombinant ZmPUMP reconstituted in liposomes. ZmPUMP activity was associated with a linoleic acid (LA)-mediated H + efflux with K m of 56.36 ± 0.27 μM and V max of 66.9 μmol H + min -1 (mg prot) -1 . LA-mediated H + fluxes were sensitive to ATP inhibition with K i of 2.61 ± 0.36 mM (at pH 7.2), a value similar to those for dicot UCPs. ZmPUMP was also used to investigate the importance of a histidine pair present in the second matrix loop of mammalian UCP1 and absent in plant UCPs. ZmPUMP with introduced His pair (Lys155His and Ala157His) displayed a 1.55-fold increase in LA-affinity while its activity remained unchanged. Our data indicate conserved properties of plant UCPs and suggest an enhancing but not essential role of the histidine pair in proton transport mechanism

Recurrent late cardiac tamponade following cardiac surgery : a deceiving and potentially lethal complication

NARCIS (Netherlands)

Harskamp, Ralf E.; Meuzelaar, Jacobus J.

2010-01-01

Background - Cardiac tamponade, characterized by inflow obstruction of the heart chambers by extracardiac compression, is a potentially lethal complication following cardiac surgery. Case report - We present a case of recurrent cardiac tamponade following valve surgery. At first presentation,

Small cardiac lesions: fibrosis of papillary muscles and focal cardiac myocytolysis

Energy Technology Data Exchange (ETDEWEB)

Steer, A [Hijiyanna Park, Hiroshima JP; Nakashima, N; Kawashima, T; Lee, K K; Danzig, M D; Robertson, T L; Dock, D S

1977-11-01

Three types of small cardiac lesions were described and illustrated: (1) focal type of papillary muscle fibrosis, evidently a healed infarct of the papillary muscle present in 13% of the autopsies, is a histologically characteristic lesion associated with coronary artery disease and healed myocardial infarction; (2) diffuse type of papillary muscle fibrosis, probably an aging change present in almost half of the autopsies, is associated with sclerosis of the arteries in the papillary muscle, is identifiable histologically; and apparently is not associated with any cardiac abnormality; and (3) focal cardiac myocytolysis, a unique histologic lesion, usually multifocal without predilection for any area of the heart, is associated with ischemic heart disease, death due to cancer complicated by non-bacterial thrombotic endocarditis and microthrombi in small cardiac arteries as well as with other diseases. Differentiation of the 2 types of papillary muscle fibrosis is important in the study of papillary muscle and mitral valve dysfunction. Focal cardiac myocytolysis may contribute to the fatal extension of myocardial infarcts.

Small cardiac lesions: fibrosis of papillary muscles and focal cardiac myocytolysis

Energy Technology Data Exchange (ETDEWEB)

Steer, A; Nakashima, T; Kawashima, T; Lee, K K; Danzig, M D; Robertson, T L; Dock, D S

1977-11-01

Three types of small cardiac lesions were described and illustrated: (1) focal type of papillary muscle fibrosis, evidently a healed infarct of the papillary muscle present in 13% of the autopsies, is a histologically characteristic lesion associated with coronary artery disease and healed myocardial infarction, (2) diffuse type of papillary muscle fibrosis, probably an aging change present in almost half of the autopsies, is associated with sclerosis of the arteries in the papillary muscle, is identifiable histologically, and apparently is not associated with any cardiac abnormality, and (3) focal cardiac myochtolysis, a unique histologic lesion, usually multifocal without predilection for any area of the heart, is associated with ischemic heart disease, death due to cancer complicated by nonbacterial thrombotic endocarditis and microthrombi in small cardiac arteries as well as with other diseases. Differentiation of the 2 types of papillary muscle fibrosis is important in the study of papillary muscle and mitral valve dysfunction. Focal cardiac myocytolysis may contribute to the fatal extension of myocardial infarcts.

Recurrent late cardiac tamponade following cardiac surgery: a deceiving and potentially lethal complication

NARCIS (Netherlands)

Harskamp, Ralf E.; Meuzelaar, Jacobus J.

2010-01-01

Cardiac tamponade, characterized by inflow obstruction of the heart chambers by extracardiac compression, is a potentially lethal complication following cardiac surgery. We present a case of recurrent cardiac tamponade following valve surgery. At first presentation, diagnosis was delayed because of

Maternal exposure to di-(2-ethylhexyl) phthalate disrupts placental growth and development in pregnant mice

Energy Technology Data Exchange (ETDEWEB)

Zong, Teng; Lai, Lidan [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China); Hu, Jia [Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi (China); Guo, Meijun; Li, Mo; Zhang, Lu; Zhong, Chengxue; Yang, Bei; Wu, Lei; Zhang, Dalei; Tang, Min [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China); Kuang, Haibin, E-mail: kuanghaibin@ncu.edu.cn [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China)

2015-10-30

Highlights: • The influence of DEHP on the development of placenta was investigated. • DEHP disrupts the growth and development of placenta. • DEHP disrupts the formation of labyrinth vascularization. • DEHP inhibits the proliferation of ectoplacental cone and placenta. • DEHP induces the apoptosis of placenta via activated MAPK signaling pathway. - Abstract: Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and widely dispersed in the environment. DEHP exposure reduces embryo implantations, increases embryonic loss, and decreases fetal body weights. However, no detailed information is available about the effect of DEHP on the placentation during pregnancy. Thus, our aim was to explore the effect of DEHP on the growth and development of placenta in vivo. Mice were administered DEHP by gavages at 125, 250, 500 mg/kg/day from gestational days (GD) 1 until sacrifice. Results showed that DEHP treatment significantly reduced the weight of placenta at GD 13. Histopathologically, in DEHP-treated group, the ectoplacental cones significantly became smaller at GD9, and total area of placenta and area of spongiotrophoblast were significantly reduced at GD 13. Expression levels of Ascl2, Esx1 and Fosl1 mRNA dramatically decreased in DEHP-treated placenta at GD 13. DEHP administration disrupted labyrinth vascularization of placentas, and inhibited proliferation and induced apoptosis of placenta by the activation of caspase-3 and -8, up-regulation of Bax and down-regulation of Bcl-2 mRNA and protein at GD 13. In conclusion, these results suggest that adverse pregnancy outcomes including low birth-weight and pregnancy loss exposed to DEHP are possibly mediated, at least in part, via the suppression of placental growth and development.

Increased Urinary Phthalate Levels in Women with Uterine Leiomyoma: A Case-Control Study.

Science.gov (United States)

Kim, Young Ah; Kho, Younglim; Chun, Kyoung Chul; Koh, Jae Whoan; Park, Jeong Woo; Bunderson-Schelvan, Melisa; Cho, Yoon Hee

2016-12-15

We assessed the urinary concentration of 16 phthalate metabolites in 57 women with and without uterine leiomyoma ( n = 30 and 27; respectively) to determine the association between phthalate exposure and uterine leiomyoma. To evaluate exposure to di-(2-ethylhexyl) phthalate (DEHP); we calculated the molar sum of DEHP metabolites; ∑3-DEHP (combining mono-(2-ethylhexyl) phthalate (MEHP); mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP); and mono-(2-ethyl-5-oxohexyl) phthalate); ∑4-DEHP (∑3-DEHP plus mono-(2-ethyl-5-carboxypentyl) phthalate); and ∑5-DEHP (∑4-DEHP plus mono (2-(carboxylmethyl)hexyl) phthalate (2cx-MMHP)). The log transformed urinary levels of MEHP; MEHHP; 2cx-MMHP; ∑3-DEHP; ∑4-DEHP; and ∑5-DEHP in the leiomyoma group were significantly higher than those of controls. When we adjusted for age; waist circumference; and parity using multiple logistic regression analyses; we found log ∑3-DEHP (OR = 10.82; 95% CI = 1.25; 93.46) and ∑4-DEHP (OR = 8.78; 95% CI = 1.03; 75.29) were significantly associated with uterine leiomyoma. Our findings suggest an association between phthalate exposure and uterine leiomyoma. However; larger studies are needed to investigate potential interactions between phthalate exposure and uterine leiomyoma.

Diffuse infiltrative cardiac tuberculosis

International Nuclear Information System (INIS)

Gulati, Gurpreet S; Kothari, Shyam S

2011-01-01

We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

Directory of Open Access Journals (Sweden)

Fernanda M Cerqueira

2011-03-01

Full Text Available Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR. Since treatment of mice with dinitrophenol (DNP promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

Stochastic calculus for uncoupled continuous-time random walks.

Science.gov (United States)

Germano, Guido; Politi, Mauro; Scalas, Enrico; Schilling, René L

2009-06-01

The continuous-time random walk (CTRW) is a pure-jump stochastic process with several applications not only in physics but also in insurance, finance, and economics. A definition is given for a class of stochastic integrals driven by a CTRW, which includes the Itō and Stratonovich cases. An uncoupled CTRW with zero-mean jumps is a martingale. It is proved that, as a consequence of the martingale transform theorem, if the CTRW is a martingale, the Itō integral is a martingale too. It is shown how the definition of the stochastic integrals can be used to easily compute them by Monte Carlo simulation. The relations between a CTRW, its quadratic variation, its Stratonovich integral, and its Itō integral are highlighted by numerical calculations when the jumps in space of the CTRW have a symmetric Lévy alpha -stable distribution and its waiting times have a one-parameter Mittag-Leffler distribution. Remarkably, these distributions have fat tails and an unbounded quadratic variation. In the diffusive limit of vanishing scale parameters, the probability density of this kind of CTRW satisfies the space-time fractional diffusion equation (FDE) or more in general the fractional Fokker-Planck equation, which generalizes the standard diffusion equation, solved by the probability density of the Wiener process, and thus provides a phenomenologic model of anomalous diffusion. We also provide an analytic expression for the quadratic variation of the stochastic process described by the FDE and check it by Monte Carlo.

Assessment of cardiac risk before non-cardiac surgery: brain natriuretic peptide in 1590 patients.

Science.gov (United States)

Dernellis, J; Panaretou, M

2006-11-01

To evaluate the predictive value of brain natriuretic peptide (BNP) for assessment of cardiac risk before non-cardiac surgery. Consecutively treated patients (947 men, 643 women) whose BNP was measured before non-cardiac surgery were studied. Clinical and ECG variables were evaluated to identify predictors of postoperative cardiac events. Events occurred in 6% of patients: 21 cardiac deaths, 20 non-fatal myocardial infarctions, 41 episodes of pulmonary oedema and 14 patients with ventricular tachycardia. All of these patients had raised plasma BNP concentrations (best cut-off point 189 pg/ml). The only independent predictor of postoperative events was BNP (odds ratio 34.52, 95% confidence interval (CI) 17.08 to 68.62, p 300 pg/ml); postoperative event rates were 0%, 5%, 12% and 81%, respectively. In this population of patients evaluated before non-cardiac surgery, BNP is an independent predictor of postoperative cardiac events. BNP > 189 pg/ml identified patients at highest risk.

123I-MIBG imaging detects cardiac involvement and predicts cardiac events in Churg-Strauss syndrome

International Nuclear Information System (INIS)

Horiguchi, Yoriko; Morita, Yukiko; Tsurikisawa, Naomi; Akiyama, Kazuo

2011-01-01

In Churg-Strauss syndrome (CSS) it is important to detect cardiac involvement, which predicts poor prognosis. This study evaluated whether 123 I-metaiodobenzylguanidine (MIBG) scintigraphy could detect cardiac damage and predict cardiac events in CSS. 123 I-MIBG scintigraphy was performed in 28 patients with CSS, 12 of whom had cardiac involvement. The early and delayed heart to mediastinum ratio (early H/M and delayed H/M) and washout rate were calculated by using 123 I-MIBG scintigraphy and compared with those in control subjects. Early H/M and delayed H/M were significantly lower and the washout rate was significantly higher in patients with cardiac involvement than in those without and in controls (early H/M, p = 0.0024, p = 0.0001; delayed H/M, p = 0.0002, p = 0.0001; washout rate, p = 0.0012, p = 0.0052 vs those without and vs controls, respectively). Accuracy for detecting cardiac involvement was 86% for delayed H/M and washout rate and 79% for early H/M and B-type natriuretic peptide (BNP). Kaplan-Meier analysis showed significantly lower cardiac event-free rates in patients with early H/M ≤ 2.18 and BNP > 21.8 pg/ml than those with early H/M > 2.18 and BNP ≤ 21.8 pg/ml (log-rank test p = 0.006). Cardiac sympathetic nerve function was damaged in CSS patients with cardiac involvement. 123 I-MIBG scintigraphy was useful in detecting cardiac involvement and in predicting cardiac events. (orig.)

CARDIAC LYMPHOMA IN DOG

Directory of Open Access Journals (Sweden)

G. D. Cruz

2016-11-01

Full Text Available Lymphoma is a lymphoid tumor that originates in hematopoietic organs such as lymph node, spleen or liver. In dogs, the overall prevalence of cardiac tumors was estimated to be only 0.19% based on the results of the survey of a large database, and lymphomas accounts for approximately 2% of all cardiac tumors. In general, the involvement of the myocardium is rarely described in canine lymphoma. Currently, there is no evidence of a viral association with primary cardiac lymphoma in dogs, but other types of immunosuppression may contribute to abnormal events, such as involvement primary cardiac. The aim of this study was to analyze a case of sudden death of a bitch, SRD, aged 10, who had the final diagnosis of cardiac lymphoma.

Cardiac cone-beam CT

International Nuclear Information System (INIS)

Manzke, Robert

2005-01-01

This doctoral thesis addresses imaging of the heart with retrospectively gated helical cone-beam computed tomography (CT). A thorough review of the CT reconstruction literature is presented in combination with a historic overview of cardiac CT imaging and a brief introduction to other cardiac imaging modalities. The thesis includes a comprehensive chapter about the theory of CT reconstruction, familiarizing the reader with the problem of cone-beam reconstruction. The anatomic and dynamic properties of the heart are outlined and techniques to derive the gating information are reviewed. With the extended cardiac reconstruction (ECR) framework, a new approach is presented for the heart-rate-adaptive gated helical cardiac cone-beam CT reconstruction. Reconstruction assessment criteria such as the temporal resolution, the homogeneity in terms of the cardiac phase, and the smoothness at cycle-to-cycle transitions are developed. Several reconstruction optimization approaches are described: An approach for the heart-rate-adaptive optimization of the temporal resolution is presented. Streak artifacts at cycle-to-cycle transitions can be minimized by using an improved cardiac weighting scheme. The optimal quiescent cardiac phase for the reconstruction can be determined automatically with the motion map technique. Results for all optimization procedures applied to ECR are presented and discussed based on patient and phantom data. The ECR algorithm is analyzed for larger detector arrays of future cone-beam systems throughout an extensive simulation study based on a four-dimensional cardiac CT phantom. The results of the scientific work are summarized and an outlook proposing future directions is given. The presented thesis is available for public download at www.cardiac-ct.net

Polymer microfiber meshes facilitate cardiac differentiation of c-kit{sup +} human cardiac stem cells

Energy Technology Data Exchange (ETDEWEB)

Kan, Lijuan [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Thayer, Patrick [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Fan, Huimin [Research Institute of Heart Failure, Shanghai East Hospital of Tongji University, Shanghai (China); Ledford, Benjamin; Chen, Miao [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Goldstein, Aaron [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Cao, Guohua [School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); He, Jia-Qiang, E-mail: jiahe@vt.edu [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States)

2016-09-10

Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit{sup +} human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5 µm) elastomeric meshes consisting of aligned 1.7 µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increased expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases. - Highlights: • First study to characterize c-kit{sup +} human cardiac stem cells on microfiber meshes. • Microfiber meshes seem reducing cell proliferation, but no effect on cell viability. • Microfiber meshes facilitate the elongation of human cardiac stem cells in culture. • Cardiac but not smooth muscle differentiation were enhanced on microfiber meshes. • Microfiber meshes may be used as cardiac patches in cell-based cardiac therapy.

Use of Hopcalite derived Cu-Mn mixed oxide as Oxygen Carrier for Chemical Looping with Oxygen Uncoupling Process

OpenAIRE

Adánez-Rubio, Iñaki; Abad Secades, Alberto; Gayán Sanz, Pilar; Adánez-Rubio, Imanol; Diego Poza, Luis F. de; Garcia-Labiano, Francisco; Adánez Elorza, Juan

2016-01-01

Chemical-Looping with Oxygen Uncoupling (CLOU) is an alternative Chemical Looping process for the combustion of solid fuels with inherent CO2 capture. The CLOU process needs a material as oxygen carrier with the ability to give gaseous O2 at suitable temperatures for solid fuel combustion, e.g. copper oxide and manganese oxide. In this work, treated commercial Carulite 300® was evaluated as oxygen carrier for CLOU. Carulite 300® is a hopcalite material composed of 29.2 wt.% CuO and 67.4 wt.% ...

Comprehensive cardiac rehabilitation

DEFF Research Database (Denmark)

Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O

2006-01-01

OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed...... and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

Autonomic cardiac innervation

Science.gov (United States)

Hasan, Wohaib

2013-01-01

Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

Directory of Open Access Journals (Sweden)

Olivia Chen

2015-01-01

Full Text Available Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming.

Biomaterials for cardiac regeneration

CERN Document Server

Ruel, Marc

2015-01-01

This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

Metoclopramide-induced cardiac arrest

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Martha M. Rumore

2011-11-01

Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

Cardiac tumours: non invasive detection and assessment by gated cardiac blood pool radionuclide imaging

International Nuclear Information System (INIS)

Pitcher, D.; Wainwright, R.; Brennand-Roper, D.; Deverall, P.; Sowton, E.; Maisey, M.

1980-01-01

Four patients with cardiac tumours were investigated by gated cardiac blood pool radionuclide imaging and echocardiography. Contrast angiocardiography was performed in three of the cases. Two left atrial tumours were detected by all three techniques. In one of these cases echocardiography alone showed additional mitral valve stenosis, but isotope imaging indicated tumour size more accurately. A large septal mass was detected by all three methods. In this patient echocardiography showed evidence of left ventricular outflow obstruction, confirmed at cardiac catheterisation, but gated isotope imaging provided a more detailed assessment of the abnormal cardiac anatomy. In the fourth case gated isotope imaging detected a large right ventricular tumour which had not been identified by echocardiography. Gated cardiac blood pool isotope imaging is a complementary technique to echocardiography for the non-invasive detection and assessment of cardiac tumours. (author)

Pregnancy as a cardiac stress model

Science.gov (United States)

Chung, Eunhee; Leinwand, Leslie A.

2014-01-01

Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation. PMID:24448313

Human technology after cardiac epigenesis. Artificial heart versus cardiac transplantation.

Science.gov (United States)

Losman, J G

1977-09-24

Cardiovascular disease is the chief cause of death in technologically advanced countries and accounts for more than 50% of all deaths in the USA. For a patient with end-stage cardiac failure the only treatment presently available is organ replacement, either by transplantation or by the use of a mechanical heart. Transplantation has demonstrated its value: survival of more than 8 years and restoration of a normal quality of life to patients who were in end-stage cardiac decompensation. However, the prospect of routine clinical application of an artificial heart remains distant. The development of a totally implantable artificial heart still presents a series of challenging engineering problems with regard to strict constraints of size, weight, blood-material compatibility, adaptability of output to demand, efficiency and reliability of the power supply, and safety if nuclear fuel is used. The totally artificial heart is presently not an alternative to the cardiac allograft, but could provide short-term support for patients awaiting cardiac transplantation.

Marketing cardiac CT programs.

Science.gov (United States)

Scott, Jason

2010-01-01

There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

Uncoupled thermoelasticity solutions applied on beam dumps

Directory of Open Access Journals (Sweden)

A. Ouzia

2016-06-01

Full Text Available In particle accelerators the process of beam absorption is vital. At CERN particle beams are accelerated at energies of the order of TeV. In the event of a system failure or following collisions, the beam needs to be safely absorbed by dedicated protecting blocks. The thermal shock caused by the rapid energy deposition within the absorbing block causes thermal stresses that may rise above critical levels. The present paper provides a convenient expression of such stresses under hypotheses described hereafter. The temperature field caused by the beam energy deposition is assumed to be Gaussian. Such a field models a non-diffusive heat deposition. These effects are described as thermoelastic as long as the stresses remain below the proportional limit and can be analytically modeled by the coupled equations of thermoelasticity. The analytical solution to the uncoupled thermoelastic problem in an infinite domain is presented herein and matched with a finite unit radius sphere. The assumption of zero diffusion as well as the validity of the match with a finite geometry is quantified such that the obtained solutions can be rigorously applied to real problems. Furthermore, truncated series solutions, which are not novel, are used for comparison purposes. All quantities are nondimensional and the problem reduces to a dependence of five dimensionless parameters. The equations of elasticity are presented in the potential formulation where the shear potential is assumed to be nil due to the source being a gradient and the absence of boundaries. Nevertheless equivalent three-dimensional stresses are computed using the compressive potential and optimized using standard analytical optimization methods. An alternative algorithm for finding the critical points of the three-dimensional stress function is presented. Finally, a case study concerning the proton synchrotron booster dump is presented where the aforementioned analytical solutions are used and the

Cardiac CT and cardiac MRI - competitive or complementary for nuclear cardiology

International Nuclear Information System (INIS)

Moshage, W.

2004-01-01

In summary, cardiac computed tomography (CT) and cardiac magnetic resonance (MR) are two different technologies with distinct imaging properties that gain increasing importance in clinical cardiology. Even though images may look similar, the areas of application of CT and MR are quite different. Clinical applications of cardiac CT focus on on-invasive imaging of the coronary arteries. In this respect, the higher spatial resolution of cardiac CT constitutes a significant advantage as compared to MR and clinical results are superior. Clinical applications of cardiac MR, next to morphologic imaging of the heart, are most frequently found in the context of intra-and pericardial masses, complex congenital anomalies, and the assessment of left ventricular function (dobutamine) and perfusion (adenosine) under stress. The evaluation of the size and localization of myocardial necrosis, scars, and fibrosis gains increasing importance, for example in the workup of myocardial infarction, but also myocarditis and cardiomyopathies. In this respect, magnetic resonance imaging partly constitutes an alternative to nuclear medicine methods. Due to the lack of ionizing radiation and a relatively high spatial resolution, an increase of MR diagnostic procedures at the expense of nuclear medicine can be expected. (orig.)

Relationship between cardiac output and effective renal plasma flow in patients with cardiac disease

Energy Technology Data Exchange (ETDEWEB)

McGriffin, D; Tauxe, W N; Lewis, C; Karp, R; Mantle, J

1984-12-01

The relationship between effective renal plasma flow (ERPF) and cardiac output was examined in 46 patients (22 with congestive heart failure and 24 following cardiac surgical procedures) by simultaneously measuring the global ERPF by the single-injection method and cardiac output by the thermodilution method. Of the patients in the heart-failure group, 21 also had pulmonary artery end diastolic pressure (PAEDP) recorded at the same time. ERPF and cardiac output were found to be related by the regression equations: cardiac output = 2.08 + 0.0065 ERPF (r, 080), with a SE of estimate of 0.81 l/min. ERPF and PAEDP were related by the regression equation: PAEDP = 42.02 - 0.0675 ERPF (r, 0.86), with a SE of estimate of 5.5 mm Hg. ERPF may be a useful noninvasive method of estimating cardiac output if it is known that no intrinsic kidney disease is present, and if the error of 0.81 l/min (1 SE of estimate) is within the range of clinical usefulness. The error is principally attributable to the determination of cardiac output by the thermodilution method.

Hybrid options for treating cardiac disease.

Science.gov (United States)

Umakanthan, Ramanan; Leacche, Marzia; Zhao, David X; Gallion, Anna H; Mishra, Prabodh C; Byrne, John G

2011-01-01

The options for treating heart disease have greatly expanded during the course of the last 2 1/2 decades with the advent of hybrid technology. The hybrid option for treating cardiac disease implies using the technology of both interventional cardiology and cardiac surgery to treat cardiac disease. This rapidly developing technology has given rise to new and creative techniques to treat cardiac disease involving coronary artery disease, coronary artery disease and cardiac valve disease, and atrial fibrillation. It has also led to the establishment of new procedural suites called hybrid operating rooms that facilitate the integration of technologies of interventional cardiology catheterization laboratories with those of cardiac surgery operating rooms. The development of hybrid options for treating cardiac disease has also greatly augmented teamwork and collaboration between interventional cardiologists and cardiac surgeons. Copyright © 2011 Elsevier Inc. All rights reserved.

Cardiac CT

International Nuclear Information System (INIS)

Dewey, Marc

2011-01-01

Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

Cardiac CT

Energy Technology Data Exchange (ETDEWEB)

Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

2011-07-01

Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

Pulmonary toxicity and adjuvant effect of di-(2-exylhexyl phthalate in ovalbumin-immunized BALB/c mice.

Directory of Open Access Journals (Sweden)

Jing Guo

Full Text Available BACKGROUND: Asthma is a complex pulmonary inflammatory disease, which is characterized by airway hyperresponsiveness, variable airflow obstruction and inflammation in the airways. The majority of asthma is allergic asthma, which is a disease caused by type I hypersensitivity mediated by IgE. Exposures to a number of environmental chemicals are suspected to lead to asthma, one such pollutant is di-(2-ethylheyl phthalate (DEHP. DEHP is a manufactured chemical that is commonly added in plastic products to make them flexible. Epidemiological studies have revealed a positive association between DEHP exposure and asthma prevalence. METHODOLOGY/PRINCIPAL FINDINGS: The present study was aimed to determine the underlying role of DEHP exposure in airway reactivity, especially when combined with allergen exposure. The biomarkers include pulmonary histopathology, airway hyperresponsiveness (lung function, IgE, IL-4, IFN-γ and eosinophils. Healthy balb/c mice were randomly divided into eight exposure groups (n = 8 each: (1 saline control, (2 30 µg/(kg•d DEHP, (3 300 µg/(kg•d DEHP, (4 3000 µg/(kg•d DEHP, and (5 ovalbumin (OVA-sensitized group, (6 OVA-combined with 30 µg/(kg•d DEHP, (7 OVA-combined with 300 µg/(kg•d DEHP, and (8 OVA-combined with 3000 µg/(kg•d DEHP. Experimental tests were conducted after 52-day DEHP exposure and subsequently one week of challenge with aerosolized OVA. The principal findings include: (1 Strong postive associations exist between OVA-combined DEHP exposure and serum total IgE (T-IgE, as well as histological findings. These positive associations show a dose-dependent low dose sensitive effect of DEHP. (2 IL-4, eosinophil recruitment and lung function are also indicators for adjuvant effect of DEHP. CONCLUSIONS/SIGNIFICANCE: Our results suggest that except the significant changes of immunological and inflammatory biomarkers (T-IgE, IL-4, IFN-γ and eosinophils, the pulmonary histological (histopathological

Cardiac function in acute hypothyroidism

International Nuclear Information System (INIS)

Donaghue, K.; Hales, I.; Allwright, S.; Cooper, R.; Edwards, A.; Grant, S.; Morrow, A.; Wilmshurst, E.; Royal North Shore Hospital, Sydney

1985-01-01

It has been established that chronic hypothyroidism may affect cardiac function by several mechanisms. It is not known how long the patient has to be hypothyroid for cardiac involvement to develop. This study was undertaken to assess the effect of a short period of hypothyroidism (10 days) on cardiac function. Nine patients who had had total tyroidectomy, had received ablative radioiodine for thyroid cancer and were euthyroid on replacement therapy were studied while both euthyroid and hypothyroid. Cardiac assessment was performed by X-ray, ECG, echocardiography and gated blood-pool scans. After 10 days of hypothyroidisms, the left-ventricular ejection fraction failed to rise after exercise in 4 of the 9 patients studied, which was significant (P<0.002). No significant changes in cardiac size or function at rest were detected. This functional abnormality in the absence of any demonstrable change in cardiac size and the absence of pericardial effussion with normal basal function suggest that short periods of hypothyroidism may reduce cardiac reserve, mostly because of alterations in metabolic function. (orig.)

Nitrates for the prevention of cardiac morbidity and mortality in patients undergoing non-cardiac surgery.

Science.gov (United States)

Zhao, Na; Xu, Jin; Singh, Balwinder; Yu, Xuerong; Wu, Taixiang; Huang, Yuguang

2016-08-04

Cardiac complications are not uncommon in patients undergoing non-cardiac surgery, especially in patients with coronary artery disease (CAD) or at high risk of CAD. Perioperative cardiac complications can lead to mortality and morbidity, as well as higher costs for patient care. Nitrates, which are among the most commonly used cardiovascular drugs, perform the function of decreasing cardiac preload while improving cardiac blood perfusion. Sometimes, nitrates are administered to patients undergoing non-cardiac surgery to reduce the incidence of cardiac complications, especially for patients with CAD. However, their effects on patients' relevant outcomes remain controversial. • To assess effects of nitrates as compared with other interventions or placebo in reducing cardiac risk (such as death caused by cardiac factors, angina pectoris, acute myocardial infarction, acute heart failure and cardiac arrhythmia) in patients undergoing non-cardiac surgery.• To identify the influence of different routes and dosages of nitrates on patient outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Chinese BioMedical Database until June 2014. We also searched relevant conference abstracts of important anaesthesiology or cardiology scientific meetings, the database of ongoing trials and Google Scholar.We reran the search in January 2016. We added three potential new studies of interest to the list of 'Studies awaiting classification' and will incorporate them into our formal review findings for the review update. We included randomized controlled trials (RCTs) comparing nitrates versus no treatment, placebo or other pharmacological interventions in participants (15 years of age and older) undergoing non-cardiac surgery under any type of anaesthesia. We used standard methodological procedures as expected by Cochrane. Two review authors selected trials, extracted data from included studies and assessed risk of bias. We

Maternal cardiac metabolism in pregnancy

Science.gov (United States)

Liu, Laura X.; Arany, Zolt

2014-01-01

Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

{sup 123}I-MIBG imaging detects cardiac involvement and predicts cardiac events in Churg-Strauss syndrome

Energy Technology Data Exchange (ETDEWEB)

Horiguchi, Yoriko; Morita, Yukiko [National Hospital Organization Sagamihara National Hospital, Department of Cardiology, Sagamihara City, Kanagawa (Japan); Tsurikisawa, Naomi; Akiyama, Kazuo [National Hospital Organization Sagamihara National Hospital, Clinical Research Centre for Allergy and Rheumatology, Sagamihara City, Kanagawa (Japan)

2011-02-15

In Churg-Strauss syndrome (CSS) it is important to detect cardiac involvement, which predicts poor prognosis. This study evaluated whether {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy could detect cardiac damage and predict cardiac events in CSS. {sup 123}I-MIBG scintigraphy was performed in 28 patients with CSS, 12 of whom had cardiac involvement. The early and delayed heart to mediastinum ratio (early H/M and delayed H/M) and washout rate were calculated by using {sup 123}I-MIBG scintigraphy and compared with those in control subjects. Early H/M and delayed H/M were significantly lower and the washout rate was significantly higher in patients with cardiac involvement than in those without and in controls (early H/M, p = 0.0024, p = 0.0001; delayed H/M, p = 0.0002, p = 0.0001; washout rate, p = 0.0012, p = 0.0052 vs those without and vs controls, respectively). Accuracy for detecting cardiac involvement was 86% for delayed H/M and washout rate and 79% for early H/M and B-type natriuretic peptide (BNP). Kaplan-Meier analysis showed significantly lower cardiac event-free rates in patients with early H/M {<=} 2.18 and BNP > 21.8 pg/ml than those with early H/M > 2.18 and BNP {<=} 21.8 pg/ml (log-rank test p = 0.006). Cardiac sympathetic nerve function was damaged in CSS patients with cardiac involvement. {sup 123}I-MIBG scintigraphy was useful in detecting cardiac involvement and in predicting cardiac events. (orig.)

Cardiac carcinoid: tricuspid delayed hyperenhancement on cardiac 64-slice multidetector CT and magnetic resonance imaging.

LENUS (Irish Health Repository)

Martos, R

2012-02-01

INTRODUCTION: Carcinoid heart disease is a rare condition in adults. Its diagnosis can be easily missed in a patient presenting to a primary care setting. We revised the advantages of using coronary multidetector computed tomography (MDCT) and cardiac magnetic resonance imaging (MRI) in diagnosing this condition. MATERIALS AND METHODS: We studied a 65-year-old patient with carcinoid heart disease and right heart failure using transthoracic Doppler-echocardiogram, cardiac MDCT and MRI. Cardiac echocardiogram revealed marked thickening and retraction of the tricuspid leaflets with dilated right atrium and ventricle. Cardiac MDCT and MRI demonstrated fixation and retraction of the tricuspid leaflets with delayed contrast hyperenhancement of the tricuspid annulus. CONCLUSION: This case demonstrates fascinating imaging findings of cardiac carcinoid disease and highlights the increasing utility of contrast-enhanced MRI and cardiac MDCT in the diagnosis of this interesting condition.

Cardiac retransplantation is an efficacious therapy for primary cardiac allograft failure

Directory of Open Access Journals (Sweden)

Acker Michael A

2008-05-01

Full Text Available Abstract Background Although orthotopic heart transplantation has been an effective treatment for end-stage heart failure, the incidence of allograft failure has increased, necessitating treatment options. Cardiac retransplantation remains the only viable long-term solution for end-stage cardiac allograft failure. Given the limited number of available donor hearts, the long term results of this treatment option need to be evaluated. Methods 709 heart transplants were performed over a 20 year period at our institution. Repeat cardiac transplantation was performed in 15 patients (2.1%. A retrospective analysis was performed to determine the efficacy of cardiac retransplantation. Variables investigated included: 1 yr and 5 yr survival, length of hospitalization, post-operative complications, allograft failure, recipient and donor demographics, renal function, allograft ischemic time, UNOS listing status, blood group, allograft rejection, and hemodynamic function. Results Etiology of primary graft failure included transplant arteriopathy (n = 10, acute rejection (n = 3, hyperacute rejection (n = 1, and a post-transplant diagnosis of metastatic melanoma in the donor (n = 1. Mean age at retransplantation was 45.5 ± 9.7 years. 1 and 5 year survival for retransplantation were 86.6% and 71.4% respectively, as compared to 90.9% and 79.1% for primary transplantation. Mean ejection fraction was 67.3 ± 12.2% at a mean follow-up of 32.6 ± 18.5 mos post-retransplant; follow-up biopsy demonstrated either ISHLT grade 1A or 0 rejection (77.5 ± 95.7 mos post-transplant. Conclusion Cardiac retransplantation is an efficacious treatment strategy for cardiac allograft failure.

Cardiac echinococcosis

Directory of Open Access Journals (Sweden)

Ivanović-Krstić Branislava A.

2002-01-01

Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

A new automated technique for the reconstitution of hydrophobic proteins into planar bilayer membranes. Studies of human recombinant uncoupling protein 1

Czech Academy of Sciences Publication Activity Database

Beck, V.; Jabůrek, Martin; Breen, E. P.; Porter, R. K.; Ježek, Petr; Pohl, E. E.

2006-01-01

Roč. 1757, č. 5-6 (2006), s. 474-479 ISSN 0005-2728 R&D Projects: GA AV ČR(CZ) IAA5011106; GA MŠk(CZ) 1P05ME794 Grant - others:Deutsche Forschungsgemeinschaft(DE) Po-524/2-2; Deutsche Forschungsgemeinschaft(DE) 436 TSE 113/44/0-1 Institutional research plan: CEZ:AV0Z50110509 Keywords : artificial membranes * uncoupling protein-1 Subject RIV: BO - Biophysics Impact factor: 4.237, year: 2006

Nuclear cardiac

International Nuclear Information System (INIS)

Slutsky, R.; Ashburn, W.L.

1982-01-01

The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques

Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration

Directory of Open Access Journals (Sweden)

A.T. Pettersson-Klein

2018-03-01

Full Text Available Objective: The peroxisome proliferator-activated receptor-γ coactivator-1α1 (PGC-1α1 regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1α1 activation is potentially beneficial for systemic metabolism. Pharmacological PGC-1α1 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-1α1 is a transcriptional coactivator with no known ligand-binding properties. While, PGC-1α1 activation is regulated by several mechanisms, protein stabilization is a crucial limiting step due to its short half-life under unstimulated conditions. Methods: We designed a cell-based high-throughput screening system to identify PGC-1α1 protein stabilizers. Positive hits were tested for their ability to induce endogenous PGC-1α1 protein accumulation and activate target gene expression in brown adipocytes. Select compounds were analyzed for their effects on global gene expression and cellular respiration in adipocytes. Results: Among 7,040 compounds screened, we highlight four small molecules with high activity as measured by: PGC-1α1 protein accumulation, target gene expression, and uncoupled mitochondrial respiration in brown adipocytes. Conclusions: We identify compounds that induce PGC-1α1 protein accumulation and show that this increases uncoupled respiration in brown adipocytes. This screening platform establishes the foundation for a new class of therapeutics with potential use in obesity and associated disorders. Keywords: Small molecule screening, PGC-1a, PGC-1alpha, PGC-1alpha1, Protein stabilization, UCP1, Mitochondrial respiration, Brown adipose tissue

Discovery and progress of direct cardiac reprogramming.

Science.gov (United States)

Kojima, Hidenori; Ieda, Masaki

2017-06-01

Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs). Following our first report of cardiac reprogramming, many researchers, including ourselves, demonstrated an improvement in cardiac reprogramming efficiency, in vivo direct cardiac reprogramming for heart regeneration, and cardiac reprogramming in human cells. However, cardiac reprogramming in human cells and adult fibroblasts remains inefficient, and further efforts are needed. We believe that future research elucidating epigenetic barriers and molecular mechanisms of direct cardiac reprogramming will improve the reprogramming efficiency, and that this new technology has great potential for clinical applications.

Optimal Technique in Cardiac Anesthesia Recovery

OpenAIRE

Svircevic, V.

2014-01-01

The aim of this thesis is to evaluate fast-track cardiac anesthesia techniques and investigate their impact on postoperative mortality, morbidity and quality of life. The following topics will be discussed in the thesis. (1.) Is fast track cardiac anesthesia a safe technique for cardiac surgery? (2.) Does thoracic epidural anesthesia have an effect on mortality and morbidity after cardiac surgery? (3.) Does thoracic epidural anesthesia have an effect on quality of life after cardiac surgery? ...

Uncoupling proteins (UCP) in unicellular eukaryotes: true UCPs or UCP1-like acting proteins?

Science.gov (United States)

Luévano-Martínez, Luis Alberto

2012-04-05

Uncoupling proteins belong to the superfamily of mitochondrial anion carriers. They are apparently present throughout the Eukarya domain in which only some members have an established physiological function, i.e. UCP1 from brown adipose tissue is involved in non-shivering thermogenesis. However, the proteins responsible for the phenotype observed in unicellular organisms have not been characterized. In this report we analyzed functional evidence concerning unicellular UCPs and found that true UCPs are restricted to some taxonomical groups while proteins conferring a UCP1-like phenotype to fungi and most protists are the result of a promiscuous activity exerted by other mitochondrial anion carriers. We describe a possible evolutionary route followed by these proteins by which they acquire this promiscuous mechanism. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

An integrated bioimpedance—ECG gating technique for respiratory and cardiac motion compensation in cardiac PET

International Nuclear Information System (INIS)

Koivumäki, Tuomas; Nekolla, Stephan G; Fürst, Sebastian; Loher, Simone; Schwaiger, Markus; Vauhkonen, Marko; Hakulinen, Mikko A

2014-01-01

Respiratory motion may degrade image quality in cardiac PET imaging. Since cardiac PET studies often involve cardiac gating by ECG, a separate respiratory monitoring system is required increasing the logistic complexity of the examination, in case respiratory gating is also needed. Thus, we investigated the simultaneous acquisition of both respiratory and cardiac gating signals using II limb lead mimicking electrode configuration during cardiac PET scans of 11 patients. In addition to conventional static and ECG-gated images, bioimpedance technique was utilized to generate respiratory- and dual-gated images. The ability of the bioimpedance technique to monitor intrathoracic respiratory motion was assessed estimating cardiac displacement between end-inspiration and -expiration. The relevance of dual gating was evaluated in left ventricular volume and myocardial wall thickness measurements. An average 7.6  ±  3.3 mm respiratory motion was observed in the study population. Dual gating showed a small but significant increase (4 ml, p = 0.042) in left ventricular myocardial volume compared to plain cardiac gating. In addition, a thinner myocardial wall was observed in dual-gated images (9.3  ±  1.3 mm) compared to cardiac-gated images (11.3  ±  1.3 mm, p = 0.003). This study shows the feasibility of bioimpedance measurements for dual gating in a clinical setting. The method enables simultaneous acquisition of respiratory and cardiac gating signals using a single device with standard ECG electrodes. (paper)

Antioxidant activity by a synergy of redox-sensitive mitochondrial phospholipase A2 and uncoupling protein-2 in lung and spleen

Czech Academy of Sciences Publication Activity Database

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

2013-01-01

Roč. 45, č. 4 (2013), s. 816-825 ISSN 1357-2725 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP303/11/P320; GA MŠk(CZ) ME09018 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : mitochondrial uncoupling protein UCP2 * mitochondrial phospholipase A(2) isoform gamma * mitochondrial oxidative stress attenuation * fatty acid * antioxidant mechanism Subject RIV: ED - Physiology Impact factor: 4.240, year: 2013

Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies

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Georges N. Kanaan

2018-04-01

Full Text Available Glutaredoxin 2 (GRX2, a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies. Keywords: Human heart, Mitochondria, Oxidative stress, Redox, Cardiac metabolism, Cardiac hypertrophy

Pseudo-reorganization of language cortical function at fMR imaging: a consequence of tumor-induced neurovascular uncoupling.

Science.gov (United States)

Ulmer, John L; Krouwer, Hendrikus G; Mueller, Wade M; Ugurel, M Sahin; Kocak, Mehmet; Mark, Leighton P

2003-02-01

A left-handed patient with a grade II left frontal lobe astrocytoma had spontaneous seizures causing speech arrest and uncontrolled right upper extremity movements. Word-generation functional MR (fMR) imaging showed activity nearly exclusively in the right inferior frontal gyrus. The clinical history of the speech arrest and the intraoperative mapping proved left-hemisphere language dominance. Tumor involvement of the left inferior frontal gyrus caused uncoupling of the blood oxygenation level-dependent (BOLD) and neuronal response, leading to the erroneous fMR imaging appearance of right-hemisphere language dominance. Discrepancies between BOLD and intraoperative mapping in areas near lesions illustrate the complementary nature of these techniques.

Hydrodynamical simulations of coupled and uncoupled quintessence models - II. Galaxy clusters

Science.gov (United States)

Carlesi, Edoardo; Knebe, Alexander; Lewis, Geraint F.; Yepes, Gustavo

2014-04-01

We study the z = 0 properties of clusters (and large groups) of galaxies within the context of interacting and non-interacting quintessence cosmological models, using a series of adiabatic SPH simulations. Initially, we examine the average properties of groups and clusters, quantifying their differences in ΛCold Dark Matter (ΛCDM), uncoupled Dark Energy (uDE) and coupled Dark Energy (cDE) cosmologies. In particular, we focus upon radial profiles of the gas density, temperature and pressure, and we also investigate how the standard hydrodynamic equilibrium hypothesis holds in quintessence cosmologies. While we are able to confirm previous results about the distribution of baryons, we also find that the main discrepancy (with differences up to 20 per cent) can be seen in cluster pressure profiles. We then switch attention to individual structures, mapping each halo in quintessence cosmology to its ΛCDM counterpart. We are able to identify a series of small correlations between the coupling in the dark sector and halo spin, triaxiality and virialization ratio. When looking at spin and virialization of dark matter haloes, we find a weak (5 per cent) but systematic deviation in fifth force scenarios from ΛCDM.

Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation.

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Emil D Bartels

Full Text Available Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and beta-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP; the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease.

Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload

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Sujith Dassanayaka

2018-07-01

Full Text Available Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2. An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesis

Biosynthesis of cardiac natriuretic peptides

DEFF Research Database (Denmark)

Goetze, Jens Peter

2010-01-01

Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...... peptides has only been elucidated during the last decade. The cellular synthesis including amino acid modifications and proteolytic cleavages has proven considerably more complex than initially perceived. Consequently, the elimination phase of the peptide products in circulation is not yet well....... An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

Expression of genes encoding F-1-ATPase results in uncoupling of glycolysis from biomass production in Lactococcus lactis

DEFF Research Database (Denmark)

Købmann, Brian Jensen; Solem, Christian; Pedersen, M.B.

2002-01-01

of the genes encoding F-1-ATPase was found to decrease the intracellular energy level and resulted in a decrease in the growth rate. The yield of biomass also decreased, which showed that the incorporated F-1-ATPase activity caused glycolysis to be uncoupled from biomass production. The increase in ATPase...... threefold in nongrowing cells resuspended in buffer, but in steadily growing cells no increase in flux was observed. The latter result shows that glycolysis occurs close to its maximal capacity and indicates that control of the glycolytic flux under these conditions resides in the glycolytic reactions...

Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.

Science.gov (United States)

Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K

2018-02-27

Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases

Evaluation of respiratory and cardiac motion correction schemes in dual gated PET/CT cardiac imaging

Energy Technology Data Exchange (ETDEWEB)

Lamare, F., E-mail: frederic.lamare@chu-bordeaux.fr; Fernandez, P. [Univ. Bordeaux, INCIA, UMR 5287, F-33400 Talence (France); CNRS, INCIA, UMR 5287, F-33400 Talence (France); Service de Médecine Nucléaire, Hôpital Pellegrin, CHU de Bordeaux, 33076 Bordeaux (France); Le Maitre, A.; Visvikis, D. [INSERM, UMR1101, LaTIM, Université de Bretagne Occidentale, 29609 Brest (France); Dawood, M.; Schäfers, K. P. [European Institute for Molecular Imaging, University of Münster, Mendelstr. 11, 48149 Münster (Germany); Rimoldi, O. E. [Vita-Salute University and Scientific Institute San Raffaele, Milan, Italy and CNR Istituto di Bioimmagini e Fisiologia Molecolare, Milan (Italy)

2014-07-15

Purpose: Cardiac imaging suffers from both respiratory and cardiac motion. One of the proposed solutions involves double gated acquisitions. Although such an approach may lead to both respiratory and cardiac motion compensation there are issues associated with (a) the combination of data from cardiac and respiratory motion bins, and (b) poor statistical quality images as a result of using only part of the acquired data. The main objective of this work was to evaluate different schemes of combining binned data in order to identify the best strategy to reconstruct motion free cardiac images from dual gated positron emission tomography (PET) acquisitions. Methods: A digital phantom study as well as seven human studies were used in this evaluation. PET data were acquired in list mode (LM). A real-time position management system and an electrocardiogram device were used to provide the respiratory and cardiac motion triggers registered within the LM file. Acquired data were subsequently binned considering four and six cardiac gates, or the diastole only in combination with eight respiratory amplitude gates. PET images were corrected for attenuation, but no randoms nor scatter corrections were included. Reconstructed images from each of the bins considered above were subsequently used in combination with an affine or an elastic registration algorithm to derive transformation parameters allowing the combination of all acquired data in a particular position in the cardiac and respiratory cycles. Images were assessed in terms of signal-to-noise ratio (SNR), contrast, image profile, coefficient-of-variation (COV), and relative difference of the recovered activity concentration. Results: Regardless of the considered motion compensation strategy, the nonrigid motion model performed better than the affine model, leading to higher SNR and contrast combined with a lower COV. Nevertheless, when compensating for respiration only, no statistically significant differences were

Effects of local cardiac denervation on cardiac innervation and ventricular arrhythmia after chronic myocardial infarction.

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Xudong Liu

Full Text Available Modulation of the autonomic nervous system (ANS has already been demonstrated to display antiarrhythmic effects in patients and animals with MI. In this study, we investigated whether local cardiac denervation has any beneficial effects on ventricular electrical stability and cardiac function in the chronic phase of MI.Twenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. Four weeks after local cardiac denervation, LSG stimulation was used to induce VPCs and VAs. The ventricular fibrillation threshold (VFT and the incidence of inducible VPCs were measured with electrophysiological protocol. Cardiac innervation was determined with immunohistochemical staining of growth associated protein-43 (GAP43 and tyrosine hydroxylase (TH. The global cardiac and regional ventricular function was evaluated with doppler echocardiography in this study.Four weeks after operation, the incidence of inducible VPC and VF in MI-ablation group were significantly reduced compared to the MI dogs (p<0.05. Moreover, local cardiac denervation significantly improved VFT in the infarcted border zone (p<0.05. The densities of GAP43 and TH-positive nerve fibers in the infarcted border zone in the MI-ablation group were lower than those in the MI group (p<0.05. However, the local cardiac denervation did not significantly improve cardiac function in the chronic phase of MI, determined by the left ventricle diameter (LV, left atrial diameter (LA, ejection fraction (EF.Summarily, in the chronic phase of MI, local cardiac denervation reduces the ventricular electrical instability, and attenuates spatial heterogeneity of sympathetic nerve reconstruction. Our study suggests that this methodology might decrease malignant ventricular arrhythmia in chronic MI, and has a great potential for clinical application.

Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

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Quan He

2014-01-01

Full Text Available Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.

Boosters and barriers for direct cardiac reprogramming.

Science.gov (United States)

Talkhabi, Mahmood; Zonooz, Elmira Rezaei; Baharvand, Hossein

2017-06-01

Heart disease is currently the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths. Recently, a promising and alchemy-like strategy has been developed called direct cardiac reprogramming, which directly converts somatic cells such as fibroblasts to cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs. The first in vitro cardiac reprogramming study, mediated by cardiac transcription factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an adequate number of fully reprogrammed, functional iCMs. As a result, numerous combinations of cardiac TFs exist for direct cardiac reprogramming of mouse and human fibroblasts. However, the efficiency of direct cardiac reprogramming remains low. Recently, a number of cellular and molecular mechanisms have been identified to increase the efficiency of direct cardiac reprogramming and the quality of iCMs. For example, microgrooved substrate, cardiogenic growth factors [VEGF, FGF, BMP4 and Activin A], and an appropriate stoichiometry of TFs boost the direct cardiac reprogramming. On the other hand, serum, TGFβ signaling, activators of epithelial to mesenchymal transition, and some epigenetic factors (Bmi1 and Ezh2) are barriers for direct cardiac reprogramming. Manipulating these mechanisms by the application of boosters and removing barriers can increase the efficiency of direct cardiac reprogramming and possibly make iCMs reliable for cell-based therapy or other potential applications. In this review, we summarize the latest trends in cardiac TF- or miRNA-based direct cardiac reprogramming and comprehensively discuses all molecular and cellular boosters and barriers affecting direct cardiac reprogramming. Copyright © 2017 Elsevier Inc. All rights reserved.

The N Terminus of Sarcolipin Plays an Important Role in Uncoupling Sarco-endoplasmic Reticulum Ca²⁺-ATPase (SERCA) ATP Hydrolysis from Ca²⁺ Transport

DEFF Research Database (Denmark)

Sahoo, Sanjaya K; Shaikh, Sana A; Sopariwala, Danesh H

2015-01-01

to bind SERCA throughout its kinetic cycle and promotes uncoupling of Ca(2+) transport from ATP hydrolysis. To determine the structural regions of SLN that mediate uncoupling of SERCA, we employed mutagenesis and generated chimeras of PLB and SLN. In this study we demonstrate that deletion of SLN N....... Interestingly, transfer of the PLB cytosolic domain to the SLN transmembrane (TM) and luminal tail causes the chimeric protein to lose SLN-like function. Further introduction of the PLB TM region into this chimera resulted in conversion to full PLB-like function. We also found that swapping PLB N and C termini...... with those from SLN caused the resulting chimera to acquire SLN-like function. Swapping the C terminus alone was not sufficient for this conversion. These results suggest that domains can be switched between SLN and PLB without losing the ability to regulate SERCA activity; however, the resulting chimeras...

Determination of di(2-ethylhexyl phthalate in plastic medical devices

Directory of Open Access Journals (Sweden)

Kostić Ivana S.

2016-01-01

Full Text Available The presence of DEHP in dialysis and infusion sets for peritoneal dialysis and parenteral nutrition, which are made of PVC and other plastic polymeric materials, were investigated. Phthalate determination was carried out by gas chromatography - mass spectrometry method (GC-MS. The results showed that the peritoneal dialysis set (bag and tubing made of PVC contains DEHP in significant amount, about 31 - 34%. Solution for peritoneal dialysis which was stored in the investigated PVC bag, contains low amount of DEHP, about 3.72 μg dm-3. Infusion bottles which are made of LDPE, also contain DEHP but in lower amount than PVC bags. LDPE bottle for packaging physiological saline solution (0.9% NaCl showed higher amount of DEHP than LDPE bottle for packaging Ringer’s solution. In contrast, solution stored in bottle with lower DEHP level, i.e. Ringer’s solution contained about three times higher concentration of DEHP than physiological saline solution stored in bottle with higher DEHP level. Concentrations of DEHP in Ringer’s solution and physiological saline solution are 17.30 and 5.83 μg dm-3, respectively. The obtained values are under estimated upper-bound dose of DEHP received by adult patients undergoing procedures of peritoneal dialysis and parenteral nutrition. [Projekat Ministarstva nauke Republike Srbije, III 41018

Activating omega-6 polyunsaturated fatty acids and inhibitory purine nucleotides are high affinity ligands for novel mitochondrial uncoupling proteins UCP2 and UCP3

Czech Academy of Sciences Publication Activity Database

Žáčková, Markéta; Škobisová, Eva; Urbánková, Eva; Ježek, Petr

2003-01-01

Roč. 278, č. 23 (2003), s. 20761-20769 ISSN 0021-9258 R&D Projects: GA AV ČR IAA5011106; GA ČR GA301/02/1215; GA MŠk ME 389 Institutional research plan: CEZ:AV0Z5011922 Keywords : uncoupling protein-2 * polyunsaturated fatty acids * recombinant yeast expression Subject RIV: CE - Biochemistry Impact factor: 6.482, year: 2003

Imaging in cardiac mass lesions

International Nuclear Information System (INIS)

Mundinger, A.; Gruber, H.P.; Dinkel, E.; Geibel, A.; Beck, A.; Wimmer, B.; Schlosser, V.

1992-01-01

In 26 patients with cardiac mass lesions confirmed by surgery, diagnostic imaging was performed preoperatively by means of two-dimensional echocardiography (26 patients), angiography (12 patients), correlative computed tomography (CT, 8 patients), and magnetic resonance imaging (MRI, 3 patients). Two-dimensional echocardiography correctly identified the cardiac masses in all patients. Angiography missed two of 12 cardiac masses; CT missed one of eight. MRI identified three of three cardiac masses. Although the sensitivity of two-dimensional echocardiography was high (100%), all methods lacked specificity. None of the methods allowed differentiation between myxoma (n=13) and thrombus (n=7). Malignancy of the lesions was successfully predicted by noninvasive imaging methods in all six patients. However, CT and MRI provided additional information concerning cardiac mural infiltration, pericardial involvement, and extracardiac tumor extension, and should be integrated within a preoperative imaging strategy. Thus two-dimensional echocardiography is the method of choice for primary assessment of patients with suspected cardiac masses. Further preoperative imaging by CT or MRI can be limited to patients with malignancies suspected on the grounds of pericardial effusion or other clinical results. (author)

Reduced Right Ventricular Function Predicts Long-Term Cardiac Re-Hospitalization after Cardiac Surgery.

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Leela K Lella

Full Text Available The significance of right ventricular ejection fraction (RVEF, independent of left ventricular ejection fraction (LVEF, following isolated coronary artery bypass grafting (CABG and valve procedures remains unknown. The aim of this study is to examine the significance of abnormal RVEF by cardiac magnetic resonance (CMR, independent of LVEF in predicting outcomes of patients undergoing isolated CABG and valve surgery.From 2007 to 2009, 109 consecutive patients (mean age, 66 years; 38% female were referred for pre-operative CMR. Abnormal RVEF and LVEF were considered 30 days outcomes included, cardiac re-hospitalization, worsening congestive heart failure and mortality. Mean clinical follow up was 14 months.Forty-eight patients had reduced RVEF (mean 25% and 61 patients had normal RVEF (mean 50% (p<0.001. Fifty-four patients had reduced LVEF (mean 30% and 55 patients had normal LVEF (mean 59% (p<0.001. Patients with reduced RVEF had a higher incidence of long-term cardiac re-hospitalization vs. patients with normal RVEF (31% vs.13%, p<0.05. Abnormal RVEF was a predictor for long-term cardiac re-hospitalization (HR 3.01 [CI 1.5-7.9], p<0.03. Reduced LVEF did not influence long-term cardiac re-hospitalization.Abnormal RVEF is a stronger predictor for long-term cardiac re-hospitalization than abnormal LVEF in patients undergoing isolated CABG and valve procedures.

The Influence of Cardiac Risk Factor Burden on Cardiac Stress Test Outcomes.

Science.gov (United States)

Schrock, Jon W; Li, Morgan; Orazulike, Chidubem; Emerman, Charles L

2011-06-01

Chest pain is the most common admission diagnosis for observation unit patients. These patients often undergo cardiac stress testing to further risk stratify for coronary artery disease (CAD). The decision of whom to stress is currently based on clinical judgment. We sought to determine the influence of cardiac risk factor burden on cardiac stress test outcome for patients tested from an observation unit, inpatient or outpatient setting. We performed a retrospective observational cohort study for all patients undergoing stress testing in our institution from June 2006 through July 2007. Cardiac risk factors were collected at the time of stress testing. Risk factors were evaluated in a summative fashion using multivariate regression adjusting for age and known coronary artery disease. The model was tested for goodness of fit and collinearity and the c statistic was calculated using the receiver operating curve. A total of 4026 subjects were included for analysis of which 22% had known CAD. The rates of positive outcome were 89 (12.0%), 95 (12.6%), and 343 (16.9%) for the OU, outpatients, and hospitalized patients respectively. While the odds of a positive test outcome increased for additional cardiac risk factors, ROC curve analysis indicates that simply adding the number of risk factors does not add significant diagnostic value. Hospitalized patients were more likely to have a positive stress test, OR 1.41 (1.10 - 1.81). Our study does not support basing the decision to perform a stress test on the number of cardiac risk factors.

Diethyl hexyl phthalate-induced changes in insulin signaling molecules and the protective role of antioxidant vitamins in gastrocnemius muscle of adult male rat

International Nuclear Information System (INIS)

Srinivasan, Chinnapaiyan; Khan, Adam Ismail; Balaji, Venkataraman; Selvaraj, Jayaraman; Balasubramanian, Karundevi

2011-01-01

Diethyl hexyl phthalate (DEHP) is an endocrine disruptor, it influences various organ systems in human beings and experimental animals. DEHP reduced the serum testosterone and increased the blood glucose, estradiol, T 3 and T 4 in rats. However, the effect of DEHP on insulin signaling and glucose oxidation in skeletal muscle is not known. Adult male albino rats were divided into four groups: Group I: Control; Groups II and III: DEHP treated (dissolved in olive oil at a dose of 10 and 100 mg/kg body weight, respectively, once daily through gastric intubation for 30 days); and Group IV: DEHP (100 mg/kg body weight) plus vitamins E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubation for 30 days. On completion of treatment, animals were euthanized and perfused (whole body); gastrocnemius muscle was dissected out and subjected to assessment of various parameters. DEHP treatment increased the H 2 O 2 , hydroxyl radical levels and lipid peroxidation which disrupt the membrane integrity and insulin receptor. DEHP impaired the insulin signal transduction, glucose uptake and oxidation through decreased expression of plasma membrane GLUT4, which may partly be responsible for the elevation of fasting blood glucose level. The present study suggests that DEHP exposure affects glucose oxidation in skeletal muscle and is mediated through enhanced lipid peroxidation, impaired insulin signaling and GLUT4 expression in plasma membrane. Antioxidant vitamins (C and E) have a protective role against the adverse effect of DEHP. -- Highlights: ► DEHP treatment significantly decreased serum insulin and testosterone levels. ► Increased ROS and decreased glucose uptake were observed in DEHP treated animals. ► Impaired insulin signaling in gastrocnemius muscle was observed in DEHP treatment. ► Vitamins C and E alter ROS, glucose uptake, oxidation and insulin signaling molecules.

Cardiac Arrest: MedlinePlus Health Topic

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... Handouts Cardiac arrest (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Cardiac Arrest updates ... this? GO MEDICAL ENCYCLOPEDIA Cardiac arrest Related Health Topics Arrhythmia CPR Pacemakers and Implantable Defibrillators National Institutes ...

Trends in Cardiac Pacemaker Batteries

Directory of Open Access Journals (Sweden)

Venkateswara Sarma Mallela

2004-10-01

Full Text Available Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads/electrodes have reduced energy requirements by two orders of magnitude. Micro-electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality, reliability, and longevity. It is reported that about 600,000 pacemakers are implanted each year worldwide and the total number of people with various types of implanted pacemaker has already crossed 3 million. A cardiac pacemaker uses half of its battery power for cardiac stimulation and the other half for housekeeping tasks such as monitoring and data logging. The first implanted cardiac pacemaker used nickel-cadmium rechargeable battery, later on zinc-mercury battery was developed and used which lasted for over 2 years. Lithium iodine battery invented and used by Wilson Greatbatch and his team in 1972 made the real impact to implantable cardiac pacemakers. This battery lasts for about 10 years and even today is the power source for many manufacturers of cardiac pacemakers. This paper briefly reviews various developments of battery technologies since the inception of cardiac pacemaker and presents the alternative to lithium iodine battery for the near future.

Maternal di-(2-ethylhexyl) phthalate exposure during pregnancy causes fetal growth restriction in a stage-specific but gender-independent manner.

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Shen, Ru; Zhao, Ling-Li; Yu, Zhen; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Xu, De-Xiang

2017-01-01

Di (2-ethylhexyl) phthalate (DEHP) is male developmental toxicant that impairs testis development with reduced anogenital distance. The present study aimed to investigate whether maternal DEHP exposure during pregnancy causes intrauterine growth restriction (IUGR) in a gender-specific manner and to identify the critical window of DEHP-induced fetal IUGR. Pregnant mice were administered with DEHP (0, 50 or 200mg/kg) by gavage. Fetal IUGR was observed not only in males but also in females when litters were exposed to DEHP on gestational day (GD)0-GD17. Interestingly, fetal weight and crown-rump length were reduced, markedly in dams with DEHP on GD13-GD17, slightly in dams with on GD7-GD12, but not in dams with on GD0-GD6. Further analysis showed that maternal DEHP exposure on GD7-GD12 inhibited cell proliferation, lowered placental weight, and reduced blood sinusoid area in placental labyrinth layer. These results suggest that maternal DEHP exposure induces IUGR in a stage-specific but gender-independent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiac radiology: centenary review.

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de Roos, Albert; Higgins, Charles B

2014-11-01

During the past century, cardiac imaging technologies have revolutionized the diagnosis and treatment of acquired and congenital heart disease. Many important contributions to the field of cardiac imaging were initially reported in Radiology. The field developed from the early stages of cardiac imaging, including the use of coronary x-ray angiography and roentgen kymography, to nowadays the widely used echocardiographic, nuclear medicine, cardiac computed tomographic (CT), and magnetic resonance (MR) applications. It is surprising how many of these techniques were not recognized for their potential during their early inception. Some techniques were described in the literature but required many years to enter the clinical arena and presently continue to expand in terms of clinical application. The application of various CT and MR contrast agents for the diagnosis of myocardial ischemia is a case in point, as the utility of contrast agents continues to expand the noninvasive characterization of myocardium. The history of cardiac imaging has included a continuous process of advances in our understanding of the anatomy and physiology of the cardiovascular system, along with advances in imaging technology that continue to the present day.

A SNP uncoupling Mina expression from the TGFβ signaling pathway.

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Lian, Shang L; Mihi, Belgacem; Koyanagi, Madoka; Nakayama, Toshinori; Bix, Mark

2018-03-01

Mina is a JmjC family 2-oxoglutarate oxygenase with pleiotropic roles in cell proliferation, cancer, T cell differentiation, pulmonary inflammation, and intestinal parasite expulsion. Although Mina expression varies according to cell-type, developmental stage and activation state, its transcriptional regulation is poorly understood. Across inbred mouse strains, Mina protein level exhibits a bimodal distribution, correlating with inheritance of a biallelic haplotype block comprising 21 promoter/intron 1-region SNPs. We previously showed that heritable differences in Mina protein level are transcriptionally regulated. Accordingly, we decided to test the hypothesis that at least one of the promoter/intron 1-region SNPs perturbs a Mina cis-regulatory element (CRE). Here, we have comprehensively scanned for CREs across a Mina locus-spanning 26-kilobase genomic interval. We discovered 8 potential CREs and functionally validated 4 of these, the strongest of which (E2), residing in intron 1, contained a SNP whose BALB/c-but not C57Bl/6 allele-abolished both Smad3 binding and transforming growth factor beta (TGFβ) responsiveness. Our results demonstrate the TGFβ signaling pathway plays a critical role in regulating Mina expression and SNP rs4191790 controls heritable variation in Mina expression level, raising important questions regarding the evolution of an allele that uncouples Mina expression from the TGFβ signaling pathway. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

Energy Technology Data Exchange (ETDEWEB)

Hannon, Patrick R., E-mail: phannon2@illinois.edu; Brannick, Katherine E., E-mail: kbran@illinois.edu; Wang, Wei, E-mail: Wei.Wang2@covance.com; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

2015-04-01

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

Energy Technology Data Exchange (ETDEWEB)

Wang, Wei, E-mail: weiwang2@illinois.edu; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbasava2@illinois.edu; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

2012-01-15

Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 31–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100 μg/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1 mM). During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1 mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10 μg/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5 mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. -- Highlights: ► DEHP inhibits growth and increases reactive oxygen species in ovarian antral follicles in vitro. ► NAC rescues the effects of DEHP on the growth and reactive oxygen species levels in follicles. ► DEHP decreases the expression and activity of Cu/Zn superoxide dismutase, which can be rescued by NAC, in antral

Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

International Nuclear Information System (INIS)

Hannon, Patrick R.; Brannick, Katherine E.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

2015-01-01

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

The impact of obesity in the cardiac lipidome and its consequences in the cardiac damage observed in obese rats.

Science.gov (United States)

Marín-Royo, Gema; Martínez-Martínez, Ernesto; Gutiérrez, Beatriz; Jurado-López, Raquel; Gallardo, Isabel; Montero, Olimpio; Bartolomé, Mª Visitación; Román, José Alberto San; Salaices, Mercedes; Nieto, María Luisa; Cachofeiro, Victoria

To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O 2 ), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levels. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

[Cardiac cachexia].

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Miján, Alberto; Martín, Elvira; de Mateo, Beatriz

2006-05-01

Chronic heart failure (CHF), especially affecting the right heart, frequently leads to malnutrition. If the latter is severe and is combined to other factors, it may lead to cardiac cachexia. This one is associated to increased mortality and lower survival of patients suffering from it. The causes of cardiac cachexia are diverse, generally associated to maintenance of a negative energy balance, with increasing evidence of its multifactorial origin. Neurohumoral, inflammatory, immunological, and metabolic factors, among others, are superimposed in the patient with CHF, leading to involvement and deterioration of several organs and systems, since this condition affects both lean (or active cellular) mass and adipose and bone tissue osteoporosis. Among all, the most pronounced deterioration may be seen at skeletal muscle tissue, at both structural and functional levels, the heart not being spared. As for treatment, it should be based on available scientific evidence. Assessment of nutritional status of any patient with CHF is a must, with the requirement of nutritional intervention in case of malnutrition. In this situation, especially if accompanied by cardiac cachexia, it is required to modify energy intake and oral diet quality, and to consider the indication of specific complementary or alternative artificial nutrition. Besides, the causal relationship of the beneficial role of moderate physical exertion is increasing, as well as modulation of metabolic and inflammatory impairments observed in cardiac cachexia with several drugs, leading to a favorable functional and structural response in CHF patients.

Cardiac Catheterization (For Kids)

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... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Cardiac Catheterization KidsHealth / For Kids / Cardiac Catheterization What's in this article? What Is ...

Imaging in blunt cardiac injury: Computed tomographic findings in cardiac contusion and associated injuries.

Science.gov (United States)

Hammer, Mark M; Raptis, Demetrios A; Cummings, Kristopher W; Mellnick, Vincent M; Bhalla, Sanjeev; Schuerer, Douglas J; Raptis, Constantine A

2016-05-01

Blunt cardiac injury (BCI) may manifest as cardiac contusion or, more rarely, as pericardial or myocardial rupture. Computed tomography (CT) is performed in the vast majority of blunt trauma patients, but the imaging features of cardiac contusion are not well described. To evaluate CT findings and associated injuries in patients with clinically diagnosed BCI. We identified 42 patients with blunt cardiac injury from our institution's electronic medical record. Clinical parameters, echocardiography results, and laboratory tests were recorded. Two blinded reviewers analyzed chest CTs performed in these patients for myocardial hypoenhancement and associated injuries. CT findings of severe thoracic trauma are commonly present in patients with severe BCI; 82% of patients with ECG, cardiac enzyme, and echocardiographic evidence of BCI had abnormalities of the heart or pericardium on CT; 73% had anterior rib fractures, and 64% had pulmonary contusions. Sternal fractures were only seen in 36% of such patients. However, myocardial hypoenhancement on CT is poorly sensitive for those patients with cardiac contusion: 0% of right ventricular contusions and 22% of left ventricular contusions seen on echocardiography were identified on CT. CT signs of severe thoracic trauma are frequently present in patients with severe BCI and should be regarded as indirect evidence of potential BCI. Direct CT findings of myocardial contusion, i.e. myocardial hypoenhancement, are poorly sensitive and should not be used as a screening tool. However, some left ventricular contusions can be seen on CT, and these patients could undergo echocardiography or cardiac MRI to evaluate for wall motion abnormalities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cardiac changes in anorexia nervosa.

Science.gov (United States)

Spaulding-Barclay, Michael A; Stern, Jessica; Mehler, Philip S

2016-04-01

Introduction Anorexia nervosa is an eating disorder, which is associated with many different medical complications as a result of the weight loss and malnutrition that characterise this illness. It has the highest mortality rate of any psychiatric disorder. A large portion of deaths are attributable to the cardiac abnormalities that ensue as a result of the malnutrition associated with anorexia nervosa. In this review, the cardiac complications of anorexia nervosa will be discussed. A comprehensive literature review on cardiac changes in anorexia nervosa was carried out. There are structural, functional, and rhythm-type changes that occur in patients with anorexia nervosa. These become progressively significant as ongoing weight loss occurs. Cardiac changes are inherent to anorexia nervosa and they become more life-threatening and serious as the anorexia nervosa becomes increasingly severe. Weight restoration and attention to these cardiac changes are crucial for a successful treatment outcome.

Obesity-associated cardiac pathogenesis in broiler breeder hens: Pathological adaption of cardiac hypertrophy.

Science.gov (United States)

Chen, C Y; Lin, H Y; Chen, Y W; Ko, Y J; Liu, Y J; Chen, Y H; Walzem, R L; Chen, S E

2017-07-01

Broiler hens consuming feed to appetite (ad libitum; AL) show increased mortality. Feed restriction (R) typically improves reproductive performance and livability of hens. Rapidly growing broilers can exhibit increased mortality due to cardiac insufficiency but it is unknown whether the increased mortality of non-R broiler hens is also due to cardiac compromise. To assess cardiac growth and physiology in fully mature birds, 45-week-old hens were either continued on R rations or assigned to AL feeding for 7 or 21 days. AL hens exhibited increased bodyweight, adiposity, absolute and relative heart weight, ventricular hypertrophy, and cardiac protein/DNA ratio by d 21 (P hens (P Hens allowed AL feeding for 70 d exhibited a higher incidence of mortality (40% vs. 10%) in association with ascites, pericardial effusion, and ventricle dilation. A higher incidence of irregular ECG patterns and rhythmicity consistent with persistently elevated systolic blood pressure and ventricle fibrosis were observed in AL hens (P feeding in broiler hens results in maladaptive cardiac hypertrophy that progresses to overt pathogenesis in contractility and thereby increases mortality. Feed restriction provides clear physiological benefit to heart function of adult broiler hens. © 2017 Poultry Science Association Inc.

Plastics derived endocrine disruptors (BPA, DEHP and DBP induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

Directory of Open Access Journals (Sweden)

Mohan Manikkam

Full Text Available Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3 following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA, bis(2-ethylhexylphthalate (DEHP and dibutyl phthalate (DBP at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

Characterization of Glutamatergic Neurons in the Rat Atrial Intrinsic Cardiac Ganglia that Project to the Cardiac Ventricular Wall

Science.gov (United States)

Wang, Ting; Miller, Kenneth E.

2016-01-01

The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside intrinsic cardiac ganglia. In the present study, rat intrinsic cardiac ganglia neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) intrinsic cardiac ganglia contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial intrinsic cardiac ganglia contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT. (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG

Scoring of late gadolinium enhancement in cardiac magnetic resonance imaging can predict cardiac events in patients with hypertrophic cardiomyopathy

International Nuclear Information System (INIS)

Nojiri, Ayumi; Hongo, Kenichi; Kawai, Makoto; Komukai, Kimiaki; Sakuma, Toru; Taniguchi, Ikuo; Yoshimura, Michihiro

2011-01-01

Late gadolinium enhancement (LGE) of cardiac magnetic resonance imaging (MRI) represents myocardial fibrosis and may be related to the clinical outcome of various heart diseases. This study evaluated the relationship between LGE and cardiac events in hypertrophic cardiomyopathy (HCM) using a new scoring method. This study retrospectively followed 46 HCM patients without heart failure symptoms for 3.8±1.8 years. Gadolinium-enhanced cardiac MRI was performed in all patients. Cardiac events including newly developed heart failure or ventricular tachyarrhythmia were evaluated during the follow-up period. We evaluated the predictive factors to identify the patients with cardiac events. None of the risk factors reported to be related to poor outcome or the existence of LGE alone could predict cardiac events, which might be due to the small number of subjects investigated in this study. A new scoring method for LGE-positive areas (LGE score) was applied and higher LGE score can predict cardiac events in this study population. The proposed LGE score for cardiac MRI is considered to be a potentially valid method for assessing cardiac events in HCM patients. (author)

Safety in cardiac surgery

NARCIS (Netherlands)

Siregar, S.

2013-01-01

The monitoring of safety in cardiac surgery is a complex process, which involves many clinical, practical, methodological and statistical issues. The objective of this thesis was to measure and to compare safety in cardiac surgery in The Netherlands using the Netherlands Association for

Uncoupling of T Cell Receptor Zeta Chain Function during the Induction of Anergy by the Superantigen, Staphylococcal Enterotoxin A

Directory of Open Access Journals (Sweden)

William D. Cornwell

2010-06-01

Full Text Available Staphylococcus aureus enterotoxins have immunomodulatory properties. In this study, we show that Staphylococcal enterotoxin A (SEA induces a strong proliferative response in a murine T cell clone independent of MHC class II bearing cells. SEA stimulation also induces a state of hypo-responsiveness (anergy. We characterized the components of the T cell receptor (TCR during induction of anergy by SEA. Most interestingly, TCR zeta chain phosphorylation was absent under SEA anergizing conditions, which suggests an uncoupling of zeta chain function. We characterize here a model system for studying anergy in the absence of confounding costimulatory signals.

Fetal Primary Cardiac Tumors During Perinatal Period

Directory of Open Access Journals (Sweden)

Shi-Min Yuan

2017-06-01

Full Text Available Fetal primary cardiac tumors are rare, but they may cause complications, which are sometimes life threatening, including arrhythmias, hydrops fetalis, ventricular outflow/inflow obstruction, cardiac failure, and even sudden death. Among fetal primary cardiac tumors, rhabdomyomas are most common, followed by teratomas, fibromas, hemangiomas, and myxomas. Everolimus, a mammalian target of rapamycin inhibitor, has been reported to be an effective drug to cause tumor remission in three neonates with multiple cardiac rhabdomyomas. Neonatal cardiac surgery for the resection of primary cardiac tumors found by fetal echocardiography has been reported sporadically. However, open fetal surgery for pericardial teratoma resection, which was performed successfully via a fetal median sternotomy in one case report, could be a promising intervention to rescue these patients with large pericardial effusions. These recent achievements undoubtedly encourage further development in early management of fetal cardiac tumors. Owing to the rarity of fetal primary cardiac tumors, relevant information in terms of prenatal diagnosis, treatment, and prognosis remains to be clarified.

Focused cardiac ultrasound is feasible in the general practice setting and alters diagnosis and management of cardiac disease

Directory of Open Access Journals (Sweden)

James Yates

2016-08-01

Full Text Available Background: Ultrasound-assisted examination of the cardiovascular system with focused cardiac ultrasound by the treating physician is non-invasive and changes diagnosis and management of patient’s with suspected cardiac disease. This has not been reported in a general practice setting. Aim: To determine whether focused cardiac ultrasound performed on patients aged over 50 years changes the diagnosis and management of cardiac disease by a general practitioner. Design and setting: A prospective observational study of 80 patients aged over 50 years and who had not received echocardiography or chest CT within 12 months presenting to a general practice. Method: Clinical assessment and management of significant cardiac disorders in patients presenting to general practitioners were recorded before and after focused cardiac ultrasound. Echocardiography was performed by a medical student with sufficient training, which was verified by an expert. Differences in diagnosis and management between conventional and ultrasound-assisted assessment were recorded. Results and conclusion: Echocardiography and interpretation were acceptable in all patients. Significant cardiac disease was detected in 16 (20% patients, including aortic stenosis in 9 (11% and cardiac failure in 7 (9%, which were missed by clinical examination in 10 (62.5% of these patients. Changes in management occurred in 12 patients (15% overall and 75% of those found to have significant cardiac disease including referral for diagnostic echocardiography in 8 (10%, commencement of heart failure treatment in 3 (4% and referral to a cardiologist in 1 patient (1%. Routine focused cardiac ultrasound is feasible and frequently alters the diagnosis and management of cardiac disease in patients aged over 50 years presenting to a general practice.

Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians.

Science.gov (United States)

Kim, Sangkyu; Myers, Leann; Ravussin, Eric; Cherry, Katie E; Jazwinski, S Michal

2016-08-01

Energy expenditure decreases with age, but in the oldest-old, energy demand for maintenance of body functions increases with declining health. Uncoupling proteins have profound impact on mitochondrial metabolic processes; therefore, we focused attention on mitochondrial uncoupling protein genes. Alongside resting metabolic rate (RMR), two SNPs in the promoter region of UCP2 were associated with healthy aging. These SNPs mark potential binding sites for several transcription factors; thus, they may affect expression of the gene. A third SNP in the 3'-UTR of UCP3 interacted with RMR. This UCP3 SNP is known to impact UCP3 expression in tissue culture cells, and it has been associated with body weight and mitochondrial energy metabolism. The significant main effects of the UCP2 SNPs and the interaction effect of the UCP3 SNP were also observed after controlling for fat-free mass (FFM) and physical-activity related energy consumption. The association of UCP2/3 with healthy aging was not found in males. Thus, our study provides evidence that the genetic risk factors for healthy aging differ in males and females, as expected from the differences in the phenotypes associated with healthy aging between the two sexes. It also has implications for how mitochondrial function changes during aging.

Cardiac integrins the ties that bind.

Science.gov (United States)

Simpson, D G; Reaves, T A; Shih, D T; Burgess, W; Borg, T K; Terracio, L

1998-01-01

An elaborate series of morphogenetic events must be precisely coordinated during development to promote the formation of the elaborate three-dimensional structure of the normal heart. In this study we focus on discussing how interconnections between the cardiac myocyte and its surrounding environment regulate cardiac form and function. In vitro experiments from our laboratories provide direct evidence that cardiac cell shape is regulated by a dynamic interaction between constituents of the extracellular matrix (ECM) and by specific members of the integrin family of matrix receptors. Our data indicates that phenotypic information is stored in the tertiary structure and chemical identity of the ECM. This information appears to be actively communicated and transduced by the α1β1 integrin molecule into an intracellular signal that regulates cardiac cell shape and myofibrillar organization. In this study we have assessed the phenotypic consequences of suppressing the expression and accumulation of the α1 integrin molecule in aligned cultures of cardiac myocytes. In related experiments we have examined how the overexpression of α2 and α5 integrin, integrins normally not present or present at very low copy number on the cell surface of neonatal cardiac myocytes, affect cardiac protein metabolism. We also consider how biochemical signals and the mechanical signals mediated by the integrins may converge on common intracellular signaling pathways in the heart. Experiments with the whole embryo culture system indicate that angiotensin II, a peptide that carries information concerning cardiac load, plays a role in controling cardiac looping and the proliferation of myofibrils during development.

Cardiac fluid dynamics meets deformation imaging.

Science.gov (United States)

Dal Ferro, Matteo; Stolfo, Davide; De Paris, Valerio; Lesizza, Pierluigi; Korcova, Renata; Collia, Dario; Tonti, Giovanni; Sinagra, Gianfranco; Pedrizzetti, Gianni

2018-02-20

Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of creating flow. Deformation imaging provided valuable contributions to understanding cardiac mechanics; more recently, several studies evidenced the existence of an intimate relationship between cardiac function and intra-ventricular fluid dynamics. This paper summarizes the recent advances in cardiac flow evaluations, highlighting its relationship with heart wall mechanics assessed through the newest techniques of deformation imaging and finally providing an opinion of the most promising clinical perspectives of this emerging field. It will be shown how fluid dynamics can integrate volumetric and deformation assessments to provide a further level of knowledge of cardiac mechanics.

Dual energy cardiac CT.

Science.gov (United States)

Carrascosa, Patricia; Deviggiano, Alejandro; Rodriguez-Granillo, Gastón

2017-06-01

Conventional single energy CT suffers from technical limitations related to the polychromatic nature of X-rays. Dual energy cardiac CT (DECT) shows promise to attenuate and even overcome some of these limitations, and might broaden the scope of patients eligible for cardiac CT towards the inclusion of higher risk patients. This might be achieved as a result of both safety (contrast reduction) and physiopathological (myocardial perfusion and characterization) issues. In this article, we will review the main clinical cardiac applications of DECT, that can be summarized in two core aspects: coronary artery evaluation, and myocardial evaluation.

Health hazards associated with the use of di-(2-ethylhexyl) phthalate (commonly referred to as DOP) in HEPA filter test

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-01-01

Di-(2-ethylhexyl) phthalate (DEHP), commonly referred to as di-octyl phthalate, is an important production chemical in the US. In addition to its major use as an additive in plastics, DEHP is widely used to evaluate the effectiveness of high efficiency particulate air (HEPA) filters. Historically, DEHP was also used in quantitative fit testing for respirators. Evaluations of this compound a decade ago showed that it can induce hepatocellular carcinomas in laboratory animals. Although most Department of Energy (DOE) facilities have since discontinued using DEHP in respirator fit testing, DEHP continues to be used for evaluating HEPA filters. This report summarizes available information on the toxicity, mutagenicity, carcinogenicity, and other hazards and problems posed by DEHP, specifically with reference to HEPA filter testing. Information on work practice improvements as well as the availability and suitability of DEHP substitutes are also presented. This material should assist the DOE in the safe use of this material.

The cardiac sonography workforce in New Zealand

Science.gov (United States)

White, Steve; Poppe, Katrina; Whalley, Gillian

2015-01-01

Abstract Introduction: The aim of this paper is to investigate the cardiac sonography workforce characteristics and registration requirements in New Zealand (NZ), with a comparison to similar workforces internationally. Methods: The Survey of Clinical Echocardiography in New Zealand 2 (SCANZ2) audit was performed in December 2010. All of NZ's public‐funded District Health Board (DHB) centers providing echocardiography services responded to questions relating to staff, equipment, procedure types and patient statistics. The Medical Radiation Technologists Board (MRTB), Clinical Physiologists Registration Board (CPRB) and Australian Sonographers Association Registry (ASAR) websites were reviewed in March 2012 for registered sonographers with a cardiac scope of practice. The cardiac sonography workforces in Australia, the UK, the USA and Canada were investigated for comparison. Results: There are 84 cardiac sonographers (60.3 full‐time equivalent) working in DHBs: 71% from a cardiac technical background; 40% have post‐graduate qualifications; a further 17% are undertaking post‐graduate qualifications; and 59 cardiac sonographers have registration with professional bodies in NZ and/or Australia. Cardiac sonographers in NZ do not undergo compulsory registration, but other sonographers in NZ have compulsory registration with the MRTB. Sonographers are predominantly not licensed internationally. Discussion: Disparity exists between registration of cardiac and non‐cardiac sonographers in NZ. Many cardiac sonographers have voluntary registration but few are registered with the MRTB. Reasons for this include professional alignment, educational qualifications and representation. International trends show increased pressure from governments and professional bodies to regulate sonographers. Conclusion: This study provides a snapshot of the cardiac sonography workforce in NZ for the first time. PMID:28191178

Optimal Technique in Cardiac Anesthesia Recovery

NARCIS (Netherlands)

Svircevic, V.

2014-01-01

The aim of this thesis is to evaluate fast-track cardiac anesthesia techniques and investigate their impact on postoperative mortality, morbidity and quality of life. The following topics will be discussed in the thesis. (1.) Is fast track cardiac anesthesia a safe technique for cardiac surgery?

Emergency room thoracotomy for acute traumatic cardiac tamponade caused by a blunt cardiac injury: A case report

Directory of Open Access Journals (Sweden)

Kenichiro Ishida

2017-01-01

Conclusion: A prompt diagnosis using FAST and treatment can be lifesaving in traumatic acute cardiac tamponade. A pericardiotomy via a thoracotomy is mandatory for lifesaving cardiac decompression in acute traumatic cardiac tamponade in cases of ineffective drainage due to clot formation within the pericardial space.

Motivational factors of adherence to cardiac rehabilitation.

Science.gov (United States)

Shahsavari, Hooman; Shahriari, Mohsen; Alimohammadi, Nasrollah

2012-05-01

Main suggested theories about patients' adherence to treatment regimens recognize the importance of motivation in positive changes in behaviors. Since cardiac diseases are chronic and common, cardiac rehabilitation as an effective prevention program is crucial in management of these diseases. There is always concern about the patients' adherence to cardiac rehabilitation. The aim of this study was to describe the motivational factors affecting the patients' participation and compliance to cardiac rehabilitation by recognizing and understanding the nature of patients' experiences. The participants were selected among the patients with cardiac diseases who were referred to cardiac rehabilitation in Isfahan Cardiovascular Research Center, Iran. The purposive sampling method was used and data saturation achieved after 8 semi-structured interviews. The three main concepts obtained from this study are "beliefs", "supporters" and "group cohesion". In cardiac rehabilitation programs, emphasis on motivational factors affects the patient's adherence. It is suggested that in cardiac rehabilitation programs more attention should be paid to patients' beliefs, the role of patients' supporters and the role of group-based rehabilitation.

Cardiac Limited Ultrasound Examination Techniques to Augment the Bedside Cardiac Physical Examination.

Science.gov (United States)

Kimura, Bruce J; Shaw, David J; Amundson, Stan A; Phan, James N; Blanchard, Daniel G; DeMaria, Anthony N

2015-09-01

The current practice of physical diagnosis is dependent on physician skills and biases, inductive reasoning, and time efficiency. Although the clinical utility of echocardiography is well known, few data exist on how to integrate 2-dimensional screening "quick-look" ultrasound applications into a novel, modernized cardiac physical examination. We discuss the evidence basis behind ultrasound "signs" pertinent to the cardiovascular system and elemental in synthesis of bedside diagnoses and propose the application of a brief cardiac limited ultrasound examination based on these signs. An ultrasound-augmented cardiac physical examination can be taught in traditional medical education and has the potential to improve bedside diagnosis and patient care. © 2015 by the American Institute of Ultrasound in Medicine.

Determination and Pharmacokinetics of Di-(2-ethylhexyl Phthalate in Rats by Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry

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Tung-Hu Tsai

2013-09-01

Full Text Available Di-(2-ethylhexyl phthalate (DEHP is used to increase the flexibility of plastics for industrial products. However, the illegal use of the plasticizer DEHP in food and drinks has been reported in Taiwan in 2011. In order to assess the exact extent of the absorption of DEHP via the oral route, the aim of this study is to develop a reliable and validated ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS method to evaluate the oral bioavailability of DEHP in rats. The optimal chromatographic separation of DEHP and butyl benzyl phthalate (BBP; used as internal standard were achieved on a C18 column. The mobile phase was consisted of 5 mM ammonium acetate-methanol (11:89, v/v with a flow rate of 0.25 mL/min. The monitoring ion transitions were m/z 391.4 → 149.0 for DEHP and m/z 313.3 → 149.0 for BBP. The mean matrix effects of DEHP at low, medium and high concentrations were 94.5 ± 5.7% and 100.1 ± 2.3% in plasma and feces homogenate samples, respectively. In conclusion, the validated UPLC-MS/MS method is suitable for analyzing the rat plasma sample of DEHP and the oral bioavailability of DEHP was about 7% in rats.

Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl phthalate in male Long Evans rats.

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Catherine A Smith

Full Text Available Early developmental exposure to di(2-ethylhexyl phthalate (DEHP has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

Crisis management during anaesthesia: cardiac arrest.

Science.gov (United States)

Runciman, W B; Morris, R W; Watterson, L M; Williamson, J A; Paix, A D

2005-06-01

Cardiac arrest attributable to anaesthesia occurs at the rate of between 0.5 and 1 case per 10 000 cases, tends to have a different profile to that of cardiac arrest occurring elsewhere, and has an in-hospital mortality of 20%. However, as individual practitioners encounter cardiac arrest rarely, the rapidity with which the diagnosis is made and the consistency of appropriate management varies considerably. To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a sub-algorithm for cardiac arrest, in the management of cardiac arrest occurring in association with anaesthesia. The potential performance of this structured approach for each the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. There were 129 reports of cardiac arrest associated with anaesthesia among the first 4000 AIMS incident reports. Identified aetiological factors were grouped into five categories: (1) anaesthetic technique (11 cases with this category alone; 32 with this and one or more of the other categories, representing 25% of all 129 cardiac arrests); (2) drug related (16; 32, 25%); (3) associated with surgical procedure (9; 29, 22%); (4) associated with pre-existing medical or surgical disease (30; 82, 64%); (5) unknown (8; 14, 11%). The "real life" presentation and management of cardiac arrest in association with anaesthesia differs substantially from that detailed in general published guidelines. Cardiac rhythms at the time were sinus bradycardia (23%); asystole (22%); tachycardia/ventricular tachycardia/ventricular fibrillation (14%); and normal (7%), with a further third unknown. Details of treatment were recorded in 110 reports; modalities employed included cardiac compression (72%); adrenaline (61%); 100% oxygen (58%); atropine (38%); intravenous fluids (25%), and electrical defibrillation (17%). There

Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring

Energy Technology Data Exchange (ETDEWEB)

Martinez–Arguelles, D.B. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); McIntosh, M.; Rohlicek, C.V. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Pediatrics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Culty, M. [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Zirkin, B.R. [Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Papadopoulos, V., E-mail: vassilios.papadopoulos@mcgill.ca [The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1A4 (Canada); Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205 (United States)

2013-01-01

Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2 month-old) and older (6.5 month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300 mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring. Highlights: ► In utero exposure to 300 mg DEHP/kg/day decreases activity at postnatal day 60. ► In utero exposure to DEHP decreases aldosterone levels at postnatal day 200. ► In utero exposure to DEHP decreases systolic blood pressure at postnatal day 200. ► An 8% salt diet recovers the decreased blood pressure at postnatal day 200.

Diethyl hexyl phthalate-induced changes in insulin signaling molecules and the protective role of antioxidant vitamins in gastrocnemius muscle of adult male rat

Energy Technology Data Exchange (ETDEWEB)

Srinivasan, Chinnapaiyan; Khan, Adam Ismail; Balaji, Venkataraman; Selvaraj, Jayaraman; Balasubramanian, Karundevi, E-mail: kbala82@rediffmail.com

2011-12-15

Diethyl hexyl phthalate (DEHP) is an endocrine disruptor, it influences various organ systems in human beings and experimental animals. DEHP reduced the serum testosterone and increased the blood glucose, estradiol, T{sub 3} and T{sub 4} in rats. However, the effect of DEHP on insulin signaling and glucose oxidation in skeletal muscle is not known. Adult male albino rats were divided into four groups: Group I: Control; Groups II and III: DEHP treated (dissolved in olive oil at a dose of 10 and 100 mg/kg body weight, respectively, once daily through gastric intubation for 30 days); and Group IV: DEHP (100 mg/kg body weight) plus vitamins E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubation for 30 days. On completion of treatment, animals were euthanized and perfused (whole body); gastrocnemius muscle was dissected out and subjected to assessment of various parameters. DEHP treatment increased the H{sub 2}O{sub 2}, hydroxyl radical levels and lipid peroxidation which disrupt the membrane integrity and insulin receptor. DEHP impaired the insulin signal transduction, glucose uptake and oxidation through decreased expression of plasma membrane GLUT4, which may partly be responsible for the elevation of fasting blood glucose level. The present study suggests that DEHP exposure affects glucose oxidation in skeletal muscle and is mediated through enhanced lipid peroxidation, impaired insulin signaling and GLUT4 expression in plasma membrane. Antioxidant vitamins (C and E) have a protective role against the adverse effect of DEHP. -- Highlights: Black-Right-Pointing-Pointer DEHP treatment significantly decreased serum insulin and testosterone levels. Black-Right-Pointing-Pointer Increased ROS and decreased glucose uptake were observed in DEHP treated animals. Black-Right-Pointing-Pointer Impaired insulin signaling in gastrocnemius muscle was observed in DEHP treatment. Black

Robotic Applications in Cardiac Surgery

Directory of Open Access Journals (Sweden)

Alan P. Kypson

2008-11-01

Full Text Available Traditionally, cardiac surgery has been performed through a median sternotomy, which allows the surgeon generous access to the heart and surrounding great vessels. As a paradigm shift in the size and location of incisions occurs in cardiac surgery, new methods have been developed to allow the surgeon the same amount of dexterity and accessibility to the heart in confined spaces and in a less invasive manner. Initially, long instruments without pivot points were used, however, more recent robotic telemanipulation systems have been applied that allow for improved dexterity, enabling the surgeon to perform cardiac surgery from a distance not previously possible. In this rapidly evolving field, we review the recent history and clinical results of using robotics in cardiac surgery.

Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue.

Science.gov (United States)

Mayorga, Maritza; Finan, Amanda; Penn, Marc

2009-03-01

Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.

[Role of cardiac magnetic resonance in cardiac involvement of Fabry disease].

Science.gov (United States)

Serra, Viviana M; Barba, Miguel Angel; Torrá, Roser; Pérez De Isla, Leopoldo; López, Mónica; Calli, Andrea; Feltes, Gisela; Torras, Joan; Valverde, Victor; Zamorano, José L

2010-09-04

Fabry disease is a hereditary disorder. Clinical manifestations are multisystemic. The majority of the patients remain undiagnosed until late in life, when alterations could be irreversible. Early detection of cardiac symptoms is of major interest in Fabry's disease (FD) in order to gain access to enzyme replacement therapy. Echo-Doppler tissular imaging (TDI) has been used as a cardiologic early marker in FD. This study is intended to determine whether the cardiac magnetic resonance is as useful tool as TDI for the early detection of cardiac affectation in FD. Echocardiography, tissue Doppler and Cardio magnetic resonance was performed in 20 patients with confirmed Fabry Disease. Left ventricular hypertrophy was defined as septum and left ventricular posterior wall thickness ≥12 mm. An abnormal TDI velocity was defined as (Sa), (Ea) and/or (Aa) velocities gadolinium-enhanced images sequences were obtained using magnetic resonance. Twenty patients included in the study were divided into three groups: 1. Those without left ventricular hypertrophy nor tissue Doppler impairment 2. Those without left ventricular hypertrophy and tissue Doppler impairment 3. Those with left ventricular hypertrophy and Tissue Doppler impairment. Late gadolinium enhancement was found in only one patient, who has already altered DTI and LVH. Tissue Doppler imaging (TDI) is the only diagnostic tool able to provide early detection of cardiac affectation in patients with FD. Magnetic resonance provides information of the disease severity in patients with LVH, but can not be used as an early marker of cardiac disease in patients with FD. However MRI could be of great value for diagnostic stratification. Copyright © 2009 Elsevier España, S.L. All rights reserved.

Mathematical Models of Cardiac Pacemaking Function

Science.gov (United States)

Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

2013-10-01

Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

Contribution of cardiac and extra-cardiac disease burden to risk of cardiovascular outcomes varies by ejection fraction in heart failure

DEFF Research Database (Denmark)

Wolsk, Emil; Claggett, Brian; Køber, Lars

2018-01-01

AIMS: Patients with heart failure (HF) often have multiple co-morbidities that contribute to the risk of adverse cardiovascular (CV) and non-CV outcomes. We assessed the relative contribution of cardiac and extra-cardiac disease burden and demographic factors to CV outcomes in HF patients...... Association class, systolic blood pressure, time since HF diagnosis, HF medication use), extra-cardiac (body mass index, creatinine, diabetes mellitus, chronic obstructive pulmonary disease, smoker), and demographic (age, gender) categories, and calculated subscores for each patient representing the burden......EF patients (PAR: 76% cardiac disease vs. 58% extra-cardiac disease, P vs. 49% extra-cardiac disease, P

Exhaustive Training Increases Uncoupling Protein 2 Expression and Decreases Bcl-2/Bax Ratio in Rat Skeletal Muscle

Directory of Open Access Journals (Sweden)

W. Y. Liu

2013-01-01

Full Text Available This work investigates the effects of oxidative stress due to exhaustive training on uncoupling protein 2 (UCP2 and Bcl-2/Bax in rat skeletal muscles. A total of 18 Sprague-Dawley female rats were randomly divided into three groups: the control group (CON, the trained control group (TC, and the exhaustive trained group (ET. Malondialdehyde (MDA, superoxide dismutase (SOD, xanthine oxidase (XOD, ATPase, UCP2, and Bcl-2/Bax ratio in red gastrocnemius muscles were measured. Exhaustive training induced ROS increase in red gastrocnemius muscles, which led to a decrease in the cell antiapoptotic ability (Bcl-2/Bax ratio. An increase in UCP2 expression can reduce ROS production and affect mitochondrial energy production. Thus, oxidative stress plays a significant role in overtraining.

Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

Science.gov (United States)

Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

2018-01-01

Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts.

Directory of Open Access Journals (Sweden)

Tae Yun Kim

Full Text Available Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs and/or cardiac fibroblasts (CFs and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair.

CaMn0.875Ti0.125O3 as oxygen carrier for chemical-looping combustion with oxygen uncoupling (CLOU)—Experiments in a continuously operating fluidized-bed reactor system

KAUST Repository

Rydé n, Magnus; Lyngfelt, Anders; Mattisson, Tobias

2011-01-01

Particles of the perovskite material CaMn0.875Ti0.125O3 has been examined as oxygen carrier for chemical-looping with oxygen uncoupling, and for chemical-looping combustion of natural gas, by 70h of experiments in a circulating fluidized-bed reactor

Physiologic stress interventions in cardiac imaging

International Nuclear Information System (INIS)

Buda, A.J.

1985-01-01

Physiologic stress interventions are designed to assess the reserve capability of coronary flow and myocardial function. In the normal individual, a sufficiently intense physiologic stress may increase coronary flow and cardiac output by 500% to 600%. However, in patients with cardiac disease, these reserve responses may be absent, or considerably blunted. Thus, physiologic stress testing has proved extremely helpful in detecting cardiac abnormalities when resting cardiac function appears normal. Although dynamic exercise remains the standard approach to physiologic stress testing, a number of other interventions have been used, including: (1) isometric exercise, (2) atrial pacing, (3) cold pressor testing, (4) postextrasystolic potentiation, (5) volume loading, and (6) negative intrathoracic pressure. Each of these may be considered an alternative physiologic intervention whenever dynamic exercise is not feasible. These alternative approaches are important since, in our experience, 20% to 30% of subjects are unable to perform dynamic exercise, or exercise inadequately to produce a sufficiently intense cardiac stress. This chapter reviews physiologic considerations, indications, contraindications, protocols, and results of these physiologic stress interventions when used in combination with cardiac radionuclide procedures

Raf-mediated cardiac hypertrophy in adult Drosophila

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Lin Yu

2013-07-01

In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for Raf

Cardiac anatomy and physiology: a review.

Science.gov (United States)

Gavaghan, M

1998-04-01

This article reviews the normal anatomy and physiology of the heart. Understanding the normal anatomic and physiologic relationships described in this article will help perioperative nurses care for patients who are undergoing cardiac procedures. Such knowledge also assists nurses in educating patients about cardiac procedures and about activities that can prevent, reverse, or improve cardiac illness.

Ca2+-induced uncoupling of Aplysia bag cell neurons.

Science.gov (United States)

Dargaei, Zahra; Standage, Dominic; Groten, Christopher J; Blohm, Gunnar; Magoski, Neil S

2015-02-01

Electrical transmission is a dynamically regulated form of communication and key to synchronizing neuronal activity. The bag cell neurons of Aplysia are a group of electrically coupled neuroendocrine cells that initiate ovulation by secreting egg-laying hormone during a prolonged period of synchronous firing called the afterdischarge. Accompanying the afterdischarge is an increase in intracellular Ca2+ and the activation of protein kinase C (PKC). We used whole cell recording from paired cultured bag cell neurons to demonstrate that electrical coupling is regulated by both Ca2+ and PKC. Elevating Ca2+ with a train of voltage steps, mimicking the onset of the afterdischarge, decreased junctional current for up to 30 min. Inhibition was most effective when Ca2+ entry occurred in both neurons. Depletion of Ca2+ from the mitochondria, but not the endoplasmic reticulum, also attenuated the electrical synapse. Buffering Ca2+ with high intracellular EGTA or inhibiting calmodulin kinase prevented uncoupling. Furthermore, activating PKC produced a small but clear decrease in junctional current, while triggering both Ca2+ influx and PKC inhibited the electrical synapse to a greater extent than Ca2+ alone. Finally, the amplitude and time course of the postsynaptic electrotonic response were attenuated after Ca2+ influx. A mathematical model of electrically connected neurons showed that excessive coupling reduced recruitment of the cells to fire, whereas less coupling led to spiking of essentially all neurons. Thus a decrease in electrical synapses could promote the afterdischarge by ensuring prompt recovery of electrotonic potentials or making the neurons more responsive to current spreading through the network. Copyright © 2015 the American Physiological Society.

Usefulness of cardiac 125I-metaiodobenzylguanidine uptake for evaluation of cardiac sympathetic nerve abnormalities in diabetic rats

International Nuclear Information System (INIS)

Abe, Nanami; Kashiwagi, Atsunori; Shigeta, Yukio

1992-01-01

We investigated cardiac sympathetic nerve abnormalities in streptozocin-induced diabetic rats using 125 I-metaiodobenzylguanidine (MIBG). The radioactivity ratio of cardiac tissue to 1 ml blood (H/B) was used as an index of cardiac MIBG uptake. Cardiac 125 I-MIBG uptake (H/B) in 4-, 8- and 20-wk diabetic rats was 48% lower than that in control rats. Similar results were obtained even when the data were corrected for g wet tissue weight. Although there was no improvement in H/B following 2-wk insulin treatment, the H/B ratio increased significantly, to 85% of control levels, following 4 wk insulin treatment indicating the reversibility of impaired MIBG uptake in diabetic rats. In vivo reserpine treatment resulted in a 50% reduction in the H/B value in control rats. However, the treatment did not significantly suppress uptake in diabetic rats. Cardiac norepinephrine content in both * 4- and ** 8-wk diabetic rats was significantly ( * p ** p 125 I-MIBG in diabetic rats is significantly impaired due to cardiac sympathetic nerve abnormalities. These abnormalities are reversible, however, dependent on the diabetic state. (author)

Cardiac troponins--Translational biomarkers in cardiology: Theory and practice of cardiac troponin high-sensitivity assays.

Science.gov (United States)

Adamcova, Michaela; Popelova-Lencova, Olga; Jirkovsky, Eduard; Simko, Fedor; Gersl, Vladimir; Sterba, Martin

2016-01-01

Tn is a unique translational biomarker in cardiology whose potential has not been diminished in the new era of high sensitive assays. cTns can be valuable markers in cardiac diseases as well as in infectious diseases and respiratory diseases. Furthermore, the role of cTns is growing in the routine evaluation of cardioxicity and in determining the efficacy/safety ratio of novel cardioprotective strategies in clinical settings. cTns can detect myocardial injury not only in a wide spectrum of laboratory animals in experimental studies in vivo, but also in isolated heart models or cardiomyocytes in vitro. The crucial issue regarding the cross-species usage of cardiac troponin investigation remains the choice of cardiac troponin testing. This review summarizes the recent proteomic data on aminoacid sequences of cTnT and cTnI in various species, as well as selected analytical characteristics of human cardiac troponin high-sensitivity assays. Due to the highly phylogenetically conserved structure of troponins, the same bioindicator can be investigated using the same method in both clinical and experimental cardiology, thus contributing to a better understanding of the pathogenesis of cardiac diseases as well as to increased effectiveness of troponin use in clinical practice. Measuring cardiac troponins using commercially available human high-sensitivity cardiac troponin tests with convenient antibodies selected on the basis of adequate proteomic knowledge can solve many issues which would otherwise be difficult to address in clinical settings for various ethical and practical reasons. Our survey could help elaborate the practical guidelines for optimizing the choice of cTns assay in cardiology. © 2016 International Union of Biochemistry and Molecular Biology.

Di-(2-ethylhexyl) phthalate affects immune cells from atopic prone mice in vitro

International Nuclear Information System (INIS)

Koike, Eiko; Inoue, Ken-ichiro; Yanagisawa, Rie; Takano, Hirohisa

2009-01-01

Phthalate esters as plasticizers have been widespread in the environment and may be associated with development of allergic diseases such as asthma and atopic dermatitis. However, the underlying mechanisms have not been fully elucidated. The present study investigated the effects of di-(2-ethylhexyl) phthalate (DEHP) on immune cells from atopic prone NC/Nga mice in vitro. Bone marrow-derived dendritic cells (BMDC) as a professional antigen-presenting cell and splenocytes as mixture of immune cells were used. BMDC were differentiated by culture with granulocyte macrophage-colony stimulating factor (GM-CSF) in the presence of DEHP (0.1-10 μM) for 6 days. In another experiments, BMDC were differentiated by culture with GM-CSF for 8 days then these BMDC were exposed to DEHP (0.1-100 μM) for 24 h. Splenocytes were exposed to DEHP for 24 h (0.1-100 μM) or 72 h (0.1-1000 nM). After the culture, the phenotypic markers and the function of BMDC and splenocytes were evaluated. BMDC differentiated in the presence of DEHP showed enhancement in the expression of MHC class II, CD86, CD11c and DEC205, and in their antigen-presenting activity. On the other hand, the function of the differentiated BMDC was not activated by DEHP although DEHP partly enhanced their expression of DEC205. DEHP-exposed splenocytes showed increases in their TCR and CD3 expression, interleukin-4 production, and antigen-stimulated proliferation. These results demonstrate that DEHP enhances BMDC differentiation but not activation and also enhances Th2 response in splenocytes from atopic prone mice. The enhancement might contribute to the aggravating effect of DEHP on allergic disorders.

Urinary di-(2-ethylhexyl) phthalate metabolites for detecting transfusion of autologous blood stored in plasticizer-free bags.

Science.gov (United States)

Leuenberger, Nicolas; Barras, Laura; Nicoli, Raul; Robinson, Neil; Baume, Norbert; Lion, Niels; Barelli, Stefano; Tissot, Jean-Daniel; Saugy, Martial

2016-03-01

Autologous blood transfusion (ABT) efficiently increases sport performance and is the most challenging doping method to detect. Current methods for detecting this practice center on the plasticizer di(2-ethlyhexyl) phthalate (DEHP), which enters the stored blood from blood bags. Quantification of this plasticizer and its metabolites in urine can detect the transfusion of autologous blood stored in these bags. However, DEHP-free blood bags are available on the market, including n-butyryl-tri-(n-hexyl)-citrate (BTHC) blood bags. Athletes may shift to using such bags to avoid the detection of urinary DEHP metabolites. A clinical randomized double-blinded two-phase study was conducted of healthy male volunteers who underwent ABT using DEHP-containing or BTHC blood bags. All subjects received a saline injection for the control phase and a blood donation followed by ABT 36 days later. Kinetic excretion of five urinary DEHP metabolites was quantified with liquid chromatography coupled with tandem mass spectrometry. Surprisingly, considerable levels of urinary DEHP metabolites were observed up to 1 day after blood transfusion with BTHC blood bags. The long-term metabolites mono-(2-ethyl-5-carboxypentyl) phthalate and mono-(2-carboxymethylhexyl) phthalate were the most sensitive biomarkers to detect ABT with BTHC blood bags. Levels of DEHP were high in BTHC bags (6.6%), the tubing in the transfusion kit (25.2%), and the white blood cell filter (22.3%). The BTHC bag contained DEHP, despite being labeled DEHP-free. Urinary DEHP metabolite measurement is a cost-effective way to detect ABT in the antidoping field even when BTHC bags are used for blood storage. © 2015 AABB.

Effects of Di-(2-ethylhexyl Phthalate on the Hypothalamus–Uterus in Pubertal Female Rats

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Te Liu

2016-11-01

Full Text Available The pollution of endocrine disruptors and its impact on human reproductive system have attracted much attention. Di-(2-ethylhexyl phthalate (DEHP, an environmental endocrine disruptor, is widely used in food packages, containers, medical supplies and children’s toys. It can cause diseases such as infertility, sexual precocity and uterine bleeding and thus arouse concerns from the society and scholars. The effect of DEHP on pubertal female reproductive system is still not well-studied. This study was to investigate the effects of DEHP on the hypothalamus–uterus in pubertal female rats, reveal the reproductive toxicity of DEHP on pubertal female rats and its mechanism, and provide scientific evidence for the evaluation of toxicity and toxic mechanism of DEHP on reproductive system. Forty-eight pubertal female rats were randomly divided into four groups and respectively administered via oral gavage 0, 250, 500, or 1000 mg/kg/d DEHP in 0.1 mL corn oil/20 g body weight for up to four weeks. Compared with control rats, the DEHP-treated rats showed: (1 higher gonadotropin-releasing hormone (GnRH level in the hypothalamus; (2 higher protein levels of GnRH in the hypothalamus; and (3 higher mRNA and protein levels of GnRH receptor (GnRHR in the uterus. Our data reveal that DEHP exposure may lead to a disruption in pubertal female rats and an imbalance of hypothalamus–uterus. Meanwhile, DEHP may, through the GnRH in the hypothalamus and its receptor on the uterus, lead to diseases of the uterus. DEHP may impose a negative influence on the development and functioning of the reproductive system in pubertal female rats.

Effects of Di-(2-ethylhexyl) Phthalate on the Hypothalamus–Uterus in Pubertal Female Rats

Science.gov (United States)

Liu, Te; Jia, Yiyang; Zhou, Liting; Wang, Qi; Sun, Di; Xu, Jin; Wu, Juan; Chen, Huaiji; Xu, Feng; Ye, Lin

2016-01-01

The pollution of endocrine disruptors and its impact on human reproductive system have attracted much attention. Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is widely used in food packages, containers, medical supplies and children’s toys. It can cause diseases such as infertility, sexual precocity and uterine bleeding and thus arouse concerns from the society and scholars. The effect of DEHP on pubertal female reproductive system is still not well-studied. This study was to investigate the effects of DEHP on the hypothalamus–uterus in pubertal female rats, reveal the reproductive toxicity of DEHP on pubertal female rats and its mechanism, and provide scientific evidence for the evaluation of toxicity and toxic mechanism of DEHP on reproductive system. Forty-eight pubertal female rats were randomly divided into four groups and respectively administered via oral gavage 0, 250, 500, or 1000 mg/kg/d DEHP in 0.1 mL corn oil/20 g body weight for up to four weeks. Compared with control rats, the DEHP-treated rats showed: (1) higher gonadotropin-releasing hormone (GnRH) level in the hypothalamus; (2) higher protein levels of GnRH in the hypothalamus; and (3) higher mRNA and protein levels of GnRH receptor (GnRHR) in the uterus. Our data reveal that DEHP exposure may lead to a disruption in pubertal female rats and an imbalance of hypothalamus–uterus. Meanwhile, DEHP may, through the GnRH in the hypothalamus and its receptor on the uterus, lead to diseases of the uterus. DEHP may impose a negative influence on the development and functioning of the reproductive system in pubertal female rats. PMID:27845755

Biodegradation of Di-(2-ethylhexyl Phthalate by Rhodococcus ruber YC-YT1 in Contaminated Water and Soil

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Ting Yang

2018-05-01

Full Text Available Di-(2-ethylehxyl phthalate (DEHP is one of the most broadly representative phthalic acid esters (PAEs used as a plasticizer in polyvinyl chloride (PVC production, and is considered to be an endocrine-disrupting chemical. DEHP and its monoester metabolites are responsible for adverse effects on human health. An efficient DEHP-degrading bacterial strain Rhodococcus ruber YC-YT1, with super salt tolerance (0–12% NaCl, is the first DEHP-degrader isolated from marine plastic debris found in coastal saline seawater. Strain YC-YT1 completely degraded 100 mg/L DEHP within three days (pH 7.0, 30 °C. According to high-performance liquid chromatography–mass spectrometry (HPLC-MS analysis, DEHP was transformed by strain YC-YT1 into phthalate (PA via mono (2-ethylehxyl phthalate (MEHP, then PA was used for cell growth. Furthermore, YC-YT1 metabolized initial concentrations of DEHP ranging from 0.5 to 1000 mg/L. Especially, YC-YT1 degraded up to 60% of the 0.5 mg/L initial DEHP concentration. Moreover, compared with previous reports, strain YC-YT1 had the largest substrate spectrum, degrading up to 13 kinds of PAEs as well as diphenyl, p-nitrophenol, PA, benzoic acid, phenol, protocatechuic acid, salicylic acid, catechol, and 1,2,3,3-tetrachlorobenzene. The excellent environmental adaptability of strain YC-YT1 contributed to its ability to adjust its cell surface hydrophobicity (CSH so that 79.7–95.9% of DEHP-contaminated agricultural soil, river water, coastal sediment, and coastal seawater were remedied. These results demonstrate that R. ruber YC-YT1 has vast potential to bioremediate various DEHP-contaminated environments, especially in saline environments.

ASCI 2010 contrast media guideline for cardiac imaging: a report of the Asian Society of Cardiovascular Imaging cardiac computed tomography and cardiac magnetic resonance imaging guideline working group

Science.gov (United States)

Kitagawa, Kakuya; Tsai, I-Chen; Chan, Carmen; Yu, Wei; Yong, Hwan Seok; Choi, Byoung Wook

2010-01-01

The use of contrast media for cardiac imaging becomes increasing as the widespread of cardiac CT and cardiac MR. A radiologist needs to carefully consider the indication and the injection protocol of contrast media to be used as well as the possibility of adverse effect. There are several guidelines for contrast media in western countries. However, these are focusing the adverse effect of contrast media. The Asian Society of Cardiovascular Imaging, the only society dedicated to cardiovascular imaging in Asia, formed a Working Group and created a guideline, which summarizes the integrated knowledge of contrast media for cardiac imaging. In cardiac imaging, coronary artery evaluation is feasible by non-contrast MR angiography, which can be an alternative examination in high risk patients for the use of iodine contrast media. Furthermore, the body habitus of Asian patients is usually smaller than that of their western counterparts. This necessitates modifications in the injection protocol and in the formula for calculation of estimated glomerular filtration rate. This guideline provided fundamental information for the use of contrast media for Asian patients in cardiac imaging. PMID:20931289

Identification of di(ethylhexyl) phthalate as impurity in the analysis by using chromatography gas tandem mass spectrometry

Science.gov (United States)

Pusfitasari, Eka Dian; Hendarsyah, Hendris; Salahuddin, Ariani, Novita

2017-01-01

Di(ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in plastics. Physically DEHP has a low vapor pressure. DEHP can seep into the liquid in direct contact with the plastic wrapping materials, and typically can occur rapidly if extractable into food or non-polar solvents, such as oil, once the food is packaged in PVC packaging materials. DEHP has been analyzed by using gas chromatography which has a high sensitivity level. If the equipment used for the analysis is made from plastic containing DEHP, then it may be possible that DEHP can be extracted and appear on the outcome of the injection. It can interfere with the process of analysis, especially for the analysis of food samples. This study has identified the present of DEHP in the blank injection performed by Gas Chromatography tandem Mass Spectrometry with Selected Ion Monitoring mode (SIM). Researchers are required to verify whether the gas chromatographic system used is ready for the analysis process. In addition, the comparison and calculation of the intensity of the ion fragmentation spectra generated by mass spectrometry detector can be used for the qualitative determination to ensure the presence of the target compound. In this study is also discussed the differences between the high-intensity fragmentation of DEHP and dioctyl phthalate (DOP).

Acupuncture therapy related cardiac injury.

Science.gov (United States)

Li, Xue-feng; Wang, Xian

2013-12-01

Cardiac injury is the most serious adverse event in acupuncture therapy. The causes include needling chest points near the heart, the cardiac enlargement and pericardial effusion that will enlarge the projected area on the body surface and make the proper depth of needling shorter, and the incorrect needling method of the points. Therefore, acupuncture practitioners must be familiar with the points of the heart projected area on the chest and the correct needling methods in order to reduce the risk of acupuncture therapy related cardiac injury.

Mathematical Models of Cardiac Pacemaking Function

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Pan eLi

2013-10-01

Full Text Available Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

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McIver Lauren J

2009-12-01

Full Text Available Abstract Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level.

47. A cardiac center experience with Brugada syndrome who survived sudden cardiac death

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I. Suliman

2016-07-01

Full Text Available Brugada syndrome is a heritable arrhythmia syndrome that is characterized by an electrocardiographic pattern consisting of coved-type ST-segment elevation (2 mm followed by a negative T wave in the right precordial leads, V1 through V3 (often referred to as type 1 Brugada electrocardiographic pattern, here we describe 3 cases of Brugada who survived sudden cardiac death (SCD cardiac center experience with survived Brugada syndrome patients – case series. First Case: The Father 45 years old male, presented in 2005 after involvement in unprovoked motor vehicle accident, the patient was the driver who lost consciousness and rushed to the hospital. On arrival to our ER and putting the patient on the bed, the ER doctor observed a brief episode of VF on the monitor. The patient was taken to the catheterization Lab , his coronaries were normal. The diagnosis of Brugada was established and the patient received a defibrillator. At That Time all family members were screened and were negative. Second Case: The Son of the first patient 5 years later his 23 years old male rushed to our ER after he lost consciousness, he was passenger in the car of his friend. Third Case: The pilot A military pilot aged a male 35 years old was in very good health when he lost consciousness and brought to the hospital after resuscitation in 2005. He had full invasive cardiac evaluation, subsequently he received a defibrillator in the same admission period, till 2015 he is doing fine. Brugada syndrome is associated with high tendency for sudden cardiac death. In our three cases the first clinical presentation was survived sudden cardiac death (SCD and all three male patients survived. We did not encounter a female patient who survived sudden cardiac death.

Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

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José Manuel Calderón-Montaño

2014-01-01

Full Text Available Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na+/K+-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studies.

[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

Science.gov (United States)

Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

2013-01-01

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

Developmental changes in uncoupling protein 1 and F(1)-ATPase subunit levels in the golden hamster brown adipose tissue mitochondria as determined by electron microscopy in situ immunocytochemistry

Czech Academy of Sciences Publication Activity Database

Bednár, Jan; Soukup, Tomáš

2003-01-01

Roč. 22, - (2003), s. 477-486 ISSN 0231-5882 R&D Projects: GA ČR GA304/00/1653 Grant - others:NATO Research project(XX) 979876 Institutional research plan: CEZ:AV0Z5011922 Keywords : immunoelectron microscopy * uncoupling protein 1 * mitochondrial ATP synthase Subject RIV: ED - Physiology Impact factor: 0.794, year: 2003

Cardiac imaging. A multimodality approach

International Nuclear Information System (INIS)

Thelen, Manfred; Erbel, Raimund; Kreitner, Karl-Friedrich; Barkhausen, Joerg

2009-01-01

An excellent atlas on modern diagnostic imaging of the heart Written by an interdisciplinary team of experts, Cardiac Imaging: A Multimodality Approach features an in-depth introduction to all current imaging modalities for the diagnostic assessment of the heart as well as a clinical overview of cardiac diseases and main indications for cardiac imaging. With a particular emphasis on CT and MRI, the first part of the atlas also covers conventional radiography, echocardiography, angiography and nuclear medicine imaging. Leading specialists demonstrate the latest advances in the field, and compare the strengths and weaknesses of each modality. The book's second part features clinical chapters on heart defects, endocarditis, coronary heart disease, cardiomyopathies, myocarditis, cardiac tumors, pericardial diseases, pulmonary vascular diseases, and diseases of the thoracic aorta. The authors address anatomy, pathophysiology, and clinical features, and evaluate the various diagnostic options. Key features: - Highly regarded experts in cardiology and radiology off er image-based teaching of the latest techniques - Readers learn how to decide which modality to use for which indication - Visually highlighted tables and essential points allow for easy navigation through the text - More than 600 outstanding images show up-to-date technology and current imaging protocols Cardiac Imaging: A Multimodality Approach is a must-have desk reference for cardiologists and radiologists in practice, as well as a study guide for residents in both fields. It will also appeal to cardiac surgeons, general practitioners, and medical physicists with a special interest in imaging of the heart. (orig.)

Cross sectional imaging of cardiac tumors

International Nuclear Information System (INIS)

Maksimovic, R.

2012-01-01

Full text: Primary cardiac tumors are a rare entity whose incidence, according to surgery and autopsy reports, is 0.3% to 0.7% of all cardiac tumors. Metastasis to the heart from other primary cancers is 30 times more common. Only 25% of primary cardiac tumors are malignant, and, of these, 75% are sarcomas. Malignant primary cardiac sarcomas are usually located in the right atrium and are most commonly angiosarcoma. In the left atrium, the most common malignant tumors are pleomorphic sarcoma and leiomyosarcoma. Symptom presentation for cardiac tumors is quite varied, but it is dependent upon tumor location and size, rather than upon histologic characteristics. Presentation includes congestive heart failure from intracardiac obstruction, systemic embolization, constitutional symptoms, and arrhythmias. Left atrial sarcomas tend to be more solid and less infiltrative than right-sided sarcomas; consequently, they tend to metastasize later. They usually present with symptoms of blood-flow obstruction and substantial, life-threatening congestive heart failure. Right-sided cardiac tumors are usually malignant and appear as bulky, infiltrative masses that grow in an outward pattern. These are usually fast-growing tumors that metastasize early and do not present with congestive heart failure until late in the disease. The diagnosis of cardiac tumors relies heavily on the use of multiple imaging techniques, including cardiac computed tomography (CT), cardiovascular magnetic resonance (CMR), and echocardiography. Important imaging data to collect include information on the size of the intracardiac mass, the mobility of the mass (an important predictor of prognosis and embolic potential), myocardial invasion, and cardiac chamber location. These factors will provide the means to diagnosis and prognosis. Other important data to collect include the mechanism of tumor implantation, the relationship of the tumor with adjacent structures, the surgeon route of access to the heart

A model of survival following pre-hospital cardiac arrest based on the Victorian Ambulance Cardiac Arrest Register.

Science.gov (United States)

Fridman, Masha; Barnes, Vanessa; Whyman, Andrew; Currell, Alex; Bernard, Stephen; Walker, Tony; Smith, Karen L

2007-11-01

This study describes the epidemiology of sudden cardiac arrest patients in Victoria, Australia, as captured via the Victorian Ambulance Cardiac Arrest Register (VACAR). We used the VACAR data to construct a new model of out-of-hospital cardiac arrest (OHCA), which was specified in accordance with observed trends. All cases of cardiac arrest in Victoria that were attended by Victorian ambulance services during the period of 2002-2005. Overall survival to hospital discharge was 3.8% among 18,827 cases of OHCA. Survival was 15.7% among 1726 bystander witnessed, adult cardiac arrests of presumed cardiac aetiology, presenting in ventricular fibrillation or ventricular tachycardia (VF/VT), where resuscitation was attempted. In multivariate logistic regression analysis, bystander CPR, cardiac arrest (CA) location, response time, age and sex were predictors of VF/VT, which, in turn, was a strong predictor of survival. The same factors that affected VF/VT made an additional contribution to survival. However, for bystander CPR, CA location and response time this additional contribution was limited to VF/VT patients only. There was no detectable association between survival and age younger than 60 years or response time over 15min. The new model accounts for relationships among predictors of survival. These relationships indicate that interventions such as reduced response times and bystander CPR act in multiple ways to improve survival.

Sudden Cardiac Arrest during Participation in Competitive Sports.

Science.gov (United States)

Landry, Cameron H; Allan, Katherine S; Connelly, Kim A; Cunningham, Kris; Morrison, Laurie J; Dorian, Paul

2017-11-16

The incidence of sudden cardiac arrest during participation in sports activities remains unknown. Preparticipation screening programs aimed at preventing sudden cardiac arrest during sports activities are thought to be able to identify at-risk athletes; however, the efficacy of these programs remains controversial. We sought to identify all sudden cardiac arrests that occurred during participation in sports activities within a specific region of Canada and to determine their causes. In this retrospective study, we used the Rescu Epistry cardiac arrest database (which contains records of every cardiac arrest attended by paramedics in the network region) to identify all out-of-hospital cardiac arrests that occurred from 2009 through 2014 in persons 12 to 45 years of age during participation in a sport. Cases were adjudicated as sudden cardiac arrest (i.e., having a cardiac cause) or as an event resulting from a noncardiac cause, on the basis of records from multiple sources, including ambulance call reports, autopsy reports, in-hospital data, and records of direct interviews with patients or family members. Over the course of 18.5 million person-years of observation, 74 sudden cardiac arrests occurred during participation in a sport; of these, 16 occurred during competitive sports and 58 occurred during noncompetitive sports. The incidence of sudden cardiac arrest during competitive sports was 0.76 cases per 100,000 athlete-years, with 43.8% of the athletes surviving until they were discharged from the hospital. Among the competitive athletes, two deaths were attributed to hypertrophic cardiomyopathy and none to arrhythmogenic right ventricular cardiomyopathy. Three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening. In our study involving persons who had out-of-hospital cardiac arrest, the incidence of sudden cardiac

Mitochondrial oxidative stress and cardiac ageing.

Science.gov (United States)

Martín-Fernández, Beatriz; Gredilla, Ricardo

According with different international organizations, cardiovascular diseases are becoming the first cause of death in western countries. Although exposure to different risk factors, particularly those related to lifestyle, contribute to the etiopathogenesis of cardiac disorders, the increase in average lifespan and aging are considered major determinants of cardiac diseases events. Mitochondria and oxidative stress have been pointed out as relevant factors both in heart aging and in the development of cardiac diseases such as heart failure, cardiac hypertrophy and diabetic cardiomyopathy. During aging, cellular processes related with mitochondrial function, such as bioenergetics, apoptosis and inflammation are altered leading to cardiac dysfunction. Increasing our knowledge about the mitochondrial mechanisms related with the aging process, will provide new strategies in order to improve this process, particularly the cardiovascular ones. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Proteostasis in cardiac health and disease.

Science.gov (United States)

Henning, Robert H; Brundel, Bianca J J M

2017-11-01

The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing. Prevailing theories about the mechanisms of ageing feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of protein quality control as central factors. In the heart, loss of protein patency, owing to flaws in genetically-determined design or because of environmentally-induced 'wear and tear', can overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac ageing. Failure of protein quality control involves impairment of chaperones, ubiquitin-proteosomal systems, autophagy, and loss of sarcomeric and cytoskeletal proteins, all of which relate to induction of cardiomyocyte senescence. Targeting protein quality control to maintain cardiac proteostasis offers a novel therapeutic strategy to promote cardiac health and combat cardiac disease. Currently marketed drugs are available to explore this concept in the clinical setting.

Home-based versus centre-based cardiac rehabilitation.

Science.gov (United States)

Taylor, Rod S; Dalal, Hayes; Jolly, Kate; Moxham, Tiffany; Zawada, Anna

2010-01-20

The burden of cardiovascular disease world-wide is one of great concern to patients and health care agencies alike. Traditionally centre-based cardiac rehabilitation (CR) programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. To determine the effectiveness of home-based cardiac rehabilitation programmes compared with supervised centre-based cardiac rehabilitation on mortality and morbidity, health-related quality of life and modifiable cardiac risk factors in patients with coronary heart disease. We updated the search of a previous review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2007, Issue 4), MEDLINE, EMBASE and CINAHL from 2001 to January 2008. We checked reference lists and sought advice from experts. No language restrictions were applied. Randomised controlled trials (RCTs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes, in adults with myocardial infarction, angina, heart failure or who had undergone revascularisation. Studies were selected independently by two reviewers, and data extracted by a single reviewer and checked by a second one. Authors were contacted where possible to obtain missing information. Twelve studies (1,938 participants) met the inclusion criteria. The majority of studies recruited a lower risk patient following an acute myocardial infarction (MI) and revascularisation. There was no difference in outcomes of home- versus centre-based cardiac rehabilitation in mortality risk ratio (RR) was1.31 (95% confidence interval (C) 0.65 to 2.66), cardiac events, exercise capacity standardised mean difference (SMD) -0.11 (95% CI -0.35 to 0.13), as well as in modifiable risk factors (systolic blood pressure; diastolic blood pressure; total cholesterol

Digital subtraction angiography in cardiac diseases

International Nuclear Information System (INIS)

Choi, Deuk Lin; Kim, Ki Jeong

1986-01-01

DSA was done in 133 examinations of 128 patients during 2 years consist of 9 examination of IV DSA and 124 examination of selective cardiac DSA after cardiac catheterization. Open heart surgery was performed in 90 patients and 12 patients showed discrepancy between pre-and post operative diagnosis, showing a total 86.7% of diagnostic accuracy with DSA. We experienced the significant reduction in dose of contrast media, 30-40% of dose of conventional cardiac angiography. It is concluded that DSA is useful in the evaluation of septal defects, valvular disease and other congenital heart disease. DSA is an accurate simple and safe method in evaluating of cardiac diseases.

Toll-like receptor 9 mediated responses in cardiac fibroblasts.

Directory of Open Access Journals (Sweden)

Ingrid Kristine Ohm

Full Text Available Altered cardiac Toll-like receptor 9 (TLR9 signaling is important in several experimental cardiovascular disorders. These studies have predominantly focused on cardiac myocytes or the heart as a whole. Cardiac fibroblasts have recently been attributed increasing significance in mediating inflammatory signaling. However, putative TLR9-signaling through cardiac fibroblasts remains non-investigated. Thus, our aim was to explore TLR9-signaling in cardiac fibroblasts and investigate the consequence of such receptor activity on classical cardiac fibroblast cellular functions. Cultivated murine cardiac fibroblasts were stimulated with different TLR9 agonists (CpG A, B and C and assayed for the secretion of inflammatory cytokines (tumor necrosis factor α [TNFα], CXCL2 and interferon α/β. Expression of functional cardiac fibroblast TLR9 was proven as stimulation with CpG B and -C caused significant CXCL2 and TNFα-release. These responses were TLR9-specific as complete inhibition of receptor-stimulated responses was achieved by co-treatment with a TLR9-antagonist (ODN 2088 or chloroquine diphosphate. TLR9-stimulated responses were also found more potent in cardiac fibroblasts when compared with classical innate immune cells. Stimulation of cardiac fibroblasts TLR9 was also found to attenuate migration and proliferation, but did not influence myofibroblast differentiation in vitro. Finally, results from in vivo TLR9-stimulation with subsequent fractionation of specific cardiac cell-types (cardiac myocytes, CD45+ cells, CD31+ cells and cardiac fibroblast-enriched cell-fractions corroborated our in vitro data and provided evidence of differentiated cell-specific cardiac responses. Thus, we conclude that cardiac fibroblast may constitute a significant TLR9 responder cell within the myocardium and, further, that such receptor activity may impact important cardiac fibroblast cellular functions.

Multimodality imaging to guide cardiac interventional procedures

NARCIS (Netherlands)

Tops, Laurens Franciscus

2010-01-01

In recent years, a number of new cardiac interventional procedures have been introduced. Catheter ablation procedures for atrial fibrillation (AF) have been refined and are now considered a good treatment option in patients with drug-refractory AF. In cardiac pacing, cardiac resynchronization

[Cardiac involvement in Churg-Strauss syndrome].

Science.gov (United States)

Brucato, Antonio; Maestroni, Silvia; Masciocco, Gabriella; Ammirati, Enrico; Bonacina, Edgardo; Pedrotti, Patrizia

2015-09-01

Churg-Strauss syndrome, recently renamed eosinophilic granulomatosis with polyangiitis (EGPA), is a rare form of systemic vasculitis, characterized by disseminated necrotizing vasculitis with extravascular granulomas occurring among patients with asthma and tissue eosinophilia. EGPA is classified as a small and medium-sized vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) and the hypereosinophilic syndrome. Typical clinical features include asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Blood eosinophils are often >1500/µl or more than 10% on the differential leukocyte count. Blood eosinophils should always be tested in unexplained cardiac disorders, and may normalize even after low doses of corticosteroids. ANCA are positive in 40-60% of cases, mainly anti-myeloperoxidase. Heart involvement occurs in approximately 15-60% of EGPA patients, especially those who are ANCA negative. Any cardiac structure can be involved, and patients present with myocarditis, heart failure, pericarditis, arrhythmia, coronary arteritis, valvulopathy, intracavitary cardiac thrombosis. Although cardiovascular involvement is usually an early manifestation, it can also occur later in the course of the disease. A significant proportion of patients with cardiac involvement is asymptomatic. In the absence of symptoms and major ECG abnormalities, cardiac involvement may be detected in nearly 40% of the patients. All patients with EGPA should be studied not only with a detailed history of cardiac symptoms and ECG, but also with echocardiography; if abnormalities are detected, a cardiac magnetic resonance study should be performed. Coronary angiography and endomyocardial biopsy should be reserved to selected cases. Heart involvement carries a poor prognosis and causes 50% of the deaths of these patients. It is often insidious and underestimated. Optimal therapy is therefore important and based on high-dose corticosteroids plus immunosuppressive

Myocardial ischaemia and the cardiac nervous system.

Science.gov (United States)

Armour, J A

1999-01-01

The intrinsic cardiac nervous system has been classically considered to contain only parasympathetic efferent postganglionic neurones which receive inputs from medullary parasympathetic efferent preganglionic neurones. In such a view, intrinsic cardiac ganglia act as simple relay stations of parasympathetic efferent neuronal input to the heart, the major autonomic control of the heart purported to reside solely in the brainstem and spinal cord. Data collected over the past two decades indicate that processing occurs within the mammalian intrinsic cardiac nervous system which involves afferent neurones, local circuit neurones (interconnecting neurones) as well as both sympathetic and parasympathetic efferent postganglionic neurones. As such, intrinsic cardiac ganglionic interactions represent the organ component of the hierarchy of intrathoracic nested feedback control loops which provide rapid and appropriate reflex coordination of efferent autonomic neuronal outflow to the heart. In such a concept, the intrinsic cardiac nervous system acts as a distributive processor, integrating parasympathetic and sympathetic efferent centrifugal information to the heart in addition to centripetal information arising from cardiac sensory neurites. A number of neurochemicals have been shown to influence the interneuronal interactions which occur within the intrathoracic cardiac nervous system. For instance, pharmacological interventions that modify beta-adrenergic or angiotensin II receptors affect cardiomyocyte function not only directly, but indirectly by influencing the capacity of intrathoracic neurones to regulate cardiomyocytes. Thus, current pharmacological management of heart disease may influence cardiomyocyte function directly as well as indirectly secondary to modifying the cardiac nervous system. This review presents a brief summary of developing concepts about the role of the cardiac nervous system in regulating the normal heart. In addition, it provides some

Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function

Science.gov (United States)

Beaumont, Eric; Salavatian, Siamak; Southerland, E Marie; Vinet, Alain; Jacquemet, Vincent; Armour, J Andrew; Ardell, Jeffrey L

2013-01-01

The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias. PMID:23818689

Di-(2-ethylhexyl) phthalate could disrupt the insulin signaling pathway in liver of SD rats and L02 cells via PPARγ

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wang; Shen, Xin-Yue; Zhang, Wen-wen; Chen, Hao [Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of Education Ministry, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, Anhui (China); Xu, Wei-ping, E-mail: xu_weiping666@163.com [Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, Anhui (China); Wei, Wei, E-mail: wwei@ahmu.edu.cn [Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of Education Ministry, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, Anhui (China)

2017-02-01

Di-(2-ethylhexyl)-phthalate (DEHP), a ubiquitous industrial pollutant in our daily life, has been reported to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies previously. Recently, it has been reported to be an endocrine disrupter and ligand to peroxisome proliferator activated receptor, which could influence the homeostasis of liver metabolic systems and contribute to the development of type-2 diabetes. However, the potential mechanisms are not known yet. This study was designed to solve these problems with male SD rats and normal human hepatocyte line, L02 cells, exposed to DEHP for toxicological experiments. Adult male SD rats were divided into four groups, normal group fed with regular diets and three DEHP-treated groups (dissolved in olive oil at doses of 0.05, 5 and 500 mg/kg body weight, respectively, once daily through gastric intubations for 15 weeks). L02 cells were divided into 6 groups, normal group with 5, 10, 25, 50, and 100 μmol/l DEHP groups. DEHP-exposed rats exhibited significant liver damage, glucose tolerance, and insulin tolerance along with reduced expression of insulin receptor and GLUT4 proteins in the liver tissues. The results of in vitro experiments could determine that the DEHP-induced activation of peroxisome proliferator activated receptor γ (PPARγ) played a key role in the production of oxidative stress and down-regulated expression of insulin receptor and GLUT4 proteins in L02 cells. This conclusion could be supported by the results of in vitro experiments, in which the cells were exposed to DEHP with GW9662 (PPARγ inhibitor). In general, these results highlight the key role of PPARγ in the process of insulin resistance induced by DEHP. - Highlights: • DEHP exacerbates insulin resistance both in liver tissues and cells. • Expression of insulin receptor and GLUT4 were altered with PPARγ. • DEHP can induce oxidative stress to disrupt the metabolic homeostasis. • The dose of

Di-(2-ethylhexyl) phthalate could disrupt the insulin signaling pathway in liver of SD rats and L02 cells via PPARγ

International Nuclear Information System (INIS)

Zhang, Wang; Shen, Xin-Yue; Zhang, Wen-wen; Chen, Hao; Xu, Wei-ping; Wei, Wei

2017-01-01

Di-(2-ethylhexyl)-phthalate (DEHP), a ubiquitous industrial pollutant in our daily life, has been reported to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies previously. Recently, it has been reported to be an endocrine disrupter and ligand to peroxisome proliferator activated receptor, which could influence the homeostasis of liver metabolic systems and contribute to the development of type-2 diabetes. However, the potential mechanisms are not known yet. This study was designed to solve these problems with male SD rats and normal human hepatocyte line, L02 cells, exposed to DEHP for toxicological experiments. Adult male SD rats were divided into four groups, normal group fed with regular diets and three DEHP-treated groups (dissolved in olive oil at doses of 0.05, 5 and 500 mg/kg body weight, respectively, once daily through gastric intubations for 15 weeks). L02 cells were divided into 6 groups, normal group with 5, 10, 25, 50, and 100 μmol/l DEHP groups. DEHP-exposed rats exhibited significant liver damage, glucose tolerance, and insulin tolerance along with reduced expression of insulin receptor and GLUT4 proteins in the liver tissues. The results of in vitro experiments could determine that the DEHP-induced activation of peroxisome proliferator activated receptor γ (PPARγ) played a key role in the production of oxidative stress and down-regulated expression of insulin receptor and GLUT4 proteins in L02 cells. This conclusion could be supported by the results of in vitro experiments, in which the cells were exposed to DEHP with GW9662 (PPARγ inhibitor). In general, these results highlight the key role of PPARγ in the process of insulin resistance induced by DEHP. - Highlights: • DEHP exacerbates insulin resistance both in liver tissues and cells. • Expression of insulin receptor and GLUT4 were altered with PPARγ. • DEHP can induce oxidative stress to disrupt the metabolic homeostasis. • The dose of

Neuromuscular diseases after cardiac transplantation

NARCIS (Netherlands)

Mateen, Farrah J.; van de Beek, Diederik; Kremers, Walter K.; Daly, Richard C.; Edwards, Brooks S.; McGregor, Christopher G. A.; Wijdicks, Eelco F. M.

2009-01-01

BACKGROUND: Cardiac transplantation is a therapeutic option in end-stage heart failure. Peripheral nervous system (PNS) disease is known to occur in cardiac transplant recipients but has not been fully characterized. METHODS: This retrospective cohort review reports the PNS-related concerns of 313

Cardiac arrest – cardiopulmonary resuscitation

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Basri Lenjani

2014-01-01

Conclusions: All survivors from cardiac arrest have received appropriate medical assistance within 10 min from attack, which implies that if cardiac arrest occurs near an institution health care (with an opportunity to provide the emergent health care the rate of survival is higher.

Synthesis of mitochondrial uncoupling protein in brown adipocytes differentiated in cell culture

International Nuclear Information System (INIS)

Kopecky, J.; Baudysova, M.; Zanotti, F.; Janikova, D.; Pavelka, S.; Houstek, J.

1990-01-01

In order to characterize the biogenesis of unique thermogenic mitochondria of brown adipose tissue, differentiation of precursor cells isolated from mouse brown adipose tissue was studied in cell culture. Synthesis of mitochondrial uncoupling protein (UCP), F1-ATPase, and cytochrome oxidase was examined by L-[35S]methionine labeling and immunoblotting. For the first time, synthesis of physiological amounts of the UCP, a key and tissue-specific component of thermogenic mitochondria, was observed in cultures at about confluence (day 6), indicating that a complete differentiation of brown adipocytes was achieved in vitro. In postconfluent cells (day 8) the content of UCP decreased rapidly, in contrast to some other mitochondrial proteins (beta subunit of F1-ATPase, cytochrome oxidase). In these cells, it was possible, by using norepinephrine, to induce specifically the synthesis of the UCP but not of F1-ATPase or cytochrome oxidase. The maximal response was observed at 0.1 microM norepinephrine and the synthesis of UCP remained activated for at least 24 h. Detailed analysis revealed a major role of the beta-adrenergic receptors and elevated intracellular concentration of cAMP in stimulation of UCP synthesis. A quantitative recovery of the newly synthesized UCP in the mitochondrial fraction indicated completed biogenesis of functionally competent thermogenic mitochondria

Blood burden of di(2-ethylhexyl) phthalate and its primary metabolite mono(2-ethylhexyl) phthalate in pregnant and nonpregnant rats and marmosets

International Nuclear Information System (INIS)

Kessler, Winfried; Numtip, Wanwiwa; Grote, Konstanze; Csanady, Gyoergy A.; Chahoud, Ibrahim; Filser, Johannes G.

2004-01-01

A comparison of the dose-dependent blood burden of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in pregnant and nonpregnant rats and marmosets is presented. Sprague-Dawley rats and marmosets were treated orally with 30 or 500 mg DEHP/kg per day, nonpregnant animals on 7 (rats) and 29 (marmosets) consecutive days, pregnant animals on gestation days 14-19 (rats) and 96-124 (marmosets). In addition, rats received a single dose of 1000 mg DEHP/kg. Blood was collected up to 48 h after dosing. Concentrations of DEHP and MEHP in blood were determined by GC/MS. In rats, normalized areas under the concentration-time curves (AUCs) of DEHP were two orders of magnitude smaller than the normalized AUCs of the first metabolite MEHP. Metabolism of MEHP was saturable. Repeated DEHP treatment and pregnancy had only little influence on the normalized AUC of MEHP. In marmosets, most of MEHP concentration-time courses oscillated. Normalized AUCs of DEHP were at least one order of magnitude smaller than those of MEHP. In pregnant marmosets, normalized AUCs of MEHP were similar to those in nonpregnant animals with the exception that at 500 mg DEHP/kg per day, the normalized AUCs determined on gestation days 103, 117, and 124 were distinctly smaller. The maximum concentrations of MEHP in blood of marmosets were up to 7.5 times and the normalized AUCs up to 16 times lower than in rats receiving the same daily oral DEHP dose per kilogram of body weight. From this toxicokinetic comparison, DEHP can be expected to be several times less effective in the offspring of marmosets than in that of rats if the blood burden by MEHP in dams can be regarded as a dose surrogate for the MEHP burden in their fetuses

Di (2-ethylhexyl Phthalate Exposure Impairs Growth of Antral Follicle in Mice.

Directory of Open Access Journals (Sweden)

Lan Li

Full Text Available Di (2-ethylhexyl phthalate (DEHP is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-pubescent mice by use of intraperitoneal injection. Our results demonstrated that the percentage of large antral follicles was significantly reduced when mice were exposed to 20 or 40 μg/kg DEHP every 5 days from postnatal day 0 (0 dpp to 15 dpp. In 20 dpp, we performed microarray of these ovaries. The microarray results indicated that mRNA levels of apoptosis related genes were increased. The mRNA levels of the apoptosis and cell proliferation (negative related genes Apoe, Agt, Glo1 and Grina were increased after DEHP exposure. DEHP induced the differential gene expression of Hsp90ab1, Rhoa, Grina and Xdh which may play an important role in this process. In addition, TUNEL staining and immunofluorescence showed that DEHP exposure significantly increased the number of TUNEL, Caspase3 and γH2AX positive ovarian somatic cells within the mouse ovaries. Flow cytometer analyses of redox-sensitive probes showed that DEHP caused the accumulation of reactive oxygen species. Moreover, the mRNA expression of ovarian somatic cell antioxidative enzymes was down-regulated both in vivo and in vitro. In conclusion, our data here demonstrated that DEHP exposure induced oxidative stress and ovarian somatic cell apoptosis, and thus may impact antral follicle enlargement during the pre-pubertal stage in mice.

FET-biosensor for cardiac troponin biomarker

Directory of Open Access Journals (Sweden)

Md Arshad Mohd Khairuddin

2017-01-01

Full Text Available Acute myocardial infarction or myocardial infarction (MI is a major health problem, due to diminished flow of blood to the heart, leads to higher rates of mortality and morbidity. The most specific markers for cardiac injury are cardiac troponin I (cTnI and cardiac troponin T (cTnT which have been considered as ‘gold standard’. Due to higher specificity, determination of the level of cardiac troponins became a predominant indicator for MI. Currently, field-effect transistor (FET-based biosensors have been main interest to be implemented in portable sensors with the ultimate application in point-of-care testing (POCT. In this paper, we review on the FET-based biosensor based on its principle of operation, integration with nanomaterial, surface functionalization as well as immobilization, and the introduction of additional gate (for ambipolar conduction on the device architecture for the detection of cardiac troponin I (cTnI biomarker.

Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation

DEFF Research Database (Denmark)

Bartels, Emil D; Nielsen, Jan M; Hellgren, Lars I

2009-01-01

Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and beta-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via...... secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism...... remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression...

Suppression of injuries caused by a lytic RNA virus (mengovirus) and their uncoupling from viral reproduction by mutual cell/virus disarmament.

Science.gov (United States)

Mikitas, Olga V; Ivin, Yuri Y; Golyshev, Sergey A; Povarova, Natalia V; Galkina, Svetlana I; Pletjushkina, Olga Y; Nadezhdina, Elena S; Gmyl, Anatoly P; Agol, Vadim I

2012-05-01

Viruses often elicit cell injury (cytopathic effect [CPE]), a major cause of viral diseases. CPE is usually considered to be a prerequisite for and/or consequence of efficient viral growth. Recently, we proposed that viral CPE may largely be due to host defensive and viral antidefensive activities. This study aimed to check the validity of this proposal by using as a model HeLa cells infected with mengovirus (MV). As we showed previously, infection of these cells with wild-type MV resulted in necrosis, whereas a mutant with incapacitated antidefensive ("security") viral leader (L) protein induced apoptosis. Here, we showed that several major morphological and biochemical signs of CPE (e.g., alterations in cellular and nuclear shape, plasma membrane, cytoskeleton, chromatin, and metabolic activity) in cells infected with L(-) mutants in the presence of an apoptosis inhibitor were strongly suppressed or delayed for long after completion of viral reproduction. These facts demonstrate that the efficient reproduction of a lytic virus may not directly require development of at least some pathological alterations normally accompanying infection. They also imply that L protein is involved in the control of many apparently unrelated functions. The results also suggest that the virus-activated program with competing necrotic and apoptotic branches is host encoded, with the choice between apoptosis and necrosis depending on a variety of intrinsic and extrinsic conditions. Implementation of this defensive suicidal program could be uncoupled from the viral reproduction. The possibility of such uncoupling has significant implications for the pathogenesis and treatment of viral diseases.

A case of multiple cardiac calcified amorphous tumours

Directory of Open Access Journals (Sweden)

Amrit Chowdhary

2017-05-01

Full Text Available Cardiac calcified amorphous tumours of the heart are rare non-neoplastic cardiac masses that can present like a malignant mass or an intra-cardiac thrombus. We report an extremely unusual case of a 73 year old man who presented to hospital with dyspnoea and subsequent investigations revealed multiple cardiac CATs.

Cardiac pacing systems and implantable cardiac defibrillators (ICDs): a radiological perspective of equipment, anatomy and complications

Energy Technology Data Exchange (ETDEWEB)

Burney, K. E-mail: apqz59@dsl.pipex.comk1511@hotmail.com; Burchard, F.; Papouchado, M.; Wilde, P

2004-08-01

Cardiac pacing is a proven and effective treatment in the management of many cardiac arrhythmias. Implantable cardiac defibrillators (ICDs) are beneficial for certain patient groups with a history of serious, recurrent ventricular dysrhythmias, with a high risk of sudden cardiac death. Pacemaker devices take many forms and are highly visible on the chest radiograph. The radiographic appearances of ICDs and pacemakers can be similar and are subject to similar complications. The anatomical approach to the implantation, the type of device used and anatomical variations will all affect the appearance of these devices on the chest film. Pacemaker complications identified radiographically include pneumothorax, lead malpositioning, lead displacement or fracture, fracture of outer conductor coil, loose connection between the lead and pacemaker connector block, lack of redundant loops in paediatric patients and excessive manipulation of the device by the patient (Twiddler's syndrome). This pictorial review highlights the role of chest radiography in the diagnosis of post-cardiac pacing and ICD insertion complications, as well as demonstrating the normal appearances of the most frequently implanted devices.

Cardiac imaging. A multimodality approach

Energy Technology Data Exchange (ETDEWEB)

Thelen, Manfred [Johannes Gutenberg University Hospital, Mainz (Germany); Erbel, Raimund [University Hospital Essen (Germany). Dept. of Cardiology; Kreitner, Karl-Friedrich [Johannes Gutenberg University Hospital, Mainz (Germany). Clinic and Polyclinic for Diagnostic and Interventional Radiology; Barkhausen, Joerg (eds.) [University Hospital Schleswig-Holstein, Luebeck (Germany). Dept. of Radiology and Nuclear Medicine

2009-07-01

An excellent atlas on modern diagnostic imaging of the heart Written by an interdisciplinary team of experts, Cardiac Imaging: A Multimodality Approach features an in-depth introduction to all current imaging modalities for the diagnostic assessment of the heart as well as a clinical overview of cardiac diseases and main indications for cardiac imaging. With a particular emphasis on CT and MRI, the first part of the atlas also covers conventional radiography, echocardiography, angiography and nuclear medicine imaging. Leading specialists demonstrate the latest advances in the field, and compare the strengths and weaknesses of each modality. The book's second part features clinical chapters on heart defects, endocarditis, coronary heart disease, cardiomyopathies, myocarditis, cardiac tumors, pericardial diseases, pulmonary vascular diseases, and diseases of the thoracic aorta. The authors address anatomy, pathophysiology, and clinical features, and evaluate the various diagnostic options. Key features: - Highly regarded experts in cardiology and radiology off er image-based teaching of the latest techniques - Readers learn how to decide which modality to use for which indication - Visually highlighted tables and essential points allow for easy navigation through the text - More than 600 outstanding images show up-to-date technology and current imaging protocols Cardiac Imaging: A Multimodality Approach is a must-have desk reference for cardiologists and radiologists in practice, as well as a study guide for residents in both fields. It will also appeal to cardiac surgeons, general practitioners, and medical physicists with a special interest in imaging of the heart. (orig.)

Cyanide-induced death of dopaminergic cells is mediated by uncoupling protein-2 up-regulation and reduced Bcl-2 expression

International Nuclear Information System (INIS)

Zhang, X.; Li, L.; Zhang, L.; Borowitz, J.L.; Isom, G.E.

2009-01-01

Cyanide is a potent inhibitor of mitochondrial oxidative metabolism and produces mitochondria-mediated death of dopaminergic neurons and sublethal intoxications that are associated with a Parkinson-like syndrome. Cyanide toxicity is enhanced when mitochondrial uncoupling is stimulated following up-regulation of uncoupling protein-2 (UCP-2). In this study, the role of a pro-survival protein, Bcl-2, in cyanide-mediated cell death was determined in a rat dopaminergic immortalized mesencephalic cell line (N27 cells). Following pharmacological up-regulation of UCP-2 by treatment with Wy14,643, cyanide reduced cellular Bcl-2 expression by increasing proteasomal degradation of the protein. The increased turnover of Bcl-2 was mediated by an increase of oxidative stress following UCP-2 up-regulation. The oxidative stress involved depletion of mitochondrial glutathione (mtGSH) and increased H 2 O 2 generation. Repletion of mtGSH by loading cells with glutathione ethyl ester reduced H 2 O 2 generation and in turn blocked the cyanide-induced decrease of Bcl-2. To determine if UCP-2 mediated the response, RNAi knock down was conducted. The RNAi decreased cyanide-induced depletion of mtGSH, reduced H 2 O 2 accumulation, and inhibited down-regulation of Bcl-2, thus blocking cell death. To confirm the role of Bcl-2 down-regulation in the cell death, it was shown that over-expression of Bcl-2 by cDNA transfection attenuated the enhancement of cyanide toxicity after UCP-2 up-regulation. It was concluded that UCP-2 up-regulation sensitizes cells to cyanide by increasing cellular oxidative stress, leading to an increase of Bcl-2 degradation. Then the reduced Bcl-2 levels sensitize the cells to cyanide-mediated cell death.

Cardiac stress test as a risk-stratification tool for posttransplant cardiac outcomes in diabetic kidney transplant recipients.

Science.gov (United States)

Singh, Neeraj; Parikh, Samir; Bhatt, Udayan; Vonvisger, Jon; Nori, Uday; Hasan, Ayesha; Samavedi, Srinivas; Andreoni, Kenneth; Henry, Mitchell; Pelletier, Ronald; Rajab, Amer; Elkhammas, Elmahdi; Pesavento, Todd

2012-12-27

The utility of cardiac stress testing as a risk-stratification tool before kidney transplantation remains debatable owing to discordance with coronary angiography and outcome yields at different centers. We conducted a retrospective study of 273 diabetic kidney transplant recipients from 2006 to 2010. By protocol, all diabetic patients underwent pharmacological radionucleotide stress test or dobutamine stress echocardiography before transplant. We compared the 1-year cardiac outcomes between those with negative stress test results and those with positive stress test results. Patients with a positive stress test result (n=67) underwent coronary angiogram, and significant coronary artery disease (≥70% coronary stenosis) was found in 35 (52.2%) patients. Of the latter, 32 (91.4%) underwent cardiac revascularization (24 underwent cardiac stenting and 8 underwent coronary artery bypass grafting). The rest (n=35) were treated medically. Within 1 year after transplant, the group with positive stress test results experienced more cardiac events (34.3% vs. 3.9%, P<0.001) including acute myocardial infarction (22.4% vs. 3.4%, P<0.001) and ventricular arrhythmias (8.9% vs. 0.05%, P=0.001), higher all-cause mortality (19.4% vs. 4.8%, P<0.001), and cardiac mortality (17.9% vs. 0.9%, P<0.001) compared with the group with negative stress test results. In this diabetic population, stress testing showed positive and negative predictive values of 34.3% and 96.1%, respectively. Pharmacological cardiac stress testing provided excellent risk stratification in diabetic kidney transplant recipients.

Association between uncoupling protein 2, adiponectin and resting energy expenditure in obese women with normal and low resting energy expenditure.

Science.gov (United States)

Taghadomi Masoumi, Zahra; Eshraghian, Mohammad Reza; Hedayati, Mahdi; Pishva, Hamideh

2018-02-01

Obesity is recognized as the most prevalent metabolic disease worldwide. Decreases in energy expenditure may increase risk of obesity. One of the key regulators of energy balance is uncoupling protein2 (UCP2), a transporter protein presents in mitochondrial inner membrane. Moreover, adiponectin is the most abundant adipocytokine, it may play a role in energy metabolism and gene expression of UCP2. The aim of this study was to investigate potential associations between the level of uncoupling protein 2 and adiponectin and their relationship with REE (Resting Energy Expenditure) in obese women with normal and low resting energy expenditure. A total of 49 subjects (women, 25-50 years old), were included in current study, 16 subjects with BMI > 30 and low resting energy expenditure, 17 subjects with BMI > 30 and normal resting energy expenditure and 16 non-obese subjects as a control group. Anthropometric, body composition parameters and resting energy expenditure were measured. Plasma adiponectin, UCP2 protein and total protein in PBMC were determined. Measured resting energy expenditure in obese subjects with low REE was significantly lower than other groups. Plasma adiponectin in the obese subjects with low REE was significantly lower compared to normal weight group. There was a significant relationship between 'UCP2 protein/Total protein' ratio and plasma adiponectin in obese group with low REE and in three groups when we pooled. There was a significant association between REE and plasma adiponectin in three groups when we pooled. There was a significant association between plasma adiponectin and REE. Moreover, there was a significant relationship between UCP2 and REE.

Pathological links between stroke and cardiac arrest

Institute of Scientific and Technical Information of China (English)

Shaila Ghanekar; Sydney Corey; Trenton Lippert; Cesar V.Borlongan

2017-01-01

There may be a pathological connection between cardiac failure and ischemic stroke.In this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic stroke brain.Current stroke therapy overlooks the connection between cardiac and cerebrovascular events and fails to address the shared risk factors.Current pre-clinical stroke investigations have provided evidence that suggests the presence of an indirect cell death pathway in which toxic molecules emanate from the stroke brain and trigger cardiac cell death.On the other hand,other studies highlight the presence of a reverse cell death cascade in which toxic molecules from the heart,following cardiac arrest,travel to the brain and induce ischemic cell death.Further examination of these putative cell death pathways between ischemic stroke and cardiac arrest will prompt the advancement of innovative treatments specifically targeting both diseases,leading to ameliorated clinical results of patients diagnosed with heart failure and ischemic stroke.

The definition of exertion-related cardiac events.

Science.gov (United States)

Rai, M; Thompson, P D

2011-02-01

Vigorous physical activity increases the risk of sudden cardiac death (SCD) and acute myocardial infarction (AMI) but there is no standard definition as to what constitutes an exertion-related cardiac event, specifically the time interval between physical exertion and cardiac event. A systematic review of studies related to exertion-related cardiac events was performed and the time interval between exertion and the event or the symptoms leading to the event was looked for in all the articles selected for inclusion. A total of 12 of 26 articles "suggested" or "defined" exertion-related events as those events whose symptoms started during or within 1 h of exertion. Others used definitions of 0.5 h, 2 h, "during exertion", "during or immediately post exertion" and "during or within several hours after exertion". It is suggested, therefore, that the definition of an exertion-related cardiac event be established as a cardiac event in which symptoms started during or within 1 h of physical exertion.

Awareness in cardiac anesthesia.

LENUS (Irish Health Repository)

Serfontein, Leon

2010-02-01

Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

Radiation exposure during cardiac catheterization procedures

International Nuclear Information System (INIS)

Kicken, P.J.H.; Huyskens, C.J.; Michels, H.R.

1988-01-01

For some time there has been an increased interest in more information about radiation exposure during cardiac catheterization because of: relatively high doses to workers and patient; rapid increase of numbers of examinations; introduction of new procedure-types (e.g. Percutaneous Transluminal Coronary Angiography, PTCA) and introduction of new techniques (e.g. Digital Subtraction Angiography, DSA). This paper reports about a study on the exposure to medical personnel and patient in two major hospitals in the Netherlands. The Total number of cardiac catheterization procedures in both hospitals amounts to circa 3000 per year (approximately 10% of all cardiac procedures c.q. 20% of all PTCA procedures in the Netherlands). This study is related to 1300 cardiac examinations

Incidental Cardiac Findings on Thoracic Imaging.

LENUS (Irish Health Repository)

Kok, Hong Kuan

2013-02-07

The cardiac structures are well seen on nongated thoracic computed tomography studies in the investigation and follow-up of cardiopulmonary disease. A wide variety of findings can be incidentally picked up on careful evaluation of the pericardium, cardiac chambers, valves, and great vessels. Some of these findings may represent benign variants, whereas others may have more profound clinical importance. Furthermore, the expansion of interventional and surgical practice has led to the development and placement of new cardiac stents, implantable pacemaker devices, and prosthetic valves with which the practicing radiologist should be familiar. We present a collection of common incidental cardiac findings that can be readily identified on thoracic computed tomography studies and briefly discuss their clinical relevance.

An update on insertable cardiac monitors

DEFF Research Database (Denmark)

Olsen, Flemming J; Biering-Sørensen, Tor; Krieger, Derk W

2015-01-01

Continuous cardiac rhythm monitoring has undergone compelling progress over the past decades. Cardiac monitoring has emerged from 12-lead electrocardiograms being performed at the discretion of the treating physician to in-hospital telemetry, Holter monitoring, prolonged external event monitoring...... turning point in the field of arrhythmia management. However, their role in the detection of paroxysmal atrial fibrillation after cryptogenic strokes has yet to evolve. This will be the main focus of this review. Issues surrounding patient selection, clinical relevance and determination of cost......-effectiveness for prolonged cardiac monitoring require further studies. Furthermore, insertable cardiac monitoring has not only the potential to augment diagnostic capabilities but also to improve the management of paroxysmal atrial fibrillation....

Cardiac output measurement

Directory of Open Access Journals (Sweden)

Andreja Möller Petrun

2014-02-01

Full Text Available In recent years, developments in the measuring of cardiac output and other haemodynamic variables are focused on the so-called minimally invasive methods. The aim of these methods is to simplify the management of high-risk and haemodynamically unstable patients. Due to the need of invasive approach and the possibility of serious complications the use of pulmonary artery catheter has decreased. This article describes the methods for measuring cardiac output, which are based on volume measurement (Fick method, indicator dilution method, pulse wave analysis, Doppler effect, and electrical bioimpedance.

Cardiac arrest

Science.gov (United States)

... magnesium. These minerals help your heart's electrical system work. Abnormally high or low levels can cause cardiac arrest. Severe physical stress. Anything that causes a severe stress on your ...

42 CFR 410.49 - Cardiac rehabilitation program and intensive cardiac rehabilitation program: Conditions of coverage.

Science.gov (United States)

2010-10-01

... of the items and services furnished under the plan. (iii) The goals set for the individual under the... prescribed exercise, cardiac risk factor modification, psychosocial assessment, and outcomes assessment... section. Intensive cardiac rehabilitation site means a hospital outpatient setting or physician's office...

Residential exposure to plasticizers and its possible role in the pathogenesis of asthma

DEFF Research Database (Denmark)

Oie, L; Hersoug, Lars-Georg; Madsen, J O

1997-01-01

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is widely used in building materials. DEHP is identified as the major plasticizer exposure in dwellings. We provide evidence that inhalation exposure to DEHP as aerosols adsorbed to particulate matter is as important, or more important, than vapor...

Seismic Assessment of Buildings: Proposal of a New Modified Uncoupled Modal Response History Analysis

International Nuclear Information System (INIS)

Jerez, Sandra; Mebarki, Ahmed

2010-01-01

This paper develops a new modified uncoupled modal response history analysis (M-UMRHA) in order to study the seismic behavior of structures. It aims to provide an acceptable accuracy with reduced calculation duration in comparison to complete analysis, i.e. the THA. The proposed method improves the existing UMRHA, developed by Chopra and Goel [1], by considering an energy based approach to build the capacity curve [2] and a pseudo-adaptive feature to account for changes in modal shapes after yielding, motivated by an adaptive method [3]. Validation is made by comparison with NLTHA as well as other simplified methods. Low and medium-rise RC buildings were analyzed under real ground motion records. Results show good estimates of structural parameters and give good correlation between damage and story displacements as well as drifts. Like other simplified methods, accuracy decreases in the inelastic domain. However, this procedure gives acceptable estimates of structural response with a few additional calculations and it has the potential to be used in large scale studies, and probabilistic approaches.

Spatial uncoupling of biodegradation, soil respiration, and PAH concentration in a creosote contaminated soil

International Nuclear Information System (INIS)

Bengtsson, Goeran; Toerneman, Niklas; Yang Xiuhong

2010-01-01

Hotspots and coldspots of concentration and biodegradation of polycyclic aromatic hydrocarbons (PAHs) marginally overlapped at the 0.5-100 m scale in a creosote contaminated soil in southern Sweden, suggesting that concentration and biodegradation had little spatial co-variation. Biodegradation was substantial and its spatial variability considerable and highly irregular, but it had no spatial autocorrelation. The soil concentration of PAHs explained only 20-30% of the variance of their biodegradation. Soil respiration was spatially autocorrelated. The spatial uncoupling between biodegradation and soil respiration seemed to be governed by the aging of PAHs in the soil, since biodegradation of added 13 C phenanthrene covaried with both soil respiration and microbial biomass. The latter two were also correlated with high concentrations of phospholipid fatty acids (PLFAs) that are common in gram-negative bacteria. However, several of the hotspots of biodegradation coincided with hotspots for the distribution of a PLFA indicative of fungal biomass. - Hotspots of PAH biodegradation in a creosote contaminated soil do not coincide with hotspots of PAH concentration, microbial biomass and respiration.

Nppa and Nppb act redundantly during zebrafish cardiac development to confine AVC marker expression and reduce cardiac jelly volume.

Science.gov (United States)

Grassini, Daniela R; Lagendijk, Anne K; De Angelis, Jessica E; Da Silva, Jason; Jeanes, Angela; Zettler, Nicole; Bower, Neil I; Hogan, Benjamin M; Smith, Kelly A

2018-05-11

Atrial natriuretic peptide ( nppa/anf ) and brain natriuretic peptide ( nppb/bnp ) form a gene cluster with expression in the chambers of the developing heart. Despite restricted expression, a function in cardiac development has not been demonstrated by mutant analysis. This is attributed to functional redundancy however their genomic location in cis has impeded formal analysis. Using genome-editing, we generated mutants for nppa and nppb and found single mutants indistinguishable from wildtype whereas nppa / nppb double mutants display heart morphogenesis defects and pericardial oedema. Analysis of atrioventricular canal (AVC) markers show expansion of bmp4 , tbx2b, has2 and versican expression into the atrium of double mutants. This expanded expression correlates with increased extracellular matrix in the atrium. Using a biosensor for Hyaluronic acid to measure the cardiac jelly (cardiac extracellular matrix), we confirm cardiac jelly expansion in nppa / nppb double mutants. Finally, bmp4 knockdown rescues the expansion of has2 expression and cardiac jelly in double mutants. This definitively shows that nppa and nppb function redundantly during cardiac development to restrict gene expression to the AVC, preventing excessive cardiac jelly synthesis in the atrial chamber. © 2018. Published by The Company of Biologists Ltd.

Preoperative cardiac computed tomography for demonstration of congenital cardiac septal defect in adults

Energy Technology Data Exchange (ETDEWEB)

Eom, Hye-Joung; Yang, Dong Hyun; Kang, Joon-Won; Lim, Tae-Hwan [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Cardiac Imaging Center, Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae-Hee; Song, Jong-Min; Kang, Duk-Hyun; Song, Jae-Kwan [University of Ulsan College of Medicine, Department of Cardiology and Heart Institute, Cardiac Imaging Center, Asan Medical Center, Seoul (Korea, Republic of); Kim, Joon Bum; Jung, Sung-Ho; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won [University of Ulsan College of Medicine, Department of Cardiothoracic surgery, Cardiac Imaging Center, Asan Medical Center, Seoul (Korea, Republic of)

2015-06-01

We aimed to evaluate the role of preoperative cardiac computed tomography (CT) for adults with congenital cardiac septal defect (CSD). Sixty-five consecutive patients who underwent preoperative CT and surgery for CSD were included. The diagnostic accuracy of CT and the concordance rate of the subtype classification of CSD were evaluated using surgical findings as the reference standard. Sixty-five patients without CSD who underwent cardiac valve surgery were used as a control group. An incremental value of CT over echocardiography was described retrospectively. Sensitivity and specificity of CT for diagnosis of CSD were 95 % and 100 %, respectively. The concordance rate of subtype classification was 91 % in CT and 92 % in echocardiography. The maximum size of the defect measured by CT correlated well with surgical measurement (r = 0.82), and the limit of agreement was -0.9 ± 7.42 mm. In comparison with echocardiography, CT was able to detect combined abnormalities in three cases, and exclusively provided correct subtype classification or clarified suspected abnormal findings found on echocardiography in seven cases. Cardiac CT can accurately demonstrates CSD in preoperative adult patients. CT may have an incremental role in preoperative planning, particularly in those with more complex anatomy. (orig.)

Pediatric cardiac postoperative care

Directory of Open Access Journals (Sweden)

Auler Jr. José Otávio Costa

2002-01-01

Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts.

Directory of Open Access Journals (Sweden)

Hieu T Nim

Full Text Available The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP, an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1 relevant to cardiac literature, and (2 differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10 are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.

CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts.

Science.gov (United States)

Nim, Hieu T; Furtado, Milena B; Costa, Mauro W; Kitano, Hiroaki; Rosenthal, Nadia A; Boyd, Sarah E

2015-01-01

The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP), an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1) relevant to cardiac literature, and (2) differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10) are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.

Occurrence, fate and effects of Di (2-ethylhexyl) Phthalate in wastewater treatment plants: a review.

Science.gov (United States)

Zolfaghari, M; Drogui, P; Seyhi, B; Brar, S K; Buelna, G; Dubé, R

2014-11-01

Phthalates, such as Di (2-ethylhexyl) Phthalate (DEHP) are compounds extensively used as plasticizer for long time around the world. Due to the extensive usage, DEHP is found in many surface waters (0.013-18.5 μg/L), wastewaters (0.716-122 μg/L), landfill leachate (88-460 μg/L), sludge (12-1250 mg/kg), soil (2-10 mg/kg). DEHP is persistent in the environment and the toxicity of the byproducts resulting from the degradation of DEHP sometime exacerbates the parent compound toxicity. Water/Wastewater treatment processes might play a key role in delivering safe, reliable supplies of water to households, industry and in safeguarding the quality of water in rivers, lakes and aquifers. This review addresses state of knowledge concerning the worldwide production, occurrence, fate and effects of DEHP in the environment. Moreover, the fate and behavior of DEHP in various treatment processes, including biological, physicochemical and advanced processes are reviewed and comparison (qualitative and quantitative) has been done between the processes. The trends and perspectives for treatment of wastewaters contaminated by DEHP are also analyzed in this review. Copyright © 2014 Elsevier Ltd. All rights reserved.

Health Instruction Packages: Cardiac Anatomy.

Science.gov (United States)

Phillips, Gwen; And Others

Text, illustrations, and exercises are utilized in these five learning modules to instruct nurses, students, and other health care professionals in cardiac anatomy and functions and in fundamental electrocardiographic techniques. The first module, "Cardiac Anatomy and Physiology: A Review" by Gwen Phillips, teaches the learner to draw…

Lentiginosis, Deafness and Cardiac Abnormalities*

African Journals Online (AJOL)

1973-01-06

Jan 6, 1973 ... His height. mass. intelligence and genitalia were normal. The aSSOCiatIOn between deafness and disturbance of cardiac conduction and between pigmented skin lesions and cardiac abnormalities, has been well described. Should. ~I patient present with multiple lentigines and/or familial sensineural ...

Biodegradation of Di-(2-ethylhexyl) Phthalate by Rhodococcus ruber YC-YT1 in Contaminated Water and Soil

OpenAIRE

Ting Yang; Lei Ren; Yang Jia; Shuanghu Fan; Junhuan Wang; Jiayi Wang; Ruth Nahurira; Haisheng Wang; Yanchun Yan

2018-01-01

Di-(2-ethylehxyl) phthalate (DEHP) is one of the most broadly representative phthalic acid esters (PAEs) used as a plasticizer in polyvinyl chloride (PVC) production, and is considered to be an endocrine-disrupting chemical. DEHP and its monoester metabolites are responsible for adverse effects on human health. An efficient DEHP-degrading bacterial strain Rhodococcus ruber YC-YT1, with super salt tolerance (0–12% NaCl), is the first DEHP-degrader isolated from marine plastic debris found in c...

Automatic referral to cardiac rehabilitation.

Science.gov (United States)

Fischer, Jane P

2008-01-01

The pervasive negative impact of cardiovascular disease in the United States is well documented. Although advances have been made, the campaign to reduce the occurrence, progression, and mortality continues. Determining evidence-based data is only half the battle. Implementing new and updated clinical guidelines into daily practice is a challenging task. Cardiac rehabilitation is an example of a proven intervention whose benefit is hindered through erratic implementation. The American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR), the American College of Cardiology (ACC), and the American Heart Association (AHA) have responded to this problem by publishing the AACVPR/ACC/AHA 2007 Performance Measures on Cardiac Rehabilitation for Referral to and Delivery of Cardiac Rehabilitation/Secondary Prevention Services. This new national guideline recommends automatic referral to cardiac rehabilitation for every eligible patient (performance measure A-1). This article offers guidance for the initiation of an automatic referral system, including individualizing your protocol with regard to electronic or paper-based order entry structures.

Solving the Coupled System Improves Computational Efficiency of the Bidomain Equations

KAUST Repository

Southern, J.A.

2009-10-01

The bidomain equations are frequently used to model the propagation of cardiac action potentials across cardiac tissue. At the whole organ level, the size of the computational mesh required makes their solution a significant computational challenge. As the accuracy of the numerical solution cannot be compromised, efficiency of the solution technique is important to ensure that the results of the simulation can be obtained in a reasonable time while still encapsulating the complexities of the system. In an attempt to increase efficiency of the solver, the bidomain equations are often decoupled into one parabolic equation that is computationally very cheap to solve and an elliptic equation that is much more expensive to solve. In this study, the performance of this uncoupled solution method is compared with an alternative strategy in which the bidomain equations are solved as a coupled system. This seems counterintuitive as the alternative method requires the solution of a much larger linear system at each time step. However, in tests on two 3-D rabbit ventricle benchmarks, it is shown that the coupled method is up to 80% faster than the conventional uncoupled method-and that parallel performance is better for the larger coupled problem.

Solving the Coupled System Improves Computational Efficiency of the Bidomain Equations

KAUST Repository

Southern, J.A.; Plank, G.; Vigmond, E.J.; Whiteley, J.P.

2009-01-01

The bidomain equations are frequently used to model the propagation of cardiac action potentials across cardiac tissue. At the whole organ level, the size of the computational mesh required makes their solution a significant computational challenge. As the accuracy of the numerical solution cannot be compromised, efficiency of the solution technique is important to ensure that the results of the simulation can be obtained in a reasonable time while still encapsulating the complexities of the system. In an attempt to increase efficiency of the solver, the bidomain equations are often decoupled into one parabolic equation that is computationally very cheap to solve and an elliptic equation that is much more expensive to solve. In this study, the performance of this uncoupled solution method is compared with an alternative strategy in which the bidomain equations are solved as a coupled system. This seems counterintuitive as the alternative method requires the solution of a much larger linear system at each time step. However, in tests on two 3-D rabbit ventricle benchmarks, it is shown that the coupled method is up to 80% faster than the conventional uncoupled method-and that parallel performance is better for the larger coupled problem.

Association of morning blood pressure surge with carotid intima-media thickness and cardiac dysfunction in patients with cardiac syndrome-X.

Science.gov (United States)

Mahfouz, Ragab A; Goda, Mohammad; Galal, Islam; Ghareb, Mohamed S

2018-05-23

Background & hypothesis: We hypothesized that exaggerated morning blood pressure surge, may contribute in cardiac dysfunction and arterial stiffness in patients with cardiac syndrome X. Thus we investigated the impact of morning blood pressure surge on cardiac function and carotid intima-media thickness in subjects with cardiac syndrome X. We studied patients with cardiac syndrome X using ambulatory blood pressure monitoring and investigated the association of morning blood pressure surge with carotid intima thickness, left atrial volume index and left ventricular filling (E/e'). Seventy patients with cardiac syndrome X were enrolled for the study and compared with 70 age and sex matched controls. Patients with cardiac syndrome X were stratified based on the systolic morning blood pressure surge value of control subjects to patients with exaggerated blood pressure surge (n = 42) and those with normal morning blood pressure surge (n = 28). Basal heart rate (p blood pressure surge group than those with morning blood pressure surge group. Morning blood pressure surge was significantly correlated with carotid intima-media thickness, high sensitive C-reactive protein, left atrial volume index and E/e' ratio in patients with cardiac syndrome X. In multivariate analysis, exaggerated morning blood pressure surge was the only independent predictor of increased carotid intima-media thickness (OR = 2.379; p blood pressure surge is an independent predictor for arterial stiffness and diastolic dysfunction in patients with cardiac syndrome X.

Pediatric cardiac emergencies: Children are not small adults

Directory of Open Access Journals (Sweden)

Frazier Aisha

2011-01-01

Full Text Available Compared with adults, cardiac emergencies are infrequent in children and clinical presentation is often quite variable. In adults, cardiac emergencies are most commonly related to complications of coronary artery disease; however, in pediatric cases, the coronaries are only rarely the underlying problem. Pediatric cardiac emergencies comprise a range of pathology including but not limited to undiagnosed congenital heart disease in the infant; complications of palliated congenital heart disease in children; arrhythmias related to underlying cardiac pathology in the teenager and acquired heart disease. The emergency room physician and pediatric intensivist will usually be the first and second lines of care for pediatric cardiac emergencies and thus it is imperative that they have knowledge of the diverse presentations of cardiac disease in order to increase the likelihood of delivering early appropriate therapy and referral. The objective of this review is to outline cardiac emergencies in the pediatric population and contrast the presentation with adults.

Cardiac biomarkers in Neonatology

OpenAIRE

Vijlbrief, D.C.

2015-01-01

In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

Di(2-ethylhexyl)phthalate Alters the Synthesis and β-Oxidation of Fatty Acids and Hinders ATP Supply in Mouse Testes via UPLC-Q-Exactive Orbitrap MS-Based Metabonomics Study.

Science.gov (United States)

Shen, Guolin; Zhou, Lili; Liu, Wei; Cui, Yuan; Xie, Wenping; Chen, Huiming; Yu, Wenlian; Li, Wentao; Li, Haishan

2017-06-21

Di(2-ethylhexyl) phthalate (DEHP) is considered to be an environmental endocrine disruptor at high levels of general exposure. Studies show that DEHP may cause testicular toxicity on human being. In this study, metabonomics techniques were used to identify differential endogenous metabolites, draw the network metabolic pathways, and conduct network analysis, to determine the underlying mechanisms of testicular toxicity induced by DEHP. The results showed that DEHP inhibited synthesis and accelerated β-oxidation of fatty acids and impaired the tricarboxylic acid cycle (TCA cycle) and gluconeogenesis, resulting in lactic acid accumulation and an insufficient ATP supply in the microenvironment of the testis. These alterations led to testicular atrophy and, thus, may be the underlying causes of testicular toxicity. DEHP also inhibited peroxisome proliferator activated receptors in the testis, which may be another potential reason for the testicular atrophy. These findings provided new insights to better understand the mechanisms of testicular toxicity induced by DEHP exposure.

Di-(2-ethylhexyl)-phthalate disrupts pituitary and testicular hormonal functions to reduce sperm quality in mature goldfish

DEFF Research Database (Denmark)

Golshan, M.; Hatef, A.; Socha, M.

2015-01-01

Di-(2-ethylhexyl) phthalate (DEHP) interferes with male reproductive endocrine system in mammals, however its effects on fish reproduction are largely unknown. We evaluated sperm quality and investigated reproductive endocrine system in mature goldfish (Carassius auratus) exposed to nominal 1, 10......, and 100μg/L DEHP. To examine DEHP estrogenic activity, one group of goldfish was exposed to 17β-estradiol (5μg/L E2) for comparison. Following 30d of exposure, sperm production was decreased and suppressed in DEHP and E2 treated goldfish, respectively. Sperm motility and velocity were decreased...... in goldfish exposed to 100 and 10μg/L DEHP at 15s post-sperm activation, respectively. Compared to control, 11-ketotestosterone (11-KT) levels were decreased at 10 and 1μg/L DEHP at day 15 and 30, respectively. In E2 treated goldfish, 11-KT levels were decreased compared to control during the period...

Cardiac sympathetic neuronal imaging using PET

International Nuclear Information System (INIS)

Lautamaeki, Riikka; Tipre, Dnyanesh; Bengel, Frank M.

2007-01-01

Balance of the autonomic nervous system is essential for adequate cardiac performance, and alterations seem to play a key role in the development and progression of various cardiac diseases. PET imaging of the cardiac autonomic nervous system has advanced extensively in recent years, and multiple pre- and postsynaptic tracers have been introduced. The high spatial and temporal resolution of PET enables noninvasive quantification of neurophysiologic processes at the tissue level. Ligands for catecholamine receptors, along with radiolabeled catecholamines and catecholamine analogs, have been applied to determine involvement of sympathetic dysinnervation at different stages of heart diseases such as ischemia, heart failure, and arrhythmia. This review summarizes the recent findings in neurocardiological PET imaging. Experimental studies with several radioligands and clinical findings in cardiac dysautonomias are discussed. (orig.)

Intrinsic cardiac nervous system in tachycardia induced heart failure.

Science.gov (United States)

Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

2003-11-01

The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to

[Cardiac sarcoidosis: Diagnosis and therapeutic challenges].

Science.gov (United States)

Cohen Aubart, F; Nunes, H; Mathian, A; Haroche, J; Hié, M; Le-Thi Huong Boutin, D; Cluzel, P; Soussan, M; Waintraub, X; Fouret, P; Valeyre, D; Amoura, Z

2017-01-01

Sarcoidosis is a granulomatous disorder of unknown cause characterized by non-caseating granuloma in young adults. Cardiac involvement is rare and range from 2 to 75% depending on diagnostic criteria. Cardiac involvement in sarcoidosis may be asymptomatic or may manifest as rhythm/conduction troubles or congestive heart failure. The diagnosis and treatment of cardiac sarcoidosis may be challenging. However, advances have come in recent years from the use of cardiac MRI and 18 FDG-TEP scanner, as well as from the stratification of the risk of ventricular tachycardia/fibrillation. Due to the rarity of the disease, there is no reliable prospective large study to guide therapeutic strategy for cardiac sarcoidosis. Corticosteroids are probably efficacious, in particular in case of atrio-ventricular block or moderate heart failure. Immunosuppressive drugs have not been largely studied but methotrexate could be helpful. In refractory forms, TNF-α antagonists have been used with success. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Robotic cardiac surgery: an anaesthetic challenge.

Science.gov (United States)

Wang, Gang; Gao, Changqing

2014-08-01

Robotic cardiac surgery with the da Vinci robotic surgical system offers the benefits of a minimally invasive procedure, including a smaller incision and scar, reduced risk of infection, less pain and trauma, less bleeding and blood transfusion requirements, shorter hospital stay and decreased recovery time. Robotic cardiac surgery includes extracardiac and intracardiac procedures. Extracardiac procedures are often performed on a beating heart. Intracardiac procedures require the aid of peripheral cardiopulmonary bypass via a minithoracotomy. Robotic cardiac surgery, however, poses challenges to the anaesthetist, as the obligatory one-lung ventilation (OLV) and CO2 insufflation may reduce cardiac output and increase pulmonary vascular resistance, potentially resulting in hypoxaemia and haemodynamic compromise. In addition, surgery requires appropriate positioning of specialised cannulae such as an endopulmonary vent, endocoronary sinus catheter, and endoaortic clamp catheter under the guidance of transoesophageal echocardiography. Therefore, cardiac anaesthetists should have a working knowledge of these systems, OLV and haemodynamic support. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Epworth HealthCare cardiac surgery audit report 2011.

Science.gov (United States)

Chorley, T; Baker, L

2012-10-01

2011 is the first year Epworth has contributed to Australian and New Zealand Society of Cardiac and Thoracic Surgeons cardiac surgery database. There is now a 30-day follow-up data for all cardiac surgical patients as well as benchmarking of our results with 19 public hospitals and 6 private hospitals contributing data to the Australian and New Zealand Society of Cardiac and Thoracic Surgeons. This is an extension of the John Fuller Melbourne University database that has compiled cardiac surgery data for the last 30 years. © 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

The potential of cardiac allografts from donors after cardiac death at the University of Wisconsin Organ Procurement Organization.

Science.gov (United States)

Osaki, Satoru; Anderson, James E; Johnson, Maryl R; Edwards, Niloo M; Kohmoto, Takushi

2010-01-01

The purpose of this study is to investigate the potential availability of hearts from adult donation after cardiac death (DCD) donors within an acceptable hypoxic period. We retrospectively reviewed a donor database from the University of Wisconsin Organ Procurement Organization Donor Tracking System between 2004 and 2006. The DCD population (n=78) was screened using our inclusion criteria for DCD cardiac donor suitability, including warm ischaemic time (WIT) limit of 30 min. In the same period, 70 hearts were donated from brain-dead donors. Of 78 DCD donors, 12 (15%) met our proposed DCD cardiac donor criteria. The mean WIT of these 12 DCD donors was 21 min (range 14-29 min). When inclusion criteria are further narrowed to (1) age Based on our proposed DCD cardiac donor criteria, the potential application of DCD cardiac donors would represent an increase in cardiac donation of 17% (12/70) during the 3-year period. When the criteria were narrowed to the initial 'ideal' case, only two donors met such criteria, suggesting that such 'ideal' DCD donors are rare but they do exist. Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Cardiac Ochronosis

Science.gov (United States)

Erek, Ersin; Casselman, Filip P.A.; Vanermen, Hugo

2004-01-01

We report the case of 67-year-old woman who underwent aortic valve replacement and mitral valve repair due to ochronotic valvular disease (alkaptonuria), which was diagnosed incidentally during cardiac surgery. PMID:15745303

STEM promotion through museum exhibits on cardiac monitoring & cardiac rhythm management.

Science.gov (United States)

Countryman, Jordan D; Dow, Douglas E

2014-01-01

Formal education in science, technology, engineering and math (STEM) does not successfully engage all of the students who have potential to become skilled in STEM activities and careers. Museum exhibits may be able to reach and engage a broader range of the public. STEM Exhibits that are both understandable and capture the imagination of viewers may contribute toward increased interest in STEM activities. One such topic for such an exhibit could be cardiac pacemakers and cardioverter defibrillators that sustain life. Although museums have existed for centuries, the available types of exhibit designs has dramatically increased in recent decades due to innovations in technology. Science and technology museums have especially taken advantage of the progression of exhibit design to developed new ways to communicate to their viewers. These novel presentation tools allow museums to more effectively convey to and engage viewers. This paper examines the techniques employed by museums in exhibits and considers the practices of several museums with exhibits related to cardiac monitoring (CM) and cardiac rhythm management (CRM).

Intake of Phthalate-tainted Foods and Serum Thyroid Hormones in Taiwanese Children and Adolescents

Science.gov (United States)

Tsai, Hui-Ju; Wu, Chia-Fang; Tsai, Yi-Chun; Huang, Po-Chin; Chen, Mei-Lien; Wang, Shu-Li; Chen, Bai-Hsiun; Chen, Chu-Chih; Wu, Wen-Chiu; Hsu, Pi-Shan; Hsiung, Chao A.; Wu, Ming-Tsang

2016-07-01

On April-May, 2011, phthalates, mainly Di-(2-ethylhexyl) phthalate (DEHP), were deliberately added to a variety of foodstuff as a substitute emulsifier in Taiwan. This study investigated the relationship between DEHP-tainted foodstuffs exposure and thyroid function in possibly affected children and adolescents. Two hundred fifty participants food items. Blood and urine samples were collected for biochemical workups to measure current exposure derived from three urinary DEHP metabolites using a creatinine excretion-based model. More than half of 250 participants were estimated to be exposed to DEHP-tainted foods found to exceed the recommend tolerable daily intake of DEHP established by the European Food Safety Authority (studies may want to follow the long-term health effects of this food scandal in affected children and adolescents.

Gas chromatographic-mass spectrometric analysis of di(2-ethylhexyl) phthalate and its metabolites in hepatic microsomal incubations

Energy Technology Data Exchange (ETDEWEB)

Pietrogrande, M.C.; Rossi, D.; Paganetto, G

2003-03-17

A method is reported for the determination of di(2-ethylhexyl) phthalate (DEHP) and its metabolites in in vitro metabolism studies. Gas chromatography-mass spectrometry (GC-MS) analysis allows separation of 18 by-products of DEHP metabolism. On the basis of retention time and specific mass spectra m/z values, three classes of compounds can be identified: (i) alcohols as hydrolysis product; (ii) acids produced by alcohol oxidation; (iii) compounds retaining phthalic moiety. The chromatogram can also be acquired in SIM mode at m/z 149 resulting in 13 well-separated chromatographic peaks: from retention time and mass spectra it can be inferred that the main peaks correspond to mono(2-ethylhexyl) phthalate (MEHP) and ({omega}-1)-hydroxyl-MEHP. The kinetics of DEHP metabolism was studied using an S9 Aroclor-induced liver fraction as in vitro model and following incubation assay after 20, 40, 60 and 90 min. The composition of incubation mixtures can be quantitatively evaluated from selected ion monitoring chromatograms at m/z 149: the by-product concentration increases during the incubation time, as a consequence of DEHP degradation. During the incubation test a significant conversion of DEHP into MEHP is observed: a conversion yield of 10, 13, 16 and 20% of the original DEHP is obtained after 20, 40, 60 and 90 min, respectively. The metabolic conversion of DEHP to MEHP explains the endocrine-disrupting activity of the original DEHP; moreover, it has been demonstrated that MEHP and its ({omega}-1)-oxidation metabolite induce peroxisome proliferation. This result strengthens the suggestion that the study of DEHP metabolic pathway is fundamental to better understanding its toxicological behavior.

Cardiac imaging in adults

International Nuclear Information System (INIS)

Jaffe, C.C.

1987-01-01

This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority

Cardiac imaging in adults

Energy Technology Data Exchange (ETDEWEB)

Jaffe, C.C.

1987-01-01

This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

C.A.U.S.E.: Cardiac arrest ultra-sound exam--a better approach to managing patients in primary non-arrhythmogenic cardiac arrest.

Science.gov (United States)

Hernandez, Caleb; Shuler, Klaus; Hannan, Hashibul; Sonyika, Chionesu; Likourezos, Antonios; Marshall, John

2008-02-01

Cardiac arrest is a condition frequently encountered by physicians in the hospital setting including the Emergency Department, Intensive Care Unit and medical/surgical wards. This paper reviews the current literature involving the use of ultrasound in resuscitation and proposes an algorithmic approach for the use of ultrasound during cardiac arrest. At present there is the need for a means of differentiating between various causes of cardiac arrest, which are not a direct result of a primary ventricular arrhythmia. Identifying the cause of pulseless electrical activity or asystole is important as the underlying cause is what guides management in such cases. This approach, incorporating ultrasound to manage cardiac arrest aids in the diagnosis of the most common and easily reversible causes of cardiac arrest not caused by primary ventricular arrhythmia, namely; severe hypovolemia, tension pneumothorax, cardiac tamponade, and massive pulmonary embolus. These four conditions are addressed in this paper using four accepted emergency ultrasound applications to be performed during resuscitation of a cardiac arrest patient with the aim of determining the underlying cause of a cardiac arrest. Identifying the underlying cause of cardiac arrest represents the one of the greatest challenges of managing patients with asystole or PEA and accurate determination has the potential to improve management by guiding therapeutic decisions. We include several clinical images demonstrating examples of cardiac tamponade, massive pulmonary embolus, and severe hypovolemia secondary to abdominal aortic aneurysm. In conclusion, this protocol has the potential to reduce the time required to determine the etiology of a cardiac arrest and thus decrease the time between arrest and appropriate therapy.

Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.

Directory of Open Access Journals (Sweden)

Yao Song

Full Text Available AIMS: It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo. METHODS AND RESULTS: We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis. CONCLUSION: CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.

Direct cone-beam cardiac reconstruction algorithm with cardiac banding artifact correction

International Nuclear Information System (INIS)

Taguchi, Katsuyuki; Chiang, Beshan S.; Hein, Ilmar A.

2006-01-01

Multislice helical computed tomography (CT) is a promising noninvasive technique for coronary artery imaging. Various factors can cause inconsistencies in cardiac CT data, which can result in degraded image quality. These inconsistencies may be the result of the patient physiology (e.g., heart rate variations), the nature of the data (e.g., cone-angle), or the reconstruction algorithm itself. An algorithm which provides the best temporal resolution for each slice, for example, often provides suboptimal image quality for the entire volume since the cardiac temporal resolution (TRc) changes from slice to slice. Such variations in TRc can generate strong banding artifacts in multi-planar reconstruction images or three-dimensional images. Discontinuous heart walls and coronary arteries may compromise the accuracy of the diagnosis. A β-blocker is often used to reduce and stabilize patients' heart rate but cannot eliminate the variation. In order to obtain robust and optimal image quality, a software solution that increases the temporal resolution and decreases the effect of heart rate is highly desirable. This paper proposes an ECG-correlated direct cone-beam reconstruction algorithm (TCOT-EGR) with cardiac banding artifact correction (CBC) and disconnected projections redundancy compensation technique (DIRECT). First the theory and analytical model of the cardiac temporal resolution is outlined. Next, the performance of the proposed algorithms is evaluated by using computer simulations as well as patient data. It will be shown that the proposed algorithms enhance the robustness of the image quality against inconsistencies by guaranteeing smooth transition of heart cycles used in reconstruction

Cardiac ablation

Directory of Open Access Journals (Sweden)

Kelly Ratheal

2016-01-01

Full Text Available Cardiac ablation is a procedure that uses either radiofrequency or cryothermal energy to destroy cells in the heart to terminate and/or prevent arrhythmias. The indications for cardiac catheter ablation include refractory, symptomatic arrhythmias, with more specific guidelines for atrial fibrillation in particular. The ablation procedure itself involves mapping the arrhythmia and destruction of the aberrant pathway in an effort to permanently prevent the arrhythmia. There are many types of arrhythmias, and they require individualized approaches to ablation based on their innately different electrical pathways. Ablation of arrhythmias, such as Wolff-Parkinson-White syndrome, AV nodal reentrant tachycardia, and atrial-fibrillation, is discussed in this review. Ablation has a high success rate overall and minimal complication rates, leading to improved quality of life in many patients.

Cardiac transplantation: 15 years experience Cardiology Institute of Child

International Nuclear Information System (INIS)

Ceruti, B; Chiesa, P.; Tambasco, J.; Anzibar, R.; Gutierrez, C.; Barboza, S.; Manfredi, A.; Leone, R.

2012-01-01

The cardiac transplant is the treatment of choice for the cardiac insufficiency when there is not another therapeutic alternative that prolongs the life expectancy. On December 1996 The Cardiology Institute of child begin the program of Cardiac Insufficiency and Transplants of the Institute of Pediatric Cardiology, achieving the first cardiac transplant in a 14-year-old child in Uruguay. Three years later they put in practice the program of cardiac transplant in adults

[Hydatidosis simulating a cardiac tumour with pulmonary metastases].

Science.gov (United States)

Martín-Izquierdo, Marta; Martín-Trenor, Alejandro

2016-01-01

The presence of multiple symptomatic pulmonary nodules and one cardiac tumour in a child requires urgent diagnosis and treatment. Until a few decades ago, the diagnosis of a cardiac tumour was difficult and was based on a high index of suspicion from indirect signs, and required angiocardiography for confirmation. Echocardiography and other imaging techniques have also helped in the detection of cardiac neoplasms. However, it is not always easy to make the correct diagnosis. The case is presented of a 12 year-old boy with pulmonary symptoms, and diagnosed with a cardiac tumour with lung metastases. The presence of numerous pulmonary nodules was confirmed in our hospital. The echocardiogram detected a solid cardiac nodule in the right ventricle. Magnetic resonance imaging confirmed the findings and the diagnosis. Puncture-aspiration of a lung nodule gave the diagnosis of hydatidosis. He underwent open-heart surgery with cardiac cyst resection and treated with anthelmintics. The lung cysts were then excised, and he recovered uneventfully. This child had multiple pulmonary nodules and a solid cardiac nodule, and was suspected of having a cardiac tumour with pulmonary metastases. However, given the clinical history, background and morphology of pulmonary nodules, another possible aetiology for consideration is echinococcosis. The clinical picture of cardiac hydatidosis and its complications is highly variable. The clinical history is essential in these cases, as well as having a high index of suspicion. Hydatidosis should be included in the differential diagnosis of a solid, echogenic, cardiac nodule. The treatment for cardiopulmonary hydatid cysts is surgical, followed by anthelmintics. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Cardiac CT for planning redo cardiac surgery: effect of knowledge-based iterative model reconstruction on image quality

International Nuclear Information System (INIS)

Oda, Seitaro; Weissman, Gaby; Weigold, W. Guy; Vembar, Mani

2015-01-01

The purpose of this study was to investigate the effects of knowledge-based iterative model reconstruction (IMR) on image quality in cardiac CT performed for the planning of redo cardiac surgery by comparing IMR images with images reconstructed with filtered back-projection (FBP) and hybrid iterative reconstruction (HIR). We studied 31 patients (23 men, 8 women; mean age 65.1 ± 16.5 years) referred for redo cardiac surgery who underwent cardiac CT. Paired image sets were created using three types of reconstruction: FBP, HIR, and IMR. Quantitative parameters including CT attenuation, image noise, and contrast-to-noise ratio (CNR) of each cardiovascular structure were calculated. The visual image quality - graininess, streak artefact, margin sharpness of each cardiovascular structure, and overall image quality - was scored on a five-point scale. The mean image noise of FBP, HIR, and IMR images was 58.3 ± 26.7, 36.0 ± 12.5, and 14.2 ± 5.5 HU, respectively; there were significant differences in all comparison combinations among the three methods. The CNR of IMR images was better than that of FBP and HIR images in all evaluated structures. The visual scores were significantly higher for IMR than for the other images in all evaluated parameters. IMR can provide significantly improved qualitative and quantitative image quality at in cardiac CT for planning of reoperative cardiac surgery. (orig.)

Residential exposure to plasticizers and its possible role in the pathogenesis of asthma

DEFF Research Database (Denmark)

Oie, L; Hersoug, Lars-Georg; Madsen, J O

1997-01-01

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is widely used in building materials. DEHP is identified as the major plasticizer exposure in dwellings. We provide evidence that inhalation exposure to DEHP as aerosols adsorbed to particulate matter is as important, or more important, than vapor...... is a characteristic of asthma....

Residential Exposure to Plasticizers and Its Possible Role in the Pathogenesis of Asthma

DEFF Research Database (Denmark)

Øie, Leif; Hersoug, Lars-Georg; Madsen, Jørgen Øgaard

1997-01-01

The plasticizer di(2-ethylhexyl)phtlalate (DEHP) is widely used in building materials. DEHP is identified as the major plasticizer exposure in dwellings. We provide evidence that inhalation exposure to DEHP as aerosols adsorbed to particulate matter is as important, or more important, than vapor...... is a characteristic of asthma....

The impact of long term exposure to phthalic acid esters on reproduction in Chinese rare minnow (Gobiocypris rarus)

International Nuclear Information System (INIS)

Guo, Yongyong; Yang, Yuanjin; Gao, Yong; Wang, Xianfeng; Zhou, Bingsheng

2015-01-01

The environmental risk of phthalic acid esters (PAEs) is of great concern. We investigated the reproductive impairment of di-(2-ethylhexyl)-phthalate (DEHP) on Chinese rare minnow, an endemic fish inhabiting the upper streams of the Yangtze River. Chinese rare minnow larvae were exposed to environmentally relevant concentrations of DEHP (0, 4.2, 13.3, and 40.8 μg/L) for 6 months. Plasma testosterone and 17β-estradiol levels decreased in females, accompanied by downregulation of cyp19a and cyp17 gene transcription in ovary. Increases in plasma testosterone concentration were observed in males, accompanied by downregulation of cyp19a gene transcription in testes. Hepatic VTG gene transcription was upregulated in males and females. Exposure to DEHP reduced egg production and inhibited oocyte maturation in females and retarded spermiation in males. Decreased egg protein content was measured in F1 embryos. These results indicate that long-term exposure to low concentrations of DEHP (13.3 μg/L) causes endocrine disruption and impairs fish reproduction. - Highlights: • PAEs in the aquatic environment may pose risk to endemic fish species. • Long-term exposure to DEHP affected sex hormone levels in rare minnow. • DEHP affected gonad development. • Long-term exposure caused reduction of fecundity, but not sex ratio. • Environmentally relevant concentrations of DEHP impair fish reproduction. - Long-term exposure to low concentrations of DEHP adversely impact Chinese rare minnow reproduction

Inpatient cardiac rehabilitation programs' exercise therapy for patients undergoing cardiac surgery: National Korean Questionnaire Survey.

Science.gov (United States)

Seo, Yong Gon; Jang, Mi Ja; Park, Won Hah; Hong, Kyung Pyo; Sung, Jidong

2017-02-01

Inpatient cardiac rehabilitation (ICR) has been commonly conducted after cardiac surgery in many countries, and has been reported a lots of results. However, until now, there is inadequacy of data on the status of ICR in Korea. This study described the current status of exercise therapy in ICR that is performed after cardiac surgery in Korean hospitals. Questionnaires modified by previous studies were sent to the departments of thoracic surgery of 10 hospitals in Korea. Nine replies (response rate 90%) were received. Eight nurses and one physiotherapist completed the questionnaire. Most of the education on wards after cardiac surgery was conducted by nurses. On postoperative day 1, four sites performed sitting on the edge of bed, sit to stand, up to chair, and walking in the ward. Only one site performed that exercise on postoperative day 2. One activity (stairs up and down) was performed on different days at only two sites. Patients received education preoperatively and predischarge for preventing complications and reducing muscle weakness through physical inactivity. The results of the study demonstrate that there are small variations in the general care provided by nurses after cardiac surgery. Based on the results of this research, we recommended that exercise therapy programs have to conduct by exercise specialists like exercise physiologists or physiotherapists for patients in hospitalization period.

Technique for producing cardiac radionuclide motion images

International Nuclear Information System (INIS)

Reese, I.C.; Mishkin, F.S.

1975-01-01

Sequential frames of different portions of the cardiac cycle are gated into a minicomputer by using an EKG signal recorded onto digital tape simultaneously with imaging information. Serial display of these frames on the computer oscilloscope or projection of 35-mm half frames of these images provides a cardiac motion image with information content adequate for qualitatively assessing cardiac motion. (U.S.)

Sudden Cardiac Arrest (SCA) Risk Assessment

Science.gov (United States)

... HRS Find a Specialist Share Twitter Facebook SCA Risk Assessment Sudden Cardiac Arrest (SCA) occurs abruptly and without ... people of all ages and health conditions. Start Risk Assessment The Sudden Cardiac Arrest (SCA) Risk Assessment Tool ...

Cardiac cell modelling: Observations from the heart of the cardiac physiome project

KAUST Repository

Fink, Martin; Niederer, Steven A.; Cherry, Elizabeth M.; Fenton, Flavio H.; Koivumä ki, Jussi T.; Seemann, Gunnar; Thul, Rü diger; Zhang, Henggui; Sachse, Frank B.; Beard, Dan; Crampin, Edmund J.; Smith, Nicolas P.

2011-01-01

In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field. © 2010 Elsevier Ltd.

High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

Directory of Open Access Journals (Sweden)

Ulises Novoa

2017-01-01

Full Text Available Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes.

The cardiac patient in Ramadan.

Science.gov (United States)

Chamsi-Pasha, Majed; Chamsi-Pasha, Hassan

2016-01-01

Ramadan is one of the five fundamental pillars of Islam. During this month, the majority of the 1.6 billion Muslims worldwide observe an absolute fast from dawn to sunset without any drink or food. Our review shows that the impact of fasting during Ramadan on patients with stable cardiac disease is minimal and does not lead to any increase in acute events. Most patients with the stable cardiac disease can fast safely. Most of the drug doses and their regimen are easily manageable during this month and may need not to be changed. Ramadan fasting is a healthy nonpharmacological means for improving cardiovascular risk factors. Most of the Muslims, who suffer from chronic diseases, insist on fasting Ramadan despite being exempted by religion. The Holy Quran specifically exempts the sick from fasting. This is particularly relevant if fasting worsens one's illness or delays recovery. Patients with unstable angina, recent myocardial infarction, uncontrolled hypertension, decompensated heart failure, recent cardiac intervention or cardiac surgery or any debilitating diseases should avoid fasting.

Investigating patients' preferences for cardiac rehabilitation in Denmark

DEFF Research Database (Denmark)

Kjaer, Trine; Gyrd-Hansen, Dorte; Willaing, Ingrid

2006-01-01

the preferences for the offer of participation in various cardiac rehabilitation program activities: smoking cessation course, physical exercise program, personal meetings with cardiac nurse, group meetings managed by cardiac nurses, and nutritional counseling guidance. The questionnaire was sent to 742 former...

Social inequality in phase II cardiac rehabilitation attendance

DEFF Research Database (Denmark)

Pedersen, Maria; Egerod, Ingrid; Overgaard, Dorthe

2018-01-01

: Thirty per cent attended full cardiac rehabilitation. Patients with low educational attainment, comorbidities, long commute to cardiac rehabilitation centre, and lone dwelling were less likely to attend full cardiac rehabilitation, whereas patients with high anxiety and depression score were more likely...

Evaluation of Paradoxical Septal Motion Following Cardiac Surgery with Gated Cardiac Blood Pool Scan

International Nuclear Information System (INIS)

Shin, Seong Hae; Chung, June Key; Lee, Myung Chul; Cho, Bo Youn; Koh, Chang Soon; Suh, Kyung Phil

1985-01-01

The development of paradoxical interventricular septal motion is a common consequence of cardiopulmonary bypass operation. The reason for this postoperative abnormal septal motion is not clear. 41 patients were studied preoperatively and postoperatively with radionuclide blood pool scan to evaluate the frequency of development of paradoxical septal motion with right ventricular volume overload before surgery and the frequency of development of paradoxical septal motion after cardiac surgery with cardiopulmonary bypass, and to evaluate the change of EF related to the development of paradoxical septal motion after cardiac surgery. The results were as follows; 1) 7 of 41 patients with right ventricular volume overload (that is 17%) showed paradoxical septal motion before surgery. But 13 of 34 patients (that is 42%) had paradoxical septal motion after cardiac surgery with cardiopulmonary bypass. So open heart surgery with cardiopulmonary bypass related the development of paradoxical septal motion after surgery. 2) EF significantly decreased in patients who developed paradoxical septal motion after surgery, whereas the EF did not change in the patients who retained normal interventricular septal motion after surgery. So paradoxical septal motion usually reflected some diminution of left ventricular function, immediately after cardiac surgery.

Evaluation of Paradoxical Septal Motion Following Cardiac Surgery with Gated Cardiac Blood Pool Scan

Energy Technology Data Exchange (ETDEWEB)

Shin, Seong Hae; Chung, June Key; Lee, Myung Chul; Cho, Bo Youn; Koh, Chang Soon; Suh, Kyung Phil [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1985-03-15

The development of paradoxical interventricular septal motion is a common consequence of cardiopulmonary bypass operation. The reason for this postoperative abnormal septal motion is not clear. 41 patients were studied preoperatively and postoperatively with radionuclide blood pool scan to evaluate the frequency of development of paradoxical septal motion with right ventricular volume overload before surgery and the frequency of development of paradoxical septal motion after cardiac surgery with cardiopulmonary bypass, and to evaluate the change of EF related to the development of paradoxical septal motion after cardiac surgery. The results were as follows; 1) 7 of 41 patients with right ventricular volume overload (that is 17%) showed paradoxical septal motion before surgery. But 13 of 34 patients (that is 42%) had paradoxical septal motion after cardiac surgery with cardiopulmonary bypass. So open heart surgery with cardiopulmonary bypass related the development of paradoxical septal motion after surgery. 2) EF significantly decreased in patients who developed paradoxical septal motion after surgery, whereas the EF did not change in the patients who retained normal interventricular septal motion after surgery. So paradoxical septal motion usually reflected some diminution of left ventricular function, immediately after cardiac surgery.

Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl phthalate and genistein

Directory of Open Access Journals (Sweden)

Lian-Dong Zhang

2013-01-01

Full Text Available Studies of developmental effects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive effects of the co-administration of di-2-(ethylhexyl phthalate (DEHP and genistein (GEN during pregnancy and lactation were studied in male rat offspring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg/kg body weight (bwyday, GEN 50 mg/kg bwday, GEN 400 mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday + GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday. The outcomes studied were general morphometry (weight, AGD, testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coefficient, AGD / body weight1/3 י, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bwday, GEN(50mg/kg bwday or GEN(400mg/kg bwday alone were not significantly different from the control group. When exposed to (DEHP 250mg/kg bwday +GEN 50mg/kg bwday together during pregnancy and lactation, serum testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA expression significantly decreased compared to the control and GEN(50mg/kg bwday. When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday together during pregnancy and lactation, AGD / body weight1/3 י, serum testosterone concentration, testis and epididymis coefficient and Star, Cypal17a1 mRNA expression appeared significantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most significant alterations in the neonate, especially with GEN at high dose, although the effect of the DEHP

[Cardiac sarcoidosis: diagnostics, treatment and follow-up].

Science.gov (United States)

Dudziak, Maria; Jankowska, Hanna; Dorniak, Karolina

2018-03-27

Sarcoidosis is a generalised granulomatous disorder of unknown aetiology. Cardiac involvement may affect conduction system, myocardium, valvular apparatus and pericardium. Clinical spectrum ranges from asymptomatic involvement to sudden cardiac death. Patients with biopsy-proven extracardiac sarcoidosis should be screened for cardiac involvement (standard ECG, 24-hour Holter ECG, echocardiography) and in case of any abnormalities found on these tests, more advanced diagnostic methods should be used. Steroid treatment is still the mainstay of therapy in cardiac sarcoidosis. Several immunosuppresive agents are also effective and used in different combinations with steroids, as well as heart failure treatment (including ACE inhibitors, angiotensin receptor blockers, beta-blockers and diuretics). Advanced heart block requires pacemaker implantation, and implantable cardioverterdefibrillator is an effective treatment in primary and secondary prophylaxis of sudden cardiac death. Heart transplantation is considered in advanced, drug-resistant heart failure or incessant ventricular arrhythmias unresponsive to other forms of therapy. © 2018 MEDPRESS.

Cardiac catheterization

Science.gov (United States)

... tests. However, it is very safe when done by an experienced team. The risks include: Cardiac tamponade Heart attack Injury to a coronary artery Irregular heartbeat Low blood pressure Reaction to the contrast dye Stroke Possible complications ...

Cardiac hybrid imaging

Energy Technology Data Exchange (ETDEWEB)

Gaemperli, Oliver [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); University Hospital Zurich, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Kaufmann, Philipp A. [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

2014-05-15

Hybrid cardiac single photon emission computed tomography (SPECT)/CT imaging allows combined assessment of anatomical and functional aspects of cardiac disease. In coronary artery disease (CAD), hybrid SPECT/CT imaging allows detection of coronary artery stenosis and myocardial perfusion abnormalities. The clinical value of hybrid imaging has been documented in several subsets of patients. In selected groups of patients, hybrid imaging improves the diagnostic accuracy to detect CAD compared to the single imaging techniques. Additionally, this approach facilitates functional interrogation of coronary stenoses and guidance with regard to revascularization procedures. Moreover, the anatomical information obtained from CT coronary angiography or coronary artery calcium scores (CACS) adds prognostic information over perfusion data from SPECT. The use of cardiac hybrid imaging has been favoured by the dissemination of dedicated hybrid systems and the release of dedicated image fusion software, which allow simple patient throughput for hybrid SPECT/CT studies. Further technological improvements such as more efficient detector technology to allow for low-radiation protocols, ultra-fast image acquisition and improved low-noise image reconstruction algorithms will be instrumental to further promote hybrid SPECT/CT in research and clinical practice. (orig.)

Cardiac Cachexia Syndrome

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Teresa Raposo André

2017-10-01

Full Text Available Heart failure is a chronic, progressive, and incurable disease. Cardiac cachexia is a strong predictor of poor prognosis, regardless of other important variables. This review intends to gather evidence to enable recognition of cardiac cachexia, identification of early stages of muscle waste and sarcopenia, and improve identification of patients with terminal heart failure in need of palliative care, whose symptoms are no longer controlled by usual medical measures. The pathophysiology is complex and multifactorial. There are many treatment options to prevent or revert muscle waste and sarcopenia; although, these strategies are less effective in advanced stages of cardiac cachexia. In these final stages, symptomatic palliation plays an important role, focussing on the patient’s comfort and avoiding the ‘acute model’ treatment of aggressive, disproportionate, and inefficient care. In order to provide adequate care and attempt to prevent this syndrome, thus reducing its impact on healthcare, there should be improved communication between general practitioners, internal medicine physicians, cardiologists, and palliative care specialists since heart failure has an unforeseeable course and is associated with an increasing number of deaths and different levels of suffering.

"Just-In-Time" Simulation Training Using 3-D Printed Cardiac Models After Congenital Cardiac Surgery.

Science.gov (United States)

Olivieri, Laura J; Su, Lillian; Hynes, Conor F; Krieger, Axel; Alfares, Fahad A; Ramakrishnan, Karthik; Zurakowski, David; Marshall, M Blair; Kim, Peter C W; Jonas, Richard A; Nath, Dilip S

2016-03-01

High-fidelity simulation using patient-specific three-dimensional (3D) models may be effective in facilitating pediatric cardiac intensive care unit (PCICU) provider training for clinical management of congenital cardiac surgery patients. The 3D-printed heart models were rendered from preoperative cross-sectional cardiac imaging for 10 patients undergoing congenital cardiac surgery. Immediately following surgical repair, a congenital cardiac surgeon and an intensive care physician conducted a simulation training session regarding postoperative care utilizing the patient-specific 3D model for the PCICU team. After the simulation, Likert-type 0 to 10 scale questionnaire assessed participant perception of impact of the training session. Seventy clinicians participated in training sessions, including 22 physicians, 38 nurses, and 10 ancillary care providers. Average response to whether 3D models were more helpful than standard hand off was 8.4 of 10. Questions regarding enhancement of understanding and clinical ability received average responses of 9.0 or greater, and 90% of participants scored 8 of 10 or higher. Nurses scored significantly higher than other clinicians on self-reported familiarity with the surgery (7.1 vs. 5.8; P = .04), clinical management ability (8.6 vs. 7.7; P = .02), and ability enhancement (9.5 vs. 8.7; P = .02). Compared to physicians, nurses and ancillary providers were more likely to consider 3D models more helpful than standard hand off (8.7 vs. 7.7; P = .05). Higher case complexity predicted greater enhancement of understanding of surgery (P = .04). The 3D heart models can be used to enhance congenital cardiac critical care via simulation training of multidisciplinary intensive care teams. Benefit may be dependent on provider type and case complexity. © The Author(s) 2016.

[Thromboelastography and its use in cardiac surgery].

Science.gov (United States)

Ak, Koray; Atalan, Nazan; Tekeli, Atike; Işbir, Selim; Civelek, Ali; Emekli, Nesrin; Arsan, Sinan

2008-04-01

Thromboelastography is an alternative method to conventional coagulation tests for the general evaluation of hemostatic system. Cardiac surgery with cardiopulmonary bypass is accomplished by complex alterations of hemostasis, including acquired dysfunction of platelets, consumption coagulopathy and increased fibrinolysis. Despite major advances in blood conservation methods and perioperative care of the patients, transfusion rates in cardiac surgery remain high. Thromboelastography has an ability to assess almost all components of haemostatic system globally. Currently, thromboelastography is used with standard coagulation tests to decrease the microvascular bleeding and homologous blood transfusion in cardiac surgery with cardiopulmonary bypass. In this review, we aimed to discuss thromboelastography technology and its usage in cardiac surgery.

Radiation exposure of children during cardiac catheterisation

International Nuclear Information System (INIS)

Popp, W.

1979-01-01

It is well known that in adults, cardiac catheterisation involves the highest possible radiation exposure for a single examination. The paper now investigates the radiation exposure in paediatric cardiac cathetrisations. Dosimeters attached to the children during the examination were used as well as phantom measurements under the conditions of cardiac catheterisation. With the aid of the phantom, also the total energy absorption during an examination procedure was determined. This value was estimated to be 80 mJ. In spite of the high individual exposure, the contribution to the population exposure is low due to the small number of cardiac catheterisations. (orig.) 891 AJ/orig. 892 MKO [de

TGF-beta Sma/Mab signaling mutations uncouple reproductive aging from somatic aging.

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Shijing Luo

2009-12-01

Full Text Available Female reproductive cessation is one of the earliest age-related declines humans experience, occurring in mid-adulthood. Similarly, Caenorhabditis elegans' reproductive span is short relative to its total life span, with reproduction ceasing about a third into its 15-20 day adulthood. All of the known mutations and treatments that extend C. elegans' reproductive period also regulate longevity, suggesting that reproductive span is normally linked to life span. C. elegans has two canonical TGF-beta signaling pathways. We recently found that the TGF-beta Dauer pathway regulates longevity through the Insulin/IGF-1 Signaling (IIS pathway; here we show that this pathway has a moderate effect on reproductive span. By contrast, TGF-beta Sma/Mab signaling mutants exhibit a substantially extended reproductive period, more than doubling reproductive span in some cases. Sma/Mab mutations extend reproductive span disproportionately to life span and act independently of known regulators of somatic aging, such as Insulin/IGF-1 Signaling and Dietary Restriction. This is the first discovery of a pathway that regulates reproductive span independently of longevity and the first identification of the TGF-beta Sma/Mab pathway as a regulator of reproductive aging. Our results suggest that longevity and reproductive span regulation can be uncoupled, although they appear to normally be linked through regulatory pathways.

Cardiac Intensive Care Unit Management of Patients After Cardiac Arrest: Now the Real Work Begins.

Science.gov (United States)

Randhawa, Varinder K; Grunau, Brian E; Debicki, Derek B; Zhou, Jian; Hegazy, Ahmed F; McPherson, Terry; Nagpal, A Dave

2018-02-01

Survival with a good quality of life after cardiac arrest continues to be abysmal. Coordinated resuscitative care does not end with the effective return of spontaneous circulation (ROSC)-in fact, quite the contrary is true. Along with identifying and appropriately treating the precipitating cause, various components of the post-cardiac arrest syndrome also require diligent observation and management, including post-cardiac arrest neurologic injury and myocardial dysfunction, systemic ischemia-reperfusion phenomenon with potential consequent multiorgan failure, and the various sequelae of critical illness. There is growing evidence that an early invasive approach to coronary reperfusion with percutaneous coronary intervention, together with active targeted temperature management and optimization of hemodynamic, ventilator, and metabolic parameters, may improve survival and neurologic outcomes in cardiac arrest survivors. Neuroprognostication is complex, as are survivorship issues and long-term rehabilitation. Our paramedics, emergency physicians, and resuscitation specialists are all to be congratulated for ever-increasing success with ROSC… but now the real work begins. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Mediator binding to UASs is broadly uncoupled from transcription and cooperative with TFIID recruitment to promoters.

Science.gov (United States)

Grünberg, Sebastian; Henikoff, Steven; Hahn, Steven; Zentner, Gabriel E

2016-11-15

Mediator is a conserved, essential transcriptional coactivator complex, but its in vivo functions have remained unclear due to conflicting data regarding its genome-wide binding pattern obtained by genome-wide ChIP Here, we used ChEC-seq, a method orthogonal to ChIP, to generate a high-resolution map of Mediator binding to the yeast genome. We find that Mediator associates with upstream activating sequences (UASs) rather than the core promoter or gene body under all conditions tested. Mediator occupancy is surprisingly correlated with transcription levels at only a small fraction of genes. Using the same approach to map TFIID, we find that TFIID is associated with both TFIID- and SAGA-dependent genes and that TFIID and Mediator occupancy is cooperative. Our results clarify Mediator recruitment and binding to the genome, showing that Mediator binding to UASs is widespread, partially uncoupled from transcription, and mediated in part by TFIID. © 2016 The Authors.

A Summary of Coupled, Uncoupled, and Hybrid Tectonic Models for the Yakima Fold Belt--Topical Report

Energy Technology Data Exchange (ETDEWEB)

Chamness, Michele A.; Winsor, Kelsey; Unwin, Stephen D.

2012-08-01

This document is one in a series of topical reports compiled by the Pacific Northwest National Laboratory to summarize technical information on selected topics important to the performance of a probabilistic seismic hazard analysis of the Hanford Site. The purpose of this report is to summarize the range of opinions and supporting information expressed by the expert community regarding whether a coupled or uncoupled model, or a combination of both, best represents structures in the Yakima Fold Belt. This issue was assessed to have a high level of contention with up to moderate potential for impact on the hazard estimate. This report defines the alternative conceptual models relevant to this technical issue and the arguments and data that support those models. It provides a brief description of the technical issue and principal uncertainties; a general overview on the nature of the technical issue, along with alternative conceptual models, supporting arguments and information, and uncertainties; and finally, suggests some possible approaches for reducing uncertainties regarding this issue.

Cardiac findings in 31 patients with Noonan's syndrome

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Bertola Débora Romeo

2000-01-01

Full Text Available OBJECTIVE: To evaluate cardiac findings in 31 Noonan syndrome patients. METHODS: Thirty-one (18 males and 13 femalespatients from 26 families affected with Noonan's syndrome were evaluated from the cardiac point of view with electrocardiography and echodopplercardiography. RESULTS: Twenty patients had some type of cardiac abnormality. The most frequent was pulmonary valve stenosis followed by hypertrophic myocardiopathy, commonly associated with valve defects. Upper deviation of the QRS axis was observed in 80% of these patients. CONCLUSION: In view of the high frequency and diversity of cardiac abnormalities present in Noonan syndrome, cardiac evaluation with electrocardiography and echocardiography should be performed in all patients diagnostically suspected of having this disease.

Drug-Induced Rhabdomyolysis with Elevated Cardiac Troponin T

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Gro Egholm

2015-01-01

Full Text Available The essential role of cardiac troponin in the diagnosis of acute myocardial infarction has led to the development of high-sensitivity assays, which are able to detect very small amounts of myocardial necrosis. The high-sensitivity cardiac troponin T assay, however, is not entirely specific for myocardial injury. This case report describes a 48-year-old woman, who, two years after cardiac transplantation, presented with rhabdomyolysis. During the course of the disease, her troponin T level was elevated on repeated occasions, but other definitive evidence of myocardial injury was not found. Asymptomatic cardiac troponin T elevations during rhabdomyolysis may be due to either cardiac involvement or false positive results stemming from skeletal muscle injury.

J Waves for Predicting Cardiac Events in Hypertrophic Cardiomyopathy.

Science.gov (United States)

Tsuda, Toyonobu; Hayashi, Kenshi; Konno, Tetsuo; Sakata, Kenji; Fujita, Takashi; Hodatsu, Akihiko; Nagata, Yoji; Teramoto, Ryota; Nomura, Akihiro; Tanaka, Yoshihiro; Furusho, Hiroshi; Takamura, Masayuki; Kawashiri, Masa-Aki; Fujino, Noboru; Yamagishi, Masakazu

2017-10-01

This study sought to investigate whether the presence of J waves was associated with cardiac events in patients with hypertrophic cardiomyopathy (HCM). It has been uncertain whether the presence of J waves predicts life-threatening cardiac events in patients with HCM. This study evaluated consecutive 338 patients with HCM (207 men; age 61 ± 17 years of age). A J-wave was defined as J-point elevation >0.1 mV in at least 2 contiguous inferior and/or lateral leads. Cardiac events were defined as sudden cardiac death, ventricular fibrillation or sustained ventricular tachycardia, or appropriate implantable cardiac defibrillator therapy. The study also investigated whether adding the J-wave in a conventional risk model improved a prediction of cardiac events. J waves were seen in 46 (13.6%) patients at registration. Cardiac events occurred in 31 patients (9.2%) during median follow-up of 4.9 years (interquartile range: 2.6 to 7.1 years). In a Cox proportional hazards model, the presence of J waves was significantly associated with cardiac events (adjusted hazard ratio: 4.01; 95% confidence interval [CI]: 1.78 to 9.05; p = 0.001). Compared with the conventional risk model, the model using J waves in addition to conventional risks better predicted cardiac events (net reclassification improvement, 0.55; 95% CI: 0.20 to 0.90; p = 0.002). The presence of J waves was significantly associated with cardiac events in HCM. Adding J waves to conventional cardiac risk factors improved prediction of cardiac events. Further confirmatory studies are needed before considering J-point elevation as a marker of risk for use in making management decisions regarding risk in patients with HCM. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Left and right ventricle assessment with Cardiac CT: validation study vs. Cardiac MR

Energy Technology Data Exchange (ETDEWEB)

Maffei, Erica; Seitun, Sara [Giovanni XXIII Hospital, Cardiovascular Radiology Unit, Monastier di Treviso (Italy); Messalli, Giancarlo; Catalano, Onofrio [SDN Foundation - IRCCS, Naples (Italy); Martini, Chiara; Cademartiri, Filippo [Giovanni XXIII Hospital, Cardiovascular Radiology Unit, Monastier di Treviso (Italy); Erasmus Medical Center, Department of Radiology and Cardiology, Rotterdam (Netherlands); Nieman, Koen; Rossi, Alexia; Mollet, Nico R. [Erasmus Medical Center, Department of Radiology and Cardiology, Rotterdam (Netherlands); Guaricci, Andrea I. [Azienda Ospedaliero-Universitaria di Foggia, Department of Cardiology, Foggia (Italy); Tedeschi, Carlo [Ospedale San Gennaro, Department of Cardiology, Naples (Italy)

2012-05-15

To compare Magnetic Resonance (MR) and Computed Tomography (CT) for the assessment of left (LV) and right (RV) ventricular functional parameters. Seventy nine patients underwent both Cardiac CT and Cardiac MR. Images were acquired using short axis (SAX) reconstructions for CT and 2D cine b-SSFP (balanced-steady state free precession) SAX sequence for MR, and evaluated using dedicated software. CT and MR images showed good agreement: LV EF (Ejection Fraction) (52 {+-} 14% for CT vs. 52 {+-} 14% for MR; r = 0.73; p > 0.05); RV EF (47 {+-} 12% for CT vs. 47 {+-} 12% for MR; r = 0.74; p > 0.05); LV EDV (End Diastolic Volume) (74 {+-} 21 ml/m{sup 2} for CT vs. 76 {+-} 25 ml/m{sup 2} for MR; r = 0.59; p > 0.05); RV EDV (84 {+-} 25 ml/m{sup 2} for CT vs. 80 {+-} 23 ml/m{sup 2} for MR; r = 0.58; p > 0.05); LV ESV (End Systolic Volume)(37 {+-} 19 ml/m{sup 2} for CT vs. 38 {+-} 23 ml/m{sup 2} for MR; r = 0.76; p > 0.05); RV ESV (46 {+-} 21 ml/m{sup 2} for CT vs. 43 {+-} 18 ml/m{sup 2} for MR; r = 0.70; p > 0.05). Intra- and inter-observer variability were good, and the performance of CT was maintained for different EF subgroups. Cardiac CT provides accurate and reproducible LV and RV volume parameters compared with MR, and can be considered as a reliable alternative for patients who are not suitable to undergo MR. circle Cardiac-CT is able to provide Left and Right Ventricular function. circle Cardiac-CT is accurate as MR for LV and RV volume assessment. (orig.)

Improved bioavailability of targeted Curcumin delivery efficiently regressed cardiac hypertrophy by modulating apoptotic load within cardiac microenvironment

International Nuclear Information System (INIS)

Ray, Aramita; Rana, Santanu; Banerjee, Durba; Mitra, Arkadeep; Datta, Ritwik; Naskar, Shaon; Sarkar, Sagartirtha

2016-01-01

Cardiomyocyte apoptosis acts as a prime modulator of cardiac hypertrophy leading to heart failure, a major cause of human mortality worldwide. Recent therapeutic interventions have focussed on translational applications of diverse pharmaceutical regimes among which, Curcumin (from Curcuma longa) is known to have an anti-hypertrophic potential but with limited pharmacological efficacies due to low aqueous solubility and poor bioavailability. In this study, Curcumin encapsulated by carboxymethyl chitosan (CMC) nanoparticle conjugated to a myocyte specific homing peptide was successfully delivered in bioactive form to pathological myocardium for effective regression of cardiac hypertrophy in a rat (Rattus norvegicus) model. Targeted nanotization showed higher cardiac bioavailability of Curcumin at a low dose of 5 mg/kg body weight compared to free Curcumin at 35 mg/kg body weight. Moreover, Curcumin/CMC-peptide treatment during hypertrophy significantly improved cardiac function by downregulating expression of hypertrophy marker genes (ANF, β-MHC), apoptotic mediators (Bax, Cytochrome-c) and activity of apoptotic markers (Caspase 3 and PARP); whereas free Curcumin in much higher dose showed minimal improvement during compromised cardiac function. Targeted Curcumin treatment significantly lowered p53 expression and activation in diseased myocardium via inhibited interaction of p53 with p300-HAT. Thus attenuated acetylation of p53 facilitated p53 ubiquitination and reduced the apoptotic load in hypertrophied cardiomyocytes; thereby limiting cardiomyocytes' need to enter the regeneration cycle during hypertrophy. This study elucidates for the first time an efficient targeted delivery regimen for Curcumin and also attributes towards probable mechanistic insight into its therapeutic potential as a cardio-protective agent for regression of cardiac hypertrophy. - Highlights: • Cardiomyocyte targeted Curcumin/CMC-peptide increases bioavailability of the drug. �

Making an APPropriate Care Program for Indigenous Cardiac Disease: Customization of an Existing Cardiac Rehabilitation Program.

Science.gov (United States)

Bradford, DanaKai; Hansen, David; Karunanithi, Mohan

2015-01-01

Cardiovascular disease is a major health problem for all Australians and is the leading cause of death in Aboriginal and Torres Strait Islanders. In 2010, more then 50% of all heart attack deaths were due to repeated events. Cardiac rehabilitation programs have been proven to be effective in preventing the recurrence of cardiac events and readmission to hospitals. There are however, many barriers to the use of these programs. To address these barriers, CSIRO developed an IT enabled cardiac rehabilitation program delivered by mobile phone through a smartphone app and succesfully trialed it in an urban general population. If these results can be replicated in Indigenous populations, the program has the potential to significantly improve life expectancy and help close the gap in health outcomes. The challenge described in this paper is customizing the existing cardiac health program to make it culturally relevant and suitable for Indigenous Australians living in urban and remote communities.

Cardiac rhabdomyoma associated with tuberosclerosis complex in a newborn

Directory of Open Access Journals (Sweden)

Birgin Torer

2016-03-01

Full Text Available Cardiac rhabdomyomas are the most comman cardiac tumors in children. They are hamartomatous benign tumors composed of myocytes. They often presents as multiple lesions involving the ventricular cavities. Rhabdomyomas are usually detected in utero by fetal echocardiography. Although patients with cardiac rhabdomyomas are generally asymptomatic these tumors may cause heart failure, severe arrhyhmias and sudden death. Cardiac rhabdomyomas are often associated with tuberosclerosis and they may be the earliest manifestation of tuberosclerosis. Here, we report a newborn infant with antenatally detected cardiac rhabdomyomas associated with tuberosclerosis and we want to emphasize that other diagnostic features of tuberosclerosis should be evaluated in patients with cardiac rhabdomyomas. [Cukurova Med J 2016; 41(0.100: 56-59

Use of I-123 MIBG cardiac scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

International Nuclear Information System (INIS)

Maunoury, C.; Acar, P.; Sidi, D.

2006-01-01

I-123 MIBG cardiac scintigraphy is a useful tool to assess cardiac adrenergic neuronal function, which is impaired in children with dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function and on left ventricular function in seventeen patients (11 female, 6 male, mean age 39 ± 57 months, range 1 - 168 months) with DCM. All patients underwent I-123 MIBG cardiac scintigraphy and equilibrium radio-nuclide angiography before and after a 6 month period of carvedilol therapy. A static anterior view of the chest was acquired 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. Cardiac neuronal uptake of I-123 MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. There was no major cardiac events (death or transplantation) during the follow-up period. I-123 MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR 223 ± 49% vs 162 ± 26%, p < 0.0001 and LVEF = 43 ± 17% vs 26 ± 11%, p < 0.0001). Carvedilol can improve cardiac adrenergic neuronal function and left ventricular function in children with DCM. Further studies are needed to assess the relationship between improvement in I-123 MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (authors)

Post cardiac injury syndrome

DEFF Research Database (Denmark)

Nielsen, S L; Nielsen, F E

1991-01-01

The post-pericardiotomy syndrome is a symptom complex which is similar in many respects to the post-myocardial infarction syndrome and these are summarized under the diagnosis of the Post Cardiac Injury Syndrome (PCIS). This condition, which is observed most frequently after open heart surgery, i...... on the coronary vessels, with cardiac tamponade and chronic pericardial exudate. In the lighter cases, PCIS may be treated with NSAID and, in the more severe cases, with systemic glucocorticoid which has a prompt effect....

Assessment of cardiac sympathetic nerve integrity with positron emission tomography

International Nuclear Information System (INIS)

Raffel, David M.; Wieland, Donald M.

2001-01-01

The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation

Postnatal ablation of Foxm1 from cardiomyocytes causes late onset cardiac hypertrophy and fibrosis without exacerbating pressure overload-induced cardiac remodeling.

Directory of Open Access Journals (Sweden)

Craig Bolte

Full Text Available Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2 plays an important role in the pathogenesis of various cancers and is a critical mediator of post-injury repair in multiple organs. Foxm1 has been previously shown to be essential for heart development and proliferation of embryonic cardiomyocytes. However, the role of Foxm1 in postnatal heart development and in cardiac injury has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, αMHC-Cre/Foxm1(fl/fl mice were generated. Surprisingly, αMHC-Cre/Foxm1(fl/fl mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had no defects in cardiac structure or function but developed cardiac hypertrophy and fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac fibrosis in aged Foxm1-deficient mice was associated with reduced expression of Hey2, an important regulator of cardiac homeostasis, and increased expression of genes critical for cardiac remodeling, including MMP9, αSMA, fibronectin and vimentin. We also found that following aortic constriction Foxm1 mRNA and protein were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate cardiac hypertrophy or fibrosis following chronic pressure overload. Our results demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte hypertrophy and cardiac fibrosis.

Cardiac complications in diphtheria and predictors of outcomes.

Science.gov (United States)

Samdani, Sunil; Jain, Avani; Meena, Vinod; Meena, C B

2018-01-01

To study the cardiac complications in diphtheria patients and to study the predictors of outcomes. Single centre prospective analysis of cardiac complications in diphtheria patients. In this study, there were 60 patients diagnosed with diphtheria with ECG changes. The ECG changes seen were sinus tachycardia (68.3%), T wave inversion (20%), ST segment depression (13.3%), right bundle branch block (5%), multiple atrial ectopics (3.3%). The case fatality rate in our study was 25% (15 patients). High CPK-MB, myoglobulin and cardiac troponin levels were associated with cardiac mortality. In our study, cardiac troponin T had the highest sensitivity (80%) and CK-MB had the highest specificity (95.56%). Cardiac involvement is a common complication of infection with C. diphtheria and is associated with high mortality. As diphtheria can be prevented by adequate vaccination, efforts should be maximized for high vaccine coverage with booster doses. Copyright © 2017. Published by Elsevier B.V.

Implementing a Cardiac Skills Orientation and Simulation Program.

Science.gov (United States)

Hemingway, Maureen W; Osgood, Patrice; Mannion, Mildred

2018-02-01

Patients with cardiac morbidities admitted for cardiac surgical procedures require perioperative nurses with a high level of complex nursing skills. Orienting new cardiac team members takes commitment and perseverance in light of variable staffing levels, high-acuity patient populations, an active cardiac surgical schedule, and the unpredictability of scheduling patients undergoing cardiac transplantation. At an academic medical center in Boston, these issues presented opportunities to orient new staff members to the scrub person role, but hampered efforts to provide active learning opportunities in a safe environment. As a result, facility personnel created a program to increase new staff members' skills, confidence, and proficiency, while also increasing the number of staff members who were proficient at scrubbing complex cardiac procedures. To address the safe learning requirement, personnel designed a simulation program to provide scrubbing experience, decrease orientees' supervision time, and increase staff members' confidence in performing the scrub person role. © AORN, Inc, 2018.

Influence of the timing of cardiac catheterization and amount of contrast media on acute renal failure after cardiac surgery

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Mohsen Mirmohammad Sadeghi

2011-01-01

Full Text Available Background: There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF. Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated. Methods: Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression. Results: The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05. Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57% and 6 (52.17% after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002, followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009 and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031. Conclusions: Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have

Influence of the timing of cardiac catheterization and amount of contrast media on acute renal failure after cardiac surgery.

Science.gov (United States)

Sadeghi, Mohsen Mirmohammad; Gharipour, Mojgan; Nilforoush, Peiman; Shamsolkotabi, Hamid; Sadeghi, Hamid Mirmohammad; Kiani, Amjad; Sadeghi, Pouya Mirmohammad; Farahmand, Niloufar

2011-04-01

There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF). Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated. Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression. The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05). Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57%) and 6 (52.17%) after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002), followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009) and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031). Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have this protective effect.

Isolated Cardiac Hydatid Cyst

International Nuclear Information System (INIS)

Shakil, U.; Rehman, A. U.; Shahid, R.

2015-01-01

Hydatid cyst disease is common in our part of the world. Cardiac hydatid cyst is its rare manifestation. We report this case of 48-year male having isolated cardiac hydatid cyst, incidentally found on computed tomography. This patient presented in medical OPD of Combined Military Hospital, Lahore with one month history of mild retrosternal discomfort. His general physical and systemic examinations as well as ECG were unremarkable. Chest X-ray showed an enlarged cardiac shadow with mildly irregular left heart border. Contrast enhanced CT scan of the chest showed a large well defined multiloculated non-enhancing cystic lesion with multiple daughter cysts involving wall of left ventricle and overlying pericardium. Serology for echinococcus confirmed the diagnosis of hydatid cyst. Patient was offered the surgical treatment but he opted for medical treatment only. Albendezol was prescribed. His follow-up echocardiography after one month showed no significant decrease in size of the cyst. (author)

Hypokalemia and sudden cardiac death

DEFF Research Database (Denmark)

Kjeldsen, Keld

2010-01-01

Worldwide, approximately three million people suffer sudden cardiac death annually. These deaths often emerge from a complex interplay of substrates and triggers. Disturbed potassium homeostasis among heart cells is an example of such a trigger. Thus, hypokalemia and, also, more transient...... of fatal arrhythmia and sudden cardiac death a patient is, the more attention should be given to the potassium homeostasis....

Real-time MRI guidance of cardiac interventions.

Science.gov (United States)

Campbell-Washburn, Adrienne E; Tavallaei, Mohammad A; Pop, Mihaela; Grant, Elena K; Chubb, Henry; Rhode, Kawal; Wright, Graham A

2017-10-01

Cardiac magnetic resonance imaging (MRI) is appealing to guide complex cardiac procedures because it is ionizing radiation-free and offers flexible soft-tissue contrast. Interventional cardiac MR promises to improve existing procedures and enable new ones for complex arrhythmias, as well as congenital and structural heart disease. Guiding invasive procedures demands faster image acquisition, reconstruction and analysis, as well as intuitive intraprocedural display of imaging data. Standard cardiac MR techniques such as 3D anatomical imaging, cardiac function and flow, parameter mapping, and late-gadolinium enhancement can be used to gather valuable clinical data at various procedural stages. Rapid intraprocedural image analysis can extract and highlight critical information about interventional targets and outcomes. In some cases, real-time interactive imaging is used to provide a continuous stream of images displayed to interventionalists for dynamic device navigation. Alternatively, devices are navigated relative to a roadmap of major cardiac structures generated through fast segmentation and registration. Interventional devices can be visualized and tracked throughout a procedure with specialized imaging methods. In a clinical setting, advanced imaging must be integrated with other clinical tools and patient data. In order to perform these complex procedures, interventional cardiac MR relies on customized equipment, such as interactive imaging environments, in-room image display, audio communication, hemodynamic monitoring and recording systems, and electroanatomical mapping and ablation systems. Operating in this sophisticated environment requires coordination and planning. This review provides an overview of the imaging technology used in MRI-guided cardiac interventions. Specifically, this review outlines clinical targets, standard image acquisition and analysis tools, and the integration of these tools into clinical workflow. 1 Technical Efficacy: Stage 5 J

Stem cell sources for cardiac regeneration

NARCIS (Netherlands)

Roccio, M.; Goumans, M. J.; Sluijter, J. P. G.; Doevendans, P. A.

Cell-based cardiac repair has the ambitious aim to replace the malfunctioning cardiac muscle developed after myocardial infarction, with new contractile cardiomyocytes and vessels. Different stem cell populations have been intensively studied in the last decade as a potential source of new

Blunt traumatic cardiac rupture: therapeutic options and outcomes.

Science.gov (United States)

Nan, Yu-Yun; Lu, Ming-Shian; Liu, Kuo-Sheng; Huang, Yao-Kuang; Tsai, Feng-Chun; Chu, Jaw-Ji; Lin, Pyng Jing

2009-09-01

Cardiac rupture following blunt thoracic trauma is rarely encountered by clinicians, since it commonly causes death at the scene. With advances in traumatology, blunt cardiac rupture had been increasingly disclosed in various ways. This study reviews our experience of patients with suspected blunt traumatic cardiac rupture and proposes treatment protocols for the same. This is a 5-year retrospective study of trauma patients confirmed with blunt traumatic cardiac rupture admitted to a university-affiliated tertiary trauma referral centre. The following information was collected from the patients: age, sex, mechanism of injury, initial effective diagnostic tool used for diagnosing blunt cardiac rupture, location and size of the cardiac injury, associated injury and injury severity score (ISS), reversed trauma score (RTS), survival probability of trauma and injury severity scoring (TRISS), vital signs and biochemical lab data on arrival at the trauma centre, time elapsed from injury to diagnosis and surgery, surgical details, hospital course and final outcome. The study comprised 8 men and 3 women with a median age of 39 years (range: 24-73 years) and the median follow-up was 5.5 months (range: 1-35 months). The ISS, RTS, and TRISS scores of the patients were 32.18+/-5.7 (range: 25-43), 6.267+/-1.684 (range: 2.628-7.841), and 72.4+/-25.6% (range: 28.6-95.5%), respectively. Cardiac injuries were first detected using focused assessment with sonography for trauma (FAST) in 4 (36.3%) patients, using transthoracic echocardiography in 3 (27.3%) patients, chest CT in 1 (9%) patient, and intra-operatively in 3 (27.3%) patients. The sites of cardiac injury comprised the superior vena cava/right atrium junction (n=4), right atrial auricle (n=1), right ventricle (n=4), left ventricular contusion (n=1), and diffuse endomyocardial dissection over the right and left ventricles (n=1). Notably, 2 had pericardial lacerations presenting as a massive haemothorax, which initially masked

NUCLEAR IMAGING IN THE DIAGNOSIS OF CARDIAC AMYLOIDOSIS

Directory of Open Access Journals (Sweden)

V. B. Sergienko

2018-01-01

Full Text Available Histological analysis of endomyocardial tissue is still the gold standard for the diagnosis of cardiac amyloidosis but has its limitations. Accordingly, there is a need for noninvasive techniques to cardiac amyloidosis diagnostics. Echocardiography and magnetic resonance imaging can show characteristics which may not be very specific for cardiac amyloid. Recently, new opportunities of nuclear imaging in risk stratification and assessment of prognosis for patients with cardiac amyloidosis have appeared. During the last two decades different classes of radiopharmaceuticals have been developed based on compounds tropic to the components of amyloid infiltrates. In this paper we describe the current possibilities and perspectives of nuclear medicine techniques in patients with cardiac amyloidosis, including osteotropic and neurotropic scintigraphy, single-photon and positron emission tomography

Peripheral vasodilatation determines cardiac output in exercising humans

DEFF Research Database (Denmark)

Bada, A A; Svendsen, J H; Secher, N H

2012-01-01

In dogs, manipulation of heart rate has no effect on the exercise-induced increase in cardiac output. Whether these findings apply to humans remain uncertain, because of the large differences in cardiovascular anatomy and regulation. To investigate the role of heart rate and peripheral...... arterial ATP infusion at rest. Exercise and ATP infusion increased cardiac output, leg blood flow and vascular conductance (P heart rate by up to 54 beats min(−1), cardiac output did not change in any of the three...... demonstrate that the elevated cardiac output during steady-state exercise is regulated by the increase in skeletal muscle blood flow and venous return to the heart, whereas the increase in heart rate appears to be secondary to the regulation of cardiac output....

Characterizing gas-particle interactions of phthalate plasticizer emitted from vinyl flooring.

Science.gov (United States)

Benning, Jennifer L; Liu, Zhe; Tiwari, Andrea; Little, John C; Marr, Linsey C

2013-03-19

Phthalates are widely used as plasticizers, and improved ability to predict emissions of phthalates is of interest because of concern about their health effects. An experimental chamber was used to measure emissions of di-2-ethylhexyl-phthalate (DEHP) from vinyl flooring, with ammonium sulfate particles introduced to examine their influence on the emission rate and to measure the partitioning of DEHP onto airborne particles. When particles were introduced to the chamber at concentrations of 100 to 245 μg/m(3), the total (gas + particle) DEHP concentrations increased by a factor of 3 to 8; under these conditions, emissions were significantly enhanced compared to the condition without particles. The measured DEHP partition coefficient to ammonium sulfate particles with a median diameter of 45 ± 5 nm was 0.032 ± 0.003 m(3)/μg (95% confidence interval). The DEHP-particle sorption equilibration time was demonstrated to be less than 1 min. Both the partition coefficient and equilibration time agree well with predictions from the literature. This study represents the first known measurements of the particle-gas partition coefficient for DEHP. Furthermore, the results demonstrate that the emission rate of DEHP is substantially enhanced in the presence of particles. The particles rapidly sorb DEHP from the gas phase, allowing more to be emitted from the source, and also appear to enhance the convective mass-transfer coefficient itself. Airborne particles can influence SVOC fate and transport in the indoor environment, and these mechanisms must be considered in evaluating exposure and human health.

Mechanical perturbation control of cardiac alternans

Science.gov (United States)

Hazim, Azzam; Belhamadia, Youssef; Dubljevic, Stevan

2018-05-01

Cardiac alternans is a disturbance in heart rhythm that is linked to the onset of lethal cardiac arrhythmias. Mechanical perturbation control has been recently used to suppress alternans in cardiac tissue of relevant size. In this control strategy, cardiac tissue mechanics are perturbed via active tension generated by the heart's electrical activity, which alters the tissue's electric wave profile through mechanoelectric coupling. We analyze the effects of mechanical perturbation on the dynamics of a map model that couples the membrane voltage and active tension systems at the cellular level. Therefore, a two-dimensional iterative map of the heart beat-to-beat dynamics is introduced, and a stability analysis of the system of coupled maps is performed in the presence of a mechanical perturbation algorithm. To this end, a bidirectional coupling between the membrane voltage and active tension systems in a single cardiac cell is provided, and a discrete form of the proposed control algorithm, that can be incorporated in the coupled maps, is derived. In addition, a realistic electromechanical model of cardiac tissue is employed to explore the feasibility of suppressing alternans at cellular and tissue levels. Electrical activity is represented in two detailed ionic models, the Luo-Rudy 1 and the Fox models, while two active contractile tension models, namely a smooth variant of the Nash-Panfilov model and the Niederer-Hunter-Smith model, are used to represent mechanical activity in the heart. The Mooney-Rivlin passive elasticity model is employed to describe passive mechanical behavior of the myocardium.

Brain-Heart Interaction: Cardiac Complications After Stroke.

Science.gov (United States)

Chen, Zhili; Venkat, Poornima; Seyfried, Don; Chopp, Michael; Yan, Tao; Chen, Jieli

2017-08-04

Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart failure), or to mild and recoverable damage such as neurogenic stress cardiomyopathy and Takotsubo cardiomyopathy. The role of location and lateralization of brain lesions after stroke in brain-heart interaction; clinical biomarkers and manifestations of cardiac complications; and underlying mechanisms of brain-heart interaction after stroke, such as the hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic and parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, and systemic inflammation, are discussed. © 2017 American Heart Association, Inc.

Role of cardiac biomarkers (troponin I and CK-MB as predictors of quality of life and long-term outcome after cardiac surgery

Directory of Open Access Journals (Sweden)

Bignami Elena

2009-01-01

Full Text Available Perioperative and postoperative morbidity and mortality associated with cardiac surgery affect both the outcome and quality of life. Markers such as troponin effectively predict short-term outcome. In a prospective cohort study in a University Hospital we assessed the role of cardiac biomarkers, also as predictors of long-term outcome and life quality after cardiac surgery with a three-year follow-up after conventional heart surgery. Patients were interviewed via phone calls with a structured questionnaire examining general health, functional status, activities of daily living, perception of life quality and need for hospital readmission. Descriptive statistics and multivariate analysis were performed. Out of 252 consecutive patients, 8 (3.2% died at the three years follow up: 7 for cardiac complications and 1 for cancer. Thirty-six patients (13.5% had hospital readmission for cardiac causes (mostly for atrial fibrillation or other arrhythmias (9.3%, but none needed cardiac surgical reintervention; 21 patients (7.9% were hospitalised for non-cardiac causes. No limitation in function activities of daily living was reported by most patients (94%, 92% perceived their general health as excellent, very good or good and none considered it insufficient; 80% were NYHA I, 17% NYHA II, 3% NYHA III and none NYHA IV. Multivariate analysis indicated preoperative treatment with digitalis or nitrates, and postoperative cardiac biomarkers release was independently associated to death. Elevated cardiac biomarker release and length of hospital stay were the only postoperative independent predictors of death in this study.

Cardiac MRI of the athlete's heart

NARCIS (Netherlands)

Prakken, N.H.J.

2010-01-01

The increase in pre-participation cardiovascular screening using the Lausanne protocol will ultimately lead to an increased use of cardiac MRI and MDCT in the cardiovascular work-up of athletes. The role of cardiac MRI is well established in the evaluation of cardiomyopathies, myocarditis, aortic

Cardiac norepinephrine kinetics in hypertrophic cardiomyopathy

International Nuclear Information System (INIS)

Brush, J.E. Jr.; Eisenhofer, G.; Garty, M.; Stull, R.; Maron, B.J.; Cannon, R.O. III; Panza, J.A.; Epstein, S.E.; Goldstein, D.S.

1989-01-01

We examined the uptake and release of norepinephrine in the cardiac circulation and other regional vascular beds in 11 patients with hypertrophic cardiomyopathy (HCM) and in 10 control subjects during simultaneous infusion of tracer-labeled norepinephrine and isoproterenol. Cardiac neuronal uptake of norepinephrine was assessed by comparing regional removal of tracer-labeled norepinephrine with that of tracer-labeled isoproterenol (which is not a substrate for neuronal uptake) and by the relation between production of dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, and regional spillover of norepinephrine. Cardiac extraction of norepinephrine averaged 59 +/- 17% in the patients with HCM, significantly less than in the control subjects (79 +/- 13%, p less than 0.05), whereas cardiac extraction of isoproterenol was similar in the two groups (13 +/- 23% versus 13 +/- 14%), indicating that neuronal uptake of norepinephrine was decreased in the patients with HCM. The cardiac arteriovenous difference in norepinephrine was significantly larger in the patients with HCM than in the control subjects (73 +/- 77 versus 13 +/- 50 pg/ml, p less than 0.05), as was the product of the arteriovenous difference in norepinephrine and coronary blood flow (7.3 +/- 7.3 versus 0.8 +/- 3.0 ng/min, p less than 0.05)

Phthalate Migration Study from PVC Grafted by Gamma Radiation

International Nuclear Information System (INIS)

Manzoli, J.E.; Duarte, C.; Somesari, E.; Silveira, C.; Paes, H.A.; Manzoli, J.E.; Araujo, F.D.C.; Panzarini, L.C.G.A.

2009-01-01

PVC is a useful polymer used for many applications, as packaging of food, blood and in contact with body fluids. The most widely-used plasticizer, to make it flexible, is the phthalate DEHP, and its toxicity is a problem. A special radiation grafting of PVC allows an important reduction of thrombogenic properties, and it could cause changes in the DEHP migration too. In this work it is presented the methodology using gas chromatography and numerical simulation for the measurement of DEHP migration from PVC grafted with monomer DMAEMA. The grafting could be an interesting way to reduce DEHP migration

Biomimetic material strategies for cardiac tissue engineering

International Nuclear Information System (INIS)

Prabhakaran, Molamma P.; Venugopal, J.; Kai, Dan; Ramakrishna, Seeram

2011-01-01

Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.

Psychosocial aspects of cardiac rehabilitation in Europe.

Science.gov (United States)

Maes, S

1992-11-01

While the present objectives of cardiac rehabilitation include recovery or restoration of everyday behaviour and secondary prevention, the effects of the traditional exercise-based, cardiac rehabilitation programmes are quite modest. It is argued that psychological interventions may affect these targets more easily, since there is evidence from controlled studies that psychological interventions may have beneficial effects on psychosocial recovery, compliance with medical advice and cardiovascular morbidity and mortality. As a consequence one may expect that psychologists would be at least part-time members of most cardiac rehabilitation teams in European countries. In order to get an impression of the position of psychologists and the share of psychosocial care in cardiac rehabilitation in Europe, a questionnaire was sent out to two or three individuals in each European country. Health care professionals from 16 European countries returned their completed questionnaires on time. Among other things, the results show that in general social workers and psychologists, who may be considered the main potential agents for psychosocial care, are largely underrepresented in cardiac rehabilitation teams. As far as psychologists are concerned, the number involved in cardiac rehabilitation varies significantly from country to country. Three groups of countries could be distinguished: a group consisting of The Netherlands, Austria, and Italy, where psychologists are fairly well represented; a second one consisting of Norway, Finland and Belgium, where small numbers of psychologists are involved in cardiac rehabilitation; and a third group (the largest) consisting of Switzerland, Poland, Czechoslovakia, Denmark, Ireland, Sweden, the UK, Greece, Portugal and Turkey, where the number of psychologists is negligible.

Biomimetic material strategies for cardiac tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Prabhakaran, Molamma P., E-mail: nnimpp@nus.edu.sg [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Venugopal, J. [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Kai, Dan [NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (Singapore); Ramakrishna, Seeram [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)

2011-04-08

Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.